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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

FORM 10-K

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
  

ý


ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the Fiscal Year Ended December 31, 20132015

OR

oOR

 

o
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the Transition Period from                                  to                                 
Commission File Number: 001-36065

Commission File Number: 001-36065

ACCELERON PHARMA INC.
(Exact name of Registrant as specified in its charter)

Delaware
(State or other jurisdiction of
incorporation or organization)
 
27-0072226
(I.R.S. Employer
Identification No.)

128 Sidney Street
Cambridge, Massachusetts
(Address of principal executive offices)

 

02139
(Zip Code)

(617) 649-9200
(Registrant's telephone number, including area code)


Securities registered pursuant to Section 12(b) of the Act

Title of Class:Name of Each Exchange on Which Registered
Common Stock, $0.001 par value NASDAQ Global Market

Securities registered pursuant to Section 12(g) of the Act:None

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ý    No o    No 
ý

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Securities Act. Yes o    No ý

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to the filing requirements for the past 90 days. Yes ý    No o

Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes ý    No o

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K (§ 229.405) is not contained herein, and will not be contained, to the best of the registrant's knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K.    ý

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definitions of "large accelerated filer," "accelerated filer" and "smaller reporting company" in Rule 12b-2 of the Exchange Act. (Check one):

Large accelerated filer oý
 
Accelerated filer o
 
Non-accelerated filer ýo
(Do not check if a
smaller reporting company)
 
Smaller reporting company o

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act.) Yes o    No ý

         As

The aggregate market value of June 30, 2013,the registrant’s voting and non-voting common stock held by non-affiliates of the registrant (without admitting that any person whose shares are not included in such calculation is an affiliate) computed by reference to the price at which the common stock was last sold (based on the closing share price as quoted on the NASDAQ Global Market) as of the last business day of the registrant'sregistrant’s most recently completed second fiscal quarter the registrant's common stock was not publicly traded. The registrant's common stock began trading on the NASDAQ Global Market on September 19, 2013. As of December 31, 2013, the aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant was approximately $559 million, based on the closing price of the registrant's common stock on December 31, 2013.

$775 million.


As of January 31, 2014,2016, the registrant had 31,160,27437,096,412 shares of Common Stock, $0.001 par value per share, outstanding.


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ACCELERON PHARMA, INC.

FORM 10-K

INDEX



Page




DOCUMENTS INCORPORATED BY REFERENCE

The following documents (or parts thereof) are incorporated by reference into the following parts of this Form 10-K: Certain information required in Part III of this Annual Report on Form 10-K is incorporated from the Registrant’s Proxy Statement for the Annual Meeting of Stockholders to be held on June 2, 2016.




ACCELERON PHARMA INC.
FORM 10-K
INDEX

PART I.

  Page
 


Item 1.


2


Business





2


Item 1A.



Risk Factors





Item 1B.



Unresolved Staff Comments





Item 2.


44


Properties





71


Item 3.



Legal Proceedings





Item 4.



Mine Safety Disclosures







PART II.





 


Item 5.



Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities





Item 6.



Selected Financial Data





Item 7.



Management's Discussion and Analysis of Financial Condition and Results of Operations





Item 7A.



Quantitative and Qualitative Disclosures aboutAbout Market Risk





Item 8.



Financial Statements and Supplementary Data





Item 9.



Changes in and Disagreements with Accountants on Accounting and Financial Disclosure





Item 9A.



Controls and Procedures





Item 9B.



Other Information







PART III.





 


Item 10.



Directors, Executive Officers and Corporate Governance





Item 11.



Executive Compensation





Item 12.



Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters





Item 13.



Certain Relationships and Related Transactions, and Director Independence





Item 14.



Principal AccountantAccounting Fees and Services







PART IV.






 


Item 15.



Exhibits and Financial Statement Schedules







FORWARD-LOOKING STATEMENTS

This Annual Report filed on Form 10-K and the information incorporated herein by reference includes statements that are, or may be deemed, "forward-looking statements." In some cases, these forward-looking statements can be identified by the use of forward-looking terminology, including theterminology. The terms "believes," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should," "approximately""anticipate", "believe", "contemplate", "continue", "could", "estimate", "expect", "forecast", "goal", "intend", "may", "plan", "potential", "predict", "project", "should", "strategy", "target", "will", "would", "vision", or, in each case, theirthe negative or other variations thereon or comparable terminology,other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. They appear
        The forward-looking statements in a number of places throughout this Annual Report on Form 10-K and include, among other things, statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, things:
our ongoing and planned preclinical studies and clinical trials, trials;
clinical trial data and the timing of results of our ongoing clinical trials; 
our plans to develop and commercialize dalantercept and ACE-083, and our and Celgene's plans to develop and commercialize luspatercept and sotatercept; 
the potential benefits of strategic partnership agreements and our ability to enter into selective strategic partnership arrangements; 
the timing of, and our and Celgene's ability to, make regulatory filings and obtain and maintain regulatory approvals for our product candidates, therapeutic candidates; 
the rate and degree of market acceptance and clinical utility of our products,any approved therapeutic candidate, particularly in specific patient populations, expectationspopulations; 
our ability to quickly and efficiently identify and develop therapeutic candidates; 
our commercialization, marketing and manufacturing capabilities and strategy; 
our intellectual property position; and 
our estimates regarding clinical trial data, our results of operations, financial condition, liquidity, capital requirements, prospects, growth and strategies, the industry in which we operate and the trends that may affect the industry or us.

strategies.    

By their nature, forward-looking statements involve risks and uncertainties because they relate to events, competitive dynamics, and industry change and depend on the economic circumstances that may or may not occur in the future or may occur on longer or shorter timelines than anticipated. We caution you that forward-looking statements are not guarantees of future performance and that our actual results of operations, financial condition and liquidity, and events in the industry in which we operate may differ materially from the forward-looking statements contained herein.

Any forward-looking statements that we make in this Annual Report on Form 10-K speak only as of the date of such statement, and we undertake no obligation to update such statements to reflect events or circumstances after the date of this Annual Report on Form 10-K or to reflect the occurrence of unanticipated events.

You should also read carefully the factors described in the "Risk Factors" section of this Annual Report on Form 10-K to better understand the risks and uncertainties inherent in our business and underlying any forward-looking statements. You are advised, however, to consult any further disclosures we make on related subjects in our Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, press releases, and our website.

Trademarks
Trademarks

We own or have rights to trademarks, service marks and trade names that we use in connection with the operation of our business, including our corporate name, logos and website names. Other trademarks, service marks and trade names appearing in this report are the property of their respective owners. The trademarks that we own include Acceleron®Acceleron Pharma® and IntelliTrap. Solely for convenience, some of the trademarks, service marks and trade names referred to in this report are listed without the ® and symbols, but we will assert, to the fullest extent under applicable law, our rights to our trademarks, service marks and trade names.



1


PART I
PART I.

Item 1.    Business

Overview

We are a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases. Our research focusestherapeutic candidates that are based on the biology ofmechanisms that the Transforming Growth Factor-Beta (TGF-b) protein superfamily, a large and diverse group of molecules that are key regulators inhuman body uses to regulate the growth and repair of tissues throughoutits cells and tissues. Our research focuses on key natural regulators of cellular growth and repair, particularly the human body.Transforming Growth Factor-Beta, or TGF-beta, protein superfamily. We are leadersa leading company in understanding the biology of the TGF-b superfamilydiscovering and in targeting these pathways to develop important new medicines.developing therapeutic candidates that regulate cellular growth and repair. By couplingcombining our discovery and development expertise, including our proprietary knowledge of the TGF-bTGF-beta superfamily, withand our internal protein engineering and manufacturing capabilities, we have built a highly productive discovery and development platform that has generated innovative protein therapeutic candidates with novel mechanisms of action. These differentiated protein therapeutic candidates have the potential to significantly improve clinical outcomes for patients withacross many fields of medicine, and we have focused our discovery and development efforts on treatments for cancer and rare diseases.
We have four internally discovered therapeutic candidates that are currently in clinical trials: luspatercept, sotatercept, dalantercept and ACE-083.
Luspatercept, our lead program, and sotatercept, are partnered with Celgene Corporation, or Celgene. Luspatercept is designed to promote red blood cell production through a novel mechanism, and we are developing luspatercept with Celgene to treat anemia and associated complications in myelodysplastic syndromes (MDS) and beta-thalassemia. In 2015, Celgene initiated two Phase 3 clinical trials for luspatercept for the treatment of MDS and beta-thalassemia. We and Celgene are developing sotatercept to treat patients with chronic kidney disease. Sotatercept has the potential to treat several complications of chronic kidney disease including mineral-bone disorder, vascular calcification and anemia. Celgene is responsible for paying 100% of the development costs for all clinical trials for luspatercept and sotatercept, including our ongoing earlier stage clinical trials for these therapeutic candidates. We may receive up to an additional $560 million of potential development, regulatory and commercial milestone payments and, if these therapeutic candidates are commercialized, we will receive a royalty on net sales in the low-to-mid 20% range. We will co-promote luspatercept and sotatercept, if approved, in North America for which our commercialization costs will be entirely funded by Celgene.
We wholly own dalantercept and ACE-083, and we are independently developing these therapeutic candidates. We are currently evaluating dalantercept in a Phase 2 clinical trial for the treatment of patients with renal cell carcinoma. ACE-083 is designed for the treatment of focal muscle disorders, such as facioscapulohumeral dystrophy, and we are currently conducting a Phase 1 clinical trial with ACE-083 in healthy volunteers. In 2015, we reported data from the Phase 1 clinical trial of ACE-083 showing marked increases in the volume of muscles treated with ACE-083.
In addition to our clinical programs, we are conducting research to identify new therapeutic candidates to bring forward into clinical trials. To this end, in 2015 we implemented a new platform technology, IntelliTrap

, that is accelerating our discovery efforts. We have nominated an IntelliTrap molecule, ACE-2494, as a candidate for clinical development and will initiate IND-enabling activities in 2016. ACE-2494 is designed to treat systemic muscle disorders.

As of December 31, 2015 our operations have been funded primarily by $105.1 million in equity investments from venture investors, $219.3 million from public investors, $64.2 million in equity investments from our collaboration partners and $233.5 million in upfront payments, milestones, and net research and development payments from our collaboration partners. We focusestimate that we have spent approximately $145.4 million on discoveringresearch and development for the three year period from 2013 through 2015.
Our Objectives for the Year 2016
By building on the milestones achieved in 2015, we intend to advance and expand our pipeline in 2016 and achieve the following objectives:
Luspatercept in Rare Blood Disorders
Continue Phase 3 trials with Celgene for the treatment of myelodysplastic syndromes, the “MEDALIST” trial and beta-thalassemia, the “BELIEVE” trial;
Report updated results from Phase 2 extension study trials in MDS and beta-thalassemia at major medical conferences during the year; and
Announce initial preliminary Phase 2 data in ring sideroblast negative and erythropoiesis stimulating agent naïve MDS patients by year-end.
ACE-083 and ACE-2494 in Muscle Disorders
Report additional ACE-083 data from Phase 1 trial;

2


Initiate ACE-083 Phase 2 trial in facioscapulohumeral muscular dystrophy in the second half of 2016; and
File an IND with the FDA for systemically-acting muscle agent, ACE-2494, by year-end.
Dalantercept in Renal Cell Carcinoma
Announce top-line progression-free survival (PFS) results from Phase 2 DART study in renal cell carcinoma patients.
Sotatercept in Chronic Kidney Disease
Provide update on development strategy in pre-dialysis chronic kidney disease patients in the second half of 2016.
The Acceleron Discovery Platform: Novel Approaches to Potent Biology
Since our founding, we have focused on developing protein therapeuticstherapeutic candidates that targetregulate cellular growth and repair. We have targeted a group of approximately 30 secreted proteins, or ligands, that are collectively referred to as the TGF-bTGF-beta superfamily. These ligands bind to subsets of 12 different receptors on the surface of cells, triggering intra-cellular changes in gene expression that guide cell growth and differentiation. The TGF-b superfamily ligands and their receptors represent an under-explored and diverse set of drug targets with the potential to yield therapeutics that modulate the growth and repair of diseased cells and tissues.

        We have three internally discovered protein therapeutic candidates that are currently being studied in numerous ongoing Phase 2 clinical trials, focused on cancer and rare diseases. Our two most advanced protein therapeutic candidates, sotatercept and ACE-536, promote red blood cell production through a novel mechanism. Together with our collaboration partner, Celgene Corporation (Celgene), we are developing sotatercept and ACE-536 to treat anemia and associated complications in patients withb-thalassemia and myelodysplastic syndromes (MDS). These red blood cell disorders are generally unresponsive to currently approved drugs. Our third clinical stage protein therapeutic candidate, dalantercept, is designed to inhibit blood vessel formation through a mechanism that is distinct from, and potentially synergistic with, the dominant class of cancer drugs that inhibit blood vessel formation, the vascular endothelial growth factor (VEGF) pathway inhibitors. We are developing dalantercept primarily for use in combination with these products to produce better outcomes for cancer patients. We estimate that we have spent approximately $152.3 million on research and development from 2010 through 2013.

        Sotatercept and ACE-536 have already shown promising biological activity in our initial clinical trials. We and Celgene have conducted six human clinical trials with sotatercept in over 160 healthy volunteers and cancer patients. We have conducted one clinical trial with ACE-536 in healthy volunteers. In these studies, both sotatercept and ACE-536 caused a dose-dependent increase in the number of red blood cells. Based on these results, we and Celgene have initiated Phase 2 clinical trials with each of these protein therapeutic candidates inb-thalassemia and MDS. In the ongoing trials of sotatercept and ACE-536 in patients withb-thalassemia, we have observed encouraging, dose-dependent increases in hemoglobin in non-transfusion dependent patients at the three dose levels tested. We and Celgene plan to initiate Phase 3 clinical trials for one or both of these protein therapeutic candidates in one or both ofb-thalassemia and MDS by the end of 2014 or early 2015.

        With respect to our third clinical stage protein therapeutic candidate, dalantercept, we have conducted a single agent Phase 1 clinical trial in patients with advanced solid tumors. Of the 29 evaluable patients treated in this clinical trial, one had a partial response and 13 had stable disease, according to RECIST criteria. Additionally, we have studied the single agent activity of dalantercept in


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a Phase 2 clinical trial in patients with advanced head and neck cancer. Our ongoing focus is on the use of dalantercept in combination with an approved VEGF pathway inhibitor where we have provided both a mechanistic rationale and supportive preclinical data demonstrating dalantercept in combination with a VEGF pathway inhibitor provides enhanced anti-tumor effects in mice bearing human renal cell carcinoma xenographs. In an ongoing Phase 2 clinical trial of dalantercept in combination with axitinib, an approved VEGF pathway inhibitor, in patients with advanced renal cell carcinoma we have completed the dose escalation stage and identified dose levels of dalantercept that are well tolerated in combination with the FDA approved dose level of axitinib. We have now initiated the dose expansion phase of this study and plan to start the randomized controlled part of the study at the end of Q1 or early Q2 2014. We also intend to initiate a Phase 2 clinical trial of dalantercept in combination with the VEGF pathway inhibitor sorafenib in patients with liver cancer in the first half of 2014.

        In addition to our clinical stage programs, we are developing a novel protein therapeutic candidate, ACE-083, for a first-in-human clinical trial that we expect to initiate by the end of 2014. ACE-083 has been designed to promote muscle growth in those muscles in which the drug is injected, with minimal systemic effect. We are focused on the development of ACE-083 for diseases in which increases in the size and function of specific muscles may provide a clinical benefit, including inclusion body myositis, facioscapulohumeral dystrophy (FSHD) and disuse atrophy.

        We are developing sotatercept and ACE-536 through our exclusive worldwide collaborations with Celgene. As of January 1, 2013, Celgene became responsible for paying 100% of worldwide development costs for both programs. We may receive up to an additional $560.0 million of potential development, regulatory and commercial milestone payments and, if these protein therapeutic candidates are commercialized, we will receive a royalty on net sales in the low-to-mid 20% range. We will co-promote sotatercept and ACE-536, if approved, in North America for which our commercialization costs will be entirely funded by Celgene.

        We have not entered into a partnership for dalantercept and retain worldwide rights to this program.

        As of December 31, 2013, our operations have been funded primarily by $105.1 million in equity investments from venture investors, $86.8 million from investors in our initial public offering, $49.2 million in equity investments from our collaboration partners Celgene and Alkermes, Inc. (Alkermes) and $203.6 million in upfront payments, milestones, and net research and development payments from our collaboration partners.

        We were incorporated in the state of Delaware in June 2003 as Phoenix Pharma, Inc., and we subsequently changed our name to Acceleron Pharma Inc. and commenced operations in February 2004. Our principal executive offices are located at 128 Sidney Street, Cambridge, Massachusetts 02139, and our telephone number is (617) 649-9200. Our Internet website iswww.acceleronpharma.com. The information on, or that can be accessed through, our website is not part of this annual report, and you should not rely on any such information in making the decision whether to purchase our common stock.

Our Strategy

        Our goal is to be a leader in the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases. Key components of our strategy are:


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The Acceleron Discovery Platform: Novel Approaches to Potent Biology

        Since our founding, we have focused on developing protein therapeutics that target a group of approximately 30 secreted proteins, or ligands, that are collectively referred to as the TGF-b superfamily. These ligands bind to subsets of 12 different receptors on the surface of cells, triggering intra-cellular changes in gene expression that guide cell growth and differentiation. The TGF-bTGF-beta superfamily ligands and their receptors represent a diverse and underexplored set of drug targets with the potential to yield potent therapeutics for the growth and repair of diseased cells and tissues.

Applying our proprietary discovery and development platform, including our knowledge of the biology of the TGF-bTGF-beta superfamily and its receptors, we have generated our novel IntelliTrap platform technology and a robust pipeline of innovative clinical and preclinical protein therapeutic candidates targeting key mechanisms underlying cancer and rare diseases.


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    Our Focus—The TGF-b Superfamily

        On a daily basis, the human body must orchestrate the growth and differentiation of cells to maintain and repair its cells and organ systems. Stem cells and precursor cells are undifferentiated cell types that reside in most tissues of the body. When tissue growth or regeneration is required, these undifferentiated cells divide and, through a series of intermediate stages, give rise to new, fully differentiated cells that build or repair the affected tissue. Decades of research have identified the TGF-b superfamily and its associated receptors as key regulators of the growth and differentiation of stem and precursor cells.

        Until recently, regulation of the erythropoietin pathway was the primary therapeutic approach to stimulate red blood cell formation. Members of the TGF-b superfamily are now recognized as important regulators of red blood cell formation. We have shown that inhibition of members of the TGF-b superfamily ameliorates anemia in mouse models ofb-thalassemia and MDS. Based on our findings, Additionally, we are developing two proteinconducting a multi-target antibody discovery collaboration with Adimab LLC, or Adimab, a leading antibody discovery company, under which Adimab is generating human antibodies against undisclosed targets that we select. We expect that this collaboration will expand our biologics platform and provide us with enhanced access to antibody therapeutic candidates, sotatercept and ACE-536, each of which is currently in Phase 2 clinical trials to treat patients with these diseases.candidates.

        Members of the TGF-b superfamily also play a significant role in regulating blood vessel formation. We and our academic collaborators have shown that mice with a genetic defect in a particular receptor for members of the TGF-b superfamily are resistant to tumor growth due to reduced blood vessel formation in the tumor. We have used this insight to design our Phase 2 anti-angiogenic agent, dalantercept, for the treatment of cancer.

        Members of the family are also significant regulators of muscle development. A genetic defect in a TGF-b superfamily ligand, known as myostatin, causes profound increases in skeletal muscle. A naturally occurring mutation in myostatin has been identified in animals, such as "double-muscled" breeds of cattle and in the "bully whippet" offspring of whippet racing dogs, which have been selectively bred to have increased muscle mass or function. Furthermore, a mutation in myostatin has been identified in a human family, members of which exhibit exceptional musculature and strength. We are actively working on preclinical programs to increase muscle mass and strength.

        Ligands of the TGF-b superfamily cause these profound biological effects by altering gene expression in target cells. As shown in the illustration below, a ligand of the superfamily initiates intracellular signaling by binding to a receptor that is located on the surface of a target cell. Upon binding to the ligand, the receptor activates specific transcription factors inside the target cell, which are called Smad proteins. The activated Smad proteins regulate gene expression and guide cellular growth and differentiation.


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        The TGF-b superfamily ligands are divided into subgroups termed the activins, the Growth and Differentiation Factors (GDFs), the Bone Morphogenetic Proteins (BMPs) and the TGF-b subgroup (for which the superfamily is named). Our clinical stage protein therapeutic candidates focus on the activin, GDF and BMP subgroups.

        We believe that, by employing our proprietary discovery and development platform, we can design protein therapeutic candidates that alter TGF-b superfamily signaling and unlock the therapeutic potential of this group of proteins.

        By combining the powerful biology of the TGF-b superfamily with our discovery and development expertise and our internal protein engineering and manufacturing capabilities, we have built a robust clinical and preclinical pipeline of protein therapeutic candidates targeting key mechanisms underlying cancer and rare diseases.

        We have taken a comprehensive, receptor-focused approach to access the biology of the TGF-b superfamily. We recognized that the 12 receptors for the superfamily act as control points for the ligands and therefore represent an attractive approach for pharmacological intervention. We have in-licensed patent rights for nine of the 12 receptors and systematically evaluated interactions between each receptor and a comprehensive panel of ligands. In the body, these ligands are naturally regulated by trap proteins that bind to the ligands thereby blocking ligand-receptor interactions and diminishing signaling in the cell. To mimic this natural regulatory approach, we have built our protein therapeutic candidates using the ligand-binding part of the receptors, depicted in the upper part of the figure below, as traps that capture the relevant groups of ligands in each biological process. We link the ligand-binding portion, the extracellular domain, of these receptors to the portion of a human antibody known as the Fc domain, depicted in the lower part of the figure below, which confers favorable pharmaceutical properties. The resulting "fused" proteins can be administered by simple intravenous or subcutaneous injection and reside in the blood for sufficient periods of time to permit dosing on a weekly or monthly basis.

        Protein therapeutics constructed this way are referred to as "receptor fusion proteins" or "ligand traps". Some of the most successful protein therapeutics on the market belong to this category including Enbrel® (etanercept), Eylea® (aflibercept) and Orencia® (abatacept).


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        As shown in the figure below, our receptor fusion proteins act as ligand traps by binding to ligands of the TGF-b superfamily, preventing those ligands from binding to the cell surface receptors, and thereby preventing activation of Smad proteins in the target cell.

        To take full advantage of our proprietary discovery and development platform, we have developed an integrated set of technologies and capabilities to rapidly and cost-effectively create, test and advance multiple protein therapeutic candidates. Our protein engineering expertise allows us to create and optimize our receptor fusion proteins. We have developed the capability to generate recombinant cell lines that produce our protein therapeutic candidates, and assess the activity of these molecules in animals using our internal animal pharmacology facility or the capabilities of our academic collaborators. We have also invested in infrastructure to manufacture Phase 1 and Phase 2 clinical material quickly and flexibly using our internal current good manufacturing practices, or cGMP, compliant protein production facility to support clinical development of our protein therapeutic candidates.

We use our integrated platform of research, development and manufacturing technologies to rapidly and cost-effectively create, test and advance our protein therapeutic candidates. Our robust clinical and preclinical pipeline is focused on areas of high-unmet medical need, particularly in the areas of cancer and rare diseases.

        We have four development stage protein therapeutic candidates, of which three are currently in numerous ongoing clinical trials and the fourth we expect to begin human clinical trials by the end of 2014. Celgene is currently conducting four Phase 2 clinical trials and overseeing three investigator-sponsored trials with sotatercept. We are conducting two Phase 2 clinical trials with ACE-536, two Phase 2 clinical trials with dalantercept and overseeing a collaborative group-sponsored Phase 2 clinical trial of dalantercept. We expect to initiate a Phase 2 clinical trial with dalantercept in patients with hepatocellular carcinoma in the first half of 2014 and to initiate a Phase 1 clinical trial with ACE-083 by the end of 2014.



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Sotatercept and ACE-536

    Anemia in Patients with ß-thalassemia and MDS

        Erythropoiesis, the process by which precursor cells proliferate and differentiate


Our Product Pipeline
Luspatercept
Luspatercept is designed to give rise to red blood cells, is one of the most important and active processes in human biology. The primary role of red blood cells is to carry and deliver oxygen to other cells throughout the body. At any given time, there are approximately 25 trillion red blood cells in normal adult circulation which account for roughly 25% of the body's total number of cells. The human body produces 2.4 million new red blood cells each second. Red blood cell formation starts in the bone marrow with cells referred to as red blood cell precursors. These precursor cells go through many rounds of cellular proliferation, combined with cellular differentiation, to become more specialized cells to carry out their role as mature, functional red blood cells. We believe this highly active process ofpromote red blood cell production is normally tightly controlled by positive and negative regulators of the erythropoietic process. Erythropoietin isthrough a positive regulator that stimulates proliferation of early red blood cell precursor cells, the BFU-E and CFU-E cells depicted in the figure below. Based on our research, it is now recognized that certain ligands in the TGF-b superfamily are negative regulators of red blood cell precursors, starting with the Pro-E cells and those that follow, as depicted in the figure below. These members of the TGF-b superfamily restrain the maturation of these precursors into later stage precursors and ultimately into functional red blood cells (RBCs).


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Depiction of Normal Erythropoiesis

        In certain diseases, the highly active process of red blood cell production does not function properly, leading to a reduction in the number of functional red blood cells, a condition known as anemia. Anemia in some disease settings is currently treated by the use of erythropoiesis stimulating agents, such as recombinant erythropoietin, that stimulate proliferation of early stage precursors of red blood cells. However, in certain diseases, such asb-thalassemia and MDS, anemia is caused by defects in the production of late stage red blood cell precursors, which is known as ineffective erythropoiesis.

        Anemias caused by ineffective erythropoiesis are not well-treated by current therapies. As shown in the illustration below, ineffective erythropoiesis is characterized by an over-abundance of early stage red blood cell precursors and a decreased ability of late stage precursor cells to properly differentiate into healthy, functional red blood cells. The resulting anemia stimulates the body's overproduction of erythropoietin, which exacerbates the over-abundance of early stage precursors. Because the defective step in ineffective erythropoiesis lies downstream of the early stage precursors, the increase in the number of these cells fails to resolve the anemia.

Depiction of Ineffective Erythropoiesis


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        Based on our preclinical research, we believe that TGF-b superfamily ligands function as negative regulators of erythropoiesis by inhibiting the maturation of these early stage red blood cell precursors. Both sotatercept and ACE-536 are ligand traps designed to inhibit these negative regulators of late stage red blood cell precursors and promote their maturation into functional red blood cells.

novel mechanism. We are developing sotatercept and ACE-536,luspatercept, through our collaborations with Celgene, as treatmentsa treatment for anemia and associated complications in diseases in which erythropoiesis-stimulating agents are either not approved or are not well-suited to treat the underlying anemia. Inanemia, such as beta-thalassemia and MDS.

MDS
With respect to MDS, both our and Celgene's objective is to develop luspatercept as a treatment to increase hemoglobin levels and decrease red blood cell transfusion burden, with patients ultimately becoming transfusion independent.
MDS is a group of heterogeneous hematologic diseases such asb-thalassemiacharacterized by abnormal proliferation and MDSdifferentiation of blood precursor cells, including red blood cell precursors, in which anemia is caused by ineffective erythropoiesis, we believe both sotatercept and ACE-536 may help correct this defective process. Although similarthe bone marrow. This leads to peripheral reductions in terms of their effects on red blood cells, thereoften accompanied by decreases in white blood cells and platelets, as well as a risk of disease progression to acute myeloid leukemia. Although MDS patients may have varying forms of the disease, anemia is present in the vast majority of MDS patients at the time of diagnosis. MDS is primarily a disease of the elderly, with 88% of cases diagnosed in individuals 60 years of age or older. Cancer surveillance databases estimate the annual incidence of MDS in the United States at 10,000 to 15,000 cases and the overall U.S./EU prevalence at approximately 125,000 patients.
Hematopoietic stem cell transplantation represents the only treatment modality with curative potential, although the relatively high morbidity and mortality of this approach limits its use. Approximately 70% of the MDS patients in the U.S. and EU are differencesclassified as lower risk and 30% are classified as higher risk. High risk patients are typically treated with inhibitors of DNA methyltransferase such as Vidaza® or Dacogen®, or generic versions that are now available in howsome countries. The patients categorized as low risk typically receive erythropoiesis stimulating agents as first-line therapy, though erythropoiesis stimulating agents are not approved by the FDA or the EMA for the treatment of anemia in MDS patients. Our internal market research estimates that erythropoiesis stimulating agents generate $500 to $700 million in annual U.S. sales from their use in this disease. After failure on erythropoiesis stimulating agents, patients are treated with red blood cell transfusion and/or Revlimid®, Vidaza® or Dacogen®. Across the disease, approximately 15% of patients have a specific chromosomal mutation and are treated with Revlimid® (2015 U.S. sales of $152 million for MDS).

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The anemia in MDS is primarily due to ineffective erythropoiesis, and a significant number of MDS patients have serum erythropoietin levels substantially above the normal range, indicating that the anemia in these two protein therapeutic candidates bindMDS patients is not a consequence of erythropoietin deficiency. The ineffective erythropoiesis of MDS may be caused by excess signaling by members of the TGF-beta superfamily, which signaling inhibits red blood cell maturation. For this reason we believe that blocking this excess signaling by luspatercept may reverse this inhibition. Approximately 50% of MDS patients are unresponsive to the administration of recombinant erythropoietin and inhibit ligands. Unlike ACE-536, sotatercept bindsinstead require red blood cell transfusions, which can increase the risk of infection and iron-overload related toxicities. Treatment-resistant anemia resulting from ineffective erythropoiesis is a major cause of morbidity in MDS patients.
Given the effects of members of the TGF-beta superfamily ligands on late-stage erythropoiesis, we have investigated our candidate therapeutics in mouse models of MDS, with a focus on luspatercept. In our 2014 publication in the journal Nature Medicine, we and our collaborators showed that the ligand GDF11 is expressed at an elevated level in a mouse model of MDS, leading to elevated levels of an activated transcription factor, P-SMAD2/3, and inhibits activin A,ineffective erythropoiesis. Treatment with a TGF-b superfamily ligand,mouse version of luspatercept, referred to as RAP-536, reduced P-SMAD2/3 levels and has been showncaused statistically significant increases in red blood cell count, hemoglobin levels and hematocrit compared to increasecontrols. Additionally, RAP-536 reduced the ineffective erythropoiesis as evidenced by the improvement in the ratio of red blood cell precursors to other cells in the bone mass and biomarkers of bone formation inmarrow.
In December 2015, Celgene initiated a Phase 3 clinical trials. Given its effects on bone, sotatercept is being studiedtrial with luspatercept in patients with chronic kidney disease, where itvery low, low and intermediate risk MDS per the Revised International Prognostic Scoring System, the "MEDALIST" trial. The MEDALIST trial targets patients with very low, low or intermediate risk MDS with ring sideroblasts who require RBC transfusions. The trial is double-blinded, placebo-controlled and will enroll an estimated 210 patients randomized 2:1, luspatercept versus placebo. In order to enroll in the trial, patients must be: refractory / intolerant to prior erythropoiesis stimulating agents (ESA) or ESA ineligible, ring sideroblast positive, receive a transfusion of at least 2 units of RBCs every 8 weeks confirmed for a minimum of 16 weeks with no consecutive 8-week period free from transfusion, and no prior lenalidomide, hypomethylating agents or immunosuppressive therapy. Patients are excluded from the study if they have del(5q) or secondary MDS. The primary endpoint for efficacy analysis will be the proportion of patients who become RBC-transfusion independent for a period of at least 8 weeks during the first 24 weeks of treatment.
In addition to the Phase 3 clinical trial, we are currently conducting two Phase 2 clinical trials of luspatercept in patients with MDS. The first clinical trial is designed as a two-part trial, with an ascending dose part to evaluate the safety and efficacy in patients with low or intermediate risk MDS per the International Prognostic Scoring System, and an expansion part in which additional patients are enrolled at a selected dose level (3-month base study). We have currently completed enrollment in all of the dose escalation cohorts and we have completed enrollment of patients in the initial expansion cohort of the trial for a total of 58 patients. We have expanded the trial to include two additional cohorts of patients to further evaluate the effects of luspatercept in selected MDS patient populations. All patients enrolled in the base study are eligible to enroll in a second Phase 2 trial (extension study) that permits dosing with luspatercept for up to an additional two years. These trials are being conducted at sites in Germany.
We believe that preliminary results from the long-term Phase 2 MDS extension study are encouraging. We presented these results, using a data cut-off date of August 31, 2015, at the 57th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2015. As of the cut-off date, a total of 32 patients were treated in the extension study in which luspatercept was administered subcutaneously once every 3 weeks. Of these 32 patients, 13 had a low red blood cell (RBC) transfusion burden (LTB; < 4 units RBC/8 weeks) and 19 had a high transfusion burden (HTB; ≥4 units RBC/8 weeks). 59% of patients had been treated previously with erythropoiesis stimulating agents (ESA) and 19% of patients had previously been treated with lenalidomide. With regard to LTB patients, 9 of 13 (69%) LTB patients achieved the International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response criterion of a hemoglobin increase ≥1.5 g/dL for ≥8 weeks. With regard to HTB patients, 13 of 19 (68%) HTB patients achieved the IWG HI-E criterion of a reduction of ≥4 units RBC over 8 weeks, and 8 of 19 (42%) HTB patients treated with luspatercept achieved RBC transfusion independence for ≥8 weeks. An additional 3 of 3 (100%) LTB patients with 2 units/8 weeks at baseline achieved RBC transfusion independence for ≥8 weeks. A substantial majority of the patients in the Phase 2 trial had a bone marrow cell morphology referred to as ring sideroblasts and given the encouraging response rates in these patients, the Phase 3 trial has the potentialbeen designed to treatfocus on patients with this particular cellular morphology. The most common adverse events observed in this extension study, which may be related to luspatercept, were bone pain, headache, hypotonia, myalgia and nausea. There were no drug-related serious adverse events.
Beta-thalassemia
With respect to beta-thalassemia, both our and Celgene's objective is to develop luspatercept as a treatment to increase hemoglobin levels, decrease transfusion burden, decrease iron overload, improve symptoms associated with anemia, and mineral and bone disorder. In addition, in preclinical studies, sotatercept inhibits the growthalleviate other disease complications, such as leg ulcers.

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The thalassemiasbeta-thalassemias comprise a heterogeneous group of disorders arising from defects in the genes that encode the proteins that comprise hemoglobin. Hemoglobin is a four-subunit protein complex formed of twoa-subunits alpha-subunits and twob-subunits, beta-subunits, each with an iron-containing heme group that binds to and carries oxygen molecules within red blood cells. There are two main classifications of thalassemia,a-thalassemia alpha-thalassemia andb-thalassemia, beta-thalassemia, depending on whether the genetic defect lies in the gene encoding thea-subunit alpha-subunit or theb-subunit.b-thalassemia beta-subunit. Beta-thalassemia is particularly prevalent throughout the Mediterranean region, Middle East, and Southeast Asia, and, due to migration and immigration, is now a global disease. The Thalassaemia International Federation estimates that there are approximately 300,000 patients worldwide withb-thalassemia, beta-thalassemia, approximately 20,000 of which are in the United States and Europe, who are dependent on frequent blood transfusions. We estimate that there are at least as manyb-thalassemia beta-thalassemia patients in the same regions who are not transfusion dependent and not included in these estimates. Many of these patients have hemoglobin levels that are approximately half that of normal individuals and experience significant complications of the disease.

        Anemia ofb-thalassemia Beta-thalassemia is treated primarily a result of ineffective erythropoiesis. The genetic defect leads to decreased production of theb-subunits of hemoglobin resulting in an excess amount of thea-subunits. In normal erythropoiesis, excess unpaireda-subunits are eliminated by a cellular component called the proteasome. The proteasome is normally required for effective red blood cell maturation to selectively remove cellular components and organelles such as mitochondria which are replaced by hemoglobin, which constitutes 90% of the protein in a mature red blood cell. In thalassemia, the proteasome becomes saturated with the abnormally high levels of unpaireda-subunits and is unable to remove other cellular components and participate in the maturation process; this causes the block in maturation. Moreover, those freea-subunits that are not eliminated by the proteasome form aggregates, called hemichromes, which damage the maturing red blood cells. These hemichromes, along with the saturation of the proteasome by unpaireda-subunits, contribute to the ineffective erythropoiesis ofb-thalassemia. The damaged red blood cells are filtered out by the spleen and have a reduced life span, resulting in anemia and enlargement of the spleen.

        Patients with the most severe form ofb-thalassemia produce few, if any,b-subunits, resulting in an increased amount of freea-subunits and consequently a high number of hemichromes. These patients typically present with life-threatening anemia within the first year of life and require regular and lifelong red blood cell transfusions usually every 2that, over time, cause a toxic accumulation of iron in the body. A central challenge for managing patients with beta-thalassemia is to 4 weeks. Becauserestore the red blood cells contain significant amounts ofcell levels while avoiding iron this intensive transfusion regimen contributes to a condition known as iron


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overload, which is the principal cause of mortality. Consequently, therapy to reduce iron overload, called iron chelation therapy, is also part of standard treatment in these patients and typically begins after patients have received approximately 20 units of blood from transfusions during their lifetime.overload. Iron chelation therapy alone costs between $25,000$40,000 and $40,000$60,000 per year in countries such as the United States and Italy and yet does not treat the underlying anemia. The course of the disease depends largely on whether patients are maintained on an adequate transfusion and iron chelation regimen. Poor compliance with transfusion and/or iron chelation is associated with a poor prognosis and shortened survival. However, even with the standard of care, patients are at risk of infection from transfusions as well as toxicities related to iron chelation therapy.

        Patients with an intermediate form ofb-thalassemia, who are not necessarily dependent on frequent transfusions early in life, nevertheless suffer from a wide range of debilitating conditions. The ongoing ineffective erythropoiesis leads to various complications affecting a wide range of organ systems. By the second decade of life, most of these patients' hemoglobin levels have declined to the 6-8 g/dL range, or approximately half that of normal individuals. In an attempt to correct this chronic anemia, the body produces high levels of erythropoietin resulting in a continued stimulation of the early red blood cell precursors in the bone marrow. The number of these precursors grows to such an extent in the bone marrow that it leads to skeletal deformities, porosity of the long bones, and bone fractures. Splenomegaly, or enlargement of the spleen, is the result in part of continuous clearance by the spleen of the malformed red blood cells damaged by hemichromes. This commonly leads patients to require removal of their spleen, which in turn leads to worsening of other complications, such as blood clots. Iron overload is another significant complication even in the absence of red blood cell transfusions. This is due to increased intestinal iron absorption as a result of the ongoing ineffective erythropoiesis. Patients also suffer from various endocrine disorders due, in large part, to the accumulation of iron in the endocrine glands. Importantly, iron can also accumulate in the liver and heart, leading to severe complications such as liver fibrosis and heart failure.

No drug is approved to treat the anemia ofb-thalassemia. beta-thalassemia. Hematopoietic stem cell transplantation is viewed as the only curative approach forb-thalassemia, beta-thalassemia, although this option is limited by the availability of appropriate donors and by risks, including death, associated with the bone marrow transplant procedure. Consequently this treatment is used only in the most severely affected patients.

Myelodysplastic Syndromes

        Myelodysplastic syndromes, or MDS, are a group of heterogeneous hematologic diseases characterized by abnormal proliferation and differentiation of blood precursor cells, including red blood cell precursors, inGiven the bone marrow. This leads to peripheral reductions in red blood cells, often accompanied by decreases in white blood cells and platelets, as well as a riskeffects of disease progression to acute myeloid leukemia. Anemia is present in the vast majority of MDS patients at the time of diagnosis. MDS is primarily a disease of the elderly, with 88% of cases diagnosed in individuals 60 years of age or older. Cancer surveillance databases estimate the annual incidence of MDS in the United States at 10,000 to 15,000 cases and the overall U.S. prevalence at approximately 30,000 to 60,000 patients.

        Hematopoietic stem cell transplantation represents the only treatment modality with curative potential, although the relatively high morbidity and mortality of this approach limits its use. Approximately 23% of MDS patients are categorized as intermediate-2 to high risk. These patients are typically treated with inhibitors of DNA methyltransferase such as Vidaza® (2012 U.S. sales of $324.0 million for MDS) or Dacogen® (2012 U.S. sales of $233 million for MDS). Of the remaining 77% of patients categorized as low to intermediate-1 risk, approximately 10% have a specific chromosomal mutation and are typically treated with Revlimid® (2012 U.S. sales of $257.0 million for MDS). The remaining 67% of patients typically receive red blood cell transfusions or erythropoiesis stimulating agents, though erythropoiesis stimulating agents are not approved by the FDA or the EMA


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for the treatment of anemia in MDS patients. Our internal market research estimates that erythropoiesis stimulating agents generate $500 to $700 million in annual U.S. sales from their use in this disease.

        The anemia in MDS is primarily due to ineffective erythropoiesis, and a significant number of MDS patients have serum erythropoietin levels substantially above the normal range, indicating that the anemia in these MDS patients is not a consequence of erythropoietin deficiency. The ineffective erythropoiesis of MDS may be caused by excess signaling by members of the TGF-bTGF-beta superfamily which signaling inhibits red blood cell maturation. For this reasonligands on late-stage erythropoiesis, we believe that blocking this excess signaling by sotatercept or ACE-536 may reverse this inhibition. Approximately 50% of MDS patients are unresponsive to the administration of recombinant erythropoietin and instead require red blood cell transfusions, which can increase the risk of infection and iron-overload related toxicities. Treatment-resistant anemia resulting from ineffective erythropoiesis is a major cause of morbidity in MDS patients.

        Anemia is a common complication of chronic kidney disease. Because erythropoietin is produced primarily in the kidney and to a lesser extent in the liver, patients with chronic kidney disease produce sub-optimal amounts of erythropoietin, which leads to anemia. Additional serious complications of chronic kidney disease include a condition known as chronic kidney disease—mineral and bone disorder that occurs when the diseased kidneys fail to maintain proper levels of calcium and phosphorous in the blood, leading to abnormal bone hormone levels, weakened bones and vascular calcification. Bone and vascular disorders are common complications in people with chronic kidney disease and bone disorders affect almost all patients receiving dialysis. According to the United States Renal Data System, there are over 400,000 chronic kidney disease patients receiving dialysis in the United States. Erythropoiesis stimulating agents have been approved for this indication for over twenty years. Sotatercept has the potential to differentiate itself from erythropoiesis stimulating agents in this patient population because of its positive effects on bone metabolism observed following the administration of sotatercept in preclinical models, healthy volunteers and cancer patients. Additionally,investigated our candidate therapeutics in mouse models of vascular calcification, sotatercept causedthis disease. We evaluated the effects of RAP-536 in a reductionseries of calcified depositsstudies using a mouse model of beta-thalassemia. These mice carry deletion mutations in the aorta.

Sotatercept Clinicalbeta-globin genes, resulting in a deficiency of beta-globin protein and Preclinical Developmenthematologic abnormalities very similar to those seen in human beta-thalassemia patients, including severe anemia and the formation of hemichromes resulting in ineffective erythropoiesis. These mice also exhibit severe complications common in patients with thalassemia, such as an enlarged spleen, bone loss and iron overload. As reported in our 2014 publication in the journal

        Sotatercept isBlood, RAP-536 treatment improved numerous hematologic parameters in these mice, including a soluble receptor fusion protein consistingdecrease in hemoglobin aggregates, significant increases in red blood cell count, hemoglobin levels, and hematocrit, decreased serum erythropoietin, normalized red blood cell size, and reduced red blood cell breakdown, as measured by serum bilirubin. Importantly, RAP-536 decreased the elevated levels of the extracellular domainactivated transcription factor, P-SMAD2/3, restored iron homeostasis and improved the maturation of the activin receptor type IIA (ActRIIA) linked to the Fc domain of human IgG1. Sotatercept acts as a protein trap for TGF-b superfamily ligands that signal through the ActRIIA receptor. Sotatercept has increasedlater-stage red blood cellscell precursor populations, in multiple clinical trials.the bone marrow and spleen, with concomitant reductions in the earlier-stage red blood cell precursor populations.

        Our collaboration partner,

In December 2015, Celgene is currently conducting four Phase 2 clinical trials of sotatercept in patients withb-thalassemia, MDS and chronic kidney disease. The FDA has granted orphan designation for sotatercept for the treatment ofb-thalassemia. We understand that Celgene plans to submit an application for orphan drug designation of sotatercept for treatment of MDS. Through collaborations with leading academic institutions, Celgene is also overseeing three investigator-sponsored trials.

        ß-thalassemia.    Celgene is conductinginitiated a Phase 23 clinical trial of sotatercept designed aswith luspatercept in regularly transfused patients with beta-thalassemia, the "BELIEVE" trial. The BELIEVE trial targets adult beta-thalassemia patients who are regularly transfused. The trial is double-blinded and placebo-controlled and will enroll an ascending dose studyestimated 300 patients randomized 2:1, luspatercept versus placebo. In order to determine the safety and efficacy of sotatercept in adults withb-thalassemia.


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The dose levels to be studied are 0.1, 0.3, 0.5 mg/kg and 0.75 mg, with the possibility of further dose escalation up to 1.0 and 1.5 mg/kg, given subcutaneously once every three weeks for a period of 6 cycles with continued treatment at the discretion of the investigator for up to 22 months. Each cohort includes six or more patients during the dose escalation phase, followed by an expansion phase at a selected dose level in up to ten additional patients. The first patientenroll in the trial, was first dosed in November 2012. Celgene has completed enrollingpatients must receive 6-20 units RBC transfused over the 0.1, 0.3,prior 24 weeks and 0.5 mg/kg cohorts and is now enrolling patients in the 0.75 mg/kg cohort.have no transfusion-free period ≥ 35 days. Patients will be monitored for a 12-week prospective pre-treatment period to calculate baseline transfusion burden. The primary outcome measureendpoint for efficacy analysis will be the proportion of patients with at least a 33% reduction in transfusion burden during weeks 13 to 24 of the trial is to identify a safe dose level and to measure efficacy (1) in transfusion dependent patients by a reduction of transfusion burden by³ 20% compared to the pretreatment transfusion burden for each patient and (2) in non-transfusion dependent patients by an increase in hemoglobin level by³1 g/dL compared12 weeks preceding treatment.

In addition to the baseline hemoglobin, sustained for 12 weeks. This trial will also evaluate as exploratory endpoints the effects of sotatercept on iron overload, which is an important cause of morbidity and mortality associated withb-thalassemia, and bone metabolism. The trial is being conducted in six sites in Italy, France, Greece, and the United Kingdom and may enroll approximately 65 patients.

        Sotatercept has generated encouraging preliminary data in the ongoing Phase 23 clinical trial, of sotatercept inb-thalassemia patients.

        As shown in the figure below, sotatercept has generated encouraging dose-dependent increases in hemoglobin levels in patients in the Phase 2 clinical trial whowe are non-transfusion dependent based on preliminary data from the three lowest dose levels in that trial.

Mean Change in Hemoglobin Level From Baseline by Dose Cohort in
Non-Transfusion Dependentb-Thalassemia Patients Treated With Sotatercept


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        Another analysis of the data from this trial also shows dose-dependent increases in hemoglobin levels. In the analysis shown below, within the first two months of receiving the first dose of sotatercept:

Maximum Change in Hemoglobin Level From Baseline in Non-Transfusion Dependent
b-Thalassemia Patients During the First 3 Cycles (Day 64) of Sotatercept Treatment

        The figure below shows that there is a statistically significant relationship (p<0.001) between drug exposure and the maximum increase in hemoglobin during the first three cycles across the three lowest dose levels of sotatercept. The x-axis shows the levels of sotatercept in patients' serum and the y-axis shows the patients' maximum change in hemoglobin. The figure illustrates that as the drug exposure in patients increases, so does the maximum increase in hemoglobin.


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Relationship Between Drug Exposure and Hemoglobin Level in Non-Transfusion Dependent
b-Thalassemia Patients Through the First 3 Cycles (Day 64) of Sotatercept Treatment

Only patients completing the first 3 planned treatment cycles are included.
(AUC) area under the curve; HgB, hemoglobin

        We expect Celgene to establish a range of recommended sotatercept dose levels, based on these data and additional data to be gathered as the clinical trials continue. We expect that in future clinical trials, patients will begin treatment at a recommended starting dose level and to undergo individualized dose titration based on hemoglobin response and tolerability to achieve and maintain an appropriate hemoglobin level. We expect Celgene to continue to dose escalate in this trial with the objective to determine the dose range for evaluation in the expansion stage of this trial. If this activity is confirmed with an acceptable safety profile, we and Celgene plan to initiate pivotal trial(s) inb-thalassemia by the end of 2014 or early 2015. At the dose levels that have been studied to date, we have not yet observed an effect in the transfusion dependent patients. Based on currently projected timelines, which are subject to change, we expect additional data from this clinical trial to become available as follows: data from additional dose levels and extended treatment in patients from the dose escalation portion of the clinical trial in the second quarter of 2014, and additional data in the fourth quarter of 2014.

        MDS.    Celgene is conducting a Phase 2 clinical trial of sotatercept for the treatment of anemia in patients with low-or intermediate-1 risk MDS. The dose levels to be studied are 0.1, 0.3, 0.5 and 1.0 and up to 2.0 mg/kg given subcutaneously once every three weeks for five cycles, and up to three additional cycles for late responders, with continued treatment at the discretion of the investigator. Each cohort may include up to 20 patients receiving a single dose level during the dose escalation phase, followed by an expansion phase at a selected dose level in up to 15 additional patients. The first patient in the trial was first dosed in December 2012. Celgene has currently completed the 0.1, 0.3 and 0.5 mg/kg cohorts and is now enrolling patients in the 1.0 mg/kg cohort. Dose escalation may go up to 2.0 mg/kg. The primary outcome measure is erythroid hematological improvement (HI-E). For patients who require transfusions of <4 units of red blood cells in the eight weeks prior to dosing, HI-E is an increase in hemoglobin of³1.5 g/dL sustained over a period³8 weeks in the absence of red blood cell transfusions. For subjects that require transfusions of³4 units of red blood cells in the eight weeks prior to dosing, HI-E is a decrease of³4 units of red blood cells transfused over a period of eight


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weeks compared to the number of units transfused in the eight weeks prior to treatment. This trial will also evaluate the effects of sotatercept on iron overload and bone metabolism. The trial is being conducted at up to 23 sites in the United States and France and may enroll up to 115 patients. Based on currently projected timelines, which are subject to change, we expect additional data from this clinical trial to become available as follows: data from the dose escalation portion of the clinical trial in the second quarter of 2014, and additional data in the fourth quarter of 2014.

Chronic Kidney Disease.

        Celgene is conducting two Phase 2 clinical trials with sotaterceptof luspatercept in patients with chronic kidney disease.beta-thalassemia. The first is a Phase 2 clinical trial with sotatercept designed as a randomized, placebo-controlled dose escalation study to evaluate the pharmacokinetics, safety, efficacy, tolerability and pharmacodynamics of sotatercept for the correction of anemia in patients with chronic kidney disease on hemodialysis. The first patient in the trial was first dosed in August 2010. The first dose level was 0.1 mg/kg administered subcutaneously as a single dose. Subsequent dose levels to be studied are 0.3, 0.5 and 0.7 mg/kg administered subcutaneously once every four weeks for up to eight cycles. Each cohort will include up to 12 (nine sotatercept-treated and three placebo-treated) patients receiving a single dose level during the dose escalation phase, followed by an additional cohort at a selected dose level. Celgene has completed enrollment in the 0.1, 0.3 and 0.5 mg/kg cohorts and is now enrolling patients in the 0.7 mg/kg cohort. The primary endpoints are pharmacokinetics and safety. Other endpoints include effects on hemoglobin and serum markers of bone metabolism. The trial is being conducted at up to 21 sites in the United States and may enroll up to 56 patients.

        Early data from this trial are encouraging. An interim analysis from this clinical trial indicates that sotatercept produces dose dependent increases in hemoglobin in end stage renal disease patients on hemodialysis. The data will be presented at the National Kidney Foundation Spring Clinical Meeting in April 2014.

        Based in part on these interim data, and previously observed effects of sotatercept on bone biomarkers, Celgene has initiated a second phase 2 clinical trial in Europe with sotatercept in patients with end stage renal disease (ESRD) who are on hemodialysis. The first patient in this trial was first dosed in December 2013. The study is designed as a two-part studytrial, with an ascending dose part to assessevaluate the safety and efficacy of sotatercept asluspatercept in patients with beta-thalassemia, and an expansion part in which additional patients are enrolled at a therapy to treat anemiaselected dose level (3-month base study). We have currently completed enrollment and to control the adverse manifestationstreatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Patients in both partsall of the study must first be ondose escalation cohorts as well as the expansion cohort of the trial. Patients enrolled in the initial 3-month trial are eligible to enroll in a stable dosesecond Phase 2 trial (extension study) that permits dosing with luspatercept for up to an additional two years. This trial is currently being conducted at sites in Italy and Greece.

We believe the preliminary results from the Phase 2 clinical trials are encouraging. We presented these results, using a data cut-off date of an erythropoiesis stimulating agent (ESA) to maintain hemoglobin levelsSeptember 25, 2015, at the 57th ASH Annual Meeting and after an ESA treatment free periodExposition in December 2015. As of approximately five days, will then be switched to treatment with sotatercept.

        The first part isthe cut-off date, a dose-escalation studytotal of intravenous and subcutaneous routes of administration of sotatercept in approximately 6064 patients to evaluate pharmacokinetics, safety and tolerability. Patientswere treated in the dose escalation partand expansion cohorts of thethis study, will be given sotaterceptin which luspatercept was administered subcutaneously, once every two weeks up to a3 weeks. A total of eight doses59 patients were evaluable for efficacy (5 patients were ongoing with <12 weeks treatment). Of these 59 patients, 31 were non-transfusion dependent and followed for approximately four months after their last dose. The first part28 were transfusion dependent. Specifically, 22 of the study is designed to inform the dosing regimens to be tested28 (79%) transfusion dependent patients had a ≥20% reduction in transfusion burden, 21 of 28 (75%) had a ≥33% reduction, and 16 of 28 (57%) had a ≥50% reduction over a 12-week period.


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A trend of reduction in liver iron concentration, or LIC, was observed in the second partmajority of non-transfusion dependent patients with or without iron chelation therapy, and in the clinical trial.majority of transfusion dependent patients receiving iron chelation therapy. Improvement in quality of life in non-transfusion dependent patients correlated with increase in hemoglobin. Rapid healing of leg ulcers, a serious complication of beta-thalassemia, was observed in 3 patients, with 2 additional patients experiencing partial healing. The second part will bemost common related adverse events were bone pain, myalgia, headache, arthralgia, musculoskeletal pain, asthenia, injection site pain, back pain and pain in jaw. There were no drug-related serious adverse events. 6 of 59 (10%) patients discontinued early with an associated adverse event: bone pain (2 patients) and arthralgia, asthenia, cerebrovascular accident and headache (1 patient each).
Sotatercept
We and Celgene are developing sotatercept for the treatment of chronic kidney disease, or CKD, a randomized, controlled study of approximately 230 patients to evaluate the efficacydisorder characterized by anemia and safety of sotatercept versus an erythropoiesis stimulating agent. Efficacy measures for part two of the study include the change in mean hemoglobin concentration from baseline and the ability of sotatercept to maintain patients' hemoglobin levels within a target range after switching from an ESA to sotatercept. Measures of biomarkers for bone formationmineral and bone resorptiondisorder that leads to bone loss and forcardiovascular disease. The mineral metabolism also will be studied, alongand bone disorder in these patients is not well-managed with imagingcurrent therapies. Studies in mice show that sotatercept may have beneficial effects on fibrotic damage to the kidney and on the development of calcified deposits that may contribute to the elevated risk of heart vascular disease in CKD patients. Data from our ongoing Phase 2 clinical trial in patients with end-stage kidney disease shows that sotatercept may have beneficial effects on the mineral and bone disorder in these patients and may decrease the accumulation of vascular calcification.

Sotatercept Investigator Sponsored Trials

        Through collaborations with leading academic institutions, Celgene is overseeing investigator-sponsoredalso being studied through investigator-initiated clinical trials in multiple myeloma, Diamond-Blackfan anemia and myelofibrosis.


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        Six human

Dalantercept
Our third clinical trials of sotatercept, including Phase 1 clinical trials in healthy volunteers and Phase 2 clinical trials of patients with multiple myeloma, breast cancer, and non-small cell lung cancer, collectively involving over 160 patients have been conductedstage therapeutic candidate, dalantercept, is designed to date. In healthy volunteers, we observed increases in red blood cells and hemoglobin. The mean change in hemoglobin for the patients who received a single dose of 1.0 mg/kg was almost 3 g/dL, which is similar to receiving a transfusion of three units of blood. We have also shown that in a randomized, placebo-controlled trial in patients with multiple myeloma receiving melphalan, prednisolone and thalidomide, sotatercept produced dose-dependent increases in hemoglobin. In the placebo and 0.1 mg/kg sotatercept cohorts, none of the patients achieved at least a 1.5 g/dL increase in hemoglobin at day 29 of the trial compared to their baseline levels. In the 0.3 and 0.5 mg/kg sotatercept cohorts, 13% and 38% of the patients, respectively, achieved at least a 1.5 g/dL increase in hemoglobin at day 29 of the trial compared to their baseline levels. In a randomized, placebo-controlled clinical trial in breast cancer patients who had anemia due to myelosuppressive chemotherapy, sotatercept produced dose-dependent increases in hemoglobin levels. In both the placebo and 0.1 mg/kg sotatercept cohorts, 20% of the patients had their hemoglobin levels increase to at least 11 g/dL maintained for 28 days in the absence of a red blood cell transfusion or use of an erythropoiesis stimulating agent. In the 0.3 mg/kg cohort, 22% of the patients achieved this outcome and in the 0.5 mg/kg cohort, 75% of the patients achieved this threshold. In a randomized, dose-ranging Phase 2 trial of sotatercept in patients with metastatic non-small cell lung cancer, sotatercept, administered at a fixed dose of 15 or 30 mg given subcutaneously every six weeks, produced increases in hemoglobin. In patients who did not receive red blood cell transfusions within the first four weeks, the change from baseline was at least 1 g/dL of hemoglobin for 40% of patients at week 2 and 16% of patients at week four. Given the results of these trials, we and Celgene may decide to pursue further clinical development in the future in one or more of these indications.

        Across the completed clinical trials, sotatercept has been generally well-tolerated. In studies with healthy volunteers, the only treatment-related serious adverse event was a report of persistent, progressive high blood pressure in one subject. While the precise cause of elevated blood pressure cannot be determined, it was an expected consequence of elevated red blood cell levels that occurred in this subject. Commonly observed adverse events included headache, infection, dizziness, hypertension, hot flush, tingling, muscle spasms, limb injury, fatigue and asthenia. In three studies of patients with


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cancer (myeloma, breast and lung cancer), one sudden death was reported in a myeloma patient. The event was evaluated as probably related to the concurrent anti-myeloma therapy of melphalan, prednisolone and thalidomide and possibly related to sotatercept. One patient with advanced breast cancer experienced serious adverse events of perforated gastric ulcer and peptic ulcer disease that were evaluated as possibly related to sotatercept. One patient with advanced lung cancer experienced a serious adverse event of a cerebrovascular accident (blockage of atreat cancers by inhibiting blood vessel information by inhibiting signaling through the brain) that was suspected as related to treatment.

        AmongALK1 receptor. This mechanism is distinct from, and potentially synergistic with, the ongoing clinical trials managed by Celgene, no treatment-related serious adverse events have been reported in the MDS trial. In theb-thalassemia trial, two patients have exhibited serious adverse events that were suspected as related to sotatercept: bone pain and superficial thrombophlebitis (an inflamed blood clot in a superficial vein) . One patient at the 0.5 mg/kg dose level had a treatment-related Grade 3 adverse event of ventricular extrasystoles (ventricular heart contractions) and discontinued treatment.

        Sotatercept is the subject of three separate company-sponsored U.S. IND applications. We submitted the first IND to the FDA on March 13, 2006 for the treatment of postmenopausal osteoporosis. There are currently no studies being conducted under this IND. We submitted the second IND to the FDA on March 27, 2009 to assess the use of sotatercept for the treatment of anemia in various cancer-related indications. We transferred sponsorship of both INDs to Celgene on January 19, 2010. Under the second IND, sotatercept is currently being studied in patients with lower-risk MDS. A third IND was submitted by Celgene to the FDA on January 25, 2010 to assess sotatercept for the treatment of anemia in patients with end-stage renal disease. In addition, sotatercept is being studied in Europe under three separate Clinical Trial Applications (CTAs). The first CTA is for a Phase 2 study for the treatment of anemia in adult patients withb-thalassemia, submitted to France on December 28, 2011, to the United Kingdom on July 26, 2012, to Italy on July 27, 2012, and to Greece on November 23, 2012. The second CTA is for a Phase 2 study for the treatment of anemia in patients with lower-risk MDS, submitted to France on October 10, 2012. The third CTA is for a Phase 2 study for the treatment of anemia in patients with chronic kidney disease, with Belgium, Germany, Portugal, Spain, and the UK joining under the Voluntary Harmonization Procedure on June 17, 2013. Sotatercept is also being studied in the United States under three investigator-sponsored INDs.

        In preclinical studies, RAP-011 (the mouse equivalent of sotatercept) was evaluated in a broad range of animal pharmacology studies to assess its biological effects. RAP-011 has been shown to increase red blood cell counts in mice, rats, and monkeys. RAP-011 showed increased hemoglobin and red blood cell counts in mouse models ofb-thalassemia and MDS, demonstrating decreased ineffective erythropoiesis in these models. RAP-011 was also able to prevent chemotherapy-induced anemia in a mouse model of this condition and was able to correct anemia in a mouse model of chronic kidney disease. RAP-011 increased bone mineral density in ovariectomized mice and has demonstrated positive effects in mice on bone lesions and bone metastases in a numberdominant class of cancer models including models of multiple myeloma. The preclinical activity of sotatercept is also being evaluated in a mouse model of sickle cell disease.

ACE-536 Clinical and Preclinical Development

        ACE-536 is a soluble receptor fusion protein consisting of a modified extracellular domain ofdrugs that inhibit blood vessel formation, the activin receptor type IIB (ActRIIB) linked to the Fc domain of human IgG1.


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        We are conducting Phase 2 clinical trials of ACE-536 in patients withb-thalassemia and in patients with MDS. The FDA has granted orphan designation for ACE-536 for the treatment ofb-thalassemia and for the treatment of MDS.

ß-thalassemia.

        We are conducting a Phase 2 clinical trial of ACE-536, designed as an ascending dose trial to evaluate the safety and efficacy in patients withb-thalassemia. The dose levels to be studied are 0.2, 0.4, 0.6, 0.8 and 1.0 mg/kg given subcutaneously once every three weeks for up to 85 days. Each cohort will include three to six patients receiving a single dose level during the dose escalation phase. This will be followed by an expansion phase at a selected dose level in up to 20 patients. We are in the process of amending the protocol to include additional types of transfusion-dependent patients, to increase the size of the expansion cohort of the trial and to potentially study higher dose levels of ACE-536. The first patient in the trial was first dosed in March 2013. We have completed enrollment of the 0.2, 0.4, 0.6 and 0.8 mg/kg cohorts and are currently enrolling patients in the 1.0 mg/kg cohort. The primary outcome measure is the proportion of patients who have an increase in hemoglobin of³1.5 g/dL from baseline for³14 days (in the absence of red blood cell transfusions) in non-transfusion dependent patients or a³20% reduction in red blood cell transfusion burden compared to the pretreatment transfusion burden in transfusion dependent patients. This trial will also examine the effects of ACE-536 on iron overload, an important cause of morbidity and mortality inb-thalassemia patients. Secondary endpoints include markers of serum iron and hemolysis. The trial is being conducted at up to seven sites in Italy and Greece, and we plan to include additional sites in Europe and may enroll up to 72 patients.

        Initial data from this clinical trial is encouraging. As of January 3, 2014, preliminary data after three cycles (approximately two months) of treatment with ACE-536 show that non-transfusion dependentb-thalassemia patients in the 0.6 mg/kg dose group achieved a mean increase in hemoglobin of approximately 1.5 g/dL, while patients in the 0.2 and 0.4 mg/kg dose groups achieved a mean increase in hemoglobin of approximately 0.0 and 0.8 g/dL, respectively. Acceleron and Celgene intend to announce interim data in June, 2014 at the annual congress of the European Hematology Association (EHA). For sotatercept and ACE-536 inb-thalassemia, we and Celgene expect to present additional interim data from non-transfusion dependent patients as well as data from transfusion dependent patients. In transfusion dependentb-thalassemia patients treated with ACE-536, preliminary data show a decrease in the frequency of red blood cell transfusions.

        Based on these data and additional data to be gathered during the clinical trial, we expect to establish a range of recommended ACE-536 dose levels. We expect that in future clinical trials, patients will begin treatment at a recommended starting dose level and to undergo individualized dose titration based on hemoglobin response and tolerability to achieve and maintain an appropriate hemoglobin level.

        Based on currently projected timelines, which are subject to change, we expect data from this clinical trial to become available as follows: data from the dose escalation portion of the clinical trial during the second quarter of 2014, and additional data in the fourth quarter of 2014.

        MDS.    We are conducting a Phase 2 clinical trial of ACE-536 designed as an ascending dose trial in patients with low or intermediate-1 risk MDS. The dose levels to be studied are 0.125, 0.25, 0.5, 0.75, 1.0, 1.33 and 1.75 mg/kg given subcutaneously once every three weeks for up to 85 days. Each cohort will include three to six patients receiving a single dose level during the dose escalation phase. This will be followed by an expansion phase at a selected dose level in up to 30 patients. The first patient in the trial was first dosed in January 2013. We have currently completed enrollment in the 0.125, 0.25, 0.5, 0.75 and 1.0 mg/kg cohorts and are now enrolling patients in the 1.33 mg/kg cohort. The primary


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outcome measure is the proportion of patients who have an increase of hemoglobin³ 1.5 g/dL from baseline for 14 days in the absence of red blood cell transfusions in non-transfusion dependent patients or a³50% or³4 unit reduction of red blood cell transfusions over a period of eight weeks compared to pretreatment transfusion burden in transfusion-dependent patients. This trial will also examine the effects of ACE-536 on iron overload. The trial is being conducted at up to nine sites in Germany and may enroll up to 72 patients. For MDS patients treated with ACE-536, interim data indicate that there is a positive effect on hemoglobin levels in these patients, and we expect to present data from both transfusion dependent and non-transfusion dependent MDS patients at EHA in June, 2014. Based on currently projected timelines, which are subject to change, we expect additional data from this clinical trial to become available as follows: data from the dose escalation portion of the clinical trial during the second quarter of 2014, and additional data in the fourth quarter of 2014.

        ACE-536 was studied in a double-blind, placebo-controlled, randomized, ascending dose Phase 1 clinical trial in 32 healthy volunteers. ACE-536 produced dose-dependent increases in hemoglobin and red blood cells. The proportion of subjects with a hemoglobin increase of³1.0 g/dL increased on a dose-dependent basis, with approximately 80% of subjects in the 0.25 mg/kg dose level achieving this threshold.

        In the completed Phase 1 clinical trial in healthy volunteers, ACE-536 was well-tolerated. No ACE-536 related serious adverse events were reported in the completed Phase 1 clinical trial. Commonly observed possibly or probably treatment-related adverse events included injection site bruising, injection site blemish, dry skin, numbness, muscle spasms, muscle pain, generalized itchiness and raised rash. In the ongoing Phase 2 clinical trials, there have been no ACE-536 related serious adverse events. One patient in the ACE-536 thalassemia trial who was treated at the 0.8 mg/kg dose level had dose-limiting toxicity of worsening bone pain. The patient had a dose reduction to 0.6 mg/kg for the second cycle and subsequently withdrew from the study.

        ACE-536 is being studied in the United States under an IND that we submitted to the FDA on June 14, 2011. The indication identified in the IND is for the treatment of anemia in patients with MDS. No studies are being conducted under this IND at this time. In addition, ACE-536 is being studied in Europe under two separate Clinical Trial Applications (CTAs). The first is for a Phase 2 study for the treatment of anemia in adult patients withb-thalassemia, submitted to Italy on August 29, 2012, to Turkey on June 14, 2013, and to Greece on July 2, 2013. The second is for a Phase 2 study for the treatment of anemia in patients with low- or intermediate-1 risk MDS, submitted to Germany on August 21, 2012.

        A number of preclinical pharmacology studies have been conducted with ACE-536 or its mouse version, RAP-536, that demonstrate its effects on red blood cells, hemoglobin and hematocrit. Collectively ACE-536 and RAP-536 have shown activity in mouse models ofb-thalassemia, MDS, chemotherapy-induced anemia, acute blood loss and renal anemia.

        ß-thalassemia.    RAP-536 has been evaluated in a series of studies using a mouse model ofb-thalassemia. These mice carry deletion mutations in theb-globin genes, resulting in a deficiency ofb-globin protein and hematologic abnormalities very similar to those seen in humanb-thalassemia patients, including severe anemia and the formation of hemichromes resulting in ineffective erythropoiesis. These mice also exhibit severe complications common in patients with thalassemia, such


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as an enlarged spleen, bone loss and iron overload. In these mice, RAP-536 treatment improved numerous hematologic parameters, including significant increases in red blood cell count, hemoglobin levels, and hematocrit, decreased serum erythropoietin, normalized red blood cell size, and reduced red blood cell breakdown, as measured by serum bilirubin.

        Representative blood smears were taken from theb-thalassemia mouse studies for both the placebo-treated animals and the RAP-536 treated animals. As shown in the image below, RAP-536 improved red blood cell morphology by reducing the number of poorly formed and damaged red blood cells, and reducing the amount of cellular debris that results from dying red blood cells.

        Importantly, RAP-536 improved the maturation of later stage red blood cell precursor populations, in the bone marrow and spleen, with concomitant reductions in the earlier-stage red blood cell precursor populations. We believe RAP-536 reduced the ineffective erythropoiesis by decreasing the formation of harmful hemichromes. It appears that RAP-536 may achieve this effect in part by stimulating the proteasome, thus promoting the removal of unpaireda-hemoglobin and stimulating red blood cell maturation.

        This reduction in ineffective erythropoiesis reduced severe and common complications of the disease in mice, evidenced by reduced iron deposition in organs, reduced spleen weights and normalized bone density. Based on the numerous beneficial effects of RAP-536 in this mouse model ofb-thalassemia, we believe that it is modifying the disease and has the potential to do so in human patients.

        MDS.    In a mouse model of MDS, RAP-536 treated animals had statistically significant increases in red blood cell count, hemoglobin levels and hematocrit compared to controls. Additionally, RAP-536 reduced the ineffective erythropoiesis as evidenced by the improvement in the ratio of red blood cell precursors to other cells in the bone marrow.

        Sickle Cell Disease.    We and Celgene are exploring the preclinical activity of ACE-536 in a mouse model of sickle cell disease.

        Taken together, our clinical and preclinical results suggest that ACE-536 could be a meaningful novel therapy to treat anemia.


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Dalantercept

        Angiogenesis is a process by which new blood vessels are formed. Angiogenesis can be simplified to two major stages—the proliferative stage followed by the maturation stage. During the proliferative stage, vascular endothelial cells, the cells lining the inside of the blood vessels, multiply in number and migrate to the site where a new vessel will be formed. This proliferative stage is followed by the maturation stage during which the endothelial cells coalesce to form tubes which are then stabilized through the recruitment of perivascular cells that form an outer layer of the blood vessels resulting in fully formed, functional vessels.

        Tumors depend on angiogenesis to form new blood vessels to supply nutrients and oxygen to feed the rapidly growing malignant cells. The principal molecule driving the proliferative stage of angiogenesis in tumors is a protein called vascular endothelial growth factor, (VEGF). Inhibiting VEGF-driven angiogenesis to control tumor growth has become an important and widely-used approach to cancer treatment. There are several FDA-approved cancer drugs that inhibit theor VEGF, pathway with over $8 billion in aggregate worldwide sales. Despite the success of these drugs, many patients fail to respond or develop resistance to VEGF pathway inhibitor therapy, resulting in an unmet need for new therapies to inhibit angiogenesis by a different mechanism.

inhibitors. We are using our knowledge of the TGF-b superfamily to developdeveloping dalantercept a novel protein therapeutic candidate targeting the maturation stage of angiogenesis. Recently, the activin receptor-like kinase 1 (ALK1) has been recognized as a key regulator of the maturation stage of angiogenesis. ALK1 is one of the 12 receptorsprimarily for ligands in the TGF-b superfamily and is found primarily on endothelial cells. The importance of the ALK1 pathway in angiogenesis was discovered, in part, through research into the genetic basis of the disease hereditary hemorrhagic telangiectasia 2 (HHT-2) in which patients manifest vascular defects including reduced ability to form capillary beds, which are the networks of small blood vessels that connect arteries to veins and are necessary for nutrient and waste exchange in tissues. This research revealed that these patients have only one of two functional copies of the ALK1 gene.

        We reasoned that leveraging the biology of the ALK1 pathway to inhibit maturation of blood vessels could impair the growth of tumors by limiting the development of capillary beds within the tumor. To test this hypothesis, mice with a predisposition to develop tumors were bred to have only one, rather than two copies, of the ALK1 gene. In response to the loss of half of the ALK1 genes, tumor growth and size and blood vessel density in the tumor were reduced by half. These results and additional research in the field have established the ALK1 signaling pathway as a promising target for developing a new class of anti-angiogenesis agents—ALK1 pathway inhibitors.

        We believe one promising opportunity for dalantercept will be its use in combination with VEGF pathway inhibitors because these agents target distinct sequential steps in angiogenesis. Moreover, we and others have hypothesized that agents, such as dalantercept, that inhibit vessel maturation are able to sensitize the tumor vasculature to the anticancer effects of VEGF pathway inhibition. We believe that newly formed blood vessels become more resistant to VEGF pathway inhibitors as they mature. Therefore we believe that by preventing blood vessel maturation, dalantercept may maintain newly formed vessels in an immature state that increases their susceptibility to VEGF pathway inhibitors.

        We and our academic collaborators have also shown in two mouseproduce better outcomes for cancer models that treatment with dalantercept decreases metastases. This is in contrast to VEGF pathway inhibitors that increase metastases in mouse cancer models.

patients.

We believe that a combination of ALK1 and VEGF pathway inhibitors could have application in a number of different oncology indications where VEGF pathway inhibitors are currently used. The


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currently approved VEGF pathway inhibitors include Avastin® (bevacizumab), Cyramza® (ramucirumab), Inlyta® (axitinib), Nexavar® (sorafenib), Stivarga® (regorafenib), Sutent® (sunitinib), Inlyta® (axitinib)Votrient® (pazopanib), Caprelsa® (vandetanib), and Votrient® (pazopanib)Zaltrap® (ziv-aflibercept). FourThree large markets for which these drugs have been approved are non-small cell lung cancer, colorectal cancer and renal cell carcinoma and liver cancer.

Non-Small Cell Lung Cancer (NSCLC).  The National Cancer Institute estimates there will be 228,190were 221,200 new cases of lung cancer in the United States in 20132015 with 159,480158,040 deaths. In 2012,2015, sales of Avastin® in NSCLC were $1.2an estimated $1.1 billion in the United States and $1.7$1.8 billion worldwide.


Colorectal Cancer.  The National Cancer Institute estimates there will be 142,820were 132,700 new cases of colon cancer or rectal cancer in the United States in 20132015 with 50,83049,700 deaths. In 2012,2015, sales of Avastin® for colorectal cancer were $1.2an estimated $1.3 billion in the United States and $3.6 billion worldwide.


Renal Cell Carcinoma.  The National Cancer Institute estimates there will be 65,150were 61,560 new cases of kidney and renal cell carcinomapelvis cancer in the United States in 20132015 with 13,68014,080 deaths. In 2012,2015, U.S. sales of drugs for renal cell carcinoma were $1.2$1.4 billion, of which $800 million$1.0 billion were anti-angiogenesis drugs that target the VEGF pathway, principally

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Sutent®, Nexavar®Inlyta®, Votrient® and Avastin®. Worldwide sales in 20122015 of drugs for renal cell carcinoma were $3.1$3.5 billion, of which $2.3$2.6 billion were drugs that target the VEGF pathway.


Liver Cancer.  The National Cancer Institute estimates there will be 30,640 new cases of liver cancer in the United States in 2013 with 21,670 deaths. The only drug approved in the United States for the treatment of liver cancer is the VEGF pathway inhibitor Nexavar®. In 2012, sales of Nexavar® for liver cancer were $189 million in the United States and $756 million worldwide.

Other Tumors.  One or more anti-angiogenesis agents are also approved as treatments for liver cancer, ovarian cancer, neuroendocrine tumors, soft tissue sarcoma, gastric cancer, thyroid cancer and glioblastoma.

Developing Indications.  It is believed that angiogenesis is important
We are evaluating dalantercept in the growth and spread ofcombination with axitinib, a number of additional highly-vascularized cancers, including endometrial cancer (cancertyrosine kinase inhibitor of the uterus), ovarian cancer, and head and neck cancer. While no anti-angiogenesis agents are approved in the U.S. for these indications, Avastin® is approved in EuropeVEGF pathway, for the treatment of ovarian cancer.

        The firstrenal cell carcinoma in the DART trial, a two cancerspart Phase 2 clinical trial. In Part 1 of the DART trial, dalantercept plus axitinib produced clinical outcomes that exceed historical results with axitinib alone. We have reported a median progression-free survival (PFS) for dalantercept plus axitinib of 8.3 months. There was no control arm in Part 1 of the DART trial, however published data from a prior phase 3 trial of axitinib alone (the AXIS trial) in a similar patient subgroup show a median PFS of 4.8 months. We are currently conducting Part 2 of the DART trial, which is a double-blind, placebo-controlled trial, in which an estimated 130 patients are randomized to dalantercept plus axitinib or placebo plus axitinib. We expect to report on progression free survival from Part 2 of the DART trial by the end of 2016. In the open-label Part 1 and blinded Part 2 of the DART trial, the following serious adverse events have been reported as related to dalantercept, dalantercept or placebo (blinded Part 2), or both dalantercept and axitinib: fluid overload, dyspnea, epistaxis, renal injury, acute renal failure and hyponatremia. Non-serious adverse events associated with axitinib did not generally occur with higher than expected frequency or severity. In addition to the DART trial, we are studyingconducting a clinical trial to evaluate the treatment of patients with advanced hepatocellular cancer (HCC) with a combination of dalantercept plus sorafenib, another tyrosine kinase inhibitor of the VEGF pathway. A total of 21 patients have been enrolled as of December 30, 2015. The preliminary data indicate a VEGF pathway inhibitor are renal cell carcinoma and liver cancer. In renal cell cancer, sunitinib and axitinib aregeneral lack of efficacy for the most prescribed VEGF pathway inhibitors for first and second line patients, respectively. In the first line setting, sunitinib results in progression-free survival rates of approximately 11 months. In the second line setting, for patients whose disease had progressed despite receiving sunitinibdalantercept plus sorafenib combination in the first line setting, axitinib produced a progression-free survival ratetreatment of approximately 4.8 months. Weadvanced HCC, and therefore we believe the combination of dalantercept plus axitinibthat it is unlikely that additional patients will be enrolled in the second line settingHCC trial.

Dalantercept has the potential to increase the rate of progression-free survival greater than axitinib alone. In liver cancer, the VEGF pathway inhibitor, sorafenib, is approved in the first line setting yet the unmet medical need remains significant. In the first line setting, sorafenib results in time to progression of approximately 5.5 months.

Dalantercept Clinical and Preclinical Development

        Dalantercept is comprised of the extracellular domain of the ALK1 receptor linked to the Fc domain of IgG1. Dalantercept actsbeen tested as a ligand trap for ligandssingle-agent therapy in the TGF-b superfamily that signal through the ALK1 receptor. We havefour completed clinical trials: a Phase 1 clinical trial of dalantercept and are pursuing a program of ongoing and planned Phase 2 trials seeking to demonstrate single agent activity of dalantercept for advanced solid tumors and activity of dalantercept in combination with approved VEGF pathway inhibitors or chemotherapy in advanced solid tumors.


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        We are currently conducting two Phase 2 clinical trials of dalantercept in head and neck cancer, ovarian cancer and renal cell carcinoma. Additionally, through collaborations with a National Cancer Institute funded collaborative research group, the Gynecologic Oncology Group, we are overseeing an additional Phase 2 clinical trial in ovarianendometrial cancer. We plan to initiate a trialIn these studies of dalantercept in hepatocellular carcinoma in the first half of 2014. We planas monotherapy, there was not sufficient activity to submit applications for orphan designationwarrant further development of dalantercept for those indications or subsets of indications that meet FDA requirements for orphan status.

        Squamous Cell Carcinoma of the Head and Neck.    We are conducting a single agent Phase 2 clinical trial of dalanterceptas monotherapy in an ascending dose trial in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The first patient in the trial was first dosed in October 2011. After an initial cohort of two patients treated at a fixed dose level of 80 mg, we amended the trial and began recruitment of patients under the amended protocol in the first quarter of 2012 to study the dose level of 0.6 mg/kg given subcutaneously once every three weeks. The protocol was subsequently amended to increase the dose level of dalantercept to 1.2 mg/kg. Patients continue to receive dalantercept until there is disease progression (either clinically or as measured by analysis of radiographic imaging according to RECIST criteria) or dalantercept is no longer tolerated. The primary outcome measure is objective response rate as measured by RECIST criteria, and there are a number of secondary outcome measures ofthese tumor response. The trial is being conducted in 12 centers in the United States, and we completed enrollment in July 2013 with a total of 46 patients, including two patients treated at the 80 mg dose, 13 at the 0.6 mg/kg dose, and 31 at the 1.2 mg/kg dose. Of these 46 patients, 41 patients (one patient at 80 mg, 13 patients at 0.6 mg/kg, and 27 patients at 1.2 mg/kg) were evaluable for radiological response according to RECIST criteria as of December 20, 2013. The preliminary data for these 41 patients are as follows: no patients at 80 mg, three patients (23%) at 0.6 mg/kg and ten patients (37%) at 1.2 mg/kg achieved stable disease as their best response at the beginning of their third cycle and, at the 1.2 mg/kg dose level, one patient (2.4%) achieved a partial response. None of these patients achieved a complete response. We intend to present additional data from this trial at the American Society of Clinical Oncology annual meeting in late May or early June 2014. These preliminary data suggest dalantercept has dose dependent but modest single agent activity in patients with advanced squamous cell carcinoma of the head and neck.types. We believe the greatest potential for dalantercept will be in combination with VEGF pathway inhibitors or in combination with cytotoxic chemotherapy.

        Renal Cell Carcinoma.    We are conducting

ACE-083
Our fourth clinical stage therapeutic candidate, ACE-083, is designed to promote muscle growth and function in specific, targeted muscles. In 2014, we initiated a two-part Phase 21 clinical trial of dalanterceptwith ACE-083 in combination with axitinib, an approved VEGF pathway inhibitor, in patients with advanced renal cell carcinoma. Part one of thishealthy volunteers. ACE-083 has been well tolerated and no serious adverse events have been reported. Initial data from the Phase 1 trial is designed as a single-arm dose escalation and expansion stage withshowed that, at the primary endpoint of evaluating the safety and tolerability of various dose levels of dalantercept in combination with axitinib to select ahighest dose level tested, ACE-083 generated a mean increase in muscle volume of dalantercept (in combination with axitinib) for further study if merited. The dose levels of dalantercept studiedapproximately 14.5% in the dose escalation stage were 0.6, 0.9, and 1.2 mg/kg given subcutaneously once every three weeks. The number of patients enrolled attreated muscle. We have completed enrollment for the 0.6, 0.9 and 1.2 mg/kg dose levels were four, four and five patients, respectively. The dose level of 1.2 mg/kg was selected for use in the expansion phaseACE-083 Phase 1 clinical trial, and we are now enrolling up to 20 additional patients in this stage of the study. The first patient in the trial was first dosed in January 2013. Patients continue to receive dalantercept and axitinib until there is disease progression (either clinically or as measured by RECIST criteria) or the combination is no longer tolerated. Up to a total of 44 patients may be enrolled in the dose escalation and expansion part of the trial. Part two of the trial will be a randomized comparison of the selected dose of dalantercept in combination with axitinib versus axitinib


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alone with a total of 112 patients. The primary endpoint of part two of the trial will be progression-free survival. The trial is currently being conducted in 7 sites in the United States.

        We believe that early preliminary data from this trial are encouraging. No dose-limiting toxicities have been observed during the 29 day assessment period for each dose cohort. Of the 13 patients enrolled in the dose escalation part of the trial, seven (54%) had received one prior therapy and six (46%) had received³ 2 prior therapies, including two patients with³ 2 prior VEGF-pathway inhibitors. As of December 24, 2013, six of eleven (55%) evaluable patients completed³ 6 cycles (approximately 4.5 months) of treatment, including two of four patients at the 0.6 mg/kg dose level, two of four patients at the 0.9 mg/kg dose level and two of three patients at the 1.2 mg/kg dose level. These data provide preliminary evidence that dalantercept can be safely combined with the VEGF-pathway inhibitor axitinib in patients with renal cell carcinoma. As of the most recent analysis (August 28, 2013) of tumor response according to RECIST criteria in the first two cohorts, one patient had achieved a partial response and one patient had achieved stable disease at the 0.6 mg/kg dose level, and one patient had achieved a partial response and three patients had achieved stable disease at the 0.9 mg/kg dose level. Data from patients at the 1.2 mg/kg dose level have not yet been analyzed. We intend to present additional data from this trial at the American Society of Clinical Oncology annual meeting in late May or early June 2014.

        Based on currently projected timelines, which are subject to change, we expect to initiate part two of this trial by the end of the first quarter or the beginning of the second quarter of 2014, which, if successful, we expect would enable a Phase 3 trial. We expect additional dose escalation data to be available when we initiate part two of the trial.

        In the first half of 2014, we plan to initiate a Phase 2 single-arm dose escalation and expansion clinical trial of dalantercept in combination with sorafenib, an approved VEGF pathway inhibitor,ACE-083 in patients with hepatocellular carcinoma. The primary endpointfacioscapulohumeral dystrophy, or FSHD, in the second half of 2016.

FSHD is a severe, disabling, and painful skeletal muscle disease that presents with muscle-by-muscle progression. Muscle weakness can be heterogeneous, but is highly focal and primarily asymmetric. Typical onset occurs between the ages 20 and 40. Most FSHD patients live a normal lifespan, but many will be to evaluate the safetysuffer from disability, pain, and tolerability of various dose levels of dalantercept in combination with sorafenib. Secondary endpoints are expected to include time to progression, progression-free survival, disease control rate, and overall survival. The dose levels planned are 0.9 mg/kg of dalantercept given subcutaneously once every three weeks in combination with 400 mg sorafenib given once daily, 1.2 mg/kg of dalantercept given subcutaneously once every three weeks in combination with 400 mg sorafenib given once daily, and 1.2 mg/kg of dalantercept given subcutaneously once every three weeks in combination with 400 mg sorafenib given twice daily. Each cohort will include up to six patients receiving a single dose level during the dose escalation phase, followed by an expansion phase in up to 20 additional patients. Patients will continue to receive dalantercept and sorafenib until theredepression. FSHD is disease progression (either clinically or as measured by RECIST criteria) or the combination is no longer tolerated.

        The Gynecologic Oncology Group, one of the National Cancer Institute's funded collaborative cancer research groups, sponsored two Phase 2 clinical trials to study the activitymost prevalent forms of dalantercept at a dose level of 1.2 mg/kg given as a single agent via subcutaneous injection every three weeks. The first trial was in patients with recurrent or persistent endometrial cancer and the second trial is in patients with recurrent or persistent ovarian cancer. Both of these clinical trials were designed as two part studies to assess the activity of dalantercept based on either of two endpoints: RECIST-defined response rate or progression free survival at 6 months. If there is sufficient activity in the first part of the trial, additional patients will be enrolled in the second, expanded part of the trial. The endometrial cancer study enrolled 28 patients in part one. Of the 28 patients, 16 (57.1%) achieved stable disease and 5 (17.9%) were alive and progression free for at least 6 months. Of these 5 patients, 3 were alive and progression free without receiving non-protocol therapy for at least 6 months. Fatigue, anemia,


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constipation, and edema were the most commonly reported toxicities regardless of attribution. The GOG has notified us that there was not sufficient activity to enroll additionalmuscular dystrophy affecting roughly 19,000 patients in the second part of the endometrial cancer trial. The GOG ovarian cancer study enrolled 30 patients to part 1. Because this part 1 of the ovarian cancer study is fully enrolled, at this time the study is closed to further enrollment. We anticipate that in the middle of 2014, we may receive notification from the GOG if there is sufficient activity to enroll additional patients in the second part of the ovarian cancer trial.

Preclinical Programs
Phase 1 Trial Results

        A Phase 1 ascending dose trial evaluated the safety, tolerability, pharmacokinetics and anti-tumor activity of dalantercept in patients with advanced solid tumors. Dalantercept was given subcutaneously approximately once every three weeks until disease progression. Thirty-seven patients were enrolled in dose groups at 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 and 4.8 mg/kg. In this trial, dalantercept demonstrated anti-tumor activity based on decreases or stabilization of tumor size. As shown in the figure below, out of the 29 evaluable patients treated, one (3%) had a partial response and 13 (45%) had stable disease according to RECIST criteria. Of the 13 who experienced stable disease, eight experienced stable disease for at least three months. Treatment continued until the patient experienced progressive disease.

        The figure below displays each patient's best overall response by the maximum percent change decrease in target lesion size. The dose level each patient received is shown below their bar.

Best Overall Response by the Maximum Percent Change Decrease in Target Lesion Size According to RECIST v1.1 Criteria

In addition to these effectsour clinical development activities, we are expanding our research capabilities in order to increase the rate at which our highly productive research group can identify and advance new, internally discovered, therapeutic candidates for clinical development. Our discovery efforts are primarily focused on tumor size, dalantercept demonstrated likely anti-angiogenic activity evidenced by a reduction of tumor metabolic activity as well as decreases in tumor blood flow. Lastly, some patients were observedidentifying new protein therapeutic candidates from our IntelliTrap platform and identifying novel antibodies. We have selected our first IntelliTrap therapeutic candidate, ACE-2494, for pre-clinical evaluation and advancement to have dilated blood vessels in the skin, similar to those in HHT-2 patients, suggesting ALK1 pathway inhibition.


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        In clinical trials to date, dalantercept has been generally well-tolerated. Inby the initial Phase 1 clinical trial in advanced cancer patients, five patients outend of 37 experienced serious adverse events deemed treatment-related that were reported2016. We are also evaluating ACE-3891 as left ventricular dysfunction, fatigue, fluid overload, and congestive heart failure. Two of these patients had prior coronary artery disease. In subsequent trials fluid overload has been successfully managed with diuretics. The following treatment related adverse events have been observed in our ongoing clinical trials. Two patients in the head and neck cancer clinical trial have experienced serious adverse events of fluid accumulation around the lungs that were determined to be possibly related to dalantercept. Another patient in the head and neck trial has experienced serious adverse events of tracheal obstruction and pulmonary edema that were determined to be possibly related to dalantercept. In the clinical trial of patients with endometrial cancer, seven patients have experienced treatment-related serious adverse events reported as fluid accumulation in the abdominal cavity, fluid accumulation around the lungs, rectal fistula, gastric bleeding, vomiting, anemia, and shortness of breath. In the clinical trial of patients with ovarian cancer, one patient has experienced treatment related serious adverse events reported as hypokalemia (decreased potassium), anorexia, dehydration and increased creatinine and another patient experienced a treatment related serious adverse event of shortness of breath. In the renal cell carcinoma trial, there has been one dalantercept-related serious adverse events of fluid overload and shortness of breath. Adverse events associated with axitinib did not occur with higher than expected frequency or severity.

        Dalantercept is being studied in the United States under an IND that we submitted to the FDA on July 29, 2009candidate therapeutic for the treatment of patients with advanced solid tumors or multiple myeloma. Dalantercept is also being studied in the United States under two INDs sponsored by the Gynecologic Oncology Group: the first was submitted on August 2, 2012muscle disease, ACE-1332, a selective TGF-beta antagonist, for the treatment of recurrent/persistent endometrial carcinoma and the second submitted on September 25, 2012 for the treatment of recurrent/persistent ovarian carcinoma.

        We have demonstrated that dalantercept as a single agent inhibits tumor growth and angiogenesis in a variety of mouse models of cancer. Importantly, we have shown that dalantercept is a potent inhibitor of the maturation stage of angiogenesis. This is in contrast with VEGF pathway inhibitors that target the proliferative stage of angiogenesis.

        We also demonstrated that dalantercept in combinationdisorders with a VEGF pathway inhibitor provides enhanced anti-tumor effects. In mice bearing human renal cell carcinoma xenografts, wefibrotic component, and our academic collaborators have shown that simultaneous administration of both dalanterceptACE-2798, ACE-2536 and sunitinib, a VEGF-receptor tyrosine kinase inhibitor, had substantially greater efficacy than either agent alone. In another mouse model of human renal cell carcinoma that develops resistance to sunitinib, tumor


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growth was blocked by the simultaneous administration of dalantercept. The figures below summarize those results.

Dalantercept/Sunitinib Combination
Exceeds Activity of Either Alone
(Mouse Model of Renal Cell Carcinoma (A498))
Dalantercept/Sunitinib Combination
Slows Tumor Growth in a Sunitinib Resistant Model
(Mouse Model of Renal Cell Carcinoma (786O))





Collaboration with Drs. Wang, Bhatt, Mier, Atkins; Beth Israel Deaconess Medical Center, Boston

Development Objectives

        For sotatercept and ACE-536, our development strategy, determined in collaboration with Celgene, for bothb-thalassemia and MDS is to conduct similar clinical trials with each protein therapeutic candidate in each disease essentially in parallel. For each disease, we and Celgene will review the data from both studies and determine which, if either, protein therapeutic candidate to move forward into subsequent, pivotal studies. It is our goal to initiate the Phase 3 clinical trials for one or both protein therapeutic candidates in one or both of these diseases by the end of 2014 or early 2015.

        In addition, we and Celgene are performing preclinical research to assess the opportunity for sotatercept and ACE-536 to treat additional red blood cell disorders known as hemoglobinopathies, which include diseases such as thalassemias and sickle cell disease. Based on our encouraging preclinical and clinical data inb-thalassemia and our emerging understanding of the mechanism of action of these protein therapeutic candidates, we believe there is a potential for activity in other diseases such as sickle cell disease and preclinical studies are currently underway.

        For dalantercept, our development strategy is to continue the renal cell carcinoma trial and to initiate during 2014 part two of the trial that compares the combination of dalantercept and axitinib to axitinib alone. We plan to initiate the hepatocellular carcinoma trial in the first half of 2014. We will also work toward completion of the ongoing single agent trial in head and neck cancer. We expect to initiate during the second half of 2014, at least one additional trial of dalantercept in cancer patients in combination with an approved VEGF pathway inhibitor. We are currently considering trials of dalantercept in combination with bevacizumab in glioblastoma (a form of brain cancer), and in colorectal cancer or lung cancer in combination with chemotherapy and/or a VEGF pathway inhibitor.

Our Preclinical Pipeline

        We are using our discovery platform and knowledge of the TGF-b superfamily to design and evaluate promising new protein therapeutic candidates that inhibit ligands of the TGF-b superfamily.


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We have preclinical stage protein therapeutic candidates in our pipeline that have shown promising activity in animal models such as:

        We are developing a novel protein therapeutic candidate, ACE-083, for a first-in-human clinical trial that we expect to initiate by the end of 2014. ACE-083 acts as a trap for ligands in the TGF-b superfamily that are known to be involved in the regulation of muscle mass. By inhibiting these ligands, ACE-083 can increase muscle mass, as we have demonstrated in animal studies. ACE-083 has been designed to affect those muscles in which the drug is injected. In preclinical animal studies, ACE-083 has shown dose dependent increases in muscle mass in the injected muscles but no systemic increases in muscle mass. We are focused on the development of ACE-083 for diseases in which increases in the size and function of specific muscles may provide a clinical benefit, including inclusion body myositis, facioscapulohumeral dystrophy (FSHD) and disuse atrophy.


ACE-083 Selectively Doubles Muscle Mass in
Injected Muscle with One Month of Treatment


**
p<0.05 vs. PBS (placebo) & vs. non-injected leg

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ALK1 Pathway Inhibitors for the Treatment of Diseases of the Eye

        Although VEGF pathway inhibitors are the standard of care for age-related macular degeneration, or AMD, there is a need for improved therapies. Perivascular cell coverage may protect endothelial cells and limit the effectiveness of VEGF pathway inhibitors in AMD. By reducing the number of perivascular cells, the activity of VEGF pathway inhibitors on unprotected endothelial cells may be potentially enhanced. Human genetic evidence indicates that patients with hereditary hemorrhagic telangiectasia (HHT-2) who lack expression of a single ALK1 gene results in defective vasculature with reduced perivascular cell coverage. We are evaluating ALK1 pathway inhibitors, distinct from dalantercept, for use in the treatment of diseases of the eye. The combination of a VEGF pathway inhibitor and an ALK1 pathway inhibitor may lead to more effective treatment of neoangiogenesis diseases of the eye including AMD.

Our Strategic Partnerships

Collaborations with corporate partners have provided us with significant funding and access to our partners' scientific, development, regulatory and commercial capabilities. We have received more than $250.0$297.7 million from our collaborations with Celgene, Alkermes plc (Alkermes) and Shire.


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Celgene

On February 20, 2008 we entered into an agreement, which we refer to as the Sotatercept Agreement, with Celgene Corporation, under which we granted to Celgene worldwide rights to sotatercept. On August 2, 2011 we entered into a second agreement with Celgene for ACE-536,luspatercept, which we refer to as the ACE-536Luspatercept Agreement under which we granted to Celgene worldwide rights to ACE-536luspatercept and also amended certain terms of the Sotatercept Agreement. These agreements provide Celgene exclusive licenses for these protein therapeutic candidates in all indications, as well as exclusive rights to obtain a license to certain future compounds.

Sotatercept Agreement.    Under the terms of the Sotatercept Agreement, we and Celgene are collaborating on the development and commercialization of sotatercept. We also granted Celgene an option to license discovery stage compounds against three specified targets. Celgene paid $45.0 million and bought $5.0 million of equity upon execution of the Sotatercept Agreement and, as of December 31, 2013,2015, we have received $41.6$43.0 million in research and development funding and milestone payments for the sotatercept program.

We retained responsibility for research, development through the end of Phase 2a clinical trials, as well as manufacturing the clinical supplies for these trials. These activities are substantially complete. Celgene is conducting the current Phase 2 trials forb-thalassemia, beta-thalassemia, MDS and chronic kidney disease and will be responsible for any future clinical trials for sotatercept as well as for all future manufacture of sotatercept. We are eligible to receive future development, regulatory and commercial milestones of up to $360.0 million for the sotatercept program and up to an additional $348.0 million for each of the three discovery stage programs. None of the three discovery stage programs has advanced to the stage to achieve payment of a milestone, nor do we expect any such milestone payments in the near future.

        ACE-536Luspatercept Agreement.    Under the terms of the ACE-536Luspatercept Agreement, we and Celgene are collaborating in the development and commercialization of ACE-536.luspatercept. We also granted Celgene an option to license products for which Acceleron files an investigational new drug application for the treatment of anemia. Celgene paid $25.0 million to us upon execution of the ACE-536Luspatercept Agreement in August 2011 and, as of December 31, 2013,2015, we have received $31.9$60.3 million in research and development funding and milestone payments for the ACE-536luspatercept program.

Under this agreement, we retained responsibility for research, development through the end of Phase 1 and the two ongoing Phase 2 clinical trials in MDS andb-thalassemia, beta-thalassemia, as well as manufacturing the clinical supplies for these studies. Celgene will conduct subsequent Phase 2 and


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Phase 3 clinical trials. Acceleron will manufacture ACE-536luspatercept for all Phase 1 and Phase 2 clinical trials, and Celgene will have responsibility for the manufacture of ACE-536luspatercept for Phase 3 clinical trials and commercial supplies. We are eligible to receive future development, regulatory and commercial milestones of up to $200.0 million for the ACE-536luspatercept program.

In November 2013, the Company has agreed to conduct additional development activities including clinical and non-clinical services, which are reimbursed under the same terms and rates of the existing Agreements. Please refer to Note 910 to the financial statements in this Annual Report on Form 10-K for the revenue recognition accounting, including changes in estimates, pursuant to the revenue recognition accounting literature.

Both Agreements.    Under each agreement, the conduct of the collaboration is managed by a Joint Development Committee and Joint Commercialization Committee. Other than with respect to certain matters related to our conduct of Phase 2 trials, in the event of a deadlock of a committee, the resolution of the relevant issue is determined by Celgene. Prior to January 1, 2013, Celgene paid the majority of development costs under the Sotatercept and ACE-536Luspatercept Agreements. As of January 1, 2013, Celgene became responsible for paying 100% of worldwide development costs for both programs. Celgene will be responsible for all commercialization costs worldwide. We are obligated to co-promote sotatercept, ACE-536luspatercept and future products, in each case if approved, under both agreements in North America, and Celgene will pay all costs related thereto. We will receive tiered royalties in the low-to-mid 20% range on net sales of sotatercept and ACE-536.luspatercept. The royalty schedules for sotatercept and ACE-536luspatercept are the same. Celgene is obligated to use commercially reasonable efforts to develop and commercialize sotatercept and ACE-536.luspatercept. Celgene may determine that it is commercially reasonable to develop and commercialize only sotaterceptluspatercept or ACE-536sotatercept and discontinue the development or commercialization of the other protein therapeutic candidate, or Celgene may determine that it is not commercially reasonable to continue development of one or both of sotatercept and ACE-536.luspatercept. In the event of any such decision, we may be unable to progress the discontinued candidate or candidates ourselves. The agreements are terminable by either party upon a breach that is uncured and continuing or by Celgene for convenience on a country by country or product by product basis, or in its entirety. Celgene may also terminate the agreement, in its entirety or on a product by product basis, for failure of a product to meet a development or clinical trial endpoint. Termination for cause by us or termination by Celgene for convenience or failure to meet an endpoint will have the effect of terminating the applicable license, while termination for cause by Celgene will have the effect of reducing remaining royalties by a certain percentage.


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Other Collaborations

Alkermes.On December 3, 2009, we entered into a Collaboration and License Agreement with Alkermes relating to a proprietary technology platform for extending the circulating half-life of certain proteins. Under the terms of the agreement, we granted Alkermes worldwide rights to apply this technology to proteins outside of the TGF-bTGF-beta superfamily in return for an upfront license payment. We are entitled to future development, regulatory and sales milestones and mid-single digit royalties on product sales for each drug developed and commercialized by Alkermes using this technology. To our knowledge, Alkermes is not currently developing any products usingpursuing technology licensed under this technology.collaboration. Rights pertaining to a lead program, referred to ACE-771, were returned pursuant to the terms of the agreement, and we are not pursuing development of ACE-771 at this point in time.

Shire.On September 8, 2010, we entered into an agreement with Shire AG for the joint development and commercialization of ACE-031, a clinical stage protein therapeutic candidate. We granted Shire an exclusive license in markets outside of North America. Under the terms of the agreement, Shire made an upfront cash payment of $45.0 million. We received $9.0 million in research and development payments from Shire during the term of the agreement. In April 2013, we and Shire determined not to further advance the development of ACE-031, and Shire terminated our collaboration agreement, effective as of June 30, 2013 and all rights reverted to us. We currently have no plans to continue the development of ACE-031.


Competition

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Competition

The development and commercialization of new drugs is highly competitive. We and our collaborators will face competition with respect to all protein therapeuticstherapeutic candidates we may develop or commercialize in the future from pharmaceutical and biotechnology companies worldwide. Many of the entities developing and marketing potentially competing products have significantly greater financial resources and expertise than we do in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing. Our commercial opportunity will be reduced or eliminated if our competitors develop and commercialize products that are more effective, have fewer side effects, are more convenient or are less expensive than any products that we may develop.

If our clinical stage protein therapeuticstherapeutic candidates are approved, they will compete with currently marketed drugs and therapies used for treatment of the following indications, and potentially with drug candidates currently in development for the same indications:

MDS
If either sotaterceptluspatercept or ACE-536 is approved for the treatment of patients withb-thalassemia, it would compete with:

        If either sotatercept or ACE-536 is approved for the treatment of patients with MDS, it would compete with the following:

Recombinant erythropoietin and other erythropoiesis stimulating agents. Although these agents are not approved to treat anemia in MDS, current practice guidelines include the use of erythropoiesis stimulating agents and granulocyte colony stimulating factor agents (G-CSF) to treat patients with MDS. Additionally, Amgen'sAmgen is currently studying erythropoiesis stimulating agent, Aranesp®, and Janssen Pharmaceuticals is currentlystudying erythropoiesis stimulating agent Eprex® in Phase 3 clinical trials in Europe for treatment of anemia in patients with lower risk MDS.


Red blood cell transfusion and iron chelation therapy, including Exjade®, which is used to treat anemia in patients with MDS.


Immunomodulators, including Celgene's approved product, Revlimid® (lenalidomide), for the treatment of anemia of certain MDS patients.

Eli Lilly and Company is studying TGF-beta receptor I kinase inhibitor, LY2157299 in a Phase 2 study in lower risk MDS patients with anemia.

Other therapies in development, including: an oral form of the hypomethylating agent azacitidine, known as CC-486, being developed by Celgene to treat patients with transfusion dependent anemia and thrombocytopenia due to lower risk MDS, which is currently in Phase 3

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MDS; and a CD95 ligand inhibitor, APG101, being studied by Apogenix in a Phase 1 study in transfusion dependent, lower risk MDS patients.

Beta-thalassemia
If either sotatercept or ACE-536luspatercept is approved for the treatment of patients with beta-thalassemia, it would compete with:

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Red blood cell transfusions and iron chelation therapy, such as Novartis's oral iron chelating agents, Exjade® and Jadenu™.

Fetal hemoglobin stimulating agents, such as hydroxyurea, which are primarily used to treat patients with anemia from sickle cell disease, are sometimes used to treat patients with beta-thalassemia.

Hematopoietic stem cell transplant treatment is given to a small percentage of patients with beta-thalassemia, since it requires a sufficiently well-matched source of donor cells. Certain academic centers around the world are seeking to develop improvements to this approach.

Other therapies in development, including gene therapy and genome editing are being developed by several different groups, including bluebird bio, Inc., Memorial Sloan Kettering Cancer Center, GlaxoSmithKline plc, and Sangamo BioSciences Inc. in collaboration with Biogen Idec.
Chronic Kidney Disease
If sotatercept is approved to treat certain aspects of chronic kidney disease-mineral and bone disorder (CKD-MBD), other drugs approved for the treatment of these patients could be considered competitive. CKD-MBD is a systemic disorder encompassing mineral, bone, and calcific cardiovascular abnormalities that develop as a complication of CKD and that contribute to CKD-related cardiovascular disease and high mortality rates. Therapies approved to treat aspects of CKD-MBD include phosphate binders to address hyperphosphatemia, including Sanofi’s Renagel® and Renvela® , Shire’s Fosrenol®,and Keryx’s newly approved product Auryxia®. Amgen’s oral calcimimetic product Sensipar®/Mimpara® is approved to treat secondary hyperparathyroidism in CKD patients on dialysis. Amgen is also studying etelcalcitide (AMG-416), an intravenously administered calcium sensing receptor agonist, and has filed for marketing approval in the United States and Europe to treat secondary hyperparathyroidism in chronic kidney disease patients on dialysis. Additionally, if sotatercept is studied and approved in patients with pre-dialysis kidney disease, other drugs that potentially slow progression of kidney disease could be considered competitors. Currently, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) therapies are standard of care in patients with chronic kidney disease it would compete primarily with erythropoiesis stimulating agents thatand have been approvedshown to treat these patients for over 20 years. In 2011,lower blood pressure, reduce proteinuria, and slow the Centers for Medicare and Medicaid Services (CMS) changed the reimbursement practice for erythropoiesis stimulating agentsprogression of kidney disease. There are also a number of drugs in chroniclate-stage clinical trials to slow progression of diabetic nephropathy, a form of kidney disease patients on dialysis, which has ledin diabetic patients. Janssen Pharmaceuticals. NephroGenex, Abbvie, and Bayer have programs in ongoing Phase 3 clinical trials, and Mitsubishi Pharma, Lilly, and Vascular Pharmaceuticals, have programs in ongoing or completed Phase 2 clinical trials, to changes in the way erythropoiesis stimulating agents are used in clinical practice, including decreasing the numberslow progression of patients treated with erythropoiesis stimulating agents as well as decreasing the average dose and duration of therapy. These changes and the anticipated future introduction of biosimilar erythropoiesis stimulating agents are expected to generate additional price pressure in this market. Additionally, we are aware that Astellas Pharma and Fibrogen are developing oral, small molecule treatments that increase the production of erythropoietin to treat patients with anemia.

Oncology Therapies

We are developing dalantercept to be used in combination with VEGF pathway inhibitors for the treatment of cancer. If dalantercept is approved, it would compete with:

Tracon is developing TRC105, an antibody to endoglin, which is a protein in the TGF-beta superfamily that is overexpressed on endothelial cells and plays a role in angiogenesis. TRC105 is currently being studied in Phase 1 and Phase 2 clinical trials for the treatment of multiple solid tumor types, including soft tissue sarcoma, renal cell carcinoma, glioblastoma, hepatocellular carcinoma and colorectal cancer, in combination with approved VEGF inhibitors.
Pfizer's fully human monoclonal antibody against the ALK1 receptor is currently being studied in a Phase 1 investigator-sponsored trial in patients with colorectal cancer, in combination with Stivarga® (regorafenib).
Other non-VEGF angiogenesis inhibitors in development, which also have the potential to be combined with VEGF pathway inhibitors or used independently of VEGF pathway inhibitors to inhibit angiogenesis. Amgen, Regeneron, MedImmune, and OncoMed Pharmaceuticals Pfizer and Tracon are each developing non-VEGF angiogenesis inhibitors.

Pfizer's fully human monoclonal antibody to the ALK1 receptor, which is in Phase 2 trials in malignant pleural mesothelioma.

In addition to the therapies mentioned above, there are many generic chemotherapy agents and other regimens commonly used to treat various types of cancer, including renal cell carcinoma, head and neck, endometrial and ovarian cancer.

Therapies for Treating Muscle Loss

We are currently studying ACE-083 in the process of moving our lead pre-clinical protein therapeutic candidate, ACE-083, into its initiala Phase 1 clinical trial. Wetrial in healthy volunteers and plan to develop ACE-083 for the treatment of neuromuscular disorders and other diseases characterized by a loss of muscle function. function including facioscapulohumeral muscular dystrophy (FSHD). One potential competitor of ACE-083 in FSHD is Resolaris® (ATYR1940), which is an investigational protein in Phase 1b/2 studies to treat adult patients with FSHD being developed by aTyr Pharma.


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We are also aware of other approaches to treatingtreat other muscle loss diseases that are in clinical trials. Novartis is developing bimagrumab (BYM338), a monoclonal antibody targeting the activin receptor type IIB (ActRIIB), in various phasePhase 2 clinical trials to treat pathological muscle loss and weakness.weakness and in Phase a 2/3 clinical trial to treat patients with sporadic inclusion body myositis (sIBM). Regeneron is developing a myostatin monoclonal antibody, REGN1033 (SAR391786), which has completed a Phase 2 clinical trial for treatment of sarcopenia. Pfizer is conducting a Phase 2 clinical study for PF-06252616, a myostatin antibody, in patients with Duchenne muscular dystrophy (DMD). Nationwide Children's Hospital, in collaboration with The Myositis Association, and Parent Project Muscular Dystrophy isand Milo Biotechnology, are conducting a phasePhase 1 clinical trial of a gene therapy delivery of follistatin (FS344) to muscle in patients with Becker muscular dystrophy (BMD) and sporadic inclusion body myositis (sIBM). Eli Lilly is developing, LY2495655, a myostatin monoclonal antibody in phase 2 clinical trials for disuse muscle atrophy and cancer-related cachexia. Regeneron and Sanofi are developing a myostatin monoclonal antibody, REGN1033 (SAR391786), which is in phase 1 clinical development for treatment of sarcopenia. Biogen Idec is conducting a phase 1 clinical trial of BIIB023, a monoclonal antibody targeting the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), to evaluate its effects on muscle atrophy in healthy male volunteers. Atara Bio is developing PINTA 745, a myostatin inhibiting peptibody to treat protein energy wasting in patients with end stage renal disease who are on dialysis.

The key competitive factors affecting the success of any approved product will be its efficacy, safety profile, price, method of administration and level of promotional activity.


Commercialization

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Commercialization

We retain co-promotion rights with our collaboration partner, Celgene, for both sotatercept and ACE-536luspatercept in North America, and under the terms of our agreements with Celgene, our commercialization costs will be entirely funded by Celgene. We also currently retain worldwide commercialization rights for our oncology protein therapeutic candidate, dalantercept, and our muscle protein therapeutic candidate, ACE-083. We intend to build hematology oncology and neuromuscular disorder focused, specialty sales forces in North America and, possibly, other markets to effectively support the commercialization of these and future products. We believe that a specialty sales force will be sufficient to target key prescribing physicians in these areas. We currently do not have any sales or marketing capabilities or experience. We will establish the required capabilities within an appropriate time frame ahead of any product approval and commercialization to support a product launch. If we are not able to establish sales and marketing capabilities or are not successful in commercializing our future products, either on our own or through collaborations with Celgene, any future product revenue will be materially adversely affected.

Intellectual Property

Our commercial success depends in part on our ability to obtain and maintain proprietary protection for our protein therapeutics,therapeutic candidates, novel biological discoveries, screening and drug development technology, to operate without infringing on the proprietary rights of others and to prevent others from infringing our proprietary rights. Our policy is to seek to protect our proprietary position by, among other methods, filing U.S. and foreign patent applications related to our proprietary technology, inventions and improvements that are important to the development and implementation of our business. We also rely on trade secrets, know-how, continuing technological innovation and potential in-licensing opportunities to develop and maintain our proprietary position. Additionally, we expect to benefit from a variety of statutory frameworks in the United States, Europe and other countries that relate to the regulation of biosimilar molecules and orphan drug status. These statutory frameworks provide periods of non-patent-based exclusivity for qualifying molecules. See "Government Regulations".

Our patenting strategy is focused on our protein therapeutics.therapeutic candidates. We seek composition-of-matter and method-of-treatment patents for each such protein in key therapeutic areas. We also seek patent protection with respect to companion diagnostic methods and compositions and treatments for targeted patient populations. We have sought patent protection alone or jointly with our collaborators, as dictated by our collaboration agreements.

Our patent estate, on a worldwide basis, includes approximately 75160 issued patents and approximately 300390 pending patent applications, with pending and issued claims relating to all of our current clinical stage protein therapeutic candidates, sotatercept, ACE-536luspatercept, dalantercept and dalantercept. Of these, approximately 20 issued patents cover the nine receptors for the TGF-b superfamily that we have selected as the core focus of our discovery approach.ACE-083. These figures include in-licensed patents and patent applications to which we hold exclusive commercial rights.

Individual patents extend for varying periods of time depending on the date of filing of the patent application or the date of patent issuance and the legal term of patents in the countries in which they are obtained. Generally, patents issued from applications filed in the United States are effective for twenty years from the earliest non-provisional filing date. In addition, in certain instances, a patent term can be extended to recapture a portion of the term effectively lost as a result of the FDA regulatory review period, however, the restoration period cannot be longer than five years and the total patent term including the restoration period must not exceed 14 years following FDA approval. The duration of foreign patents varies in accordance with provisions of applicable local law, but typically is also twenty years from the earliest international filing date. Our issued patents with respect to our receptor-focused platform will expire on dates ranging from 2013 to 2018, and our issued patents and


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pending applications with respect to our protein therapeutic candidates will expire on dates ranging from 2026 to 2033,2035, exclusive of possible patent term extensions, However, the actual protection afforded by a patent varies on a product by product basis, from country to country and depends upon many factors, including the type of patent, the scope of its coverage, the availability of extensions of patent term, the availability of legal remedies in a particular country and the validity and enforceability of the patent.


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National and international patent laws concerning protein therapeuticstherapeutic candidates remain highly unsettled. No consistent policy regarding the patent-eligibility or the breadth of claims allowed in such patents has emerged to date in the United States, Europe or other countries. Changes in either the patent laws or in interpretations of patent laws in the United States and other countries can diminish our ability to protect our inventions and enforce our intellectual property rights. Accordingly, we cannot predict the breadth or enforceability of claims that may be granted in our patents or in third-party patents. The biotechnology and pharmaceutical industries are characterized by extensive litigation regarding patents and other intellectual property rights. Our ability to maintain and solidify our proprietary position for our drugs and technology will depend on our success in obtaining effective claims and enforcing those claims once granted. We do not know whether any of the patent applications that we may file or license from third parties will result in the issuance of any patents. The issued patents that we own or may receive in the future, may be challenged, invalidated or circumvented, and the rights granted under any issued patents may not provide us with sufficient protection or competitive advantages against competitors with similar technology. Furthermore, our competitors may be able to independently develop and commercialize similar drugs or duplicate our technology, business model or strategy without infringing our patents. Because of the extensive time required for clinical development and regulatory review of a drug we may develop, it is possible that, before any of our drugs can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby reducing any advantage of any such patent. The patent positions for our most advanced programs are summarized below:

Luspatercept Patent Coverage
We hold two issued patents covering the luspatercept composition of matter in the United States, and additional patents issued or pending in many other major jurisdictions worldwide, including Europe, Australia, Canada, Japan, China, South Korea, Brazil, Mexico, Russia and India. The expected expiration dates for these composition of matter patents are 2028 and 2029, exclusive of possible patent term extensions.
We hold two issued patents covering the treatment of anemia by administration of luspatercept in the United States and similar patents issued or pending in other major jurisdictions worldwide, including Europe, Australia, Canada, Japan, China, South Korea, Brazil, Mexico, Russia and India. The expected expiration date for these method of treatment patents is 2029, exclusive of possible patent term extensions.
We also hold patent applications directed to a variety of other uses for luspatercept, including the treatment of complications of thalassemia, such as iron overload and ulcers, and treatment of patient sub-groups with MDS. The expected expiration date for these method of treatment patents ranges from 2029 to 2035 exclusive of possible patent term extensions.
Sotatercept Patent Coverage

We hold two issued patents covering the sotatercept composition of matter in the United States, one issued patent in Europe (registered in most countries of the European Patent Convention) and additional patents issued or pending in many other major jurisdictions worldwide, including Australia, Canada, Japan, China, South Korea, Brazil, Mexico, Russia, Israel and India. The expected expiration date for these composition of matter patents is 2026, plus any extensionsexclusive of possible patent term available under national law.

extensions.

We hold twothree issued patents covering the treatment of anemia by administration of sotatercept in the United States and similar patents issued or pending in many other major jurisdictions worldwide, including Europe, Australia, Canada, Japan, China, South Korea, Brazil, Mexico, Russia, Israel and India. The expected expiration date for these compositionmethod of mattertreatment patents is 2027, exclusive of possible patent term extensions.

We also hold patents and patent applications directed to a variety of other uses for sotatercept, including the reductiontreatment of tumor cell burden in multiple myeloma.

        We hold two issued patents covering the ACE-536 composition of matter in the United States,myeloma and additional patents issued or pending in many other major jurisdictions worldwide, including Europe, Japan, China, South Korea, Brazil, Mexico, Russia and India. The expected expiration dates for these composition of matter patents are 2028 and 2029, exclusive of possible patent term extensions.

        We hold one issued patent covering the treatment of anemia by administration of ACE-536bone loss in the United States and similar patents issued or pending in other major jurisdictions worldwide, including

patients with chronic kidney disease.

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Europe, Japan, China, South Korea, Brazil, Mexico, Russia and India. The expected expiration date for these method of treatment patents is 2029 exclusive of possible patent term extensions.

We hold one issued patent covering the dalantercept composition of matter in the United States, which is expected to expire in 2029, exclusive of possible patent term extensions, and we hold additional pending patent applications. We hold additional issued patents and pending patent applications covering composition of matter in many other major jurisdictions worldwide, including Europe, Australia, Canada, Japan, China, South Korea, Brazil, Mexico, Russia and India. The expected expiration dates for these patent filings, claiming the dalantercept composition of matter, if issued, are either 2027 or 2029, exclusive of possible patent term extensions.

We hold one issued patent covering the treatment of tumor angiogenesis by administration of dalantercept in the United States and similar patents issued or pending in other major jurisdictions worldwide, including Europe, Japan, China, South Korea, Brazil, Mexico, Russia and India. The expected expiration date for these method of treatment patents is 2027, exclusive of possible patent term extensions.


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We also hold patent applications directed to a variety of other uses for dalantercept, including the treatment of renal cell carcinoma with a combination of dalantercept and a VEGF-targeted tyrosine kinase inhibitor. This patent application is jointly invented and owned with the Beth Israel Deaconess Medical Center, or BIDMC, and we have secured an exclusive license to the BIDMC rights. The expected expiration date for these patent applications, should they issue as patents, is 2033 plus any extensions of term available under national law.

ACE-083 Patent Coverage
We hold two pending patent applications covering the ACE-083 composition of matter in the United States, which, if issued are expected to expire in 2029 and 2035, respectively, exclusive of possible patent term extensions. These patent applications are also eligible for filing in major jurisdictions worldwide.
Trade Secrets

In addition to patents, we rely upon unpatented trade secrets and know-how and continuing technological innovation to develop and maintain our competitive position. We seek to protect our proprietary information, in part, using confidentiality agreements with our commercial partners, collaborators, employees and consultants and invention assignment agreements with our employees. These agreements are designed to protect our proprietary information and, in the case of the invention assignment agreements, to grant us ownership of technologies that are developed through a relationship with a third party. These agreements may be breached, and we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors. To the extent that our commercial partners, collaborators, employees and consultants use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions.

In-Licenses

Effective June 21, 2012, we entered into a license agreement with the Beth Israel Deaconess Medical Center, or BIDMC, to obtain worldwide, exclusive rights under patent filings jointly invented by us and BIDMC. The patent rights relate to the treatment of renal cell cancer by combination therapy with dalantercept and VEGF-receptor tyrosine kinase inhibitors (TKIs). The intellectual property includes one pending U.S. patent filing and one pending PCT (international) patent filing. If issued, the patents are predicted to expire in 2033. Under the agreement, BIDMC retained rights, on behalf of itself and other non-profit academic institutions, to practice under the licensed rights for non-profit purposes. The license rights granted to us are further subject to any rights the United States Government may have in such licensed rights due to its sponsorship of research that led to the creation of the licensed rights. We agreed to pay BIDMC specified development and sales milestone payments aggregating up to $1.0 million. In addition, we are required to pay BIDMC royalties in the low single-digits on worldwide net product sales of drug labeled for treatment regimens that are claimed in the


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licensed patents. The agreement terminates upon the expiration of the last valid claim of the licensed patent rights. We may terminate the agreement at any time by giving BIDMC advance written notice. The agreement may also be terminated by BIDMC in the event of a material breach by us or in the event we become subject to specified bankruptcy or similar circumstances. In any termination event, we retain our joint ownership of the patent rights and a worldwide non-exclusive license with right to sublicense.

        In

On August 6, 2010, we entered into an amended and restated license agreement with the Ludwig Institute for Cancer Research, or LICR, to obtain worldwide, exclusive rights under patent filings solely owned by LICR and patent rights jointly invented by us and LICR. The LICR-owned patent rights relate to the first cloning of the type I activin receptors, ALK1, ALK2, ALK3, ALK4, ALK5 and ALK6, and include claims to nucleic acids, proteins and antibodies with respect to each of the foregoing. These patent rights expire between the years 2013 and 2018. The license excludes the rights with regard to anti-ALK2 antibodies. The joint patent rights relate to the treatment of pancreatic tumors with dalantercept and, if issued, such patent rights are expected to expire in 2029. Under the agreement, LICR retained rights, on behalf of itself and other non-profit academic institutions, to practice under the licensed rights for non-profit purposes. We agreed to pay LICR specified development and sales milestone payments aggregating up to $1.6 million for dalantercept. In addition, we are required to pay LICR royalties in the low single-digits on worldwide net product sales of products claimed in the licensed patents, with royalty obligations continuing at a 50% reduced rate for eight years after patent expiration. If we sublicense the LICR patent rights, we will owe LICR a percentage of sublicensing revenue, excluding payments based on the level of sales, profits or other levels of commercialization. The agreement terminates upon the expiration of royalty obligations. We may terminate the agreement at any time by giving LICR advance written notice. The agreement may also be terminated by LICR in the event of a material breach by us or in the event we become subject to specified bankruptcy or similar circumstances. In any termination we retain our joint ownership right in the jointly owned patent filings.

In August 2010, we entered into two amended and restated license agreements with the Salk Institute for Biological Studies, or Salk, providing rights under U.S. patent filings solely owned by Salk. The agreements for the licensed patent rights relate to the first cloning of the type II activin receptors, human ActRIIA and frog ActRIIB, respectively, and include claims to

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vertebrate homolog nucleic acids and proteins with respect to each of the foregoing. These patent rights expire between the years 2016 and 2017. One of these agreements relates to ActRIIA and sotatercept; the other agreement relates to ActRIIB, ACE-536luspatercept and the discontinued program ACE-031.ACE-031, which we refer to as the ActRIIB Agreement. The licenses granted are exclusive as to the therapeutic products that are covered by the patents and non-exclusive as to diagnostic products and other products that are developed using the Salk patent rights. If we sublicense the Salk patent rights, we will owe Salk a percentage of sublicensing revenue, excluding payments based on sales. Under the agreements, Salk retained rights, on behalf of itself and other non-profit academic institutions, to practice under the licensed rights for non-profit purposes. We agreed to pay Salk specified development milestone payments totaling up to $2.0 million for sotatercept and $0.7 million for ACE-536.luspatercept. In addition, we are required to pay Salk royalties in the low single-digits on worldwide net product sales by us or our sublicensees of products claimed in the licensed patents, or derived from use of the licensed patent rights, with royalty obligations continuing at a reduced rate for a period of time after patent expiration. The agreements terminate upon the expiration of royalty obligations. We may terminate either agreement at any time by giving Salk advance written notice. Either agreement may also be terminated by Salk in the event of a material breach by us or in the event we become subject to bankruptcy or similar circumstances.

In October 2012, Salk filed a lawsuit against us alleging that we breached the ActRIIB Agreement. In July 2014, we settled the Salk lawsuit and entered into an amendment to the ActRIIB Agreement with Salk. Pursuant to the settlement, we made a one-time total payment of $5 million, inclusive of interest, to Salk and we agreed to pay Salk 6% of future development milestone payments received under the agreement with Celgene relating to luspatercept. Finally, we and Salk have further agreed that the royalty percentage on net sales of luspatercept will remain at 1% as provided in the ActRIIB Agreement with Salk, and that such royalty will be payable until June 2022.
Government Regulation

The preclinical studies and clinical testing, manufacture, labeling, storage, record keeping, advertising, promotion, export, marketing and sales, among other things, of our protein therapeutic


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candidates and future products, are subject to extensive regulation by governmental authorities in the United States and other countries. In the United States, pharmaceutical products are regulated by the FDA under the Federal Food, Drug, and Cosmetic Act and other laws, including, in the case of biologics, the Public Health Service Act. We expect sotatercept, ACE-536,luspatercept, dalantercept, ACE-083 and dalanterceptACE-2494 to be regulated by the FDA as biologics and to be reviewed by the Center for Drug Evaluation and Research (CDER) as proteins intended for therapeutic use. Protein therapeuticsTherapeutic candidates require the submission of a Biologics License Application, or BLA, and approval by the FDA prior to being marketed in the U.S. Manufacturers of protein therapeuticstherapeutic candidates may also be subject to state regulation. Failure to comply with FDA requirements, both before and after product approval, may subject us or our partners, contract manufacturers, and suppliers to administrative or judicial sanctions, including FDA refusal to approve applications, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, fines and/or criminal prosecution.

The steps required before a biologic may be approved for marketing of an indication in the United States generally include:

completion of preclinical laboratory tests, animal studies and formulation studies conducted according to Good Laboratory Practices, or GLPs, and other applicable regulations;

submission to the FDA of an Investigational New Drug application or IND, which must become effective before human clinical trials may commence;

completion of adequate and well-controlled human clinical trials in accordance with Good Clinical Practices, or GCPs, to establish that the biological product is "safe, pure and potent", which is analogous to the safety and efficacy approval standard for a chemical drug product for its intended use;

submission to the FDA of a BLA;

satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with applicable current Good Manufacturing Practice requirements, or cGMPs; and

FDA review of the BLA and issuance of a biologics license which is the approval necessary to market a protein therapeutic.

therapeutic candidate.

Preclinical studies include laboratory evaluation of product chemistry, toxicity and formulation as well as animal studies to assess the potential safety and efficacy of the biologic candidate. Preclinical studies must be conducted in compliance with FDA regulations regarding GLPs. The results of the preclinical tests, together with manufacturing information and analytical

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data, are submitted to the FDA as part of an IND. Some preclinical testing may continue even after the IND is submitted. In addition to including the results of the preclinical testing, the IND will also include a protocol detailing, among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated if the first phase or phases of the clinical trial lends themselves to an efficacy determination. The IND will automatically become effective 30 days after receipt by the FDA, unless the FDA within the 30-day time period places the IND on clinical hold because of its concerns about the drug candidate or the conduct of the trial described in the clinical protocol included in the IND. The IND sponsor and the FDA must resolve any outstanding concerns before clinical trials can proceed.

All clinical trials must be conducted under the supervision of one or more qualified principal investigators in accordance with GCPs. They must be conducted under protocols detailing the objectives of the applicable phase of the trial, dosing procedures, research subject selection and exclusion criteria and the safety and effectiveness criteria to be evaluated. Each protocol must be submitted to the FDA as part of the IND, and progress reports detailing the status of the clinical trials must be submitted to the FDA annually. Sponsors also must timely report to the FDA serious and unexpected adverse reactions, any clinically important increase in the rate of a serious suspected adverse reaction over that


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listed in the protocol or investigator's brochure, or any findings from other studies or animal or in vitro testing that suggest a significant risk in humans exposed to the drug. An institutional review board, or IRB, at each institution participating in the clinical trial must review and approve the protocol before a clinical trial commences at that institution, approve the information regarding the trial and the consent form that must be provided to each research subject or the subject's legal representative, and monitor the study until completed.

Clinical trials are typically conducted in three sequential phases, but the phases may overlap and different trials may be initiated with the same drug candidate within the same phase of development in similar or differing patient populations. Phase 1 trials may be conducted in a limited number of patients, but are usually conducted in healthy volunteer subjects. The drug candidate is initially tested for safety and, as appropriate, for absorption, metabolism, distribution, excretion, pharmacodynamics and pharmacokinetics.

Phase 2 trials usually involves trials ininvolve a larger, but still limited, patient population to evaluate preliminarily the efficacy of the drug candidate for specific, targeted indications to determine dosage tolerance and optimal dosage and to identify possible short-term adverse effects and safety risks.

Phase 3 trials are undertaken to further evaluate clinical efficacy of a specific endpoint and to test further for safety within an expanded patient population at geographically dispersed clinical trial sites. Phase 1, Phase 2, or Phase 3 testing might not be completed successfully within any specific time period, if at all, with respect to any of our protein therapeutic candidates. Results from one trial are not necessarily predictive of results from later trials. Furthermore, the FDA or the sponsor may suspend clinical trials at any time on various grounds, including a finding that the subjects or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB's requirements or if the drug candidate has been associated with unexpected serious harm to patients.

The results of the preclinical studies and clinical trials, together with other detailed information, including information on the manufacture and composition of the product, are submitted to the FDA as part of a BLA requesting approval to market the drug candidate for a proposed indication. Under the Prescription Drug User Fee Act, as re-authorized most recently in July 2012, the fees payable to the FDA for reviewing a BLA, as well as annual fees for commercial manufacturing establishments and for approved products, can be substantial. The fee for review of an application that requires clinical data, such as a BLA, for the one year period ending September 30, 2013,2016, is almost $2.0approximately $2.4 million, subject to certain limited deferrals, waivers, and reductions that may be available. The fees typically increase each year. Each BLA submitted to the FDA for approval is reviewed for administrative completeness and reviewability within 60 days following receipt by the FDA of the application. If the BLA is found complete, the FDA will file the BLA, triggering a full review of the application. The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission. The FDA's established goal is to review 90% of priority BLA applications within six months after the application is accepted for filing and 90% of standard BLA applications within 10 months of the acceptance date, whereupon a review decision is to be made. The FDA, however, may not approve a drug candidate within these established goals and its review goals are subject to change from time to time. Further, the outcome of the review, even if generally favorable, may not be an actual approval but a "complete response letter" that describes additional work that must be done before the application can be approved. Before approving a BLA, the FDA may inspect the facility or facilities at which the product is manufactured and will not approve the product unless the facility complies with cGMPs. The FDA may deny approval of a BLA if applicable statutory or regulatory criteria are not satisfied, or may require additional testing or information, which can extend the review process. FDA approval of any application may include many delays or never be granted. If a product is approved, the approval may impose limitations on the uses for which the product may be marketed, may require that


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warning statements be included in the product labeling, may require that additional studies be conducted following approval as a condition of the approval, and may impose restrictions and conditions on product distribution, prescribing, or dispensing in the form of a Risk Evaluation and Mitigation Strategy, or REMS, or


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otherwise limit the scope of any approval. The FDA must approve a BLA supplement or a new BLA before a product may be marketed for other uses or before certain manufacturing or other changes may be made. Further post-marketing testing and surveillance to monitor the safety or efficacy of a product is required. Also, product approvals may be withdrawn if compliance with regulatory standards is not maintained or if safety or manufacturing problems occur following initial marketing. In addition, new government requirements may be established that could delay or prevent regulatory approval of our protein therapeutic candidates under development.

As part of the recently-enacted Patient Protection and Affordable Care Act of 2010, under the subtitle of Biologics Price Competition and Innovation Act of 2009, or the BPCI, a statutory pathway has been created for licensure, or approval, of biological products that are biosimilar to, and possibly interchangeable with, earlier biological products licensed under the Public Health Service Act. Also under the BPCI, innovator manufacturers of original reference biological products are granted 12 years of exclusivity before biosimilars can be approved for marketing in the United States. The objectives of the BPCI are conceptually similar to those of the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the "Hatch-Waxman Act", which established abbreviated pathways for the approval of drug products. The implementation of an abbreviated approval pathway for biological products is under the direction of the FDA and is currently being developed. In late 2010, the FDA held a hearing to receive comments from a broad group of stakeholders regarding the implementation of the BPCI. Since that hearing in 2010, the FDA, in February 2012 and February 2013, has issued several draft guidances for industry related to the BPCI, addressing scientific, quality and procedural issues relevant to an abbreviated application for a biosimilar product. The approval of a biologic product biosimilar to one of our products could have a material adverse impact on our business as it may be significantly less costly to bring to market and may be priced significantly lower than our products.

Both before and after the FDA approves a product, the manufacturer and the holder or holders of the BLA for the product are subject to comprehensive regulatory oversight. For example, quality control and manufacturing procedures must conform, on an ongoing basis, to cGMP requirements, and the FDA periodically inspects manufacturing facilities to assess compliance with cGMPs. Accordingly, manufacturers must continue to spend time, money and effort to maintain cGMP compliance.

Orphan Drug Act

The Orphan Drug Act provides incentives to manufacturers to develop and market drugs for rare diseases and conditions affecting fewer than 200,000 persons in the United States at the time of application for orphan drug designation. Orphan drug designation must be requested before submitting a BLA. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process. If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the holder of the approval is entitled to a seven-year exclusive marketing period in the United States for that product except in very limited circumstances. For example, a drug that the FDA considers to be clinically superior to, or different from, another approved orphan drug, even though for the same indication, may also obtain approval in the United States during the seven-year exclusive marketing period. In addition, holders of exclusivity for orphan drugs are expected to assure the availability of sufficient quantities of their orphan drugs to meet the needs of patients. Failure to do so could result in the withdrawal of marketing exclusivity for the drug. ACE-536Luspatercept has orphan drug designation in the United States for the treatment ofb-thalassemia beta-thalassemia and for the treatment of MDS. The FDA has granted orphan designation for sotatercept for the treatment ofb-thalassemia.


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Legislation similar to the Orphan Drug Act has been enacted outside the U.S., including in the EU. The orphan legislation in the EU is available for therapies addressing chronic debilitating or life-threatening conditions that affect five or fewer out of 10,000 persons or are financially not viable to develop. The market exclusivity period is for ten years, although that period can be reduced to six years if, at the end of the fifth year, available evidence establishes that the product is sufficiently profitable not to justify maintenance of market exclusivity. The market exclusivity may be extended to 12 years if sponsors complete a pediatric investigation plan agreed upon with the relevant committee of the EMA.

The FDA has various programs, including Fast Track, priority review, and accelerated approval, which are intended to expedite or simplify the process for reviewing drugs, and/or provide for the approval of a drug on the basis of a surrogate endpoint. Even if a drug qualifies for one or more of these programs, the FDA may later decide that the drug no longer meets the conditions for qualification or that the time period for FDA review or approval will be shortened. Generally, drugs that are eligible for these programs are those for serious or life-threatening conditions, those with the potential to address unmet medical needs and those that offer meaningful benefits over existing treatments. For example, Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious or life- threatening diseases or conditions and fill unmet medical needs. Priority review is designed to give drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists an initial review within six months as compared to a standard review time of ten months. Although Fast Track and priority review do not affect the standards for approval, the FDA will attempt to facilitate early and frequent meetings with a sponsor of a Fast Track designated drug and expedite review of the application for a drug designated for priority review. Accelerated approval provides for an earlier approval for a new drug that is intended to treat a serious or

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life-threatening disease or condition and that fills an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a laboratory measurement or physical sign used as an indirect or substitute measurement representing a clinically meaningful outcome. As a condition of approval, the FDA may require that a sponsor of a drug candidate receiving accelerated approval perform post-marketing clinical trials to confirm the clinically meaning full outcome as predicted by the surrogate marker trial.

In the Food and Drug Administration Safety and Innovation Act, or FDASIA, which was signed into law in July 2012, Congress encouraged the FDA to utilize innovative and flexible approaches to the assessment of products under accelerated approval. The law required the FDA to issue related draft guidance within a year after the law's enactment and also promulgate confirming regulatory changes. In June 2013,May 2014, the FDA published a draft Guidance for Industry entitled, "Expedited Programs for Serious Conditions—Drugs and Biologics" which provides guidance on FDA programs that are intended to facilitate and expedite development and review of new drugs as well as threshold criteria generally applicable to concluding that a drug is a candidate for these expedited development and review programs. In addition to the Fast Track, accelerated approval and priority review programs discussed above, the FDA also provided guidance on a new program for Breakthrough Therapy designation. A request for Breakthrough Therapy designation should be submitted concurrently with, or as an amendment to an IND. FDA has already granted this designation to over 30100 new drugs and recentlyhas approved a couple ofmore than 25 Breakthrough Therapy designated drugs.

Pediatric Exclusivity and Pediatric Use

Under the Best Pharmaceuticals for Children Act, or BPCA, certain drugs may obtain an additional six months of exclusivity, if the sponsor submits information requested in writing by the FDA, or a Written Request, relating to the use of the active moiety of the drug in children. The FDA may not issue a Written Request for studies on unapproved or approved indications or where it


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determines that information relating to the use of a drug in a pediatric population, or part of the pediatric population, may not produce health benefits in that population.

We have not received a Written Request for such pediatric studies, although we may ask the FDA to issue a Written Request for such studies in the future. To receive the six-month pediatric market exclusivity, we would have to receive a Written Request from the FDA, conduct the requested studies in accordance with a written agreement with the FDA or, if there is no written agreement, in accordance with commonly accepted scientific principles, and submit reports of the studies. A Written Request may include studies for indications that are not currently in the labeling if the FDA determines that such information will benefit the public health. The FDA will accept the reports upon its determination that the studies were conducted in accordance with and are responsive to the original Written Request or commonly accepted scientific principles, as appropriate, and that the reports comply with the FDA's filing requirements.

In addition, the Pediatric Research Equity Act, or PREA, requires a sponsor to conduct pediatric studies for most drugs and biologicals, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration. Under PREA, original NDAs, BLAs and supplements thereto must contain a pediatric assessment unless the sponsor has received a deferral or waiver. The required assessment must include the evaluation of the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The sponsor or FDA may request a deferral of pediatric studies for some or all of the pediatric subpopulations. A deferral may be granted for several reasons, including a finding that the drug or biologic is ready for approval for use in adults before pediatric studies are complete or that additional safety or effectiveness data needs to be collected before the pediatric studies begin. After April 2013, the FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.

As part of the FDASIA, Congress made a few revisions to BPCA and PREA, which were slated to expire on September 30, 2012, and made both laws permanent.

Reimbursement

In both domestic and foreign markets, sales and reimbursement of any approved products will depend, in part, on the extent to which the costs of such products will be covered by third-party payors,payers, such as government health programs, commercial insurance and managed healthcare organizations. These third-party payorspayers are increasingly challenging the prices charged for medical products and services and imposing controls to manage costs. The containment of healthcare costs has become a priority of federal and state governments and the prices of drugs have been a focus in this effort. Governments have shown significant interest in implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit our net revenue and results. In addition, there is significant uncertainty regarding the reimbursement status of newly approved healthcare products. We may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products. If third-party payorspayers do not consider our products to be cost-effective compared to other therapies, the payorspayers may not cover our

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products after approved as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our products on a profitable basis.

Within the United States, if we obtain appropriate approval in the future to market any of our current protein therapeutic candidates, we may seek approval and coverage for those products under Medicaid, Medicare and the Public Health Service (PHS) pharmaceutical pricing program and also seek to sell the products to federal agencies.


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Medicaid is a joint federal and state program that is administered by the states for low income and disabled beneficiaries. Under the Medicaid Drug Rebate Program, manufacturers are required to pay a rebate for each unit of product reimbursed by the state Medicaid programs. The amount of the rebate for each product is set by law and may be subject to an additional discount if certain pricing increases more than inflation.

Medicare is a federal program administered by the federal government that covers individuals age 65 and over as well as those with certain disabilities. Medicare Part D provides coverage to enrolled Medicare patients for self-administered drugs (i.e., drugs that do not need to be administered by a physician). Medicare Part D is administered by private prescription drug plans approved by the U.S. government and each drug plan establishes its own Medicare Part D formulary for prescription drug coverage and pricing, which the drug plan may modify from time-to-time.

Medicare Part B covers most injectable drugs given in an in-patient setting, and some drugs administered by a licensed medical provider in hospital outpatient departments and doctors offices. Medicare Part B is administered by Medicare Administrative Contractors, which generally have the responsibility of making coverage decisions. Subject to certain payment adjustments and limits, Medicare generally pays for Part B covered drugs based on a percentage of manufacturer-reported average sales price.

Drug products are subject to discounted pricing when purchased by federal agencies via the Federal Supply Schedule (FSS). FFSFSS participation is required for a drug product to be covered and paid for by certain federal agencies and for coverage under Medicaid, Medicare Part B and the PHS pharmaceutical pricing program. FSS pricing is negotiated periodically with the Department of Veterans Affairs. FSS pricing is intended to not exceed the price that a manufacturer charges its most-favored non-federal customer for its product. In addition, prices for drugs purchased by the Veterans Administration, Department of Defense (including drugs purchased by military personnel and dependents through the TRICARE retail pharmacy program), Coast Guard, and PHS are subject to a cap on pricing (known as the "federal ceiling price") and may be subject to an additional discount if pricing increases more than inflation.

To maintain coverage of drugs under the Medicaid Drug Rebate Program, manufacturers are required to extend discounts to certain purchasers under the PHS pharmaceutical pricing program. Purchasers eligible for discounts include hospitals that serve a disproportionate share of financially needy patients, community health clinics and other entities that receive health services grants from the PHS.

The American Recovery and Reinvestment Act of 2009 provides funding for the federal government to compare the effectiveness of different treatments for the same illness. A plan for the research will be developed by the Department of Health and Human Services, the Agency for Healthcare Research and Quality and the National Institutes for Health, and periodic reports on the status of the research and related expenditures will be made to Congress. Although the results of the comparative effectiveness studies are not intended to mandate coverage policies for public or private payors,payers, it is not clear what effect, if any, the research will have on the sales of any product, if any such product or the condition that it is intended to treat is the subject of a study. It is also possible that comparative effectiveness research demonstrating benefits in a competitor's product could adversely affect the sales of any of our approved protein therapeutics.therapeutic candidates. If third-party payorspayers do not consider our products to be cost-effective compared to other available therapies, they may not cover our products as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our products on a profitable basis.

The United States and state governments continue to propose and pass legislation designed to reduce the cost of healthcare. In March 2010, the United States Congress enacted the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act which


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includes changes to the coverage and payment for drug products under government health carehealthcare programs. Adoption of other new legislation at the federal or state level could further limit reimbursement for pharmaceuticals.

Outside the United States, ensuring adequate coverage and payment for our products will face challenges. Pricing of prescription pharmaceuticals is subject to governmental control in many countries. Pricing negotiations with governmental authorities can extend well beyond the receipt of regulatory marketing approval for a product and may require us to conduct a clinical trial that compares the cost effectiveness of our protein therapeutic candidates or products to other available therapies. The conduct of such a clinical trial could be expensive and result in delays in our commercialization efforts. Third-party payorspayers are challenging the prices charged for medical products and services, and many third-party payorspayers limit reimbursement for newly-approved health carehealthcare products. Recent budgetary pressures in many European Union countries are also causing governments to

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consider or implement various cost-containment measures, such as price freezes, increased price cuts and rebates. If budget pressures continue, governments may implement additional cost-containment measures. Cost-control initiatives could decrease the price we might establish for products that we may develop or sell, which would result in lower product revenues or royalties payable to us. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products.

Foreign Regulation

In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our protein therapeutic candidates. Whether or not we obtain FDA approval for a protein therapeutic candidate, we must obtain approval from the comparable regulatory authorities of foreign countries or economic areas, such as the European Union, before we may commence clinical trials or market products in those countries or areas. The approval process and requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from place to place, and the time may be longer or shorter than that required for FDA approval.

Certain countries outside of the United States have a process that requires the submission of a clinical trial application much like an IND prior to the commencement of human clinical trials. In Europe, for example, a clinical trial application, or CTA, must be submitted to the competent national health authority and to independent ethics committees in each country in which a company intends to conduct clinical trials. Once the CTA is approved in accordance with a country's requirements, clinical trial development may proceed in that country. In all cases, the clinical trials must be conducted in accordance with good clinical practices, or GCPs and other applicable regulatory requirements.

Under European Union regulatory systems, a company may submit marketing authorization applications either under a centralized or decentralized procedure. The centralized procedure is compulsory for medicinal products produced by biotechnology or those medicinal products containing new active substances for specific indications such as the treatment of AIDS, cancer, neurodegenerative disorders, diabetes, viral diseases and designated orphan medicines, and optional for other medicines which are highly innovative. Under the centralized procedure, a marketing application is submitted to the European Medicines Agency where it will be evaluated by the Committee for Medicinal Products for Human Use and a favorable opinion typically results in the grant by the European Commission of a single marketing authorization that is valid for all European Union member states within 67 days of receipt of the opinion. The initial marketing authorization is valid for five years, but once renewed is usually valid for an unlimited period. The decentralized procedure provides for approval by one or more "concerned" member states based on an assessment of an application performed by one member state, known as the "reference" member state. Under the decentralized approval procedure, an applicant submits an application, or dossier, and related materials to the reference member state and


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concerned member states. The reference member state prepares a draft assessment and drafts of the related materials within 120 days after receipt of a valid application. Within 90 days of receiving the reference member state's assessment report, each concerned member state must decide whether to approve the assessment report and related materials. If a member state does not recognize the marketing authorization, the disputed points are eventually referred to the European Commission, whose decision is binding on all member states.

As in the United States, we may apply for designation of a product as an orphan drug for the treatment of a specific indication in the European Union before the application for marketing authorization is made. Orphan drugs in Europe enjoy economic and marketing benefits, including up to 10 years of market exclusivity for the approved indication unless another applicant can show that its product is safer, more effective or otherwise clinically superior to the orphan designated product.

Fraud and Abuse Laws

In addition to FDA restrictions on marketing of pharmaceutical products, several other types of state and federal laws have been applied to restrict certain marketing practices in the pharmaceutical industry in recent years. These laws include anti-kickback and false claims statutes.

The federal healthcare program anti-kickback statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any healthcare item or service reimbursable under Medicare, Medicaid or other federally financed healthcare programs. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers, and formulary managers on the other. Although there are a number of statutory exemptions and regulatory safe harbors protecting certain common activities from prosecution, the exemptions and safe harbors are drawn narrowly and practices that involve remuneration intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exemption or safe harbor. Our practices may not in all cases meet all of the criteria for safe harbor protection from anti-kickback liability.

Federal false claims laws prohibit any person from knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly making, or causing to be made, a false statement


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Additional Regulation

We are also subject to regulation under the Occupational Safety and Health Act, the Environmental Protection Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act and other present and potential federal, state or local regulations. These and other laws govern our use, handling and disposal of various biological and chemical substances used in, and waste generated by our operations. Our research and development involves the controlled use of hazardous materials, chemicals and viruses. Although we believe that our safety procedures for handling and disposing of such materials comply with the standards prescribed by state and federal regulations, the risk of accidental contamination or injury from these materials cannot be completely eliminated. In the event of such an accident, we could be held liable for any damages that result and any such liability could exceed our resources.

There have been a number of federal and state proposals during the last few years regarding the pricing of pharmaceutical and biological products, government control and other changes to the healthcare system of the U.S. It is uncertain what legislative proposals will be adopted or what actions federal, state or private payers for medical goods and services may take in response to any healthcare reform proposals or legislation. We cannot predict the effect medical or healthcare reforms may have on our business, and no assurance can be given that any such reforms will not have a material adverse effect.


Manufacturing

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Manufacturing

We currently manufacture drug substance for our preclinical studies, Phase 1 clinical trials and Phase 2 clinical trials of ACE-536luspatercept, dalantercept, ACE-083 and dalantercept.ACE-2494. We manufacture material compliant to U.S. and European cGMP at our 12,000 square foot multi-product facility located at our corporate headquarters in Cambridge, Massachusetts. We have the capabilities to manufacture receptor fusion proteins, monoclonal antibodies, and other protein therapeutics.

therapeutic candidates.

Our manufacturing facility is based on single use, disposable technology to maximize the focus of personnel and other resources on the production process, minimizing the need for cleaning and sterilization while optimizing the efficiency of product change-over. The facility consists of four independent clean rooms totaling 4,000 square feet. The facility includes one 250 liter and one 1,000 liter single use bioreactor and has space for two additional 1,000 liter bioreactors.

Approximately 20 fulltime22 full time employees focus on our process development and manufacturing activities. We believe that our strategic investment in manufacturing capabilities allows us to advance our protein therapeutic candidates at a more rapid pace and provides us with more portfolio flexibility than if we used a contract manufacturer. The facility produces drug substance in a cost-effective manner while allowing us to retain control over the process and provides an ability to balance the requirements of multiple programs and avoid costly commitments of funds before clinical data are available.

Our manufacturing capabilities encompass the full manufacturing process through quality control and quality assurance. These groups are integrated with our project teams from discovery through development. This structure enables us to efficiently transfer researchpreclinical stage lead molecules into manufacturing. We have designed our manufacturing facility and processes to provide maximum flexibility and rapid change over for the manufacture of different protein therapeutic candidates. We outsource fill-finish, packaging, labeling, shipping, and distribution.

We manufacture our protein therapeutic candidates using readily available raw materials and well established manufacturing procedures based on a standardized process modified for each of our protein therapeutic candidates. We produce our proteins in bioreactors using Chinese hamster ovary cells that have been genetically engineered to produce our specific protein therapeutic candidates. We then purify the proteins using industry standard methods, which include affinity chromatography and ultrafiltration operations. Processes developed within our facility have been successfully transferred to commercial facilities based on stainless steel bioreactors. We have conducted comparability characterization on sotatercept between our Phase 2 material and material made at a commercial manufacturer and found them to be comparable.

We believe that we can scale our manufacturing processes to support our clinical development programs and the potential commercialization of our protein therapeutic candidates. For our early phase protein therapeutic candidates, we intend to continue to manufacture drug substance for preclinical testing and Phase 1 and Phase 2 clinical development at our current facilities. As ACE-536luspatercept progresses to Phase 3 clinical trials, we intend to transfer the process for Phase 3 production to Celgene, under the terms of our collaboration agreements. We have already successfully transferred the manufacturing process for sotatercept to Celgene, and we expect Celgene will use a contract manufacturer for Phase 3 and commercial supply of sotatercept and ACE-536.luspatercept. We intend to contract with a third party manufacturer for the supply of dalantercept and ACE-083 for Phase 3 clinical trials.


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Employees

As of December 31, 2013,2015, we had 80102 full-time employees, 6376 of whom are involved in research, development or manufacturing, and 2027 of whom have Ph.D. or M.D. degrees. We have no collective bargaining agreements with our employees and we have not experienced any work stoppages. We consider our relations with our employees to be good.


Corporate Information

TableWe were incorporated in the state of ContentsDelaware in June 2003 as Phoenix Pharma, Inc., and we subsequently changed our name to Acceleron Pharma Inc. and commenced operations in February 2004. Our principal executive offices are located at 128 Sidney Street, Cambridge, Massachusetts 02139, and our telephone number is (617) 649-9200. Our Internet address is

Information Available on the Internet

Our internet addressis www.acceleronpharma.com. The contents of our website are not part of this Annual Report on Form 10-K and our internet address is included in this document as an inactive textual reference.10-K. We make available free of charge through our web sitewebsite our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to these reports filed or furnished pursuant to Section 12(a)13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, or the Exchange Act, as soon as reasonably practicable after we electronically file or furnish such materials to the Securities and Exchange Commission. You may read and copy any materials filed with the Securities and Exchange Commission at the Securities and Exchange Commission's Public Reference Room at 100 F Street, NE, Washington, DC 20549. You may obtain information on the operation



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Table of the Public Reference Room by calling the Securities and Exchange Commission at 1-800-SEC-0330. This information is also available atContents

www.sec.gov. The reference to these website addresses does not constitute incorporation by reference of the information contained on the websites and should not be considered part of this document.

Item 1A.    Risk Factors

RISK FACTORS

Investing in our common stock involves a high degree of risk. You should carefully consider the risks and uncertainties described below in addition to the other information included or incorporated by reference in this Annual Report on Form 10-K before purchasing our common stock. If any of the following risks actually occurs, our business, financial condition or results of operations would likely suffer, possibly materially. In that case, the trading price of our common stock could fall, and you may lose all or part of the money you paid to buy our common stock. The risks and uncertainties described below are not the only ones we face. Additional risks and uncertainties not presently known to us or that we currently believe to be immaterial may also adversely affect our business.

Risks relatedRelated to our financial positionOur Financial Position and needNeed for additional capital

Additional Capital

We have incurred net operating losses since our inception and anticipate that we will continue to incur substantial operating losses for the foreseeable future. We may never achieve or sustain profitability.

We have incurred net losses during most fiscal periods since our inception. As of December 31, 2013,2015, we had an accumulated deficit of $192.3$307.5 million. We do not know whether or when we will become profitable. To date, we have not commercialized any products or generated any revenues from the sale of products, and we do not expect to generate any product revenues in the foreseeable future. Our losses have resulted principally from costs incurred in our discovery and development activities.

We anticipate that our expenses will increase in the future as we expand our discovery, research, development, manufacturing and commercialization activities. However, we also anticipate that these increased expenses will be partially offset by milestone payments we expect to receive under our agreements with Celgene and potentially by payments we may receive under new collaboration arrangements we may enter into with third parties for dalantercept, ACE-083 or other protein therapeutic candidates. If we do not receive the anticipated milestone payments or do not enter into partnerships for dalantercept, ACE-083 or other protein therapeutic candidates on acceptable terms, our operating losses will substantially increase over the next several years as we execute our plan to expand our discovery, research, development, manufacturing and commercialization activities. There can be no assurance that we will enter into a new collaboration or achieve milestones and, therefore, no assurance our losses will not increase prohibitively in the future.


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To become and remain profitable, we or our partners must succeed in developing our protein therapeutic candidates, obtaining regulatory approval for them, and manufacturing, marketing and selling those products for which we or our partners may obtain regulatory approval. We or they may not succeed in these activities, and we may never generate revenue from product sales that is significant enough to achieve profitability. Even if we achieve profitability in the future, we may not be able to sustain profitability in subsequent periods. Our failure to become or remain profitable would depress our market value and could impair our ability to raise capital, expand our business, discover or develop other protein therapeutic candidates or continue our operations. A decline in the value of our company could cause you to lose all or part of your investment.

We will require substantial additional financing to achieve our goals, and a failure to obtain this necessary capital when needed could force us to delay, limit, reduce or terminate our product development or commercialization efforts.

As of December 31, 2013,2015, our cash, and cash equivalents and investments were $113.2$136.0 million. We believe that we will continue to expend substantial resources for the foreseeable future developing dalantercept, ACE-083 and new protein therapeutic candidates. These expenditures will include costs associated with research and development, potentially acquiring new technologies, conducting preclinical studies and clinical trials, potentially obtaining regulatory approvals and manufacturing products, as well as marketing and selling products approved for sale, if any. In addition, other unanticipated costs may arise. Because the outcome of our planned and anticipated clinical trials is highly uncertain, we cannot reasonably estimate the actual amounts necessary to successfully complete the development and commercialization of our protein therapeutic candidates.

Celgene pays development, manufacturing and commercialization and certain patent costs for sotatercept and ACE-536.luspatercept. Other than those costs, our future capital requirements depend on many factors, including:

the scope, progress, results and costs of researching and developing our other protein therapeutic candidates, and conducting preclinical studies and clinical trials;


the timing of, and the costs involved in, obtaining regulatory approvals for our other protein therapeutic candidates if clinical trials are successful;


the cost of commercialization activities for our other protein therapeutics,therapeutic candidates, if any of these protein therapeuticstherapeutic candidates is approved for sale, including marketing, sales and distribution costs;

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the cost of manufacturing our other protein therapeutic candidates for clinical trials in preparation for regulatory approval and in preparation for commercialization;


our ability to establish and maintain strategic partnerships, licensing or other arrangements and the financial terms of such agreements;


the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing patent claims, including litigation costs and the outcome of such litigation; and


the timing, receipt, and amount of sales of, or royalties on, our future products, if any.

Based on our current operating plan, we believe that our current cash, cash equivalents and investments, together with the net proceeds we received from our initial public offering and the concurrent private placement, and the follow-on public offering together within January 2016 and receipt of anticipated milestone payments, and our existing cash and cash equivalents will be sufficient to fund our projected operating requirements into the second half of 2017.2019. However, our operating plan may change as a result of many factors currently unknown to us, and we may need additional funds sooner than planned. In addition, we may seek additional capital due to favorable market conditions or strategic considerations even if we believe that we have sufficient funds for our current or future operating plans. Additional funds may not be available when we need them on terms that are


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acceptable to us, or at all. If adequate funds are not available to us on a timely basis, we may be required to delay, limit, reduce or terminate preclinical studies, clinical trials or other development activities for one or more of our protein therapeutic candidates or delay, limit, reduce or terminate our establishment of sales and marketing capabilities or other activities that may be necessary to commercialize our protein therapeutic candidates.

Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or protein therapeuticstherapeutic candidates on unfavorable terms to us.

We may seek additional capital through a variety of means, including through private and public equity offerings and debt financings. To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted, and the terms may include liquidation or other preferences that adversely affect your rights as a stockholder. Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take certain actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise additional funds through strategic partnerships with third parties, we may have to relinquish valuable rights to our technologies or protein therapeutics,therapeutic candidates, or grant licenses on terms that are not favorable to us. If we are unable to raise additional funds through equity or debt financing when needed, we may be required to delay, limit, reduce or terminate our product development or commercialization efforts for dalantercept, ACE-083 or any protein therapeuticstherapeutic candidates other than sotaterceptluspatercept or ACE-536,sotatercept, or grant rights to develop and market protein therapeuticstherapeutic candidates that we would otherwise prefer to develop and market ourselves.


Risks Related to Regulatory Review and Approval of Our Protein Therapeutic Candidates

If we or our partners do not obtain regulatory approval for our current and future protein therapeutics,therapeutic candidates, our business will be adversely affected.

Our protein therapeutic candidates will be subject to extensive governmental regulations relating to, among other things, development, clinical trials, manufacturing and commercialization. In order to obtain regulatory approval for the commercial sale of any protein therapeutic candidates, we or our partners must demonstrate through extensive preclinical studies and clinical trials that the protein therapeutic candidate is safe and effective for use in each target indication. Clinical testing is expensive, time-consuming and uncertain as to outcome. We or our partners may gain regulatory approval for sotatercept, ACE-536,luspatercept, dalantercept, ACE-083 or any other protein therapeutic candidate in some but not all of the territories available or some but not all of the target indications or may receive approval with limited labeling or boxed warnings, resulting in limited commercial opportunity for the approved protein therapeutics,therapeutic candidates, or we or they may never obtain regulatory approval for these protein therapeutic candidates.

Delays in the commencement, enrollment or completion of clinical trials of our protein therapeutic candidates could result in increased costs to us as well as a delay or failure in obtaining regulatory approval, or prevent us from commercializing our protein therapeutic candidates on a timely basis, or at all.

We cannot guarantee that clinical trials will be conducted as planned or completed on schedule, if at all. A failure of one or more clinical trials can occur at any stage of testing. Events that may prevent successful or timely commencement, enrollment or completion of clinical development include:


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delays by us or our current or future partners in reaching a consensus with regulatory agencies on trial design;


delays in reaching agreement on acceptable terms with prospective clinical research organizations, or CROs, and clinical trial sites;


delays in obtaining required Institutional Review Board, or IRB, approval at each clinical trial site;

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Delays, including delays caused by the above factors, can be costly and could negatively affect our or Celgene's ability to complete a clinical trial. If we or Celgene are not able to successfully complete clinical trials, we will not be able to obtain regulatory approval and will not be able to commercialize our protein therapeutic candidates.

Clinical

There is a high risk of clinical failure may occur at any stage of clinical development, and because our protein therapeutic candidates are in an early stage of development, there is a high risk of failure, and we may never succeed in developing marketable products or generating product revenue.

Our early encouraging preclinical and clinical results to date for sotatercept, ACE-536luspatercept, dalantercept and dalanterceptACE-083 are not necessarily predictive of the results of our ongoing or future clinical trials. Promising results in preclinical studies of a drug candidate may not be predictive of similar results in humans during clinical trials, and successful results from early clinical trials of a drug candidate may not be replicated in later and larger clinical trials or in clinical trials for different indications. If the results of our or our current or future partners' ongoing or future clinical trials are inconclusive with respect to the efficacy of our protein therapeutic candidates or if we or they do not meet the clinical endpoints with statistical significance or if there are safety concerns or adverse events associated with our protein therapeutic candidates, we or our partner may be prevented or delayed in obtaining marketing approval for our protein therapeutic candidates. In addition, data obtained from trials and studies are susceptible to varying interpretations, and regulators may not interpret our data as favorably as we do, which may delay or prevent regulatory approval. Alternatively, even if we or our partners obtain regulatory approval, that approval may be for indications or patient populations that are not as broad as intended or desired or may require labeling that includes significant use or distribution restrictions or safety warnings. We or our partners may also be required to perform additional or unanticipated clinical trials to obtain approval or be subject to additional post-marketing testing requirements to maintain regulatory approval. In addition, regulatory authorities may withdraw their approval of a product or impose restrictions on its distribution, such as in the form of a modified risk evaluation and mitigation strategy.

If we or our current or future partners fail to obtain regulatory approval in jurisdictions outside the United States, we and they will not be able to market our products in those jurisdictions.
We and our current or future partners intend to market our therapeutic candidates, if approved, in international markets. Such marketing will require separate regulatory approvals in each market and compliance with numerous and varying regulatory requirements. The approval procedures vary from country-to-country and may require additional testing. Moreover, the time required to obtain approval may differ from that required to obtain FDA approval. In addition, in many countries outside the United States, a therapeutic candidate must be approved for reimbursement before it can be approved for sale in that country. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and

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approval by one foreign regulatory authority does not ensure approval by regulatory authorities in other foreign countries or by the FDA. The foreign regulatory approval process may include all of the risks associated with obtaining FDA approval. We or our current or future partners may not obtain foreign regulatory approvals on a timely basis, if at all. We or our partners may not be able to file for regulatory approvals and may not receive necessary approvals to commercialize our products in any market.
We and Celgene regularly request and receive guidance from the FDA and foreign regulators regarding the design or conduct of clinical trials with our therapeutic candidates. This guidance is not binding on these agencies and could change substantially and unpredictably, potentially in a way that makes our clinical trials or our path to regulatory approval longer, more expensive or otherwise more difficult.
Any guidance that we or Celgene receive from the FDA or foreign regulators regarding the design or conduct of our clinical trials is not necessarily indicative of what these regulators will eventually require from us or Celgene to obtain regulatory approval of our therapeutic candidates. These regulators typically caution that any guidance received from them represents their then-current thinking, does not create or confer any rights to us or Celgene, and does not operate to bind the regulator. If later guidance that we or Celgene receive from the FDA or foreign regulators regarding our clinical trial design or conduct is materially different than the current guidance we have received from these regulators, we may need to change our clinical development plans and it may take longer, be more expensive or otherwise be more difficult to obtain FDA or foreign regulatory approval of our therapeutic candidates and our business may be materially harmed.
We undertake no obligation to disclose guidance that we or Celgene may receive from the FDA or foreign regulators. Any guidance from the FDA or foreign regulators that we may disclose publicly speaks only as of the date of such disclosure. We undertake no obligation to update any disclosure we make regarding regulator guidance to reflect additional regulatory guidance received after the date of such disclosure or to reflect the occurrence of unanticipated events that may affect the guidance.
Even if we or our current or future partners receive regulatory approval for our therapeutic candidates, such products will be subject to ongoing regulatory review, which may result in significant additional expense. Additionally, our therapeutic candidates, if approved, could be subject to labeling and other restrictions, and we or our current or future partners may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products.
Any regulatory approvals that we or our current or future partners receive for our therapeutic candidates may also be subject to limitations on the approved indicated uses for which the product may be marketed or to conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials, and surveillance to monitor safety and efficacy. In addition, if the FDA approves any of our therapeutic candidates, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for the product will be subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with current good manufacturing practice, or cGMP, and GCP, for any clinical trials that we or our partners conduct post-approval.
Later discovery of previously unknown problems with an approved therapeutic candidate, including adverse events of unanticipated severity or frequency, or with manufacturing operations or processes, or failure to comply with regulatory requirements, may result in, among other things:
restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or voluntary or mandatory product recalls;

fines, warning letters, or holds on clinical trials;

refusal by the FDA to approve pending applications or supplements to approved applications filed by us or our partners, or suspension or revocation of product license approvals;

product seizure or detention, or refusal to permit the import or export of products; and

injunctions or the imposition of civil or criminal penalties.
The FDA's policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our therapeutic candidates. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad. If we or our partners are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or not able to

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maintain regulatory compliance, we or our partners may lose any marketing approval that may have been obtained and we may not achieve or sustain profitability, which would adversely affect our business.
A Fast Track designation by the FDA may not actually lead to a faster development or regulatory review or approval process.
In the United States, luspatercept received Fast Track designation for the treatment of anemia in patients with lower-risk myelodysplastic syndromes, or MDS, for the treatment of patients with transfusion-dependent beta-thalassemia, and for the treatment of patients with non-transfusion-dependent beta-thalassemia. The FDA grants Fast Track designation to therapies that are considered capable of addressing unmet medical needs and possess the potential to treat serious or life-threatening disease conditions in order to facilitate its development and expedite the review procedure. The FDA has broad discretion in granting Fast Track designation, so even if we believe that a particular product candidate is eligible for such designation, the FDA could decide not to grant it. Even though luspatercept has received Fast Track designation for multiple indications, we may not experience a faster development process, review or approval compared to conventional FDA procedures. The FDA may also withdraw Fast Track designation if it believes that the designation is no longer supported by data from our clinical development program.
The Phase 3 MEDALIST and BELIEVE clinical trials may be delayed, suspended or terminated, or may not lead to marketing approval.
In December 2015, Celgene initiated two Phase 3 clinical trials with luspatercept for the treatment of patients with lower risk MDS, the "MEDALIST" trial, or beta-thalassemia, the "BELIEVE" trial. These trials may not be successful and the delay or failure of either one of these clinical trials will materially harm our business. Celgene may experience delays in the conduct of these clinical trials, including delays related to clinical trial site initiation, patient enrollment, patients withdrawing from the trial, or drug supply. If patients experience adverse events while in these or other clinical trials with luspatercept, then one or both of the MEDALIST or BELIEVE trials may be delayed, suspended or terminated. Celgene may not achieve the primary endpoint for one or both trials, or may not achieve one or more secondary endpoints. Data from our luspatercept Phase 2 trials may not be predictive of results obtained in the MEDALIST or BELIEVE trials. Even if the primary endpoint is achieved, one or more health authorities may not approve luspatercept for the desired indication. The MEDALIST and BELIEVE trials were designed with input from health authorities in many different countries, but this guidance is not binding on these regulators, and it may be necessary to conduct one or more additional clinical trials in order to achieve marketing authorization in one or more regulatory jurisdictions. Guidance that we or Celgene receive from the FDA or foreign regulators regarding the design or conduct of the MEDALIST or BELIEVE clinical trials is not necessarily indicative of what these regulators will eventually require from us or Celgene to obtain regulatory approval of luspatercept in these indications. Any regulatory approvals that we or Celgene receive for luspatercept may also be subject to limitations on the approved indicated uses for which the product may be marketed or to conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials, and surveillance to monitor safety and efficacy.
If we or any of our current or future partners violate the guidelines pertaining to promotion and advertising of any of our protein therapeutics,therapeutic candidates, if approved, we or they may be subject to disciplinary action by the FDA's Office of Prescription Drug Promotion (OPDP) or other regulatory authorities.

The FDA's Office of Prescription Drug Promotion, or OPDP, is responsible for reviewing prescription drug advertising and promotional labeling to ensure that the information contained in these materials is not false or misleading. There are specific disclosure requirements, and the applicable regulations mandate that advertisements cannot be false or misleading or omit material facts about the product. Prescription drug promotional materials must present a fair balance between the drug's effectiveness and the risks associated with its use. Most warning letters from OPDP cite inadequate disclosure of risk information.

OPDP prioritizes its actions based on the degree of risk to the public health, and often focuses on newly introduced drugs and those associated with significant health risks. There are two types of letters that OPDP typically sends to companies that violate its drug advertising and promotional guidelines: notice of violation letters, or untitled letters, and warning letters. In the case of an untitled letter, OPDP typically alerts the drug company of the violation and issues a directive to refrain from future violations, but does not typically demand other corrective action. A warning letter is typically issued in cases that are more serious or where the company is a repeat offender. Although we have not received any such letters from OPDP, we or any partner may inadvertently violate OPDP's guidelines in the future and be subject to a OPDP untitled letter or warning letter, which may have a negative impact on our business.

If we or our partners fail to obtain regulatory approval in jurisdictions outside the United States, we and they will not be able to market our products in those jurisdictions.

        We and our partners intend to market our protein therapeutic candidates, if approved, in international markets. Such marketing will require separate regulatory approvals in each market and compliance with numerous and varying regulatory requirements. The approval procedures vary from country-to-country and may require additional testing. Moreover, the time required to obtain approval may differ from that required to obtain FDA approval. In addition, in many countries outside the United States, a protein therapeutic must be approved for reimbursement before it can be approved for sale in that country. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one foreign regulatory authority does not ensure approval by regulatory authorities in other foreign countries or by the FDA. The foreign regulatory approval process may include all of the risks associated with obtaining FDA approval. We or our partners may not obtain foreign regulatory approvals on a timely basis, if at all. We or our partners may not be able to file for regulatory approvals and may not receive necessary approvals to commercialize our products in any market.

Even if we or our partners receive regulatory approval for our protein therapeutic candidates, such products will be subject to ongoing regulatory review, which may result in significant additional expense. Additionally, our protein therapeutic candidates, if approved, could be subject to labeling and other restrictions, and we or our partners may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products.

        Any regulatory approvals that we or our partners receive for our protein therapeutic candidates may also be subject to limitations on the approved indicated uses for which the product may be marketed or to conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials, and surveillance to monitor safety and efficacy. In addition, if the FDA approves any of our protein therapeutic candidates, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for the product will be subject to extensive and ongoing regulatory requirements. These requirements



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include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with current good manufacturing practice, or cGMP, and GCP, for any clinical trials that we or our partners conduct post-approval.

        Later discovery of previously unknown problems with an approved protein therapeutic, including adverse events of unanticipated severity or frequency, or with manufacturing operations or processes, or failure to comply with regulatory requirements, may result in, among other things:



fines, warning letters, or holds on clinical trials;

refusal by the FDA to approve pending applications or supplements to approved applications filed by us or our partners, or suspension or revocation of product license approvals;

product seizure or detention, or refusal to permit the import or export of products; and

injunctions or the imposition of civil or criminal penalties.

        The FDA's policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our protein therapeutic candidates. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad. If we or our partners are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or not able to maintain regulatory compliance, we or our partners may lose any marketing approval that may have been obtained and we may not achieve or sustain profitability, which would adversely affect our business.

Risks Related to Our Reliance on Third Parties

We are dependent on Celgene for the successful development and commercialization of two of our three clinical stage protein therapeutic candidates, sotatercept and ACE-536.our most advanced therapeutic candidate, luspatercept. If Celgene does not devote sufficient resources to the development of these candidates, discontinues development of these candidates, is unsuccessful in its efforts, or chooses to terminate its agreements with us, our business will be materially harmed.

We have entered into collaboration agreements with Celgene to develop and commercialize sotatercept and ACE-536.luspatercept. Pursuant to the sotatercept agreement, responsibility for all clinical and other product development activities and for manufacturing sotatercept has been transferred to Celgene. For ACE-536,luspatercept, we are responsible for conducting the two ongoing Phase 2 clinical trials in MDS, and we are also responsible for manufacturing supplies for Phase 1 and Phase 2 studies. Celgene will be responsible for all clinical development and manufacturing activities after such studies are completed. As of January 1, 2013, Celgene became responsible for paying 100% of worldwide development costs for sotatercept and ACE-536.luspatercept. We will co-promote sotatercept and ACE-536,luspatercept, if approved by the FDA and its counterparties, in North America. Celgene will be responsible for all commercialization costs, including the cost of our promotion activities.

Celgene is obligated to use commercially reasonable efforts to develop and commercialize sotatercept and ACE-536.luspatercept. Celgene may determine that it is commercially reasonable to develop and commercialize only sotaterceptluspatercept or ACE-536sotatercept and discontinue the development or commercialization of the other protein therapeutic candidate, or Celgene may determine that it is not commercially reasonable to continue development of one or both of sotatercept and ACE-536.luspatercept. For example, Celgene may elect not to undertake the development of sotatercept for the treatment of pre-dialysis patients. This may occur for many reasons, including internal business reasons or because of unfavorable regulatory feedback. Further, on review of the safety and efficacy data available to date, the FDA may impose requirements on the clinical trial program that render such a program commercially nonviable. In the event of any such decision, we maywould be unable to progress the discontinued candidatesotatercept for this or candidatesother indications ourselves. In addition, under our collaboration agreements, once Celgene takes over development activities of a protein therapeutic candidate, it may determine the development plan and activities for that protein therapeutic candidate. We may disagree with Celgene about the development strategy it employs, but


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we will have no rights to impose our development strategy on Celgene. Similarly, Celgene may decide to seek regulatory approval for, and limit commercialization of, either or both of sotatercept and ACE-536luspatercept to narrower indications than we would pursue. We would be prevented from developing or commercializing a candidate in an indication that Celgene has chosen not to pursue.

More broadly, if Celgene elects to discontinue the development of both sotatercept and luspatercept, we may be unable to advance the products ourselves.

This partnership may not be scientifically or commercially successful due to a number of important factors, including the following:

Celgene has wide discretion in determining the efforts and resources that it will apply to its partnership with us. The timing and amount of any development milestones, and downstream commercial milestones and royalties that we may receive under such partnership will depend on, among other things, the efforts, allocation of resources and successful development and commercialization of these protein therapeutic candidates by Celgene.


Celgene may develop and commercialize, either alone or with others, products that are similar to or competitive with the protein therapeutic candidates that are the subject of its partnerships with us. For example, Celgene is currently commercializing and/or developing certain of its existing products, lenalidomide and azacitidine, for certain MDS patients for which sotatercept and ACE-536 areluspatercept is also being developed.


Celgene may terminate its partnership with us without cause and for circumstances outside of our control, which could make it difficult for us to attract new strategic partners or adversely affect how we are perceived in scientific and financial communities.


Celgene may develop or commercialize our protein therapeutic candidates in such a way as to elicit litigation that could jeopardize or invalidate our intellectual property rights or expose us to potential liability.


Celgene may not comply with all applicable regulatory requirements, or may fail to report safety data in accordance with all applicable regulatory requirements.


If Celgene were to breach its arrangements with us, we may need to enforce our right to terminate the agreement in legal proceedings, which could be costly and cause delay in our ability to receive rights back to the relevant protein therapeutic candidates. If we were to terminate an agreement with Celgene due to Celgene's breach or Celgene terminated the agreement without cause, the development and commercialization of sotatercept and ACE-536luspatercept could be delayed, curtailed or terminated because we may not have sufficient financial resources or capabilities to continue

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development and commercialization of these candidates on our own.own if we choose not to, or are unable to, enter into a new collaboration for these candidates.


Celgene may enter into one or more transactions with third parties, including a merger, consolidation, reorganization, sale of substantial assets, sale of substantial stock or other change in control, which could divert the attention of its management and adversely affect Celgene's ability to retain and motivate key personnel who are important to the continued development of the programs under the strategic partnership with us. In addition, the third-party to any such transaction could determine to reprioritize Celgene's development programs such that Celgene ceases to diligently pursue the development of our programs and/or cause the respective partnership with us to terminate.

We currently have limited marketing, sales and distribution experience and capabilities and will be dependent upon Celgene to commercialize luspatercept and sotatercept outside the United States.
We and Celgene share the obligations to commercialize luspatercept and sotatercept in the United States and we are solely dependent on Celgene to commercialize luspatercept and sotatercept outside of the United States. As a company without any commercial products, we have very limited marketing, sales and distribution experience and capabilities in the United States. To successfully commercialize luspatercept and sotatercept in the United States, we will need to establish adequate marketing, sales and distribution capabilities. Failure to establish these capabilities, whether due to insufficient resources or some other cause, will limit or potentially halt our ability to successfully commercialize any therapeutic candidates, and will adversely affect our financial results. Even if we do develop such capabilities, we will compete with other companies that have more experienced and well-funded marketing, sales and distribution operations.
We and Celgene rely on third parties to conduct preclinical studies and clinical trials for our protein therapeutic candidates, and if they do not properly and successfully perform their obligations to us, we may not be able to obtain regulatory approvals for our protein therapeutic candidates.

We design the clinical trials for dalantercept and ACE-083 and will do so for any future unpartnered protein therapeutic candidates, and we will continue to work with Celgene on trials for sotatercept and ACE-536.luspatercept. However, we and Celgene rely on CROs and other third parties to assist in managing,


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monitoring and otherwise carrying out many of these trials. We and Celgene compete with many other companies for the resources of these third parties. The third parties on whom we and Celgene rely generally may terminate their engagements at any time, and having to enter into alternative arrangements would delay development and commercialization of our protein therapeutic candidates.

The FDA and foreign regulatory authorities require compliance with regulations and standards, including GCP, for designing, conducting, monitoring, recording, analyzing, and reporting the results of clinical trials to assure that the data and results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected. Although we and Celgene rely on third parties to conduct many of our and their clinical trials, we and Celgene are responsible for ensuring that each of these clinical trials is conducted in accordance with its general investigational plan, protocol and other requirements.

If these third parties do not successfully carry out their duties under their agreements, if the quality or accuracy of the data they obtain is compromised due to their failure to adhere to clinical trial protocols or to regulatory requirements, or if they otherwise fail to comply with clinical trial protocols or meet expected deadlines, the clinical trials of our protein therapeutic candidates may not meet regulatory requirements.requirements or may be delayed. If clinical trials do not meet regulatory requirements or if these third parties need to be replaced, preclinical development activities or clinical trials may be extended, delayed, suspended or terminated. If any of these events occur, we or Celgene may not be able to obtain regulatory approval of our protein therapeutic candidates on a timely basis or at all.

We and Celgene intend to rely on third-party manufacturers to make our protein therapeutics,therapeutic candidates, and any failure by a third-party manufacturer may delay or impair our and Celgene's ability to complete clinical trials or commercialize our protein therapeutic candidates.

Manufacturing biologic drugs is complicated and is tightly regulated by the FDA, the European Medicines Agency, or EMA, and comparable regulatory authorities around the world. We currently manufacture drug substance for our preclinical studies, Phase 1 clinical trials and Phase 2 clinical trials of ACE-536luspatercept, dalantercept, ACE-083 and dalantercept.ACE-2494. For Phase 3 and commercial supply of our products that we have not partnered, we expect to use contract manufacturing organizations. Successfully transferring complicated manufacturing techniques to contract manufacturing organizations and scaling up these techniques for commercial quantities will be time consuming and we may not be able to achieve such transfer. Moreover, the market for contract manufacturing services for protein therapeuticstherapeutic candidates is highly cyclical, with periods of relatively abundant capacity alternating with periods in which there is little available capacity. If any need we or Celgene have for contract manufacturing services increases during a period of industry-wide tight capacity, we or Celgene may not be able to access the required capacity on a timely basis or on commercially viable terms.


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In addition, we contract with fill & finishing providers with the appropriate expertise, facilities and scale to meet our needs. Failure to maintain cGMP can result in a contractor receiving FDA sanctions, which can impact our and Celgene's contractors' ability to operate or lead to delays in our clinical development programs. We believe that our current fill & finish contractors are operating in accordance with cGMP, but we can give no assurance that FDA or other regulatory agencies will not conclude that a lack of compliance exists. In addition, any delay in contracting for fill & finish services, or failure of the contract manufacturer to perform the services as needed, may delay clinical trials, registration and launches. Any such issues may have a substantial negative effect on our business.


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For our two lead products, sotatercept and ACE-536,our most advanced therapeutic candidate, luspatercept, we rely on our collaboration partner Celgene to produce, or contract for the production of, bulk drug substance and finished drug product for late stage clinical trials and for commercial supplies of any approved candidates. Any failure by Celgene or by third-parties with which Celgene contracts may delay or impair the ability to complete late stage clinical trials or commercialize either or both of sotatercept and ACE-536,luspatercept, if approved.

        We produced drug substance for preclinical and Phase 1 and 2 clinical trials for sotatercept and ACE-536.

Celgene is now responsible for manufacturing sotatercept and will be responsible for manufacturing ACE-536luspatercept for future late-stage clinical trials. Celgene generally does not perform the manufacture of the drug substance or drug product for either sotatercept or ACE-536luspatercept itself. Celgene has used and may continue to use contract manufacturers for the manufacture of drug substance and drug product for sotatercept and we have no expectation that Celgene plans to perform the manufacture of bulk drug substance or drug product for either sotatercept or ACE-536luspatercept in the future. However, Celgene would have the right to manufacture sotatercept or ACE-536,luspatercept, itself or through the use of contract manufacturers. We understand that they have entered into a manufacturing arrangementarrangements for Phase 2clinical and commercial supplies of sotatercept and luspatercept bulk drug substance with contract manufacturers with considerable biotherapeutics manufacturing experience, including manufacturing monoclonal antibodies through processes similar to those used for sotatercept. To date Celgene has not entered into an arrangement with a third party to manufacture suppliesIf any of sotaterceptthese manufacturers is unwilling or ACE-536 for commercial sales. If they are unable to contract at the appropriate time with a manufacturer willing and able to manufacture sufficient quantities of sotatercept and ACE-536and/or luspatercept to meet clinical or commercial demand, either for technical or business reasons, the development and commercialization of sotatercept and ACE-536and/or luspatercept may be delayed.

We may not be successful in establishing and maintaining additional strategic partnerships, which could adversely affect our ability to develop and commercialize products, negatively impacting our operating results.

In addition to our current collaborations with Celgene, a part of our strategy is to strategically evaluate and as deemed appropriate, enter into additional partnerships in the future for our other product candidates when strategically attractive, including potentially with major biotechnology or pharmaceutical companies. We face significant competition in seeking appropriate partners for our protein therapeutic candidates, and the negotiation process is time-consuming and complex. In order for us to successfully partner our protein therapeutic candidates, potential partners must view these protein therapeutic candidates as economically valuable in markets they determine to be attractive in light of the terms that we are seeking and other available products for licensing by other companies. Even if we are successful in our efforts to establish new strategic partnerships, the terms that we agree upon may not be favorable to us, and we may not be able to maintain such strategic partnerships if, for example, development or approval of a protein therapeutic candidate is delayed or sales of an approved product are disappointing. Any delay in entering into new strategic partnership agreements related to our proteinother therapeutic candidates could delay the development and commercialization of our proteinthese therapeutic candidates and reduce their competitiveness even if they reach the market.

If we fail to establish and maintain additional strategic partnerships related to our proteindalantercept, ACE-083 or other therapeutic candidates, we will bear all of the risk and costs related to the development of any such protein therapeutic candidate, and we may need to seek additional financing, hire additional employees and otherwise develop expertise for which we have not budgeted. This could negatively affect the development of any unpartnered protein therapeutic candidate.


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Risks Related to Our Intellectual Property

If we are unable to obtain or protect intellectual property rights related to our protein therapeutic candidates, we may not be able to compete effectively.

We rely upon a combination of patents, trade secret protection and confidentiality agreements to protect the intellectual property related to our platform technology and protein therapeutic candidates. The patent position of biotechnology companies is generally uncertain because it involves complex legal and factual considerations. The standards applied by the United States Patent and Trademark Office, or USPTO, and foreign patent offices in granting patents are not always applied uniformly or predictably. For example, there is no uniform worldwide policy regarding patentable subject matter or the scope of claims allowable in biotechnology patents. The patent applications that we own or in-license may fail to result in issued patents with claims that cover our protein therapeutic candidates in the United States or in other countries. There is no assurance that all potentially relevant prior art relating to our patents and patent applications has been found. We may be unaware of prior art that could be used to invalidate an issued patent or prevent our pending patent applications from issuing as patents. Even if patents do

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successfully issue and even if such patents cover our protein therapeutic candidates, third parties may challenge their validity, enforceability or scope, which may result in such patents being narrowed or invalidated. Furthermore, even if they are unchallenged, our patents and patent applications may not adequately protect our intellectual property, provide exclusivity for our protein therapeutic candidates or prevent others from designing around our claims. Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.

If patent applications we hold or have in-licensed with respect to our platform or protein therapeutic candidates fail to issue, if their breadth or strength of protection is threatened, or if they fail to provide meaningful exclusivity for our protein therapeutic candidates, it could dissuade companies from collaborating with us. Several patent applications covering our protein therapeutic candidates have been filed recently. We cannot offer any assurances about which, if any, patents will issue, the breadth of any such patents or whether any issued patents will be found invalid and unenforceable or will be threatened by third parties. Any successful challenge to these patents or any other patents owned by or licensed to us could deprive us of rights necessary for the successful commercialization of any protein therapeutic candidate that we or our current or future partners may develop. Since patent applications in the United States and most other countries are confidential for a period of time after filing, and some remain so until issued, we cannot be certain that we were the first to file any patent application related to a protein therapeutic candidate. Furthermore, if third parties have filed such patent applications, an interference proceeding in the United States can be initiated by the USPTO or a third party to determine who was the first to invent any of the subject matter covered by the patent claims of our applications. In addition, patents have a limited lifespan. In the United States, the natural expiration of a patent is generally 20 years after it is filed. Various extensions may be available; however, the life of a patent and the protection it affords is limited. If we encounter delays in obtaining regulatory approvals, the period of time during which we could market a protein therapeutic candidate under patent protection could be reduced. Even if patents covering our protein therapeutic candidates are obtained, once the patent life has expired for a product, we may be open to competition from biosimilar products.

Any loss of patent protection could have a material adverse impact on our business. We and our partnercurrent or future partners may be unable to prevent competitors from entering the market with a product that is similar to or the same as our protein therapeutics.therapeutic candidates. In addition, the royalty we would receive under our collaboration agreements with Celgene for sotatercept and ACE-536luspatercept would be reduced by 50% if such product ceases to be covered by a valid claim of our patents even if no competitor with a similar product has entered the market.


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Third-party claims of intellectual property infringement or misappropriation may prevent or delay our development and commercialization efforts.

Our commercial success depends in part on us and our current or future partners not infringing the patents and proprietary rights of third parties. There is a substantial amount of litigation, both within and outside the United States, involving patent and other intellectual property rights in the biotechnology and pharmaceutical industries, including patent infringement lawsuits, interferences, oppositions and inter partes reexamination proceedings before the USPTO and corresponding foreign patent offices. Numerous U.S. and foreign issued patents and pending patent applications owned by third parties exist in the fields in which we and our current or future partners are developing and may develop our protein therapeutic candidates. As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our protein therapeutic candidates may be subject to claims of infringement of the patent rights of third parties.

Third parties may assert that we are employing their proprietary technology without authorization. There may be third-party patents or patent applications with claims to materials, formulations, methods of manufacture or methods for treatment related to the use or manufacture of our protein therapeutic candidates, that we failed to identify. For example, applications filed before November 29, 2000 and certain applications filed after that date that will not be filed outside the United States remain confidential until issued as patents. Except for the preceding exceptions, patent applications in the United States and elsewhere are generally published only after a waiting period of approximately 18 months after the earliest filing. Therefore, patent applications covering our platform technology or our protein therapeutic candidates could have been filed by others without our knowledge. Additionally, pending patent applications which have been published can, subject to certain limitations, be later amended in a manner that could cover our platform technologies, our protein therapeutic candidates or the use or manufacture of our protein therapeutic candidates.

If any third-party patents were held by a court of competent jurisdiction to cover aspects of our materials, formulations, methods of manufacture or methods for treatment, the holders of any such patents would be able to block our ability to develop and commercialize the applicable protein therapeutic candidate until such patent expired or unless we or our partners obtain a license. These licenses may not be available on acceptable terms, if at all. Even if we or our partners were able to obtain a license, the rights may be nonexclusive, which could result in our competitors gaining access to the same intellectual property. Ultimately, we or our partners could be prevented from commercializing a product, or be forced to cease some aspect of our business operations, if, as a result of actual or threatened patent infringement claims, we or our partners are unable to enter into licenses on acceptable terms. If Celgene is required to enter a license agreement with a third party in order to import, develop,

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manufacture or commercialize sotatercept or ACE-536,luspatercept, the royalty rate and sales milestone payments that we could receive may be reduced by up to 50%. This could harm our business significantly.

Parties making claims against us or our partners may obtain injunctive or other equitable relief, which could effectively block our or our partners' ability to further develop and commercialize one or more of our protein therapeutic candidates. Defending against claims of patent infringement or misappropriation of trade secrets could be costly and time consuming, regardless of the outcome. Thus, even if we were to ultimately prevail, or to settle at an early stage, such litigation could burden us with substantial unanticipated costs. In addition, litigation or threatened litigation could result in significant demands on the time and attention of our management team, distracting them from the pursuit of other company business. In the event of a successful claim of infringement against us or our partners, we may have to pay substantial damages, including treble damages and attorneys' fees for willful infringement, pay royalties, redesign our infringing products or obtain one or more licenses from third parties, which may be impossible or require substantial time and monetary expenditure.


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We may face a claim of misappropriation if a third party believes that we inappropriately obtained and used trade secrets of such third party. If we are found to have misappropriated a third party's trade secrets, we may be prevented from further using such trade secrets, limiting our ability to develop our protein therapeutic candidates, and we may be required to pay damages.

During the course of any patent or other intellectual property litigation, there could be public announcements of the results of hearings, rulings on motions, and other interim proceedings in the litigation. If securities analysts or investors regard these announcements as negative, the perceived value of our protein therapeutics,therapeutic candidates, programs, or intellectual property could be diminished. Accordingly, the market price of our common stock maycould decline.

We have in-licensed a portion of our intellectual property, and, if we fail to comply with our obligations under these arrangements, we could lose such intellectual property rights or owe damages to the licensor of such intellectual property.

We are a party to a number of license agreements that are important to our business, and we may enter into additional license agreements in the future. Our discovery and development platform is built, in part, around patents exclusively in-licensed from academic or research institutions. Certain of our in-licensed intellectual property also covers sotatercept and dalantercept. See "Business—Intellectual Property—In-Licenses" for a description of our license agreements with the Beth Israel Deaconess Medical Center, the Ludwig Institute for Cancer Research and the Salk Institute for Biological Studies.

Our existing license agreements impose, and we expect that future license agreements will impose, various diligence, milestone payment, royalty and other obligations on us. If there is any conflict, dispute, disagreement or issue of non-performance between us and our licensing partners regarding our rights or obligations under the license agreements, including any such conflict, dispute or disagreement arising from our failure to satisfy payment obligations under any such agreement, we may owe damages, our licensor may have a right to terminate the affected license, and our and our partners' ability to utilize the affected intellectual property in our drug discovery and development efforts, and our ability to enter into collaboration or marketing agreements for an affected protein therapeutic candidate, may be adversely affected.

        For example, the Salk Institute for Biological Studies recently filed a lawsuit against us alleging under one of our license agreements with them, which pertains to ActRIIB, its entitlement to a further share of certain payments received by us under our now-terminated agreement with Shire AG and a share of certain payments received by us under our on-going collaboration agreement with Celgene in connection with ACE-536. Although we and Salk have agreed that ACE-536 is not covered by any patent rights licensed from Salk, an unfavorable outcome in this litigation may lead to us owing significant damages to Salk and higher-than-anticipated future payments under this license in connection with development milestone payments that we may receive from Celgene. It is possible that Salk may seek to terminate the license covering the receptor. We do not believe that such a termination would have a material impact on our business or the development of any of our products. The patents under this license covered only one of our protein therapeutic candidates, ACE-031, the development of which has been discontinued. See "Business—Legal Proceedings" for a description of this proceeding.

Confidentiality agreements with employees and third parties may not prevent unauthorized disclosure of trade secrets and other proprietary information.

In addition to the protection afforded by patents, we rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable or that we elect not to patent, processes for which patents are difficult to enforce and any other elements of our platform technology and discovery and development processes that involve proprietary know-how, information or


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technology that is not covered by patents. However, trade secrets can be difficult to protect. We seek to protect our proprietary technology and processes, in part, by entering into confidentiality agreements with our employees, consultants, and outside scientific advisors, contractors and collaborators. Although we use reasonable efforts to protect our trade secrets, our employees, consultants, contractors, or outside scientific advisors might intentionally or inadvertently disclose our trade secret information to competitors. In addition, competitors may otherwise gain access to our trade secrets or independently develop substantially equivalent information and techniques.

Enforcing a claim that a third party illegally obtained and is using any of our trade secrets is expensive and time consuming, and the outcome is unpredictable. In addition, courts outside the United States sometimes are less willing than U.S. courts to protect trade secrets. Misappropriation or unauthorized disclosure of our trade secrets could impair our competitive position and may have a material adverse effect on our business

business.

Risks Related to Development and Commercialization of Our Protein Therapeutic Candidates

Our future commercial success depends upon attaining significant market acceptance of our protein therapeutic candidates, if approved, among physicians, patients, health carehealthcare payers and in cancer markets, acceptance by the operators of major cancer clinics.

medical providers.


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Even if we or our current or future partners obtain regulatory approval for sotatercept, ACE-536,luspatercept, dalantercept, ACE-083 or any other protein therapeuticstherapeutic candidates that we may develop or acquire in the future, the product may not gain market acceptance among physicians, health care payors,healthcare payers, patients and the medical community. Market acceptance of any approved products depends on a number of factors, including:

the efficacy and safety of the product, as demonstrated in clinical trials;


the clinical indications for which the product is approved and the label approved by regulatory authorities for use with the product, including any warnings that may be required on the label;


acceptance by physicians and patients of the product as a safe and effective treatment;

decisions by healthcare organizations to utilize the product;

the cost, safety and efficacy of treatment in relation to alternative treatments;


the availability of adequate reimbursement and pricing by third party payers and government authorities;


the continued projected growth of drug markets in our various indications;


relative convenience and ease of administration;


the prevalence and severity of adverse side effects; and


the effectiveness of our and our current or future partners' sales and marketing efforts.

Market acceptance is critical to our ability to generate significant revenue. Any protein therapeutic candidate, if approved and commercialized, may be accepted in only limited capacities or not at all. If any approved products are not accepted by the market to the extent that we expect, we may not be able to generate significant revenue and our business would suffer.

Reimbursement may be limited or unavailable in certain market segments for our protein therapeutic candidates, which could make it difficult for us to sell our products profitably.

Market acceptance and sales of any approved protein therapeuticstherapeutic candidates will depend significantly on the availability of adequate coverage and reimbursement from third-party payers and may be affected by existing and future health carehealthcare reform measures. Government authorities and third-party payors,payers, such as private health insurers and health maintenance organizations, decide which drugs they will pay for


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and establish reimbursement levels. Reimbursement by a third-party payer may depend upon a number of factors, including the third-party payor'spayer's determination that use of a product is:

a covered benefit under its health plan;


safe, effective and medically necessary;


appropriate for the specific patient;


cost-effective; and


neither experimental nor investigational.

Obtaining coverage and reimbursement approval for a product from a government or other third party payer is a time consuming and costly process that could require us to provide supporting scientific, clinical and cost-effectiveness data for the use of our products to the payer. We or our current or future partners may not be able to provide data sufficient to gain acceptance with respect to coverage and reimbursement. We cannot be sure that coverage or adequate reimbursement will be available for any of our protein therapeutic candidates. Also, we cannot be sure that reimbursement amounts will not reduce the demand for, or the price of, our products. If reimbursement is not available or is available only to limited levels, we may not be able to commercialize certain of our products. In addition in the United States, third-party payers are increasingly attempting to contain health carehealthcare costs by limiting both coverage and the level of reimbursement of new drugs. As a result, significant uncertainty exists as to whether and how much third-party payers will reimburse patients for their use of newly approved drugs, which in turn will put pressure on the pricing of drugs.


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Price controls and price pressure may be imposed in foreign and U.S. markets, which may adversely affect our future profitability.

In some countries, particularly member states of the European Union, the pricing of prescription drugs is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take considerable time after receipt of marketing approval for a product. In addition, there can be considerable pressure by governments and other stakeholders on prices and reimbursement levels, including as part of cost containment measures. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various European Union member states and parallel distribution, or arbitrage between low-priced and high-priced member states, can further reduce prices. In some countries, we or our current or future partners may be required to conduct a clinical trial or other studies that compare the cost-effectiveness of our protein therapeutic candidates to other available therapies in order to obtain or maintain reimbursement or pricing approval. Publication of discounts by third-party payers or authorities may lead to further pressure on the prices or reimbursement levels within the country of publication and other countries. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be adversely affected.

The impact of recent

Recent and future healthcare reform legislation and other changes in the healthcare industry and in healthcare spending on us is currently unknown, and may adversely affect our business model.

Our revenue prospects could be affected by changes in healthcare spending and policy in the United States and abroad. We operate in a highly regulated industry and new laws, regulations or judicial decisions, or new interpretations of existing laws, regulations or decisions, related to health carehealthcare availability, the method of delivery or payment for health carehealthcare products and services could negatively impact our business, operations and financial condition. There is significant interest in promoting health carehealthcare reform, as evidenced by the enactment in the United States of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act in 2010. It is likely that federal and state legislatures within the United States and foreign governments will continue to


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consider changes to existing health carehealthcare legislation. We cannot predict the reform initiatives that may be adopted in the future or whether initiatives that have been adopted will be repealed or modified. The continuing efforts of the government, insurance companies, managed care organizations and other payers of healthcare services to contain or reduce costs of healthcare may adversely affect:

the demand for any drug products for which we may obtain regulatory approval;


our ability to set a price that we believe is fair for our products;


our ability to obtain coverage and reimbursement approval for a product;


our ability to generate revenues and achieve or maintain profitability; and


the level of taxes that we are required to pay.

We face substantial competition, which may result in others discovering, developing or commercializing products before, or more successfully, than we do.

Our future success depends on our or our partners' ability to demonstrate and maintain a competitive advantage with respect to the design, development and commercialization of our protein therapeutic candidates. Our objective is to design, develop and commercialize new products with superior efficacy, convenience, tolerability and safety. In many cases, the protein therapeuticstherapeutic candidates that we commercialize with our strategic partners or on our own will compete with existing, market-leading products.

There are products currently approved to treat patients with MDS, including iron chelation therapy, immunomodulators and various chemotherapeutic agents. In addition, erythropoiesis stimulating agents and red blood cell transfusions are extensively used to treat anemia in MDS. ACE-536Luspatercept or sotatercept, if approved, will compete with these therapies. In addition, one or more products not currently approved for the treatment of anemia in MDS may in the future be granted marketing approval for the treatment of anemia in MDS or other conditions for which ACE-536luspatercept or sotatercept might be approved, including Aranesp®, being developed by Amgen, which is in Phase 3 trials. While there are currently no drug products approved for the treatment of anemia inb-thalassemia, beta-thalassemia, red blood cell transfusions are extensively used and sotatercept or ACE-536,luspatercept, if approved, would compete with this therapy. In addition, HQK-1001, a fetal hemoglobin stimulating agent being developed by HemaQuest Pharmaceuticals, has completed a Phase1/2 clinical trial and an investigator sponsored Phase 2 clinical trial in patients withb-thalassemia. Further, the future approval, in one or more regions, of a biosimilar product to one of our products could create substantial competition and have a material impact on our business.

In addition, the success of gene and/or cell therapy in beta-thalassemia patients could materially reduce the potential patient population for luspatercept, especially in transfusion dependent patients.


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Sotatercept or ACE-536,luspatercept, if approved for the treatment of chemotherapy-induced anemia or anemia of chronic kidney disease, would compete with erythropoiesis-stimulating agents, such as Epogen® and Aranesp®, marketed by Amgen, and Procrit®, marketed by Johnson & Johnson, that are currently approved for the treatment of chemotherapy-induced anemia or anemia of chronic kidney disease and other therapies in development including oral, small molecule treatments being developed by Astellas Pharma and Fibrogen designed to increase the body's production of erythropoietin.

While we anticipate that dalantercept, if approved for the treatment of cancer, would likely be approved in combination with certain VEGF pathway inhibitors that are currently approved for the treatment of various cancer types, dalantercept would compete with other products, including other angiogenesis inhibitors as well as immuno-oncology agents, approved for the treatment of these cancers.

If ACE-083 is approved for the treatment of neuromuscular disorders or other diseases characterized by a loss of muscle function, it could compete with a variety of other approaches to treating neuromuscular disorders or muscle loss that are currently in clinical trials, including, among others, a monoclonal antibody targeting the activin receptor type IIB, bimagrumab, being studied by Novartis to treat pathological muscle loss and weakness, and various myostatin monoclonal antibodies being studied to treat disuse muscle atrophy, cancer-related cachexia, and sarcopenia. We intend to conduct our first phase 2 trial of ACE-083 in patients with facioscapulohumeral muscular dystrophy, or FSHD. We are aware of competitors also developing products to treat this disease, including aTyr Pharma. If competitive products prove to be superior to ACE-083, our business may be harmed. (See "Competition").
Many of our potential competitors have significantly greater financial, manufacturing, marketing, drug development, technical and human resources than we do. Large pharmaceutical companies, in particular, have extensive experience in clinical testing, obtaining regulatory approvals, recruiting patients and in manufacturing pharmaceutical products. These companies also have significantly greater


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research and marketing capabilities than we do and may also have products that have been approved or are in late stages of development, and have collaborative arrangements in our target markets with leading companies and research institutions. Established pharmaceutical companies may also invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds that could make the protein therapeuticstherapeutic candidates that we develop obsolete. As a result of all of these factors, our competitors may succeed in obtaining patent protection and/or FDA approval or discovering, developing and commercializing protein therapeuticstherapeutic candidates before we do. In addition, any new product that competes with an approved product must demonstrate compelling advantages in efficacy, convenience, tolerability and safety in order to overcome price competition and to be commercially successful. If we are not able to compete effectively against potential competitors, our business will not grow and our financial condition and operations will suffer.

Our protein therapeutics

If our clinical trials fail to demonstrate the safety and efficacy of our therapeutic candidates to the satisfaction of regulatory authorities or do not otherwise produce positive results, we may cause undesirable side effectsincur additional costs or have other properties that delayexperience delays in completing, or prevent their regulatory approval or limit their commercial potential.

ultimately be unable to complete, the development and commercialization of our therapeutic candidates.

Undesirable side effects caused by our protein therapeuticstherapeutic candidates could cause us, Celgene or regulatory authorities to interrupt, delay or halt clinical trials and could result in the denial of regulatory approval by the FDA or other regulatory authorities and potential products liability claims. We and Celgene are currently conducting a number of Phase 2clinical trials for our clinical stage protein therapeutic candidates. Serious adverse events deemed to be caused by our protein therapeuticstherapeutic candidates could have a material adverse effect on the development of our protein therapeutic candidates and our business as a whole. The most common adverse event to dateFor a more complete description of the safety profile for our therapeutic candidates, see the description of each of our therapeutic candidates in the clinical trials evaluating the safety and efficacy"Business" section of our protein therapeutic candidates has been hypertension in our clinical trials for sotatercept and fluid retention in our clinical trials for dalantercept. this Annual Report on Form 10-K.
Our understanding of the relationship between our protein therapeutic candidates and these events may change as we gather more information, and additional unexpected adverse events may occur. There can be no assurance that additional adverse events associated with our protein therapeutic candidates will not be observed. Recently, we discontinued the development of ACE-031, another of our clinical stage protein therapeutics that binds to ligands of the TGF-b superfamily. Clinical development of ACE-031 was put on clinical hold in 2011 due to preliminary safety observations in patients. After gathering further information from animal toxicology studies, we and our ACE-031 partner, Shire AG, determined that the risk-benefit profile of ACE-031 was not appropriate for the intended patient population, boys aged four and older with a genetic muscle wasting disease, and we discontinued development of this protein therapeutic candidate. As is typical in drug development, we have a program of ongoing toxicology studies in animals for our other clinical stage protein therapeuticstherapeutic candidates and cannot provide assurance that the findings from such studies or any ongoing or future clinical trials will not adversely affect our clinical development activities.

Before obtaining marketing approval from regulatory authorities for the sale of our therapeutic candidates, we must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our therapeutic candidates in humans. Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. In addition, preclinical and clinical data are often susceptible to varying interpretations and analyses. Many companies that have believed their therapeutic candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products.

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We or our current or future partners may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive marketing approval or commercialize our therapeutic candidates, including:
regulators or institutional review boards may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;

we may have delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;

clinical trials of our therapeutic candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs;

the number of patients required for clinical trials of our therapeutic candidates may be larger than we anticipate; enrollment in these clinical trials may be slower than we anticipate; or participants may drop out of these clinical trials at a higher rate than we anticipate;

third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;

we might have to suspend or terminate clinical trials of our therapeutic candidates for various reasons, including a finding that the participants are being exposed to unacceptable health risks;

regulators, institutional review boards, or the data safety monitoring board for such trials may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;

the cost of clinical trials of our therapeutic candidates may be greater than we anticipate;

the supply or quality of our therapeutic candidates or other materials necessary to conduct clinical trials of our therapeutic candidates may be insufficient or inadequate; and

our therapeutic candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or institutional review boards to suspend or terminate the trials.

If we or our current or future partners are required to conduct additional clinical trials or other testing of our therapeutic candidates beyond those that we currently contemplate, if we or our current or future partners are unable to successfully complete clinical trials of our therapeutic candidates or other testing, if the results of these trials or tests are not positive or are only modestly positive or if we or others identify undesirable side effects caused by our protein therapeutic candidates either before or after receipt of marketing approval, then a number of potentially significant negative consequences could result, including:


be delayed in obtaining or be unable to obtain regulatorymarketing approval for our protein therapeutic candidates;

obtain approval for indications or patient populations that are not as broad as intended or desired;

regulatory authorities may withdraw approvals of our protein therapeutic candidates;

regulatory authorities may require additional warnings on the label;

be required to provide a medication guide outlining the risks of such side effects for distribution to patients may be required;patients;

obtain approval with labeling that includes significant use or distribution restrictions or safety warnings, including boxed warnings;

we could
suffer reputational harm;

be sued and held liable for harm caused to patients; and

our reputation may suffer.

be subject to additional post-marketing testing requirements; or

have the product removed from the market after obtaining marketing approval.

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        Any


Product development costs will also increase if we or our current or future partners experience delays in testing or marketing approvals. We do not know whether any clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Significant clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our therapeutic candidates, could allow our competitors to bring products to market before we do, and could impair our ability to successfully commercialize our therapeutic candidates, any of these events could prevent us from achieving or maintaining market acceptancewhich may harm our business and results of operations.
Our results to date do not guarantee that any of our proteintherapeutic candidates will be safe or effective, or receive regulatory approval.
The risk of failure of our current therapeutic candidates is high. To date, the data supporting our clinical development strategy for our therapeutic candidates are derived solely from laboratory and preclinical studies and limited early-to-mid-stage clinical trials. Later clinical trials may not yield data consistent with earlier clinical trials. Similarly, clinical responses seen in patients enrolled at early stages of a clinical trial may not be replicated in patients enrolled in that trial at a later time. In addition, adverse events not observed in early clinical trials may be seen for the first time in later studies, or adverse events observed in a small number of patients in early trials may be seen in a greater number of patients in later studies and have greater statistical significance than previously anticipated. In the event that our clinical trials do not yield data consistent with earlier experience, it may be necessary for us to change our development strategy or abandon development of that therapeutic candidate, either of which could result in delays, additional costs and a decrease in our stock price.
Our Phase 2 clinical trial results for luspatercept are not necessarily indicative or predictive of the results of Celgene's Phase 3 clinical trials. It is impossible to predict when or if any of our therapeutic candidates will prove safe or effective in humans or receive regulatory approval. These therapeutic candidates may not demonstrate in patients the chemical and pharmacological properties ascribed to them in laboratory studies or early-to-mid-stage clinical trials, and they may interact with human biological systems or other drugs in unforeseen, ineffective or harmful ways. If we are unable to discover or successfully develop drugs that are safe and effective in humans, we will not have a viable business.
We manufacture ACE-083, ACE-2494 and earlier stage luspatercept at our manufacturing facility. If our manufacturing facility is damaged or destroyed or production at this facility is otherwise interrupted, our business and prospects would be negatively affected.
If the manufacturing facility at our corporate headquarters or the equipment in it is damaged or destroyed, we may not be able to quickly or economically replace our manufacturing capacity or replace it at all. In the event of a temporary or protracted loss of this facility or equipment, we might not be able to transfer manufacturing to a third party. Even if we could transfer manufacturing to a third party, the shift would likely be expensive and time-consuming, particularly since the new facility would need to comply with the necessary regulatory requirements and we would need approval from the FDA and foreign regulators before administering any products manufactured at that facility to patients. Such an event could delay our clinical trials or, if our therapeutic candidates are approved by the FDA or foreign regulators, reduce our product sales.
Our expanded research activities may not identify new therapeutic candidates, and we may not be successful in developing any new therapeutic candidates that are identified.
        Discovery and development of new therapeutic candidates is an unpredictable activity. We may not succeed in identifying new therapeutic candidates, and if we are unable to do so, our pipeline of clinical stage therapeutic candidates will be reduced in size, potentially harming our business. Our discovery efforts are primarily focused on IntelliTrap therapeutic candidates and antibodies. We have not previously manufactured or developed antibodies or IntelliTrap proteins, and we may not be successful at doing so. We may be unable to manufacture these candidate therapeutics, and could substantially increase commercialization costs.

these candidate therapeutics may show unacceptable toxicity or pharmacokinetic properties, or these therapeutic candidates may not be safe or effective in clinical trials.



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Risks Related to Our Business and Industry

If we fail to attract and keep senior management and key scientific personnel, we may be unable to successfully develop our protein therapeutics,therapeutic candidates, conduct our clinical trials and commercialize our protein therapeutic candidates.

We are highly dependent on members of our senior management, including John L. Knopf, Ph.D., our Chief Executive Officer and President and one of our founders. The loss of the services of any of these persons could impede the achievement of our research, development and commercialization objectives. We do not maintain "key person" insurance for any of our executives or other employees.

Recruiting and retaining qualified scientific, clinical, regulatory, manufacturing, sales and marketing personnel will also be critical to our success. We may not be able to attract and retain these personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel. We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy. Our consultants and advisors including our scientific co-founders, may be employed by employers other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us.

Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements and insider trading.

        We are exposed to the risk of employee fraud or other misconduct. Misconduct by employees could include intentional failures to comply with FDA regulations, to provide accurate information to the FDA, to comply with manufacturing standards we have established, to comply with federal and state healthcare fraud and abuse laws and regulations, to report financial information or data accurately or to disclose unauthorized activities to us. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. It is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant fines or other sanctions.

We may encounter difficulties in managing our growthorganizational changes and expandingsuccessfully adjusting our operations successfully.

operations.

As we seek to advance our protein therapeutic candidates through clinical trials and commercialization, we will need to expand our development, regulatory, manufacturing, marketing and sales capabilities or contract with third parties to provide these capabilities for us. As our operations expand, we expect that we will need to manage additional relationships with various strategic partners, suppliers and other third parties. Future growth will impose significant added responsibilities on members of management. Our future financial performance and our ability to commercialize our


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protein therapeutic candidates and to compete effectively will depend, in part, on our ability to manage any future growth effectively. To that end, we must be able to manage our development efforts and clinical trials effectively and hire, train and integrate additional management, administrative and, if necessary, sales and marketing personnel. We may not be able to accomplish these tasks, and our failure to accomplish any of them could prevent us from successfully growing our company.

If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of our protein therapeutics.

therapeutic candidates.

We face an inherent risk of product liability as a result of the clinical testing of our protein therapeutic candidates and will face an even greater risk if we commercialize any products. For example, we may be sued if any product we develop allegedly causes injury or is found to be otherwise unsuitable during product testing, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability, and a breach of warranties. Claims could also be asserted under state consumer protection acts. If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to limit commercialization of our protein therapeutic candidates. Even a successful defense would require significant financial and management resources. Regardless of the merits or eventual outcome, liability claims may result in:

injury to our reputation;


withdrawal of clinical trial participants;


costs to defend the related litigations;


a diversion of management's time and our resources;


substantial monetary awards to trial participants or patients;


product recalls, withdrawals, or labeling, marketing or promotional restrictions;


loss of revenue;


the inability to commercialize our protein therapeutic candidates; and


a decline in our stock price.

Failure to obtain and retain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could prevent or inhibit the commercialization of products we develop. We currently carry product liability

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insurance covering our clinical trials in the amount of $10.0 million in the aggregate. Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage. Our insurance policies also have various exclusions, and we may be subject to a product liability claim for which we have no coverage. We will have to pay any amounts awarded by a court or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, and we may not have, or be able to obtain, sufficient capital to pay such amounts.

We could be subject to securities class action litigation.
In the past, securities class action litigation has often been brought against companies following a decline in the market price of their securities. This risk is especially relevant for us because biopharmaceutical companies have experienced significant stock price volatility in recent years. If we face such litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.
We must comply with environmental laws and regulations, and failure to comply with these laws and regulations could expose us to significant liabilities.

We use hazardous chemicals and radioactive and biological materials in certain aspects of our business and are subject to a variety of federal, state and local laws and regulations governing the use, generation, manufacture, distribution, storage, handling, treatment and disposal of these materials.materials that we use in our manufacturing process. Although we believe our safety procedures for handling and disposing of these materials and waste products comply with these laws and regulations, we cannot eliminate the risk of accidental injury or


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contamination from the use, manufacture, distribution, storage, handling, treatment or disposal of hazardous materials. In the event of contamination or injury, or failure to comply with environmental, occupational health and safety and export control laws and regulations, we could be held liable for any resulting damages and any such liability could exceed our assets and resources. We are uninsured for third-party contamination injury.

Unfavorable global economic conditions could adversely affect our business, financial condition or results of operations.
Our results of operations could be adversely affected by general conditions in the global economy and in the global financial markets. A severe or prolonged economic downturn could result in a variety of risks to our business, including, weakened demand for our therapeutic candidates and our ability to raise additional capital when needed on acceptable terms, if at all. Weak global economic conditions, especially in Europe, could decrease the number of clinical trial sites available to us and hinder our ability to conduct clinical trials, which would have a material adverse effect on our business and the development of our therapeutic candidates. A weak or declining economy could also strain our suppliers, possibly resulting in supply disruption, or cause our customers to delay making payments for our services. Any of the foregoing could harm our business and we cannot anticipate all of the ways in which the current economic climate and financial market conditions could adversely impact our business.
Our internal computer systems, or those of our partners, third-party CROs or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our therapeutic candidate development programs.

Despite the implementation of security measures, our internal computer systems and those of our current and any future CROs and other contractors, consultants and collaborators are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. While we have not experienced any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our development programs and our business operations. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our or our partners' regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Likewise, we rely on third parties to manufacture our therapeutic candidates and conduct clinical trials, and similar events relating to their computer systems could also have a material adverse effect on our business. To the extent that any disruption or security breach were to result in a loss of, or damage to, our or any of our partners' data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development and commercialization of our therapeutic candidate could be delayed.


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Risks Related to Our Common Stock

We are eligible to be treated as an "emerging growth company" as defined in the Jumpstart Our Business Startups Act of 2012, and we cannot be certain if the reduced disclosure requirements applicable to emerging growth companies will make our common stock less attractive to investors.

        We are an "emerging growth company", as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act. For as long as we continue to be an emerging growth company, we may take advantage of exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies, including (1) not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act of 2002, which we refer to as the Sarbanes-Oxley Act, (2) reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements and (3) exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any golden parachute payments not previously approved. We could be an emerging growth company for up to five years, although circumstances could cause us to lose that status earlier, including if the

The market valueprice of our common stock held by non-affiliates exceeds $700.0 million as of any June 30 before that time or if we have total annual gross revenue of $1.0 billion or more during any fiscal year before that time, in which cases we would no longer be an emerging growth company as of the following December 31 or, if we issue more than $1.0 billion in non-convertible debt during any three-year period before that time, we would cease to be an emerging growth company immediately. We cannot predict if investors will find our common stock less attractive because we may rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile.

        Under the JOBS Act, emerging growth companies can also delay adopting new or revised accounting standards until such time as those standards apply to private companies. We have irrevocably elected not to avail ourselves of this exemption from new or revised accounting standards and, therefore, will be subject to the same new or revised accounting standards as other public companies that are not emerging growth companies.

Our stock price could be highly volatile, and as a result you may not be able to resell your shares at or above the public offering price.

price at which you purchased them.

Since our initial public offering in September 2013, the price of our common stock as reported on The NASDAQ Global Market has ranged from a low of $16.78 on November 6 and 8, 2013 to a high of $57.89 on January 22, 2014. The market price of shares of our common stock could be subject to wide fluctuations in response to many risk factors listed in this section, and others beyond our control, including:

results of clinical trials of our protein therapeutic candidates, including sotatercept, ACE-536luspatercept, dalantercept and dalantercept;ACE-083;


the timing of the release of results of our clinical trials that are being conducted by Celgene;


results of clinical trials of our competitors' products;


regulatory actions with respect to our products or our competitors' products;

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In addition, the stock market has recently experienced significant volatility, particularly with respect to pharmaceutical, biotechnology and other life sciences company stocks. The volatility of pharmaceutical, biotechnology and other life sciences company stocks often does not relate to the operating performance of the companies represented by the stock. As we operate in a single industry, we are especially vulnerable to these factors to the extent that they affect our industry or our products, or to a lesser extent our markets. In the past, securities class action litigation has often been initiated against companies following periods of volatility in their stock price. This type of litigation could result in substantial costs and divert our management's attention and resources, and could also require us to make substantial payments to satisfy judgments or to settle litigation.

Our principal stockholders and management own a significant percentage of our stock and will be able to exercise significant influence over matters subject to stockholder approval.

        As of December 31, 2013, our executive officers, directors and principal stockholders, together with their respective affiliates, beneficially owned approximately 66.6% of our common stock, including shares subject to outstanding options and warrants that are exercisable within 60 days after such date, Accordingly, these stockholders will be able to exert a significant degree of influence over our management and affairs and over matters requiring stockholder approval, including the election of our board of directors and approval of significant corporate transactions. This concentration of ownership could have the effect of entrenching our management and/or the board of directors, delaying or preventing a change in our control or otherwise discouraging a potential acquirer from attempting to obtain control of us, which in turn could have a material and adverse effect on the fair market value of our common stock.



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Sales of a substantial number of shares of our common stock in the public market could cause our stock price


We continue to fall.

        As of January 31, 2014, we have 31,160,274 shares of common stock outstanding. Sales of a substantial number of shares of our common stock in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock. Of these outstanding shares, 14,544,551 are currently held by directors, executive officers and other parties that may be deemed to be their or our affiliates and are available for sale subject to volume limitations, other restrictions under the securities laws and, in some cases, vesting schedules. We also have registered shares of common stock that we may issue under our equity compensation plans. These shares can be freely sold in the public market upon issuance, subject to volume limitations applicable to affiliates and, in certain cases, lock-up agreements that we expect to expire on April 22, 2014

We are incurringincur significant increased costs as a result of operating as a public company and complying with the Sarbanes-Oxley Act, especially now that we are a large accelerated filer and are no longer an ""emerging growth company,"" and our management iscontinues to be required to devote substantial time to new compliance initiatives.

As a newly public company, we are incurringincur significant legal, accounting and other expenses that we did not incur as a private company. In addition, the Sarbanes-Oxley Act, and rules of the SEC and those of The NASDAQ Global Market, or NASDAQ have imposed various requirements on public companies including requiring establishment and maintenance of effective disclosure and financial controls. Our management and other personnel will need to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have increased and will continue to increase our legal and financial compliance costs and will make some activities more time-consuming and costly.

The Sarbanes-Oxley Act requires, among other things, that we maintain effective internal control over financial reporting and disclosure controls and procedures. In particular, we must perform system and process evaluation and testing of our internal control over financial reporting to allow management to report on the effectiveness of our internal control over financial reporting, as required by Section 404 of the Sarbanes-Oxley Act, beginning with our annual report on Form 10-K for the fiscal year ended December 31, 2013.Act. In addition, because we will beare no longer an emerging growth company under the JOBS Act, we are required to have our independent registered public accounting firm attest to the effectiveness of our internal control over financial reporting beginning with our annual report on Form 10-K following the date on which we are no longer an emerging growth company.reporting. Our compliance with Section 404 of the Sarbanes-Oxley Act will requirerequires that we incur substantial accounting expense and expend significant management efforts. We currently do not have an internal audit group, and we willmay need to hire additional accounting and financial staff with appropriate public company experience and technical accounting knowledge. If we are not able to comply with the requirements of Section 404 in a timely manner, or if we or our independent registered public accounting firm identify deficiencies in our internal control over financial reporting that are deemed to be material weaknesses, the market price of our stock could decline and we could be subject to sanctions or investigations by NASDAQ, the SEC or other regulatory authorities, which would require additional financial and management resources.

Our ability to successfully implement our business plan and comply with Section 404 requires us to be able to prepare timely and accurate financial statements. We expect that we will need to continue to improve existing, and implement new operational and financial systems, procedures and controls to manage our business effectively. Any delay in the implementation of, or disruption in the transition to, new or enhanced systems, procedures or controls, may cause our operations to suffer and we may be unable to conclude that our internal control over financial reporting is effective and to obtain an unqualified report on internal controls from our auditors as required under Section 404 of the Sarbanes-Oxley Act. This, in turn, could have an adverse impact on trading prices for our common stock, and could adversely affect our ability to access the capital markets.


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If we fail to maintain an effective system of internal control over financial reporting in the future, we may not be able to accurately report our financial condition, results of operations or cash flows, which may adversely affect investor confidence in us and, as a result, the value of our common stock.

The Sarbanes-Oxley Act requires, among other things, that we maintain effective internal controls for financial reporting and disclosure controls and procedures. Commencing with our annual report on Form 10-K for the year ending December 31, 2014, we will beWe are required, under Section 404 of the Sarbanes-Oxley Act, to furnish a report by management on, among other things, the effectiveness of our internal control over financial reporting. This assessment will need tomust include disclosure of any material weaknesses identified by our management in our internal control over financial reporting. A material weakness is a control deficiency, or combination of control deficiencies, in internal control over financial reporting that results in more than a reasonable possibility that a material misstatement of annual or interim financial statements will not be prevented or detected on a timely basis. Section 404 of the Sarbanes-Oxley Act also generally requires an attestation from our independent registered public accounting firm on the effectiveness of our internal control over financial reporting. However, forNow that we no longer qualify as long as we remain an emerging growth company as defined in the JOBS Act, we intend to take advantage ofare no longer exempted from certain exemptions from various reporting requirements, that are applicable to other public companies that are not emerging growth companies including, but not limited to, not being required to comply withsuch as the independent registered public accounting firm attestation requirement.

        Our compliance with Section 404 will require that we incur substantial accounting expense and expend significant management efforts. We currently do not have an internal audit group, and we will need to hire additional accounting and financial staff with appropriate public company experience and technical accounting knowledge, and compile the system and process documentation necessary to perform the evaluation needed to comply with Section 404. We may not be able to complete our evaluation, testing and any required remediation in a timely fashion. attestation.

During the evaluation and testing process, if we identify one or more material weaknesses in our internal control over financial reporting, we will be unable to assert that our internal control over financial reporting is effective. We cannot assure you that there will not be material weaknesses or significant deficiencies in our internal control over financial reporting in the future. Any failure to maintain internal control over financial reporting could severely inhibit our ability to accurately report our financial condition, results of operations or cash flows. If we are unable to conclude that our internal control over financial reporting is effective, or if our independent registered public accounting firm determines we have a material weakness or significant deficiency in our internal control over financial reporting, once that firm begin its Section 404 reviews, we could lose investor confidence in the accuracy and completeness of our financial reports, the market price of our common stock could decline, and we could be subject to sanctions or investigations by the NASDAQ, the SEC or other regulatory authorities. Failure to remedy any material weakness in our internal control over financial reporting, or to implement or maintain other effective control systems required of public companies, could also restrict our future access to the capital markets.

We do not expect to pay any cash dividends for the foreseeable future.


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You should not rely on an investment in our common stock to provide dividend income. We do not anticipate that we will pay any cash dividends to holders of our common stock in the foreseeable future. Instead, we plan to retain any earnings to maintain and expand our operations. In addition, our ability to pay cash dividends is currently prohibited by the terms of our debt financing arrangement, and any future debt financing arrangement may contain terms prohibiting or limiting the amount of dividends that may be declared or paid on our common stock. Accordingly, investors must rely on sales of their common stock after price appreciation, which may never occur, as the only way to realize any


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return on their investment. As a result, investors seeking cash dividends should not purchase our common stock.

Provisions in our restated certificate of incorporation, our amended and restated by-laws and Delaware law may have anti-takeover effects that could discourage an acquisition of us by others, even if an acquisition would be beneficial to our stockholders, and may prevent attempts by our stockholders to replace or remove our current management.

Our restated certificate of incorporation, amended and restated by-laws and Delaware law contain provisions that may have the effect of delaying or preventing a change in control of us or changes in our management. Our restated certificate of incorporation and by-laws include provisions that:

authorize "blank check" preferred stock, which could be issued by our board of directors without stockholder approval and may contain voting, liquidation, dividend and other rights superior to our common stock;


create a classified board of directors whose members serve staggered three-year terms;


specify that special meetings of our stockholders can be called only by our board of directors;


prohibit stockholder action by written consent;


establish an advance notice procedure for stockholder approvals to be brought before an annual meeting of our stockholders, including proposed nominations of persons for election to our board of directors;


provide that our directors may be removed only for cause;


provide that vacancies on our board of directors may be filled only by a majority of directors then in office, even though less than a quorum;


specify that no stockholder is permitted to cumulate votes at any election of directors;


expressly authorize our board of directors to modify, alter or repeal our amended and restated by-laws; and


require supermajority votes of the holders of our common stock to amend specified provisions of our restated certificate of incorporation and amended and restated by-laws

These provisions, alone or together, could delay or prevent hostile takeovers and changes in control or changes in our management.

In addition, because we are incorporated in the state of Delaware, we are governed bysubject to the provisions of Section 203 of the Delaware General Corporation Law, which limitsprohibits a publicly-held Delaware corporation from engaging in a "business combination" with an "interested stockholder" for a three-year period following the time that this stockholder becomes an interested stockholder, unless the business combination is approved in a prescribed manner. As a result, you may lose your ability of stockholders owningto sell your stock for a price in excess of 15%the prevailing market price due to these protective measures and efforts by stockholders to change the direction or management of our outstanding voting stock to merge or combine with us.

the company may be unsuccessful.

Any provision of our restated certificate of incorporation or amended and restated by-laws or Delaware law that has the effect of delaying or deterring a change in control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock, and could also affect the price that some investors are willing to pay for our common stock.

Our restated certificate of incorporation designates the Court of Chancery of the State of Delaware and federal court within the State of Delaware as the exclusive forum for certain types of actions and proceedings that may be initiated by our stockholders, which could limit our stockholders' ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.

Our restated certificate of incorporation provides that, subject to limited exceptions, the Court of Chancery of the State of Delaware and federal court within the State of Delaware will be exclusive


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forums for (1) any derivative action or proceeding brought on our behalf, (2) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers or


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other employees to us or our stockholders, (3) any action asserting a claim against us arising pursuant to any provision of the Delaware General Corporation Law, our restated certificate of incorporation or our amended and restated by-laws, or (4) any other action asserting a claim against us that is governed by the internal affairs doctrine. Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock shall be deemed to have notice of and to have consented to the provisions of our restated certificate of incorporation described above. This choice of forum provision may limit a stockholder's ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers or other employees, which may discourage such lawsuits against us and our directors, officers and employees. Alternatively, if a court were to find these provisions of our restated certificate of incorporation inapplicable to, or unenforceable in respect of, one or more of the specified types of actions or proceedings, we may incur additional costs associated with resolving such matters in other jurisdictions, which could adversely affect our business and financial condition.

Sales of our common stock by our employees, including our executive officers, could cause our stock price to fall or prevent it from increasing for numerous reasons, and sales by such persons could be viewed negatively by other investors.
In accordance with the guidelines specified under Rule 10b5-1 of the Securities Exchange Act of 1934, as amended, and our policies regarding stock transactions, a number of our employees, including executive officers, have adopted and may continue to adopt stock trading plans pursuant to which they have arranged to sell shares of our common stock from time to time in the future. Generally, sales under such plans by our executive officers and directors require public filings. Sales of our common stock by such persons could cause the price of our common stock to fall or prevent it from increasing. If sales by employees, executive officers or directors cause a substantial number of shares of our common stock to become available for purchase in the public market, the price of our common stock could fall or may not increase. Also, sales by such persons could be viewed negatively by holders and potential purchasers of our common stock. If securities or industry analysts do not continue to publish research or publish inaccurate or unfavorable research about our business, our share price and trading volume could decline.
If securities analysts do not publish research or reports about our business or if they publish negative, or inaccurate, evaluations of our stock, the price of our stock and trading volume could decline.
The trading market for our common stock may be impacted, in part, by the research and reports that securities or industry analysts publish about us or our business. There can be no assurance that analysts will cover us, continue to cover us or provide favorable coverage. If one or more analysts downgrade our stock or change their opinion of our stock, our share price may decline. In addition, if one or more analysts cease coverage of our company or fail to regularly publish reports on us, we could lose visibility in the financial markets, which could cause our share price or trading volume to decline.

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Item 1B.    Unresolved Staff Comments.
Comments

Not applicable.

Item 2.    Properties.
Properties

Our corporate, research and development, manufacturing, and clinical trial operations are located in Cambridge, Massachusetts. We lease approximately 94,50088,000 square feet of office and laboratory space in three adjacent buildings with aggregate monthly net-rentrent expense of approximately $0.3 million. We have subletmillion, which will increase to approximately 20,000 square feet$0.4 million in April 2016. Two of space in one of our leased buildings. Two leases expire in September 2018 and one lease expires in May 2015. March 2021.
We believe our facilities are adequate for our current needs and that suitable additional substitute space would be available if needed.

Item 3.    Legal Proceedings.
Proceedings

        On October 18, 2012, the Salk Institute for Biological Studies, which

While we referare not currently a party to as Salk, filed a complaintany material legal proceedings, we could become subject to legal proceedings in the Massachusetts Superior Court for Suffolk County, alleging that we breached oneordinary course of business. We do not expect any such potential items to have a significant impact on our two licensing agreements with Salk. The licensing agreement in dispute provides us with a license with respect to certain of Salk's U.S. patents related to the ActRIIB activin receptor proteins. Salk contends that, under the licensing agreement, we owed Salk a greater share of the upfront payment that we received under our now-terminated agreement with Shire AG regarding ACE-031 and a share of the upfront payment and development milestone payments that we have received under our ongoing collaboration agreement with Celgene regarding ACE-536. Salk is seeking a total of approximately $10.5 million plus interest in payment and a 15% share of future development milestone payments received under our agreement with Celgene regarding ACE-536. We contend that no additional amounts are due to Salk and that we have complied with all of our payment obligations under the applicable Salk license agreement.

        We moved to dismiss the complaint on December 3, 2012. The Court denied our motion on February 28, 2013. On March 14, 2013, Acceleron answered the complaint and asserted patent invalidity counterclaims. On the basis of those counterclaims, Acceleron removed the action on March 28, 2013 to the United States District Court for the District of Massachusetts. The parties have since reached an agreement on a stipulation as to certain patent issues raised in the action, and Acceleron has dismissed its counterclaims. The Court held an initial scheduling conference on May 30, 2013, and the fact discovery is now closed. The case is currently scheduled for trial in September 2014. We intend to defend our position vigorously.

financial position.

Item 4.    Mine Safety Disclosures.
Disclosures

Not applicable.



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PART II

Item 5.    Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.
Securities

Market Information and Holders

Stockholders

Our common stock has been listed on The NASDAQ Global Market under the symbol "XLRN" since September 19, 2013. Prior to that, there was no public market for our common stock. The following table sets forth for the periods indicated the high and low sales prices per share of our common stock as reported on The NASDAQ Global Market:

 Common Stock Price
 2015 2014
 High Low High Low
First Quarter$43.00
 $35.11
 $57.89
 $33.81
Second Quarter$37.90
 $26.94
 $42.24
 $28.53
Third Quarter$36.31
 $20.00
 $35.00
 $23.61
Fourth Quarter$50.86
 $21.93
 $48.50
 $27.64

Year ended December 31, 2013:
 High Low 

Third quarter(1)

 $23.41 $18.50 

Fourth quarter

 $40.02 $16.78 

(1)
Represents the period from September 19, 2013, the date on which our common stock first began to trade on The NASDAQ Global Market after the pricing of our initial public offering, through September 30, 2013, the end of our third fiscal quarter.

As of January 31, 2014,2016, there were approximately 173105 holders of record of our common stock.

Dividends

We have never declared or paid cash dividends on our common stock. We currently intend to retain all available funds and any future earnings, if any, to fund the development and expansion of our business and we do not anticipate paying any cash dividends in the foreseeable future. In addition, our ability to pay cash dividends is currently prohibited by the terms of our debt financing arrangements, and any future debt financing arrangement may contain terms prohibiting or limiting the amount of dividends that may be declared or paid on our common stock. Any future determination to pay dividends will be made at the discretion of our board of directors.

Securities Authorized for Issuance Under Equity Compensation Plans
Information about our equity compensation plans is incorporated herein by reference to Item 12 of Part III of this Annual Report on Form 10-K.


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Performance Graph(1)

Graph

The following graph shows a comparison from September 19, 2013 through December 31, 20132015 of cumulative total return on assumed investment of $100.00 in cash in our common stock, the NASDAQ Composite Index and the NASDAQ Biotechnology Index. Such returns are based on historical results and are not intended to suggest future performance. Data for the NASDAQ Composite Index and the NASDAQ Biotechnology Index assume reinvestment of dividends.


COMPARISON OF 327 MONTH CUMULATIVE TOTAL RETURN*
RETURN(1)(2)
Among Acceleron Pharma Inc., the NASDAQ Composite Index,
and the NASDAQ Biotechnology Index


*
$100 invested on 9/19/13 in stock or 8/31/13 in index, including reinvestment of dividends.
Fiscal year ending December 31.

(1)This performance graph shall not be deemed "soliciting material" or to be "filed" with the SEC for purposes of Section 18 of the Securities and Exchange Act of 1934, as amended, or otherwise subject to the liabilities under that Section, and shall not be deemed incorporated by reference into any filing of Acceleron Pharma Inc. under the Securities Act of 1933, as amended.
(2)$100 invested on September 19, 2013 in stock, or on August 31, 2013 in each index, including reinvestment of dividends.

Recent Sales of Unregistered Securities

        During the year ended December 31, 2013, we have issued the following securities that were not registered under the Securities Act. The following share numbers reflect the 1-for-4 reverse split of our common stock and preferred stock effected on September 5, 2013.

        On September 24, 2013, we issued 666,667 shares of common stock for total consideration of $10,000,000. This issuance of common stock was exempt pursuant to Rule 506 and Section 4(a)(2) of the Securities Act of 1933.

        On September 24, 2013, we issued 18,516,993 shares of common stock upon conversion of all of our outstanding shares of preferred stock.

        The issuance of the common stock upon conversion of the preferred stock was exempt pursuant to Section 3(a)(9) of the Securities Act of 1933.


(1)
This performance graph shall not be deemed "soliciting material" or to be "filed" with the SEC for purposes of Section 18 of the Securities and Exchange Act of 1934, as amended, or otherwise subject to the liabilities under that Section, and shall not be deemed incorporated by reference into any filing of Acceleron Pharma, Inc. under the Securities Act of 1933, as amended.

None.

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        From January 1, 2013 through December 31, 2013, we granted options to purchase a total of 552,750 shares of our common stock to employees at a weighted-average exercise price of $23.88 per share. During the same period, we issued 45,900 shares of common stock upon the exercise of options to purchase such shares of common stock at a weighted average price of $1.44 per share.

        Option grants and the issuances of common stock upon exercise of such options were exempt pursuant to Rule 701 and Section 4(2) of the Securities Act of 1933.

Use of Proceeds from Initial Public Offering of Common Stock

        On September 24, 2013, we completed the initial public offering (IPO) of our common stock pursuant to a registration statement on Form S-1(File No. 333-190417) and issued and sold 6,417,000 shares of our common stock, including 837,000 shares of common stock sold pursuant to the underwriters' full exercise of their option to purchase additional shares at a public offering price of $15.00 per share, for aggregate gross proceeds of $96.3 million. All of the shares issued and sold in the IPO were registered under the Securities Act pursuant to a Registration Statement on Form S-1 (File No. 333-190417), which was declared effective by the SEC on September 18, 2013, and a registration statement filed pursuant to Rule 462(b) of the Securities Act. Citigroup Global Markets Inc. Leerink Swann LLC acted as joint book-running managers of the offering and as representatives of the underwriters. JMP Securities LLC and Piper Jaffray & Co. acted as co-managers for the offering.

        The net proceeds to us, after deducting underwriting discounts of $6.8 million and offering expenses totaling $2.7 million, were approximately $86.8 million. No offering expenses were paid directly or indirectly to any of our directors or officers (or their associates) or persons owning 10.0% or more of any class of our equity securities or to any other affiliates.

        As of December 31, 2013, we had used approximately $10.3 million of the net proceeds from our initial public offering to fund operations, capital expenditures, working capital and other general corporate purposes. On March 12, 2014, the Company paid off the remaining principal outstanding under the Loan Agreement, the deferred fees and early repayment fees, totalling $17.8 million. None of the net proceeds have been paid directly or indirectly to any of our directors or officers (or their associates) or persons owning ten percent or more of any class of our equity securities or to any other affiliates. We are holding the remaining balance of the net proceeds from the offering in prime money market funds. There has been no material change in our planned use of the balance of the net proceeds from our initial public offering as described in our final prospectus filed with the SEC on September 19, 2013 pursuant to Rule 424(b) under the Securities Act.

Purchases of Equity Securities by the Issuer or Affiliated Purchasers

        There were no repurchases of shares of common stock made during the year ended December 31, 2013.

None.
Item 6.    Selected Financial Data.
Data

SELECTED FINANCIAL DATA

The information set forth below should be read in conjunction with the "Management's Discussion and Analysis of Financial Condition and Results of Operations" section and with our consolidated financial statements and notes thereto included elsewhere in this Annual Report on Form 10-K. The selected financial data in this section is not intended to replace the consolidated financial statements and are qualified in their entirety by the consolidated financial statements and related notes included elsewhere in this Annual Report on Form 10-K.


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The selected consolidated statements of operations and comprehensive (loss) income data for the years ended December 31, 2013, 20122015, 2014 and 20112013 and the consolidated balance sheet data as of December 31, 20132015 and 20122014 have been derived from our audited consolidated financial statements included elsewhere in this Annual Report on Form 10-K. We derived the selected consolidated financial data for the years ended December 31, 2012 and 2011 and as of December 31, 2013, 2012 and 2011 from audited financial statements which are not included in this Annual Report on Form 10-K.

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Historical results are not necessarily indicative of the results to be expected in future periods.

 
 Year Ended December 31, 
(in thousands, except per share data)
 2013 2012 2011 

Revenue:

          

Collaboration revenue:

          

License and milestone

 $43,948 $9,696 $74,406 

Cost-sharing, net

  13,282  5,558  4,760 

Contract manufacturing

      1,745 
        

Total revenue

  57,230  15,254  80,911 
        

Costs and expenses:

          

Research and development

  36,051  35,319  32,713 

General and administrative

  14,227  8,824  8,142 

Cost of contract manufacturing revenue

      1,500 
        

Total costs and expenses

  50,278  44,143  42,355 
        

Income (loss) from operations

  6,952  (28,889) 38,556 

Total other expense, net

  (28,850) (3,693) (2,290)
        

Net (loss) income

 $(21,898)$(32,582)$36,266 
        
        

Comprehensive (loss) income

 $(21,898)$(32,582)$36,266 
        
        

Net (loss) income per share applicable to common stockholders(1)

          

Basic

 $(4.15)$(24.84)$0.80 
        
        

Diluted

 $(4.15)$(24.84)$0.78 
        
        

Weighted-average number of common shares used in computing net (loss) income per share applicable to common stockholders

          

Basic

  9,407  2,401  2,328 

Diluted

  9,407  2,401  2,716 


 
 December 31, 
(in thousands)
 2013 2012 2011 

Balance Sheet Data:

          

Cash and cash equivalents

 $113,163 $39,611 $65,037 

Total assets

  123,732  49,212  73,789 

Total current liabilities

  18,162  38,802  23,853 

Long term deferred revenue

  5,620  6,760  33,350 

Long-term notes payable

  9,048  16,525   

Warrants to purchase redeemable convertible preferred stock

    1,422  1,046 

Warrants to purchase common stock

  30,753  5,229  3,347 

Redeemable convertible preferred stock

    268,610  241,549 

Total stockholder's equity (deficit)

  57,812  (290,973) (232,691)

 Year Ended December 31,
(in thousands, except per share data)2015 2014 2013 2012 2011
Consolidated Statements of Operations Data:         
Revenue:   
  
  
  
Collaboration revenue:   
  
  
  
License and milestone$1,184
 $1,673
 $43,948
 $9,696
 $74,406
Cost-sharing, net16,913
 12,959
 13,282
 5,558
 4,760
Contract manufacturing
 
 
 
 1,745
Total revenue18,097
 14,632
 57,230
 15,254
 80,911
Costs and expenses:   
  
  
  
Research and development58,404
 50,897
 36,051
 35,319
 32,713
Litigation Settlement
 5,000
 
 
 
General and administrative20,572
 14,199
 14,227
 8,824
 8,142
Cost of contract manufacturing revenue
 
 
 
 1,500
Total costs and expenses78,976
 70,096
 50,278
 44,143
 42,355
(Loss) income from operations(60,879) (55,464) 6,952
 (28,889) 38,556
Total other (expense) income, net(3,015) 4,205
 (28,850) (3,693) (2,290)
Net (loss) income$(63,894) $(51,259) $(21,898) $(32,582) $36,266
Net (loss) income per share applicable to common stockholders(1)   
  
  
  
Basic$(1.92) $(1.63) $(4.15) $(24.84) $0.80
Diluted$(1.92) $(1.63) $(4.15) $(24.84) $0.78
Weighted-average number of common shares used in computing net (loss) income per share applicable to common stockholders     
  
  
Basic33,303
 31,515
 9,407
 2,401
 2,328
Diluted33,303
 31,515
 9,407
 2,401
 2,716
(1)
See Note 2 within the notes to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K for a description of the method used to calculate basic and diluted net (loss) income per common share.


 As of December 31,
(in thousands)2015 2014 2013 2012 2011
Consolidated Balance Sheet Data:   
  
  
  
Cash and cash equivalents$27,783
 $176,460
 $113,163
 $39,611
 $65,037
Short and long-term investments108,198
 
 
 
 
Total assets146,337
 186,296
 123,732
 49,212
 73,789
Total current liabilities14,491
 9,253
 18,162
 38,802
 23,853
Long-term deferred revenue4,239
 4,816
 5,620
 6,760
 33,350
Long-term deferred rent1,157
 1,818
 2,337
 2,837
 3,335
Long-term notes payable
 
 9,048
 16,525
 
Warrants to purchase redeemable convertible preferred stock
 
 
 1,422
 1,046
Warrants to purchase common stock17,187
 14,124
 30,753
 5,229
 3,347
Redeemable convertible preferred stock
 
 
 268,610
 241,549
Total stockholder's equity (deficit)109,263
 156,285
 57,812
 (290,973) (232,691)



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(1)See Note 2 within the notes to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K for a description of the method used to calculate basic and diluted net (loss) income per common share.


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Item 7.    Management's Discussion and Analysis of Financial Condition and Results of Operations

The following discussion of our financial condition and results of operations should be read in conjunction with our consolidated financial statements and the notes to those consolidated financial statements included in Item 15 of this Annual Report on Form 10-K. This discussion contains forward-looking statements that involve significant risks and uncertainties. As a result of many factors, such as those set forth under "Risk Factors" and elsewhere in this Annual Report on Form 10-K, our actual results may differ materially from those anticipated in these forward-looking statements. Please also refer to the section under heading "Forward-Looking Statements."

Overview

We are a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases. Our research focusestherapeutic candidates that are based on the biology ofmechanisms that the Transforming Growth Factor-Beta (TGF-b) protein superfamily, a large and diverse group of molecules that are key regulators inhuman body uses to regulate the growth and repair of tissues throughoutits cells and tissues. Our research focuses on key natural regulators of cellular growth and repair, particularly the human body.Transforming Growth Factor-Beta, or TGF-beta, protein superfamily. We are leadersa leading company in understanding the biology of the TGF-b superfamilydiscovering and in targeting these pathways to develop important new medicines.developing therapeutic candidates that regulate cellular growth and repair. By couplingcombining our discovery and development expertise, including our proprietary knowledge of the TGF-bTGF-beta superfamily, withand our internal protein engineering and manufacturing capabilities, we have built a highly productive research &discovery and development platform that has generated innovative protein therapeutic candidates with novel mechanisms of action. These differentiated protein therapeutic candidates have the potential to significantly improve clinical outcomes for patients withacross many fields of medicine, and we have focused our discovery and development efforts on treatments for cancer and rare diseases.

We have threefour internally discovered protein therapeutic candidates that are currently being studied in numerous ongoing Phase 2 clinical trials, focused on cancertrials: luspatercept, sotatercept, dalantercept and rare diseases. Our two most advanced protein therapeutic candidates,ACE-083.
Luspatercept, our lead program, and sotatercept, and ACE-536,are partnered with Celgene Corporation, or Celgene. Luspatercept is designed to promote red blood cell production through a novel mechanism. Together with our collaboration partner, Celgene Corporation, which we refer to as Celgene,mechanism, and we are developing sotatercept and ACE-536luspatercept with Celgene to treat anemia and associated complications in patients withb-thalassemia and myelodysplastic syndromes (MDS), red blood cell disorders that are generally unresponsive to currently approved drugs. Our third and beta-thalassemia. In 2015, Celgene initiated two Phase 3 clinical stage protein therapeutic candidate, dalantercept, is designed to inhibit blood vessel formation through a mechanism that is distinct from,trials for luspatercept for the treatment of MDS and potentially synergistic with, the dominant class of cancer drugs that inhibit blood vessel formation, the vascular endothelial growth factor (VEGF) pathway inhibitors.beta-thalassemia. We are developing dalantercept primarily for use in combination with these successful products to produce better outcomes for cancer patients.

        Weand Celgene are developing sotatercept to treat patients with chronic kidney disease. Sotatercept has the potential to treat several complications of chronic kidney disease including mineral-bone disorder, vascular calcification and ACE-536 through our exclusive worldwide collaborations with Celgene. As of January 1, 2013,anemia. Celgene becameis responsible for paying 100% of worldwidethe development costs for both programs.all clinical trials for luspatercept and sotatercept, including our ongoing earlier stage clinical trials for these therapeutic candidates. We may receive up to an additional $560.0 million of potential development, regulatory and commercial milestone payments still outstanding and, if these protein therapeutic candidates are commercialized, we will receive a royalty on net sales in the low-to-mid 20% range. We also will co-promote luspatercept and sotatercept, and ACE-536if approved, in North America if approved, for which our commercialization costs will be entirely funded by Celgene.

We wholly own dalantercept and ACE-083, and we are independently developing these therapeutic candidates. We are currently evaluating dalantercept in a Phase 2 clinical trial for the treatment of patients with renal cell carcinoma. ACE-083 is designed for the treatment of focal muscle disorders, such as facioscapulohumeral dystrophy, and we are currently conducting a Phase 1 clinical trial with ACE-083 in healthy volunteers. In 2015, we reported data from the Phase 1 clinical trial of ACE-083 showing marked increases in the volume of muscles treated with ACE-083.
In addition to our clinical programs, we are conducting research to identify new therapeutic candidates to bring forward into clinical trials. To this end, in 2015 we implemented a new platform technology, IntelliTrap, that is accelerating our discovery efforts. We have not entered intonominated an IntelliTrap molecule, ACE-2494, as a partnershipcandidate for dalanterceptclinical development and retain worldwide rightswill initiate IND-enabling activities in 2016. ACE-2494 is designed to this program.

treat systemic muscle disorders.

As of December 31, 2013,2015, our operations have been funded primarily funded by $105.1 million in equity investments from venture investors, $86.8$219.3 million in net proceeds from our initial public offering, $49.2investors, $64.2 million in equity investments from our collaboration partners and $203.6$233.5 million in upfront payments, milestones, and net research and development payments from our strategiccollaboration partners.

We estimate that we have spent approximately $145.4 million on research and development for the three year period from 2013 through 2015.

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We expect to continue to incur significant expenses and increasing operating losses over at least the next several years. We expect our expenses will increase substantially in connection with our ongoing activities, as we:

We will not generate revenue from product sales unless and until we or a partner successfully complete development and obtain regulatory approval for one or more of our protein therapeutic candidates, which wecandidates. We expect that this will take a number of years and is subject to significant uncertainty. All current and future development and commercialization costs for sotatercept and ACE-536luspatercept are paid by Celgene. If we obtain regulatory approval for dalantercept, ACE-083 or any future protein therapeutic candidate, we expect to incur significant commercialization expenses related to product sales, marketing, manufacturing and distribution to the extent that such costs are not paid by future partners. We will seek to fund our operations through the sale of equity, debt financings or other sources, including potential additional collaborations. However, we may be unable to raise additional funds or enter into such other arrangements when needed on favorable terms, or at all. If we fail to raise capital or enter into such other arrangements as, and when, needed, we may have to significantly delay, scale back or discontinue the development or commercialization of one or more of our protein therapeutics.

therapeutic candidates.

Our ability to generate product revenue and become profitable depends upon our and our partners' ability to successfully commercialize products. We expect to incur losses for the foreseeable future, and we expect these losses to increase as we continue our development of, and seek regulatory approvals for, our protein therapeuticstherapeutic candidates and potentially begin to commercialize any approved products. For a description of the numerous risks and uncertainties associated with product development, see "Risk Factors".

Financial Operations Overview

Revenue

Collaboration Revenue

We have not generated any revenue from the sale of products. Our revenue to date has been predominantly derived from collaboration revenue, which includes license and milestone revenues and cost sharing revenue, generated through collaboration and license agreements with partners for the development and commercialization of our protein therapeutics.therapeutic candidates. Cost sharing revenue represents amounts reimbursed by our collaboration partners for expenses incurred by us for research and development activities and, potentially, co-promotion activities, under our collaboration agreements. Cost sharing revenue is recognized in the period that the related activities are performed. To the extent that we reimburse collaborators for costs incurred in connection with activities performed by them, we record these costs as a reduction of cost-sharing revenue.

        We have generated contract manufacturing revenue in the past but have no current contract manufacturing arrangements. Contract manufacturing revenue consists of revenue received for producing bulk drug substance for third parties other than our partners.


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Costs and Expenses

Research and development expenses consist primarily of costs directly incurred by us for the development of our protein therapeutic candidates, which include:

direct employee-related expenses, including salaries, benefits, travel and stock-based compensation expense of our research and development personnel;

expenses incurred under agreements with clinical research organizations, or CROs, and investigative sites that will conduct our clinical trials;

the cost of acquiring and manufacturing preclinical and clinical study materials and developing manufacturing processes;

allocated facilities, depreciation, and other expenses, which include rent and maintenance of facilities, insurance and other supplies;

expenses associated with obtaining and maintaining patents; and

costs associated with preclinical activities and regulatory compliance.


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Research and development costs are expensed as incurred. Costs for certain development activities are recognized based on an evaluation of the progress to completion of specific tasks using information and data provided to us by our vendors and our clinical sites.

We cannot determine with certainty the duration and completion costs of the current or future clinical trials of our protein therapeutic candidates or if, when, or to what extent we will generate revenues from the commercialization and sale of any of our protein therapeutic candidates for which we or any partner obtain regulatory approval. We or our partners may never succeed in achieving regulatory approval for any of our protein therapeutic candidates. The duration, costs and timing of clinical trials and development of our protein therapeutic candidates will depend on a variety of factors, including:

the scope, rate of progress, and expense of our ongoing, as well as any additional, clinical trials and other research and development activities;

future clinical trial results;

potential changes in government regulation; and

the timing and receipt of any regulatory approvals.

A change in the outcome of any of these variables with respect to the development of a protein therapeutic candidate could mean a significant change in the costs and timing associated with the development of that protein therapeutic candidate. For example, if the FDA, or another regulatory authority were to require us to conduct clinical trials beyond those that we currently anticipate will be required for the completion of the clinical development of protein therapeutics,therapeutic candidates, or if we experience significant delays in the enrollment in any clinical trials, we could be required to expend significant additional financial resources and time on the completion of clinical development.

From inception through December 31, 2013,2015, we have incurred $287.2$396.5 million in research and development expenses. We plan to increase our research and development expenses for the foreseeable future as we continue the development of our TGF-bTGF-beta platform protein therapeutics,therapeutic candidates, the discovery and development of preclinical protein therapeutics, including ACE-083,therapeutic candidates, and the development of sotatercept, ACE-536luspatercept, dalantercept and dalantercept. BeginningACE-083. As of January 1, 2013, expenses associated with sotatercept and ACE-536luspatercept are reimbursed 100% by Celgene. These reimbursements are recorded as revenue. Of the Phase 2 clinical trials that are underway for sotatercept, ACE-536luspatercept and dalantercept, we are expensing


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the costs of sixseven clinical trials of ACE-536luspatercept and dalantercept, of which the twofour for ACE-536luspatercept are reimbursed by Celgene.

We are also expensing the costs of a Phase 1 clinical trial for ACE-083.


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We manage certain activities such as clinical trial operations, manufacture of protein therapeutic candidates, and preclinical animal toxicology studies through third-party CROs. The only costs we track by each protein therapeutic candidate are external costs such as services provided to us by CROs, manufacturing of preclinical and clinical drug substance,product, and other outsourced research and development expenses. We do not assign or allocate to individual development programs internal costs such as salaries and benefits, facilities costs, lab supplies and the costs of preclinical research and studies. Our external research and development expenses for sotatercept, ACE-536,luspatercept, dalantercept, ACE-031 (for which development was suspended in April 2013) and ACE-083 (for which development commenced in the fourth quarter of 2013) during the years ended December 31, 2013, 20122015, 2014 and 2011,2013, are as follows:

 Year ended December 31,
(in thousands)2015 2014 2013
Sotatercept(1)$
 $
 $2
Luspatercept(1)9,744
 7,944
 5,081
Dalantercept8,864
 7,526
 4,636
ACE-0833,293
 5,111
 105
ACE-031(2)3
 8
 1,023
Total direct research and development expenses21,904
 20,589
 10,847
Other expenses(3)36,500
 30,308
 25,204
Total research and development expenses$58,404
 $50,897
 $36,051

 
 Year ended December 31, 
(in thousands)
 2013 2012 2011 

Sotatercept(1)

 $2 $6 $974 

ACE-536(1)

  5,081  2,885  681 

Dalantercept

  4,636  3,422  1,323 

ACE-083

  105     

ACE-031(2)

  1,023  3,453  4,240 
        

Total direct research and development expenses

  10,847  9,766  7,218 

Other expenses(3)

  25,204  25,553  25,495 
        

Total research and development expenses

 $36,051 $35,319 $32,713 
        
        


(1)As of January 1, 2013, expenses associated with sotatercept and luspatercept are reimbursed 100% by Celgene. These reimbursements are recorded as revenue and are presented as cost-sharing, net. In the periods presented, Celgene conducted most of the development activities for sotatercept, and we do not incur and are not reimbursed for expenses related to development activities directly conducted by Celgene.

(2)In April 2013, we and Shire AG, or Shire, determined not to further advance the development of ACE-031, and Shire terminated our collaboration agreement, effective as of June 30, 2013.
(1)
Beginning January 1, 2013, expenses associated with sotatercept and ACE-536 are reimbursed 100% by Celgene. These reimbursements are recorded as revenue and are presented as cost-sharing, net.

(2)
In April 2013, we and Shire AG, which we refer to as Shire, determined not to further advance the development of ACE-031, and Shire terminated our collaboration agreement, effective as of June 30, 2013.

(3)
Other expenses include unallocated employee and contractor-related expenses, facility expenses, lab supplies and miscellaneous expenses.

        Contract manufacturing expenses consist primarily of costs incurred for the production of bulk drug substance for third parties other than our partners. The costs generally include employee-related expenses including salary and benefits, direct materials and overhead costs including rent, depreciation, utilities, facility maintenance and insurance. We do not have any current contract manufacturing arrangements.

General and administrative expenses consist primarily of salaries and related costs for personnel, including stock-based compensation and travel expenses for our employees in executive, operational, finance and human resource functions and other general and administrative expenses including directors' fees and professional fees for accounting and legal services.

Since the completion of our initial public offering in September 2013, we have experienced increased expenses related to audit, legal, regulatory and tax-related services associated with maintaining compliance with exchange listing and Securities and Exchange Commission requirements,


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director and officer insurance premiums, and investor relations costs associated with being a public company. We anticipate that our general and administrative expenses will increase in the future as we increase our headcount to support our continued research and development and potential commercialization of our protein therapeutics.therapeutic candidates. Additionally, if and when we believe regulatory approval of a protein therapeutic candidate appears likely, to the extent that we are undertaking commercialization of such protein therapeutic candidate ourselves, we anticipate an increase in payroll and related expenses as a result of our preparation for commercial operations.

Other Expense, Net

Other expense, net consists primarily of interest expense from our previous venture debt facility, interest income earned on cash and cash equivalents, and the re-measurement gain or loss associated with the change in the fair value of our preferred stock and common stock warrant liabilities.

We use the Black-Scholes option pricing model to estimate the fair value of the warrants. We base the estimates in the Black-Scholes option pricing model, in part, on subjective assumptions, including stock price volatility, risk-free interest rate, dividend yield, and the fair value of the preferred stock or common stock underlying the warrants.


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Critical Accounting Policies and Significant Judgments and Estimates

Our management's discussion and analysis of our financial condition and results of operations are based on our consolidated financial statements, which have been prepared in accordance with U.S. generally accepted accounting principles. The preparation of these consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, and expenses and the disclosure of contingent assets and liabilities in our consolidated financial statements. On an ongoing basis, we evaluate our estimates and judgments, including those related to revenue recognition, accrued expenses and stock-based compensation. We also utilize significant estimates and assumptions in determining the fair value of our common stock and the fair value of our liability-classified warrants to purchase preferred stock and common stock. We base our estimates on historical experience, known trends and events, and various other factors that are believed to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.

While our significant accounting policies are described in more detail in the notes to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K, we believe the following accounting policies to be most critical to the judgments and estimates used in the preparation of our consolidated financial statements.

Revenue Recognition

We have primarily generated revenue through collaboration arrangements with strategic partners for the development and commercialization of our protein therapeutics.

therapeutic candidates.

We recognize revenue in accordance with Accounting Standards Codification (ASC) Topic 605,Revenue Recognition. Accordingly, revenue is recognized for each unit of accounting when all of the following criteria are met: (1) persuasive evidence of an arrangement exists; (2) delivery has occurred or services have been rendered; (3) the fee is fixed or determinable; and (4) collectability is reasonably assured.

Amounts received prior to satisfying the revenue recognition criteria are recorded as deferred revenue on our consolidated balance sheets. Amounts expected to be recognized as revenue within the 12 months following the balance sheet date are classified as deferred revenue, current portion and


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amounts not expected to be recognized as revenue within the 12 months following the balance sheet date are classified as deferred revenue, net of current portion.

Under collaboration agreements, we may receive payments for non-refundable up-front fees, milestone payments upon achieving significant development events, research and development reimbursements and royalties on future product sales. These payments are received in connection with the deliverables contained in the arrangements which may include (1) licenses, or options to obtain licenses, to our technology, (2) research and development activities performed for the collaboration partner, (3) participation on joint committees and (4) manufacturing clinical or preclinical material.

Effective January 1, 2011, we adopted Accounting Standards Update (ASU) No. 2009-13,Multiple-Deliverable Revenue Arrangements, which amends ASC Topic 605-25,Revenue Recognition—Multiple Element Arrangements. This guidance applies to new arrangements as well as existing agreements that are significantly modified after January 1, 2011.

The application of the multiple element guidance requires subjective determinations, and requires management to make judgments about the individual deliverables, and whether such deliverables are separable from the other aspects of the contractual relationship. Deliverables are considered separate units of accounting provided that: (1) the delivered item(s) has value to the customer on a stand-alone basis and (2) if the arrangement includes a general right of return relative to the delivered item(s), delivery or performance of the undelivered item(s) is considered probable and substantially in our control. In determining the units of accounting, management evaluates certain criteria, including whether the deliverables have stand-alone value, based on the consideration of the relevant facts and circumstances for each arrangement, such as the research, manufacturing and commercialization capabilities of the collaboration partner and the availability of the associated expertise in the general marketplace. In addition, we consider whether the collaboration partner can use the other deliverable(s) for their intended purpose without the receipt of the remaining element(s), whether the value of the deliverable is dependent on the undelivered item(s), and whether there are other vendors that can provide the undelivered element(s).

Arrangement consideration that is fixed or determinable is allocated among the separate units of accounting using the relative selling price method, and the applicable revenue recognition criteria, as described above, are applied to each of the separate units of accounting in determining the appropriate period or pattern of recognition. We determine the estimated selling price for deliverables within each agreement using vendor-specific objective evidence (VSOE) of selling price, if available, third-party evidence (TPE) of selling price if VSOE is not available, or management's best estimate of selling price (BESP) if neither VSOE nor TPE is available. Subsequent to the adoption of ASU 2009-13, we typically use BESP to estimate the selling price of the deliverables. Determining the BESP for a unit of accounting requires significant judgment. In developing the BESP

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for a unit of accounting, we consider applicable market conditions and relevant entity-specific factors, including factors that were contemplated in negotiating the agreement with the customer and estimated costs. We validate the BESP for units of accounting by evaluating whether changes in the key assumptions used to determine the BESP will have a significant effect on the allocation of arrangement consideration between multiple units of accounting.

Our agreements may contain options which provide the collaboration partner the right to obtain additional licenses. Options are considered substantive if, at the inception of the arrangement, we are at risk as to whether the collaboration partner will choose to exercise the option. Factors that we consider in evaluating whether an option is substantive include the overall objective of the arrangement, the benefit the collaborator might obtain from the arrangement without exercising the option, the cost to exercise the option and the likelihood that the option will be exercised. For arrangements under which an option is considered substantive, we do not consider the item underlying the option to be a deliverable at the inception of the arrangement and the associated option fees are not included in allocable arrangement consideration, assuming the option is not priced at a significant


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and incremental discount. Conversely, for arrangements under which an option is not considered substantive or if an option is priced at a significant and incremental discount, we would consider the item underlying the option to be a deliverable at the inception of the arrangement and a corresponding amount would be included in allocable arrangement consideration.

We typically receive up-front, non-refundable payments when licensing our intellectual property in conjunction with a research and development agreement. When we believe the license to our intellectual property has stand-alone value, we generally recognize revenue attributed to the license upon delivery. When we believe the license to our intellectual property does not have stand-alone value from the other deliverables to be provided in the arrangement, we generally recognize revenue attributed to the license on a straight-line basis over our contractual or estimated performance period, which is typically the term of our research and development or manufacturing obligations. We continually evaluate these periods, and will adjust the period of revenue recognition if circumstances change.

Research and development funding is recognized as revenue in the period that the related services are performed. When we act as the principal under our collaboration arrangements, we record payments received for the reimbursement of research and development costs as cost-sharing revenue. To the extent that we reimburse the collaborator for costs incurred, we record these costs as a reduction of cost-sharing revenue.

We periodically review the basis for our estimates, and we may change the estimates if circumstances change. These changes can significantly increase or decrease the amount of revenue recognized. As we apply our policy to our collaboration arrangements we make judgments which affected the pattern of revenue recognition. For instance, in our arrangement with Celgene, we are obligated to provide research and development services. We are recognizing revenue related to these research and development services over the estimated period of our performance, which was initially estimated to end in December 2014. The Company re-assessed the duration of its deliverables under the collaboration agreement and now estimates the new term to end in the first quarter of 2015,2016, the expected completion date of the proof-of-concept trials for ACE-536luspatercept under the Celgene collaboration. Another instance relates to our arrangement with Shire AG, where in April 2013, we and Shire determined not to further advance the development of ACE-031 or back-up compounds and Shire terminated our collaboration agreement effective as of June 30, 2013.

In addition to up-front payments and research and development funding, we may also be entitled to milestone payments that are contingent upon achievement of a predefined objective. At the inception of each arrangement that includes milestone payments, we evaluate whether the milestone is substantive and at-risk. This evaluation includes an assessment of whether (1) the consideration is commensurate with either the entity's performance to achieve the milestone, or the enhancement of the value of the delivered item(s) as a result of a specific outcome resulting at least in part from the entity's performance to achieve the milestone, (2) the consideration relates solely to past performance, and (3) the consideration is reasonable relative to all of the deliverables and payment terms within the arrangement. We evaluate factors such as the scientific, regulatory, commercial and other risks that must be overcome to achieve the respective milestone, the level of effort and investment required to achieve the respective milestone, and whether the milestone consideration is reasonable relative to all deliverables and payment terms in the arrangement in making this assessment. On the milestone achievement date, assuming all other revenue recognition criteria are met and the milestone is deemed substantive and at-risk, we recognize the payment as license and milestone revenue. For milestones that are not deemed substantive and at-risk, where payment is reasonably assured, we recognize the milestone payment over the remaining service period.

Sales and commercial milestones and royalties will be recognized when and if earned, provided collectability is reasonably assured.


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Clinical Trial Accruals and Related Expenses


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We accrue and expense costs for clinical trial activities performed by third parties, including CROs and clinical investigators, based upon estimates made as of the reporting date of the work completed over the life of the individual study in accordance with agreements established with CROs and clinical trial sites. Some CROs invoice us on a monthly basis, while others invoice upon achievement of milestones and the expense is recorded as services are rendered. We determine the estimates of clinical activities incurred at the end of each reporting period through discussion with internal personnel and outside service providers as to the progress or stage of completion of trials or services, as of the end of each reporting period, pursuant to contracts with numerous clinical trial centers and CROs and the agreed upon fee to be paid for such services. The significant factors considered in estimating accruals include the number of patients enrolled and the percentage of work completed to date. Costs of setting up clinical trial sites for participation in the trials that are paid for in advance are expensed over the estimated set-up period. While the set-up periods vary from one arrangement to another, such set-up periods generally take approximately three months. Set-up activities include clinical site identification, institutional review board, or IRB, submissions, regulatory submissions, clinical investigator kick-off meetings and pre-study site visits. Clinical trial site costs related to patient enrollments are accrued as patients are entered into the trial.

Stock-Based Compensation

We account for our stock-based awards in accordance with ASC Topic 718,Compensation—Stock Compensation, or ASC 718, which requires all stock-based payments to employees, including grants of employee stock options, and modifications to existing stock options, and restricted stock unit awards, to be recognized in the statements of operations and comprehensive income (loss) based on their fair values. We recognize the compensation cost of awards subject to service-based vesting conditions over the requisite service period, which is generally equal to the vesting term. For awards subject to both performance and service-based vesting conditions, we recognize compensation cost using an accelerated recognition method when it is probable that the performance condition will be achieved. If achievement of the performance condition is not probable, but the award will vest based on the service condition, we recognize the expense over the requisite service period. We account for stock-based awards to non-employees using the fair value method. Stock options granted to non-employees are subject to periodic revaluation over their vesting terms and stock-based compensation cost is recognized using an accelerated recognition method.

We estimate the fair value of our stock-based awards to employees and non-employees using the Black-Scholes option pricing model, which requires the input of highly subjective assumptions, including (1) the expected volatility of our stock, (2) the expected term of the award, (3) the risk-free interest rate and (4) expected dividends. Due to the lack of a public market for our common stock prior to the completion of our initial public offering in September 2013, and resulting lack of company-specific historical and implied volatility data, we have based our estimate of expected volatility on the historical volatility of a group of similar companies that are publicly traded. For these analyses, we have selected companies with characteristics that we believe are comparable to ours, including enterprise value, risk profiles, position within the industry, and with historical share price information sufficient to meet the expected life of the stock-based awards. We compute the historical volatility data using the daily closing prices for the selected companies' shares during the equivalent period as the calculated expected term of our stock-based awards. We will continueDuring 2015 we began to apply this process untilestimate our volatility by using a sufficient amountblend of our stock price history, for the length of time we have market data for our stock and the historical information regarding the volatility of our own stock price becomes available.similar public companies for the expected term of each grant. We have estimated the expected life of our employee stock options using the "simplified" method, whereby, the expected life equals the average of the vesting term and the original contractual term of the option. The risk-free interest rates for periods within the expected life of the option are based on the U.S. Treasury yield curve in effect during the period the options were granted.


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We also estimate forfeitures at the time of grant, and revise those estimates in subsequent periods if actual forfeitures differ from estimates. We use historical data to estimate pre-vesting option forfeitures to the extent that actual forfeitures differ from our estimates, the difference is recorded as a cumulative adjustment in the period the estimates were revised. Stock-based compensation expense recognized in the consolidated financial statements is based on awards that are ultimately expected to vest. For the years ended December 31, 2015, 2014 and 2013, 2012 and 2011, we used arespectively, the Company applied an estimated forfeiture rate of approximately 4%, 5% and 5%, respectively.

.

Stock-based compensation totaled approximately $2.2$12.1 million, $1.2$4.8 million and $1.4$2.2 million for the years ended December 31, 2015, 2014 and 2013, 2012 and 2011, respectively. As of December 31, 2013, we had $10.1 million of unrecognized compensation expense, net of related forfeiture estimates, which is expected to be recognized over a weighted-average remaining vesting period of approximately 2.66 years. We expect the impact of our stock-based compensation expense for stock-based awards granted to employees and non-employees to grow in future periods due to the potential increases in the value of our common stock and headcount.


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Warrants to Purchase Preferred Stock and Common Stock

As of December 31, 2013,2015, we had warrants outstanding to purchase 979,699398,011 shares of common stock, of which warrants to purchase 857,586392,805 shares of our common stock contain a provision requiring an adjustment to the number of shares in the event we issue common stock, or securities convertible into or exercisable for common stock, at a price per share lower than the warrant exercise price. The anti-dilution feature requires the warrants to be classified as liabilities and measured at fair value, with changes in fair value recognized as a component of other income (expense). The fair value of the warrants to purchase common stock on the date of issuance and on each re-measurement date for those warrants to purchase common stock are classified as liabilities and arewas estimated using either the Monte Carlo simulation framework, up until September 30, 2013, which incorporated threeincorporates future financing events over the remaining life of the warrants to purchase common stock. Duestock, or for certain re-measurement dates including December 31, 2015, 2014 and 2013, due to the warrants being deeply in the money, as of December 31, 2013, the valuation method to estimate the warrants to purchase common stock was changed to the Black-Scholes option pricing model.model was used. At each reporting period the company evaluates the best valuation methodology. Any modifications to the warrant liabilities are recorded in earnings during the period of the modification. The significant assumptions used in estimating the fair value of our warrant liabilities include the exercise price, volatility of the stock underlying the warrant, risk-free interest rate, estimated fair value of the stock underlying the warrant, and the estimated life of the warrant. The common stock warrant liability was $17.2 million, $14.1 million and $30.8 millions and $5.2 millionsmillion as of December 31, 2015, 2014 and 2013, and 2012, respectively. The remeasurementAt the end of each reporting period, the Company remeasured the fair value of the outstanding warrants, using current assumptions, resultedresulting in an increase (decrease) in fair value of $26.9$3.5 million, $1.9$(5.0) million and $0.3$26.9 million, respectively, which was recorded in other expenseincome (expense), net in the accompanying consolidated statements of operations and comprehensive (loss) incomeloss for the years ended December 31, 2013, 20122015, 2014 and 2011 respectively.2013. The changes in value of the warrant liability were primarily due to increasesfluctuations in the estimated value during 2011 and 2012 and in market price during 2013, of our common stock.

Additionally, prior to the completion of our initial public offering in September 2013, we had warrants outstanding to purchase shares of Series B, Series C-1 and Series D-1 preferred stock. Freestanding warrants that are related to the purchase of redeemable preferred stock were classified as liabilities and recorded at fair value regardless of the timing of the redemption feature or the redemption price or the likelihood of redemption. The warrants were subject to re-measurement at each balance sheet date and any change in fair value was recognized as a component of other income (expense), net. We measured the fair value of our warrants to purchase preferred stock using a Black-Scholes option pricing model. In connection with the closing of our initial public offering on September 24, 2013, the outstanding warrants to purchase Series B Preferred Stock, Series C-1 Preferred Stock, and Series D-1 Preferred Stock were converted into warrants to purchase common


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stock and are now classified as a component of equity and are no longer subject to remeasurement. The exercise prices for each of these warrants remained unchanged.

Emerging Growth Company Status

        The Jumpstart our Business Startups Act of 2012, or the JOBS Act, permits an "emerging growth company" such as us to take advantage of an extended transition period to comply with new or revised accounting standards applicable to public companies. We are choosing to "opt out" of this provision and, as a result, we will comply with new or revised accounting standards as required when they are adopted. This decision to opt out of the extended transition period under the JOBS Act is irrevocable.

Results of Operations

Comparison of the Years Ended December 31, 20132015 and 2012

2014


 Year Ended
December 31,
  
 Year Ended
December 31,
  

 Increase
(Decrease)
 Increase
(Decrease)
(in thousands)
 2013 2012 2015 2014 

Revenue:

        
  
  

Collaboration revenue:

        
  
  

License and milestone

 $43,948 $9,696 $34,252 $1,184
 $1,673
 $(489)

Cost-sharing, net

 13,282 5,558 7,724 16,913
 12,959
 3,954
       

Total revenue

 57,230 15,254 41,976 18,097
 14,632
 3,465
       

Costs and expenses:

            

Research and development

 36,051 35,319 732 58,404
 50,897
 7,507
Litigation settlement
 5,000
 (5,000)

General and administrative

 14,227 8,824 5,403 20,572
 14,199
 6,373
       

Total costs and expenses

 50,278 44,143 6,135 78,976
 70,096
 8,880
       

Income (loss) from operations

 6,952 (28,889) 35,841 

Other expense, net

 (28,850) (3,693) (25,157)
       
(Loss) income from operations(60,879) (55,464) (5,415)
Other (expense) income, net(3,015) 4,205
 (7,220)

Net loss

 $(21,898)$(32,582)$10,684 $(63,894) $(51,259) $(12,635)
       
       


Revenue.    We recognized revenue of $57.2$18.1 million in the year ended December 31, 2013,2015, compared to $15.3$14.6 million in year ended December 31, 2012. The $42.02014. All of the revenue in both periods was derived from the Celgene agreements. This $3.5 million

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increase was primarily due to higher cost sharing revenue of $4.0 million caused by higher expenses for luspatercept clinical trials and manufacturing bulk drug substance during 2015, offset by a decrease in Celgene deferred revenue of $0.5 million during 2015 as we complete our deliverables under the collaboration agreement.
Research and Development Expenses.    Research and development expenses were $58.4 million in the year ended December 31, 2015, compared to $50.9 million in the year ended December 31, 2014. This $7.5 million increase was primarily due to increases in personnel expenses of $3.2 million, including an increase of $2.8 million in stock compensation expense, an increase in clinical and toxicology expenses totaling $1.3 million and an increase of $2.5 million in miscellaneous expenses primarily for drug supply and outsourced research.
Litigation Settlement. Litigation settlements in the $10.0year ended December 31, 2015 were zero compared to $5.0 million in the same period in 2014. This decrease was due to the settlement of litigation with the Salk Institute in July 2014.
General and Administrative Expenses.    General and administrative expenses were $20.6 million in the year ended December 31, 2015, compared to $14.2 million in the year ended December 31, 2014. The $6.4 million increase was primarily due to an increase in personnel expenses, including an increase in stock compensation expense of $4.5 million.
Other (Expense) Income, Net.    Other expense, net was $3.0 million in the year ended December 31, 2015, compared to $4.2 million of income in the year ended December 31, 2014. This $7.2 million increase was primarily due to an $8.6 million increase in the effect of marking the common stock warrant liability to market in each period, offset by a $0.9 million decrease in interest expense from retiring the outstanding long term debt in March 2014 and an increase in interest income of $0.4 million.
Comparison of the Years Ended December 31, 2014 and 2013
 
Year Ended
December 31,
  
 
Increase
(Decrease)
(in thousands)2014 2013 
Revenue: 
  
  
Collaboration revenue: 
  
  
License and milestone$1,673
 $43,948
 $(42,275)
Cost-sharing, net12,959
 13,282
 (323)
Total revenue14,632
 57,230
 (42,598)
Costs and expenses:   
  
Research and development50,897
 36,051
 14,846
Litigation settlement5,000
 
 5,000
General and administrative14,199
 14,227
 (28)
Total costs and expenses70,096
 50,278
 19,818
(Loss) income from operations(55,464) 6,952
 (62,416)
Other income (expense), net4,205
 (28,850) 33,055
Net loss$(51,259) $(21,898) $(29,361)

Revenue.    We recognized revenue of $14.6 million in the year ended December 31, 2014, compared to $57.2 million in year ended December 31, 2013. The $42.6 million decrease was primarily due to the $17.0 million in milestone paymentpayments received during 2013 in connection with our Celgene collaboration for the first patient dosed in a Phase 2 trial in ACE-536, $7.0 million milestone payment received in connection with our Celgene collaboration forluspatercept and initiation of a phasePhase 2b study of sotatercept in end-stage renal disease patients, and recognizing an additional $16.7$24.3 million of deferred revenue becauserelated to Shire. Shire ended our collaboration as of June 30, 2013. The remaining increase of $8.32013 and there is no Shire related revenue during 2014. Celgene deferred revenue also decreased $1.0 million was primarilyduring 2014 as we complete our deliverables under the collaboration agreement. Net cost sharing revenue decreased $0.3 million due to an increase in net cost-sharingCelgene cost sharing revenue from Celgene of $9.8$0.3 million due to Celgene assuming 100% of the costs of development for these protein therapeutic candidates as of January 1, 2013, and recognition of $0.6 million deferred revenue from Celgene, offset by a $0.6 million decrease in net cost-sharing revenue from Shire of $2.1 million due to the end of the collaboration as of June 30, 2013.Shire.



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The following table shows revenue from all sources for the years presented.


 Year Ended
December 31,
  
 Year Ended
December 31,
  

 Increase
(Decrease)
 Increase
(Decrease)
(in thousands)
 2013 2012 2014 2013 

Collaboration revenue:

        
  
  

Celgene:

        
  
  

License and milestone

 $19,626 $2,035 $17,591 $1,673
 $19,626
 $(17,953)

Cost-sharing, net

 12,658 2,879 9,779 12,959
 12,658
 301
       

Total Celgene

 32,284 4,914 27,370 14,632
 32,284
 (17,652)

Shire:

          
 

License and milestone

 24,322 7,661 16,661 
 24,322
 (24,322)

Cost-sharing, net

 624 2,679 (2,055)
 624
 (624)
       

Total Shire

 24,946 10,340 14,606 
 24,946
 (24,946)
       

Total collaboration revenue

 57,230 15,254 41,976 14,632
 57,230
 (42,598)
       

Total revenue

 $57,230 $15,254 $41,976 $14,632
 $57,230
 $(42,598)
       
       

Research and Development Expenses.    Research and development expenses were $50.9 million in the year ended December 31, 2014, compared to $36.1 million in the year ended December 31, 2013, compared to $35.3 million in the year ended December 31, 2012.2013. This $0.7$14.8 million increase was primarily due to an increase in expenses associated with clinical activity totaling $3.1$9.6 million, an increase inhigher personnel related expenses associated with clinical drug supplyof $3.9 million, higher legal expenses of $1.0 million higher spend for in-licensing of $0.3 million, higher compensation related expense of $0.3 million, and a $0.7 million increase in miscellaneous research and development expenses primarily due to an antibody collaboration agreement, executed in 2014, offset by a reduction of $0.5 million because of a royalty owedpayment due to the Salk Institute for a milestone achieved during 2013.
Litigation Settlement. Litigation settlements in the year ended December 31, 2014 were $5.0 million compared to zero in the same period in 2013. This increase was due to the settlement of $0.5 million, partially offset by a reductionlitigation with the Salk Institute in preclinical animal studies totaling $3.0 million, legal spend for patent related matters of $0.8 million, and depreciation of $0.4 million.July 2014.

General and Administrative Expenses.    General and administrative expenses were $14.2 million in the year ended December 31, 2013,2014, compared to $8.8$14.2 million in the year ended December 31, 2012. This $5.42013. During 2014, increases of $0.7 million increase was primarilyfor higher personnel related expenses and $2.0 million related to higher professional fees and insurance were primarily offset by a decrease of $2.8 million for legal services in connection with our litigation withexpenses due to the Salk Institute and for increased professional fees and financial consulting services in connection with business development activities totaling $3.3 million, $0.2 million for higher insurance expenses, and higher total compensation expenses totaling $1.8 million.settlement of ongoing litigation.

Other Expense,Income (Expense), Net.    Other expense,income, net was $4.2 million in the year ended December 31, 2014, compared to expense of $28.9 million in the year ended December 31, 2013, compared to $3.7 million in the year ended December 31, 2012.2013. This $25.2$33.1 million increase was primarily due to highera $30.7 million difference in the effect of marking the common stock warrant liability to market in each period. The additional increase was a $1.2 million decrease in interest expense associated withbecause the increase in fair value of the liability for warrants of $24.5 millionoutstanding long term debt was retired during March 2014 and an increase in interest expense of $0.6 million due to a higher average outstanding debt balance in the year ended December 31, 2013.


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Comparison of Years Ended December 31, 2012 and 2011

 
 Year Ended
December 31,
  
 
 
 Increase
(Decrease)
 
(in thousands)
 2012 2011 

Revenue:

          

Collaboration revenue:

          

License and milestone

 $9,696 $74,406 $(64,710)

Cost-sharing, net

  5,558  4,760  798 

Contract manufacturing

    1,745  (1,745)
        

Total revenue

  15,254  80,911  (65,657)
        

Costs and operating expenses:

          

Research and development

  35,319  32,713  2,606 

General and administrative

  8,824  8,142  682 

Cost of contract manufacturing revenue

    1,500  (1,500)
        

Total costs and expenses

  44,143  42,355  1,788 
        

Income (loss) from operations

  (28,889) 38,556  (67,445)

Other expense, net

  (3,693) (2,290) (1,403)
        

Net (loss) income

 $(32,582)$36,266 $(68,848)
        
        

        Revenue.    We recognized revenue of $15.3$1.3 million for the year ended December 31, 2012, compared to $80.9 million for the year ended December 31, 2011. The $65.6 million decrease in revenue in 2012 was primarily due to a decreaseeffect of $64.7 million in license and milestone revenue, because during 2011, upon signing the ACE-536 Celgene collaboration and amending the sotatercept agreement, we recognized upfront payments and deferred revenue totaling $54.8 million. During 2011, we also recognized the remaining $2.4 million of deferred revenue from the Alkermes collaboration. Also, in 2012 we did not recognize any milestone payments compared to $7.0 million during 2011. The decrease in license and milestone revenue was offset by higher 2012 cost-sharing revenue due primarily to lower reimbursements paid to Shire for ACE-031. We also recognized $1.7 million for a contract manufacturing project during 2011.


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        The following table shows revenue from all sources for the periods presented.

 
 Year Ended
December 31,
  
 
 
 Increase (Decrease) 
(in thousands)
 2012 2011 

Collaboration revenue:

          

Celgene:

          

License and milestone

 $2,035 $63,607 $(61,572)

Cost-sharing, net

  2,879  (121) 3,000 
        

Total Celgene

  4,914  63,486  (58,572)

Shire:

          

License and milestone

  7,661  8,392  (731)

Cost-sharing, net

  2,679  4,148  (1,469)
        

Total Shire

  10,340  12,540  (2,200)

Alkermes:

          

License and milestone

    2,407  (2,407)

Cost-sharing, net

    733  (733)
        

Total Alkermes

    3,140  (3,140)
        

Total collaboration revenue

  15,254  79,166  (63,912)

Contract manufacturing revenue

    1,745  (1,745)
        

Total revenue

 $15,254 $80,911 $(65,657)
        
        

        Research and Development Expenses.    Research and development expenses were $35.3 million in the year ended December 31, 2012, compared to $32.7 million for the year ended December 31, 2011. This $2.6 million increase was primarily due to increases in expenses related to preclinical animal toxicology studies of $2.6 million, patent-related legal services of $0.9 million, external testing of $0.6 million, clinical trial activities of $0.5 million, contract labor of $0.5 million, outsourced research of $0.3 million and management bonuses of $0.3 million partially offset by decreases in expenses related to depreciation of $1.3 million, contract manufacturing of $0.7 million, supplies of $0.4 million, and in-licensing of $0.5 million.

        General and Administrative Expenses.    General and administrative expenses were $8.8 million in the year ended December 31, 2012, compared to $8.1 million for the year ended December 31, 2011. This $0.7 million increase was primarily related to higher professional fees for legal costs of $0.4 million in connection with litigation activities and higher compensation costs of $0.3 million.

        Cost of Contract Manufacturing Revenue.    There was no cost of contract manufacturing revenue for the year ended December 31, 2012, compared to $1.5 million for the year ended December 31, 2011. This decrease was due to there being no contract manufacturing services provided during 2012.

        Other Expense, Net.    Other expense, net was $3.7 million in the year ended December 31, 2012, compared to $2.3 million for the year ended December 31, 2011. The increase was primarily due to a $1.8 million increase in fair value of the liability formarking preferred stock warrants to purchase redeemable convertible preferred stock and common stock.market prior to their conversion during the initial public offering.

Liquidity and Capital Resources

We have incurred losses and cumulative negative cash flows from operations since our inception in June 2003, and as of December 31, 2013,2015, we had an accumulated deficit of $192.3$307.5 million. We anticipate that we will continue to incur losses for at least the next several years. We expect that our research and development and general and administrative expenses will continue to increase and, as a result, we will need additional capital to fund our operations, which we may raise through a combination of the sale of equity, debt financings or other sources, including potential additional collaborations.


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As of December 31, 2013,2015, our operations have been primarily funded by $105.1 million in equity investments from venture investors $49.2prior to the IPO, $219.3 million from public investors, $64.2 million in equity investments from our partners and $203.6$233.5 million in upfront payments, milestones, and net research and development payments from our collaboration partners.

        In

On September 24, 2013, we completed the sale of 6,417,000 shares of our common stock, including 837,000 shares of common stock sold pursuant to the underwriters' full exercise of their option to purchase additional shares at a public offering price of $15.00 per share, resulting in net proceeds to us of $86.8 million, after deducting underwriting discounts and offering expenses. Also in September 2013, we completed a private placement of $10.0 million of our common stock at a price of $15.00 per share.

        As


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Table of December 31, 2013, we had $113.2 million in cash and cash equivalents. Cash in excess of immediate requirements is invested in accordance with our investment policy, primarily with a view to liquidity and capital preservation. Currently, our funds are held in money market mutual funds consisting of U.S. government-backed securities.

        We entered into a new venture debt facility on June 7, 2012 and, as of December 31, 2013 we had $16.9 million in venture debt outstanding. After an interest-only period, we began paying down principal on the debt facility in July 2013. Interest accrues at a rate of 8.5% per annum and is payable monthly. The debt facility also included a closing fee of $0.2 million and is also subject to an additional deferred payment of $1.2 million which is due at the time of the final payment. We are amortizing the cost over the 42 months of the loan resulting in an effective interest rate of approximately 11.8%. The debt facility is secured by a lien on all of our property as of, or acquired after, June 7, 2012, except for intellectual property. On December 30, 2013, in conjunction with the establishment of the Company's wholly owned subsidiary, Acceleron Security Corporation Inc., the Loan Agreement was modified to add a debt covenant that requires the Company to maintain a cash balance equal to 150% of the outstanding principal debt balance in a separate bank account, at all times. That bank account can be subject to the lender's exclusive control in the event of a default. As of December 31, 2013 and 2012, there have been no events of default under the loan and the Company was in compliance with all financial and nonfinancial covenants at December 31, 2013. The debt facility matures in December 2015.

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On January 28, 2014, we completed the sale of 2,760,000 shares of our common stock, including 360,000 shares of common stock sold pursuant to the underwriters' full exercise of their option to purchase additional shares at a public offering price of $50.00 per share, resulting in net proceeds to us of $129.0$129.2 million, after deducting underwriting discounts and offering expenses.

On January 11, 2016, we completed the sale of 3,750,000 shares of our common stock, at a public offering price of $40.00 per share, resulting in net proceeds to us of approximately $140.4 million, after deducting underwriting discounts and offering expenses.
We entered into a new venture debt facility on June 7, 2012 and, as of December 31, 2013 we had $16.9 million in venture debt outstanding. After an interest-only period, we began paying down principal on the debt facility in July 2013. Interest accrued at a rate of 8.5% per annum and was payable monthly. The debt facility also included a closing fee of $0.2 million and was also subject to an additional deferred payment of $1.2 million which is due at the time of the final payment. We were amortizing the cost over the 42 months of the loan resulting in an effective interest rate of approximately 11.8%. The debt facility was paid off in March 2014.
As of December 31, 2015, we had $136.0 million in cash, cash equivalents and investments. Cash in excess of immediate requirements is invested in accordance with our investment policy, primarily with a view to liquidity and capital preservation. Currently, our funds are held in bank deposits and money market mutual funds consisting of U.S. government-backed securities.
Cash Flows

The following table sets forth the primary sources and uses of cash for each of the years set forth below:

 
 Year Ended December 31, 
(in thousands)
 2013 2012 2011 

Net cash provided by (used in):

          

Operating activities

 $(19,650)$(38,884)$9,056 

Investing activities

  (307) (441) (27)

Financing activities

  93,509  13,899  21,092 
        

Net increase (decrease) in cash and cash equivalents

 $73,552 $(25,426)$30,121 
        
        
 Year Ended December 31,
(in thousands)2015 2014 2013
Net cash (used in) provided by:   

 
Operating activities$(44,211) $(53,220)
$(19,650)
Investing activities(108,971) (514)
(307)
Financing activities4,505
 117,031

93,509
Net (decrease) increase in cash and cash equivalents$(148,677) $63,297

$73,552

Operating Activities.    The significant decrease in net
Net cash used in operating activities was $44.2 million for the year ended December 31, 2013, compared to the year ended December 31, 2012, is2015, and consisted primarily of a net loss of $63.9 million adjusted for non-cash items including an increase in fair value of warrants of $3.5 million, stock-based compensation expense of $12.1 million, depreciation and amortization of $1.2 million, and a net increase due to the receiptchanges in operating assets and liabilities of a $10.0 million milestone payment from Celgene$3.3 million. The significant items in the first quarterchange in operating assets and liabilities include a decrease in deferred revenue of 2013,$1.2 million for the Celgene Collaboration. Other components of the change in operating assets and $7.0liabilities include a decrease in deferred rent of $0.5 million in the fourth quarter, and an increase in proceeds from cost-sharing revenue, net. The significant decrease


Tableaccrued expenses of Contents

in$5.0 million.

Net cash provided byused in operating activities was $53.2 million for the year ended December 31, 2012, compared to the year ended December 31, 2011, is2014, and consisted primarily of a net loss of $51.3 million adjusted for non-cash items including a decrease in fair value of warrants of $5.0 million, stock-based compensation expense of $4.8 million, depreciation and amortization of $1.1 million, payments of deferred interest of $0.5 million, and a net decrease due to changes in operating assets and liabilities of $2.3 million. The significant items in the upfrontchange in operating assets and milestone paymentsliabilities include a decrease in deferred revenue of $32.5$1.7 million related tofor the ACE-536 Agreement received during 2011.

Celgene Collaboration. Other components of the change in operating assets and liabilities include a decrease in collaboration receivables of $0.2 million, a decrease in deferred rent of $0.5 million, a decrease in accounts payable of $0.2 million, and an increase in prepaid and other current assets of $0.3 million.

Net cash used in operating activities was $19.6 million for the year ended December 31, 2013, and consisted primarily of a net loss of $21.9 million adjusted for non-cash items including an increase in fair value of warrants of $26.9 million, stock-based compensation expense of $2.2 million, depreciation and amortization of $0.9 million, forgiveness of the related party receivable of $0.2 million, accretion of deferred interest of $0.3 million, and amortization of deferred debt issuance costs of $0.2 million, and a net decrease due to changes in operating assets and liabilities of $28.5 million. The significant items in the change in operating assets and liabilities include a decrease in deferred revenue of $26.9 million due primarily to the recognition of $24.3 million of deferred revenue for the Shire collaboration agreement, which was terminated effective June 30, 2013. Other components of the change in operating assets and liabilities include an increase in accrued expenses of $0.7

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$0.7 million, an increase in collaboration receivables of $0.8 million, an increase in prepaid expenses of $0.8 million, a decrease in deferred rent of $0.5 million and a decrease in accounts payable of $0.1 million.

Investing Activities.
Net cash used in operatinginvesting activities was $38.9$109.0 million, $0.5 million and $0.3 million for the years ended December 31, 2015, 2014 and 2013, respectively. The significant increase during 2015 was due to the purchase of investments. During 2014 and 2013 cash used in investing activities consisted of purchases of property and equipment.
Financing Activities.
Net cash provided by financing activities was $4.5 million for the year ended December 31, 20122015 and iswas primarily due to a net loss$4.6 million in proceeds received from the employee stock purchase plan, and the exercise of $32.6 million adjusted for non-cash items including an increase in the fair value ofstock options and warrants of $2.3 million, stock-based compensation of $1.2 million, depreciation and amortization of $1.3 million, and accretion of deferred interest of $0.3 million and a net decrease in operating assets and liabilities of $11.5 million. The significant items in the change in operating assets and liabilities include a decrease in deferred revenue of $9.7 million due to the ongoing recognition of revenue deferred in connection with up-front payments for the Celgene and Shire collaboration agreements, a decrease in accounts payable of $1.3 million and an increase in collaboration receivables of $1.1 million, offset in part by an increase in accrued expenses of $1.6 million. Other components of the change in operating assets and liabilities include an increase in prepaid expenses and other current assets of $0.6 million and a decrease in deferred rent of $0.5 million.

purchase common stock.

Net cash provided by operatingfinancing activities was $9.1$117.0 million for the year ended December 31, 20112014 and is primarily due toconsisted of $129.2 million in net incomeproceeds received from our follow on public offering and $4.2 million from the exercise of $36.3 million, which was impacted by non-cash items including depreciationstock options and amortization of $3.1 million, stock-based compensation of $1.4 million, an increase in the fair value of warrants, of $0.5 million, accretion of deferred interest of $0.3 million and amortization of debt discount of $0.2 million and a net decrease in operating assets and liabilities of $32.8 million. The significant items in the change in operating assets and liabilities include a decrease in deferred revenue of $35.1 million due primarily to the acceleration of deferred revenue associated with the Celgene collaboration upfront payments as a result of the modification of the collaboration agreement, as well as a decrease in accrued expenses of $2.8 million, offset in part by a decrease in prepaid expenses and other current assets$16.3 million of $2.6 million and a decrease in collaboration receivables of $1.8 million. Other components of the change in operating assets and liabilities include an increase in accounts payable of $0.3 million and an increase in deferred rent of $0.2 million.

        Investing Activities.    Net cash used in investing activities was $0.3 million for the year ended December 31, 2013, $0.4 million for the year ended December 31, 2012 and $27,000 for the year ended December 31, 2011 and consisted of purchases of property and equipment.

        Financing Activities.principal repayments to pay off our venture debt credit facility. 

Net cash provided by financing activities was $93.5 million for the year ended December 31, 2013 and consisted of $96.8 million in net proceeds received from our initial public offering and concurrent private placement, and $0.7 million of proceeds from the exercise of stock options and warrants to purchase common stock, offset in part by $3.7 million of principal payments made to pay down our venture debt line,credit facility, and $0.3 million paid to repurchase and retire redeemable convertible preferred stock, common stock and warrants to purchase common stock.


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        Net cash provided by financing activities was $13.9 million for the year ended December 31, 2012 and consisted of $19.9 million in net proceeds received from the drawdown of our new venture debt line in June 2012, as well as $0.2 million received from the exercise of stock options and warrants to purchase common stock, offset by $6.2 million of principal payments made to pay down our previous venture debt line.

        Net cash provided by financing activities was $21.1 million for the year ended December 31, 2011 and consisted primarily of $30.4 million of net proceeds received from the sale of 9,704,756 shares of our Series F preferred stock, as well as $0.2 million received from the exercise of stock options and warrants to purchase common stock, offset in part by $9.5 million of principal payments made to pay down a previous venture debt facility.

Operating Capital Requirements

To date, we have not generated any revenue from product sales. We do not know when, or if, we will generate any revenue from product sales. We will not generate revenue from product sales unless and until we or our partners obtain regulatory approval of and commercialize one of our current or future protein therapeutics.therapeutic candidates. We anticipate that we will continue to generate losses for the foreseeable future, and we expect the losses to increase as we continue the development of, and seek and obtain regulatory approvals for, dalantercept, ACE-083 and any future protein therapeutics,therapeutic candidates, and begin to commercialize any approved products. We are subject to all of the risks incident in the development of protein therapeutics,therapeutic candidates, and we may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. Since the closing of our initial public offering, we have incurred, and expect to continue to incur, additional costs associated with operating as a public company. We anticipate that we will need additional funding in connection with our continuing operations.

We believe that our existing cash, cash equivalents and investments, including the net proceeds we receive from our January 2016 public offerings, together with receipt of anticipated milestone payments and our existing cash and cash equivalentsoffering, will be sufficient to fund our projected operating requirements into the second half of 2017.2019. However, we will require additional capital for the further development of our existing protein therapeutic candidates and may also need to raise additional funds sooner to pursue other development activities related to additional protein therapeutic candidates.

Until we can generate a sufficient amount of revenue from our products, if ever, we expect to fund our operations through a combination of equity offerings, or debt financings or other sources including potential additional collaborations. Additional capital may not be available on favorable terms, if at all. If we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may have to significantly delay, scale back or discontinue the development or commercialization of one or more of our protein therapeutic candidates. If we raise additional funds through the issuance of additional debt or equity securities, it could result in dilution to our existing stockholders and increased fixed payment obligations, and these securities may have rights senior to those of our common stock. If we incur indebtedness, we could become subject to covenants that would restrict our operations and potentially impair our competitiveness, such as limitations on our ability to incur additional debt, limitations on our ability to acquire, sell or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business. We may not be able to enter into new collaboration arrangements for any of our proprietary protein therapeutic candidates. Any of these events could significantly harm our business, financial condition and prospects.

Our forecast of the period of time through which our financial resources will be adequate to support our operations is a forward-looking statement and involves risks and uncertainties, and actual results could vary as a result of a number of factors. We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we currently


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expect. Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to:

the achievement of milestones under our agreement with Celgene;

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the terms and timing of any other collaborative, licensing and other arrangements that we may establish;


the initiation, progress, timing and completion of preclinical studies and clinical trials for our protein therapeutic candidates and potential protein therapeutic candidates;


the number and characteristics of protein therapeutic candidates that we pursue;


the progress, costs and results of our clinical trials;


the outcome, timing and cost of regulatory approvals;


delays that may be caused by changing regulatory requirements;


the cost and timing of hiring new employees to support our continued growth;


the costs involved in filing and prosecuting patent applications and enforcing and defending patent claims;


the costs and timing of procuring clinical and commercial supplies of our protein therapeutic candidates;


the extent to which we acquire or invest in businesses, products or technologies; and


the costs involved in defending and prosecuting litigation regarding in-licensed intellectual property including our litigation with the Salk Institute. See "Business—Litigation".

property.

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Contractual Obligations and Commitments

The following is a summary of our long-term contractual cash obligations as of December 31, 2013.

2015.
(in thousands)Total 2016 2017 through 2018 2019 through 2020 After 2020
Operating lease obligations(1)$13,971
 $4,386
 $8,124
 $1,296
 $165
Total$13,971
 $4,386
 $8,124
 $1,296
 $165

(in thousands)
 Total 1 year 2 - 3 years 4 - 5 years 

Operating lease obligations(1)

 $19,457 $4,522 $8,044 $6,891 

Less: sublease income(2)

  (1,084) (832) (252)  

Venture debt facility(3)

  18,194  18,194     
          

Total

 $36,567 $21,884 $7,792 $6,891 
          
          


(1)We lease office and lab space at 128 Sidney Street and 149 Sidney Street in Cambridge, Massachusetts under noncancelable operating leases that expire in September 2018. We also lease space at 125 Sidney Street under a noncancelable operating lease that expires in March 2021. Our leasehold improvements are being amortized over 2-10 years which represent the shorter of their useful life or remaining lease term.
(1)
We lease office space at 128 Sidney Street and 149 Sidney Street in Cambridge, Massachusetts under noncancelable operating leases that expire in September 2018, and at 12 Emily Street in Cambridge, Massachusetts under a noncancelable operating lease that expires in May 2015. Our leasehold improvements are being amortized over 3-10 years which represent the shorter of their useful life or remaining lease term.

(2)
In February 2011, we entered into a sublease for 14,214 square feet of office space at 12 Emily Street in Cambridge, Massachusetts, that expires in May 2015. On December 31, 2013 the sublease was expanded to the remaining space in that facility. The expansion portion sublease expires in December 2014.

(3)
In June 2012, we entered into a $20.0 million venture debt facility to provide working capital to fund operating activities. The loans under this debt facility are secured by our assets and are being repaid over 42 months beginning with a 12 month interest only period. Interest rates were fixed at the time of drawdown, with an effective rate of 11.8%. On March 12, 2014, the Company paid off the remaining principal outstanding under the Loan Agreement. The cash obligation balance includes the principal, the interest through the date of repayment, deferred fees and early repayment fees.

We also have obligations to make future payments to third party licensors that become due and payable on the achievement of certain development, regulatory and commercial milestones. We have not included these commitments on our consolidated balance sheet or in the table above because the achievement and timing of these milestones is not fixed or determinable. These commitments include the following:



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Under our two license agreements with the Salk Institute for Biological Studies, or Salk, relating to the first cloning of the type II activin receptors, if we sublicense the Salk patent rights, we will owe Salk a percentage of sublicensing revenue, excluding payments based on sales. Under one agreement, we also agreed to pay Salk specified development milestone payments totaling up to $2.0 million for sotatercept. Under the other agreement, we also agreed to pay Salk specified development milestone payments of up to $0.7 million for ACE-536.luspatercept. In addition, under both agreements, we are required to pay Salk royalties in the low single-digits on worldwide net product sales by us or our sublicensees under the licensed patent rights of products claimed in the licensed patents, or products derived from use of the licensed patent rights, with royalty obligations for sotatercept continuing at a reduced rate for a period of time after patent expiration.


In May 2014, we executed a collaboration agreement with a research technology company. We paid an upfront and research fee of $0.3 million upon execution of the agreement. We also received an option to obtain a commercial license to the molecules developed during the collaboration, which, if exercised, would obligate us to pay royalty and milestone payments.
We enter into contracts in the normal course of business with CROs for clinical trials and clinical supply manufacturing and with vendors for preclinical safety and research studies, research supplies and other services and products for operating purposes. These contracts generally provide for termination on notice, and therefore are cancelable contracts and not included in the table of contractual obligations and commitments.


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Net Operating Loss (NOL) Carryforwards

We have deferred tax assets of approximately $66.1$109.8 million as of December 31, 2013,2015, which have been fully offset by a valuation allowance due to uncertainties surrounding our ability to realize these tax benefits. The deferred tax assets are primarily composed of federal and state tax net operating loss, or NOL, carryforwards, research and development tax credit carryforwards, and deferred revenue, accruals and other temporary differences. As of December 31, 2013,2015, we had federal NOL carryforwards of approximately $141.0$276.1 million and state NOL carryforwards of $122.9$229.8 million available to reduce future taxable income, if any. These federal NOL carryforwards expire at various times through 2033 and the state NOL carryforwards expire at various times through 2033.2035. In general, if we experience a greater than 50 percent aggregate change in ownership of certain significant stockholders over a three-year period, or a Section 382 ownership change, utilization of our pre-change NOL carryforwards are subject to an annual limitation under Section 382 of the Internal Revenue Code of 1986, as amended, and similar state laws. Such limitations may result in expiration of a portion of the NOL carryforwards before utilization and may be substantial. If we experience a Section 382 ownership change in connection with our public offerings or as a result of future changes in our stock ownership, some of which changes are outside our control, the tax benefits related to the NOL carryforwards may be limited or lost. For additional information about our taxes, see Note 1213 to the financial statements in this Annual Report on Form 10-K.


Off-Balance Sheet Arrangements

We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined in the rules and regulations of the Securities and Exchange Commission.


CERTAIN RELATIONSHIPS AND RELATED PARTY TRANSACTIONS

        The following is a description of transactions, since January 1, 2012, to which we have been a party, in which the amount involved exceeded or will exceed $120,000, and in which any related person had a direct or indirect material interest.

Indemnification Agreements

        We have entered into indemnification agreements with each of our directors and executive officers. These agreements will require us to indemnify these individuals and, in certain cases, affiliates of such


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individuals, to the fullest extent permissible under Delaware law against liabilities that may arise by reason of their service to us or at our direction, and to advance expenses incurred as a result of any proceeding against them as to which they could be indemnified.

Registration Rights Agreement

        In connection with our Series F preferred stock financing, on December 22, 2011, we entered into an amended and restated registration rights agreement with the holders of all of our then-outstanding shares of preferred stock including certain of our named executive officers and entities with which certain of our directors are affiliated. The agreement provides that these holders, for so long as they may hold registrable securities, as defined in the agreement, have the right to demand that we file a registration statement with respect to the common stock issued upon conversion of our preferred stock. These holders may also request that shares of common stock held by them be included in certain registration statements that we are otherwise filing. See "Description of Capital Stock—Registration Rights".

Right of First Refusal and Co-Sale Agreement

        In connection with our Series F preferred stock financing, on December 22, 2011, we entered into an amended and restated right of first refusal and co-sale agreement with the holders of all of our then-outstanding shares of preferred stock including certain of our named executive officers and entities with which certain of our directors are affiliated. Pursuant to the terms of this agreement, in the event of a proposed sale of shares of our common or preferred stock, the seller was required to first offer such shares to the company and to the other investors, subject to certain conditions and restrictions. This agreement terminated upon the completion of our initial public offering on September 24, 2013.

Voting Agreement

        In connection with our Series F preferred stock financing on December 22, 2011, we entered into an amended and restated voting agreement with the holders of all of our then-outstanding shares of preferred stock including certain of our named executive officers and entities with which certain of our directors are affiliated, with respect to the election of directors and certain other matters. All of our current directors were elected pursuant to the terms of this agreement. This agreement terminated upon the completion of our initial public offering on September 24, 2013.

Investor Rights Agreement

        In connection with our Series F preferred stock financing, on December 22, 2011, we entered into an amended and restated investor rights agreement with the holders of all of our then-outstanding shares of preferred stock including certain of our named executive officers and entities with which certain of our directors are affiliated. Pursuant to the terms of this agreement, we granted our investors certain information rights as well as the right to participate pro rata in any future private financing rounds. This agreement terminated upon the completion of our initial public offering on September 24, 2013.

Transactions with Our Executive Officers, Directors and 5% Stockholders

        On March 13, 2013, we repurchased shares of our common and preferred stock, as well as warrants to purchase shares of our common stock, from UBS Juniper Crossover Fund, LLC, an affiliate of OrbiMed Advisors, for $300,000 in aggregate.

        On January 28, 2008, we entered into a secured promissory note with our chief executive officer, which was amended on November 13, 2012, with a principal balance of $200,000 and an interest rate of


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3.11% per annum. The note was secured by a pledge of shares of the company's stock under a pledge agreement dated January 28, 2008. The terms of the note provided that it would mature on January 28, 2014, or be forgiven upon the occurrence of certain corporate events, including the filing of a registration statement with the SEC. The outstanding principal balance and accrued and unpaid interest on the note was forgiven on August 7, 2013. See "Executive Compensation—Executive Loan".

        For additional Related Party transactions disclosure, please see Note 14 to the financial statement in this Annual Report on Form 10-K.

Item 7A.    Quantitative and Qualitative Disclosures About Market Risks

We are exposed to market risk related to changes in interest rates. As of December 31, 2013,2015 and December 31, 2014, we had cash, and cash equivalents and investments of $113.2 million.$136.0 million and $176.5 million, respectively. Our cash equivalents are invested primarily in bank deposits and money market mutual funds consisting of U.S. government-backed securities.funds. Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because ourrates. Our investments are subject to interest rate risk and could fall in short-term securities.value if market interest rates increase. Due to the short-term duration of our investment portfolio and the low risk profile of our investments, we do not believe an immediate 100 basis point change in interest rates would not have a material effect on the fair market value of our portfolio.

We have the ability to hold our investments until maturity, and therefore we would not expect our operating results or cash flows to be affected to any significant degree by the effect of a change in market interest rates on our investments.

Item 8.    Financial Statements and Supplementary Data.Data

All financial statements and supplementary data required to be filed hereunder are filed as listed under Item 15(a) of this Annual Report on Form 10-K and are incorporated herein by this reference.

Item 9.    Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.Disclosure

None.

Item 9A.    Controls and Procedures.Procedures

Conclusion Regarding the Effectiveness of Disclosure Controls and Procedures

As of December 31, 2013,2015, management, with the participation of our Chief Executive Officer and Chief Financial Officer, performed an evaluation of the effectiveness of the design and operation of our disclosure controls and procedures as defined in Rules 13a-15(e) and 15d-15(e) of the Exchange Act. Our disclosure controls and procedures are designed to ensure that information required to be disclosed in the reports we file or submit under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in the Securities and Exchange Commission's rules and forms, and that such information is accumulated and communicated to our management, including the Chief Executive Officer and the Chief Financial Officer, to allow timely decisions regarding required disclosures. Any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objective. Based on this evaluation, our Chief Executive Officer and Chief Financial Officer concluded that, as of December 31, 2013,2015, the design and operation of our disclosure controls and procedures were effective.

Management's Report on Internal Control Over Financial Reporting

        This Annual Report on Form 10-K does not include a report


63


Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, is responsible for establishing and maintaining adequate internal control over financial reporting, as defined in Rule 13a-15(f) and 15d-15(f) of the Exchange Act. Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policy or procedures may deteriorate. Under the supervision and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer, management has conducted an attestation reportevaluation of the effectiveness of our internal control over financial reporting as of December 31, 2015 based upon the Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework). Based on this evaluation, management, including our Chief Executive Officer and Chief Financial Officer, has concluded that our internal control over financial reporting was effective as of December 31, 2015.
The effectiveness of our internal control over financial reporting as of December 31, 2015 has been audited by Ernst & Young LLP, our independent registered public accounting firm, due to the transition period established by rules of the SEC for newly public companies.

as stated in their report which is included herein.

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Changes in Internal Control over Financial Reporting

There were no changes in our internal control over financial reporting (as defined in Rule 13a-15(f) under the Exchange Act) during the quarteryear ended December 31, 2013,2015, that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

Item 9B.    Other Information

        None.

Report of Independent Registered Public Accounting Firm
The Board of Directors and Stockholders of
Acceleron Pharma Inc.

We have audited Acceleron Pharma Inc.’s internal control over financial reporting as of December 31, 2015, based on criteria established in Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) (the COSO criteria). Acceleron Pharma Inc.’s management is responsible for maintaining effective internal control over financial reporting, and for its assessment of the effectiveness of internal control over financial reporting included in the accompanying Management’s Report on Internal Control Over Financial Reporting. Our responsibility is to express an opinion on the company’s internal control over financial reporting based on our audit.

We conducted our audit in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standards require that we plan and perform the audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all material respects. Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, testing and evaluating the design and operating effectiveness of internal control based on the assessed risk, and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion.

A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial statements.

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.

In our opinion, Acceleron Pharma Inc. maintained, in all material respects, effective internal control over financial reporting as of December 31, 2015, based on the COSO criteria.


We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States), the consolidated balance sheets of Acceleron Pharma Inc. as of December 31, 2015 and 2014, and the related

64

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consolidated statements of operations and comprehensive loss, redeemable convertible preferred stock and stockholders' equity (deficit) and cash flows for each of the three years in the period ended December 31, 2015 of Acceleron Pharma Inc. and our report dated February 25, 2016 expressed an unqualified opinion thereon.
/s/ Ernst & Young LLP
Boston, Massachusetts
February 25, 2016

Item 9B.    Other Information
None.

65


PART III

Certain information required by Part III is omitted from this Annual Report on Form 10-K and is incorporated herein by reference from our definitive proxy statement relating to our 20142016 annual meeting of stockholders, pursuant to Regulation 14A of the Securities Exchange Act of 1934, as amended, also referred to in this Form 10-K as our 20142016 Proxy Statement, which we expect to file with the SEC no later than April 30, 2014.

2015.

Item 10.    Directors, Executive Officers and Corporate Governance

The information required by this Item 10 is incorporated herein by reference to our 20142016 Proxy Statement.

Item 11.    Executive and Director Compensation

The information required by this Item 11 is incorporated herein by reference to our 20142016 Proxy Statement.

Item 12.    Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

The information required by this Item 12 is incorporated herein by reference to our 20142016 Proxy Statement.

Item 13.    Certain Relationships and Related Transactions, and Director Independence.
Independence

The information required by this Item 13 is incorporated herein by reference to our 20142016 Proxy Statement.

Item 14.    Principal Accounting Fees and Services

The information required by this Item 14 is incorporated herein by reference to our 20142016 Proxy Statement.



66

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PART IV

Item 15.    Exhibits and Financial Statement Schedules.
Schedules

(a)The following documents are filed as part of this report:
(1)Financial Statements.


Page number in
this Report

Report of Independent Registered Public Accounting Firm

Consolidated Balance Sheets at December 31, 20132015 and 2012

2014

Consolidated Statements of Operations and Comprehensive (Loss) IncomeLoss for the years ended December 31, 2013, 20122015, 2014 and 2011

2013

Consolidated Statements of Redeemable Convertible Preferred Stock and Stockholders' Equity (Deficit) for the years ended December 31, 2013, 20122015, 2014 and 2011

2013

Consolidated Statements of Cash Flows for the years ended December 31, 2013, 20122015, 2014 and 2011

2013

Notes to Consolidated Financial Statements

(2)Financial Statement Schedules.

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Acceleron Pharma Inc.
Index to Consolidated Financial Statements



Pages

Report of Independent Registered Public Accounting Firm

Consolidated Balance Sheets as of December 31, 2013 and 2012

Consolidated Statements of Operations and Comprehensive (Loss) Income for the Years Ended December 31, 2013, 2012 and 2011

Loss

Consolidated Statements of Redeemable Convertible Preferred Stock and Stockholders' Equity (Deficit) for the Years Ended December 31, 2013, 2012 and 2011

Consolidated Statements of Cash Flows for the Years Ended December 31, 2013, 2012 and 2011

Notes to Consolidated Financial Statements



F-1

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Report of Independent Registered Public Accounting Firm

The Board of Directors and Stockholders of
Acceleron Pharma Inc.


We have audited the accompanying consolidated balance sheets of Acceleron Pharma Inc. (the Company) as of December 31, 20132015 and 2012,2014, and the related consolidated statements of operations and comprehensive (loss) income,loss, redeemable convertible preferred stock and stockholders'stockholders’ equity (deficit), and cash flows for each of the three years in the period ended December 31, 2013.2015. These financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on these financial statements based on our audits.


We conducted our audits in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement. We were not engaged to perform an audit of the Company's internal control over financial reporting. Our audits included consideration of internal control over financial reporting as a basis for designing audit procedures that are appropriate in the circumstances, but not for the purpose of expressing an opinion on the effectiveness of the Company's internal control over financial reporting. Accordingly, we express no such opinion. An audit also includes examining, on a test basis, evidence supporting the amounts and disclosures in the financial statements,statements. An audit also includes assessing the accounting principles used and significant estimates made by management, andas well as evaluating the overall financial statement presentation. We believe that our audits provide a reasonable basis for our opinion.


In our opinion, the financial statements referred to above present fairly, in all material respects, the consolidated financial position of Acceleron Pharma Inc. at December 31, 20132015 and 2012,2014, and the consolidated results of its operations and its cash flows for each of the three years in the period ended December 31, 2013,2015, in conformity with U.S. generally accepted accounting principles.


We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States), Acceleron Pharma Inc.’s internal control over financial reporting as of December 31, 2015, based on criteria established in Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) and our report dated February 25, 2016 expressed an unqualified opinion thereon.
  /s/ Ernst & Young LLP


Boston, Massachusetts
March 17, 2014

February 25, 2016



F-2

Table of Contents


Acceleron Pharma Inc.

Consolidated Balance Sheets

(amounts in thousands except share and per share data)

 
 December 31, 
 
 2013 2012 

Assets

       

Current assets:

       

Cash and cash equivalents

 $113,163 $39,611 

Collaboration receivables (includes related party amounts of $3,616 and $1,840 at December 31, 2013 and 2012, respectively)

  3,616  2,776 

Prepaid expenses and other current assets

  2,243  1,474 
      

Total current assets

  119,022  43,861 

Property and equipment, net

  3,705  4,059 

Restricted cash

  913  913 

Related party receivables

    233 

Other assets

  92  146 
      

Total assets

 $123,732 $49,212 
      
      

Liabilities, redeemable convertible preferred stock and stockholders' equity (deficit)

       

Current liabilities:

       

Accounts payable

 $885 $642 

Accrued expenses (includes related party amounts of $0 and $861at December 31, 2013 and 2012, respectively)

  6,927  6,153 

Deferred revenue

  2,031  27,840 

Deferred rent

  499  499 

Notes payable, net of discount

  16,868  3,668 
      

Total current liabilities

  27,210  38,802 

Deferred revenue, net of current portion

  5,620  6,760 

Deferred rent, net of current portion

  2,337  2,837 

Notes payable, net of current portion and discount

    16,525 

Warrants to purchase redeemable convertible preferred stock

    1,422 

Warrants to purchase common stock

  30,753  5,229 
      

Total liabilities

  65,920  71,575 

Commitments and contingencies (Note 7)

       

Redeemable convertible preferred stock (Note 8)

    268,610 

Stockholders' equity (deficit):

       

Undesignated preferred stock, $0.001 par value: 25,000,000 shares authorized and no shares issued or outstanding at December 31, 2013; No shares authorized, issued or outstanding at December 31, 2012

     

Common stock, $0.001 par value: 175,000,000 and 104,013,161 shares authorized at December 31, 2013 and 2012, respectively; 28,348,630 and 2,432,155, shares issued and outstanding at December 31, 2013 and 2012,
respectively

  29  3 

Additional paid-in capital

  250,107   

Accumulated deficit

  (192,324) (290,976)
      

Total stockholders' equity (deficit)

  57,812  (290,973)
      

Total liabilities, redeemable convertible preferred stock and stockholders' equity (deficit)

 $123,732 $49,212 
      
      
 December 31,
 2015 2014
Assets   
Current assets:   
Cash and cash equivalents$27,783
 $176,460
Short-term investments77,064
 
Collaboration receivables (all amounts are with a related party)3,628
 3,367
Prepaid expenses and other current assets2,458
 2,480
Total current assets110,933
 182,307
Property and equipment, net3,106
 3,087
Long-term investments31,134
 
Restricted cash796
 902
Other assets368
 
Total assets$146,337
 $186,296
Liabilities and stockholders' equity   
Current liabilities:   
Accounts payable$875
 $724
Accrued expenses12,400
 6,848
Deferred revenue555
 1,162
Deferred rent661
 519
Total current liabilities14,491
 9,253
Deferred revenue, net of current portion4,239
 4,816
Deferred rent, net of current portion1,157
 1,818
Warrants to purchase common stock17,187
 14,124
Total liabilities37,074
 30,011
Commitments and contingencies (Note 8)
 
Stockholders' equity:   
Undesignated preferred stock, $0.001 par value: 25,000,000 shares authorized and no shares issued or outstanding
 
Common stock, $0.001 par value: 175,000,000 shares authorized; 33,313,355 and 32,432,025, shares issued and outstanding at December 31, 2015 and 2014, respectively34
 33
Additional paid-in capital416,926
 399,835
Accumulated deficit(307,477) (243,583)
Accumulated other comprehensive loss(220) 
Total stockholders' equity109,263
 156,285
Total liabilities and stockholders' equity$146,337
 $186,296

See accompanying notes to consolidated financial statements.



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Table of Contents


Acceleron Pharma Inc.

Consolidated Statements of Operations and Comprehensive (Loss) Income

Loss

(amounts in thousands except per share data)

 Year Ended December 31,
 2015 2014 2013
Revenue:     
Collaboration revenue:     
License and milestone$1,184
 $1,673
 $43,948
Cost-sharing, net16,913
 12,959
 13,282
Total revenue(1)18,097
 14,632
 57,230
Costs and expenses:  

  
Research and development58,404
 50,897
 36,051
Litigation settlement
 5,000
 
General and administrative20,572
 14,199
 14,227
Total costs and expenses78,976
 70,096
 50,278
(Loss) income from operations(60,879) (55,464) 6,952
Other (expense) income:  

  
Other (expense) income, net(3,527) 5,044
 (26,797)
Interest income512
 83
 39
Interest expense
 (922) (2,092)
Total other (expense) income, net(3,015) 4,205
 (28,850)
Net loss$(63,894) $(51,259) $(21,898)
Other comprehensive loss:     
Net unrealized holding (losses) on short-term and long-term investments during the period$(220) $
 $
Comprehensive loss$(64,114) $(51,259) $(21,898)
      
Reconciliation of net loss to net loss applicable to common stockholders:  

  
Net loss$(63,894) $(51,259) $(21,898)
Accretion of dividends, interest, redemption value and issuance costs on redeemable convertible preferred stock
 
 (19,870)
Gain on extinguishment of redeemable convertible preferred stock
 
 2,765
Net loss applicable to common stockholders—basic and diluted$(63,894) $(51,259) $(39,003)
Net loss per share applicable to common stockholders-basic and diluted$(1.92) $(1.63) $(4.15)
      
Weighted-average number of common shares used in computing net loss per share applicable to common stockholders-basic and diluted33,303
 31,515
 9,407
___________________________________________________________     
(1)    Includes related party revenue (Note 15)$18,097
 $14,632
 $32,284
 
 Year Ended December 31, 
 
 2013 2012 2011 

Revenue:

          

Collaboration revenue:

          

License and milestone

 $43,948 $9,696 $74,406 

Cost-sharing, net

  13,282  5,558  4,760 

Contract manufacturing

      1,745 
        

Total revenue(1)

  57,230  15,254  80,911 
        

Costs and expenses:

          

Research and development

  36,051  35,319  32,713 

General and administrative

  14,227  8,824  8,142 

Cost of contract manufacturing revenue

      1,500 
        

Total costs and expenses

  50,278  44,143  42,355 
        

Income (loss) from operations

  6,952  (28,889) 38,556 

Other (expense) income:

          

Other expense, net

  (26,797) (2,255) (485)

Interest income

  39  91  17 

Interest expense

  (2,092) (1,529) (1,822)
        

Total other expense, net

  (28,850) (3,693) (2,290)
        

Net (loss) income

 $(21,898)$(32,582)$36,266 
        
        

Comprehensive (loss) income

 $(21,898)$(32,582)$36,266 
        
        

Reconciliation of net (loss) income to net (loss) income applicable to common stockholders:

          

Net (loss) income

 $(21,898)$(32,582)$36,266 

Accretion of dividends, interest, redemption value and issuance costs on redeemable convertible preferred stock

  (19,870) (27,061) (21,757)

Gain on extinguishment of redeemable convertible preferred stock

  2,765     

Net (loss) income applicable to participating securities

      (12,645)
        

Net (loss) income applicable to common stockholders—basic

 $(39,003)$(59,643)$1,864 
        
        

Net (loss) income

 $(21,898)$(32,582)$36,266 

Accretion of dividends, interest, redemption value and issuance costs on redeemable convertible preferred stock

  (19,870) (27,061) (21,757)

Gain on extinguishment of redeemable convertible preferred stock

  2,765     

Net (loss) income applicable to participating securities

      (12,395)
        

Net (loss) income applicable to common stockholders—diluted

 $(39,003)$(59,643)$2,114 
        
        

Net (loss) income per share applicable to common stockholders: (Note 2)

          

Basic

 $(4.15)$(24.84)$0.80 
        
        

Diluted

 $(4.15)$(24.84)$0.78 
        
        

Weighted-average number of common shares used in computing net (loss) income per share applicable to common stockholders:

          

Basic

  9,407  2,401  2,328 

Diluted

  9,407  2,401  2,716 



          

(1)    Includes related party revenue (Note 14)

 $32,284 $4,914 $64,220 
        
        

See accompanying notes to consolidated financial statements.



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Acceleron Pharma Inc.
Consolidated Statements of Redeemable Convertible Preferred Stock and Stockholders' Equity (Deficit)
(amounts in thousands except share and per share data)


 Series A Redeemable
Convertible
Preferred Stock
 Series B Redeemable
Convertible
Preferred Stock
 Series C Redeemable
Convertible
Preferred Stock
 Series C-1
Redeemable
Convertible
Preferred Stock
 Series D
Redeemable
Convertible
Preferred Stock
 Series D-1
Redeemable
Convertible
Preferred Stock
 

 Number of
Shares
 Value Number of
Shares
 Value Number of
Shares
 Value Number of
Shares
 Value Number of
Shares
 Value Number of
Shares
 Value 
Series A Redeemable
Convertible
Preferred Stock
 
Series B Redeemable
Convertible
Preferred Stock
 
Series C Redeemable
Convertible
Preferred Stock
 
Series C-1
Redeemable
Convertible
Preferred Stock
 
Series D
Redeemable
Convertible
Preferred Stock
 
Series D-1
Redeemable
Convertible
Preferred Stock

Balance at December 31, 2010

 6,410,976 $57,433 4,204,185 $55,880 2,978,062 $48,726 457,875 $7,571 234,940 $2,989 636,942 $8,392 

Sale of Series F redeemable convertible preferred stock net of issuance costs of $92

             

Accretion of dividends, interest, redemption value and issuance costs related to redeemable convertible preferred stock

  4,616  5,584  5,594  908  668  1,736 

Compensation expense associated with stock options

             

Grant of stock options to nonemployees

             

Exercise of stock options

             

Exercise of common warrants

             

Net loss

             
                         
Number 
of
Shares
 Value 
Number 
of
Shares
 Value 
Number 
of
Shares
 Value 
Number 
of
Shares
 Value 
Number 
of
Shares
 Value 
Number 
of
Shares
 Value

Balance at December 31, 2011

 6,410,976 62,049 4,204,185 61,464 2,978,062 54,320 457,875 8,479 234,940 3,657 636,942 10,128 

Accretion of dividends, interest, redemption value and issuance costs related to redeemable convertible preferred stock

  4,616  5,580  5,589  908  668  1,736 

Compensation expense associated with stock options

             

Exercise of stock options

             

Net loss

             
                         

Balance at December 31, 2012

 6,410,976 66,665 4,204,185 67,044 2,978,062 59,909 457,875 9,387 234,940 4,325 636,942 11,864 
December 31, 20126,410,976
 $66,665
 4,204,185
 $67,044
 2,978,062
 $59,909
 457,875
 $9,387
 234,940
 $4,325
 636,942
 $11,864

Accretion of dividends, interest, redemption value and issuance costs related to redeemable convertible preferred stock

  3,408  4,138  4,068  661  487  1,273 
 3,408
 
 4,138
 
 4,068
 
 661
 
 487
 
 1,273

Repurchase and retirement of redeemable convertible preferred stock

   (139,741) (2,267) (21,744) (445)   (2,906) (54)   
 
 (139,741) (2,267) (21,744) (445) 
 
 (2,906) (54) 
 

Exercise of warrants to purchase convertible preferred stock

 46,668 678           46,668
 678
 
 
 
 
 
 
 
 
 
 

Exercise of warrants to purchase common stock

             
 
 
 
 
 
 
 
 
 
 
 

Compensation expense associated with stock options

             
 
 
 
 
 
 
 
 
 
 
 

Exercise of stock options

             
 
 
 
 
 
 
 
 
 
 
 

Conversion of redeemable convertible preferred stock into common stock

 (6,457,644) (70,751) (4,064,444) (68,915) (2,956,318) (63,532) (457,875) (10,048) (232,034) (4,758) (636,942) (13,137)(6,457,644) (70,751) (4,064,444) (68,915) (2,956,318) (63,532) (457,875) (10,048) (232,034) (4,758) (636,942) (13,137)

Reclassification of warrants to purchase shares of redeemable convertible preferred stock into warrants to purchase common stock

             
 
 
 
 
 
 
 
 
 
 
 

Issuance of common stock in connection with initial public offering and private placement, net of issuance costs of $2,692

             
 
 
 
 
 
 
 
 
 
 
 

Net loss

             
 
 
 
 
 
 
 
 
 
 
 
                         

Balance at December 31, 2013

  $  $  $  $  $  $ 
                         
                         
December 31, 2013
 
 
 
 
 
 
 
 
 
 
 
Issuance of common stock net of expenses of $554
 
 
 
 
 
 
 
 
 
 
 
Stock-based compensation

 
 
 
 
 
 
 
 
 
 
 
Exercise of stock options
 
 
 
 
 
 
 
 
 
 
 
Net exercise of warrants to purchase common stock
 
 
 
 
 
 
 
 
 
 
 
Exercise of warrants to purchase common stock
 
 
 
 
 
 
 
 
 
 
 
Net loss
 
 
 
 
 
 
 
 
 
 
 
Balance at December 31, 2014
 
 
 
 
 
 
 
 
 
 
 
Stock-based compensation

 
 
 
 
 
 
 
 
 
 
 
Exercise of stock options
 
 
 
 
 
 
 
 
 
 
 
Issuance of common stock related to ESPP
 
 
 
 
 
 
 
 
 
 
 
Net exercise of warrants to purchase common stock
 
 
 
 
 
 
 
 
 
 
 
Unrealized loss on available-for-sale securities
 
 
 
 
 
 
 
 
 
 
 
Net loss
 
 
 
 
 
 
 
 
 
 
 
Balance at December 31, 2015
 $
 
 $
 
 $
 
 $
 
 $
 
 $

See accompanying notes to consolidated financial statements.



F-5


Acceleron Pharma Inc.
Consolidated Statements of Redeemable Convertible Preferred Stock and Stockholders' Equity (Deficit) (Continued)
(amounts in thousands except share and per share data)


 Series E Redeemable
Convertible
Preferred Stock
 Series F Redeemable
Convertible
Preferred Stock
  
  
  
  
  
  
 

 Total
Redeemable
Convertible
Preferred
Stock
 Common Stock  
  
  
 
Series E Redeemable
Convertible
Preferred Stock
 
Series F Redeemable
Convertible
Preferred Stock
              

 Number of
Shares
 Value Number of
Shares
 Value Number of
Shares
 $0.001 Par
Value
 Additional
Paid-In
Capital
 Accumulated
Deficit
 Total
Stockholders'
Equity (deficit)
 
Total
Redeemable
Convertible
Preferred
Stock
 Common Stock        

Balance at December 31, 2010

 816,060 $8,423  $ $189,414 2,261,461 $3 $ $(248,820)$(248,817)

Sale of Series F redeemable convertible preferred stock net of issuance costs of $92

   2,426,171 30,378 30,378      

Accretion of dividends, interest, redemption value and issuance costs related to redeemable convertible preferred stock

  2,511  140 21,757   (1,617) (20,140) (21,757)

Compensation expense associated with stock options

        1,212  1,212 

Grant of stock options to nonemployees

        215  215 

Exercise of stock options

      94,748  190  190 

Exercise of common warrants

      37,249  (0)   

Net income

         36,266 36,266 
                     
Number
of
Shares
 Value 
Number
of
Shares
 Value 
Total
Redeemable
Convertible
Preferred
Stock
 
Number
of
Shares
 
$0.001 Par
Value
 
Additional
Paid-In
Capital
 
Accumulated
Deficit
 Comprehensive Income (Loss) 
Total
Stockholders'
Equity (Deficit)

Balance at December 31, 2011

 816,060 10,934 2,426,171 30,518 241,549 2,393,458 3  (232,694) (232,691)

Accretion of dividends, interest, redemption value and issuance costs related to redeemable convertible preferred stock

  2,459  5,505 27,061   (1,361) (25,700) (27,061)

Compensation expense associated with stock options

        1,206  1,206 

Exercise of stock options

      38,697  155  155 

Net loss

         (32,582) (32,582)
                     

Balance at December 31, 2012

 816,060 13,393 2,426,171 36,023 268,610 2,432,155 3  (290,976) (290,973)816,060
 $13,393
 2,426,171
 $36,023
 $268,610
 2,432,155
 $3
 $
 $(290,976) $
 $(290,973)

Accretion of dividends, interest, redemption value and issuance costs related to redeemable convertible preferred stock

  1,802  4,033 19,870   (4,230) (15,640) (19,870)
 1,802
 
 4,033
 19,870
 
 
 (4,230) (15,640) 
 (19,870)

Repurchase and retirement of redeemable convertible preferred stock

 (13,103) (224) (4,825) (74) (3,064) (722)  2,773  2,773 (13,103) (224) (4,825) (74) (3,064) (722) 
 2,773
 
 
 2,773

Exercise of warrants to purchase convertible preferred stock

     678      
 
 
 
 678
 
 
 
 
 
 

Exercise of warrants to purchase common stock

      23,735     
 
 
 
 
 23,735
 
 
 
 
 

Compensation expense associated with stock options

        2,196  2,196 
 
 
 
 
 
 
 2,196
 
 
 2,196

Exercise of stock options

      292,802  653  653 
 
 
 
 
 292,802
 
 653
 
 
 653

Conversion of redeemable convertible preferred stock into common stock

 (802,957) (14,971) (2,421,346) (39,982) (286,094) 18,516,993 19 149,885 136,190 286,094 (802,957) (14,971) (2,421,346) (39,982) (286,094) 18,516,993
 19
 149,885
 136,190
 
 286,094

Reclassification of warrants to purchase shares of redeemable convertible preferred stock into warrants to purchase common stock

        2,012  2,012 
 
 
 
 
 
 
 2,012
 
 
 2,012

Issuance of common stock in connection with initial public offering and private placement, net of issuance costs of $2,692

      7,083,667 7 96,818  96,825 
 
 
 
 
 7,083,667
 7
 96,818
 
 
 96,825

Net loss

         (21,898) (21,898)
 
 
 
 
 
 
 
 (21,898) 
 (21,898)
                     

Balance at December 31, 2013

  $  $ $ 28,348,630 $29 $250,107 $(192,324)$57,812 
 
 
 
 
 28,348,630
 29
 250,107
 (192,324) 
 57,812
                     
                     
Issuance of common stock net of expenses of $554
 
 
 
 
 2,760,000
 3
 129,171
 
 
 129,174
Stock-based compensation

 
 
 
 
 
 
 4,778
 
 
 4,778
Exercise of stock options
 
 
 
 
 853,507
 1
 3,207
 
 
 3,208
Net exercise of warrants to purchase common stock
 
 
 
 
 303,204
 
 7,422
 
 
 7,422
Exercise of warrants to purchase common stock
 
 
 
 
 166,684
 
 5,150
 
 
 5,150
Net loss
 
 
 
 
 
 
 
 (51,259) 
 (51,259)
Balance at December 31, 2014
 
 
 
 
 32,432,025
 33
 399,835
 (243,583) 
 156,285
Stock-based compensation

 
 
 
 
 
 
 12,075
 
 
 12,075
Exercise of stock options
 
 
 
 
 837,361
 1
 3,962
 
 
 3,963
Issuance of common stock related to ESPP
 
 
 
 
 23,787
 
 589
 
 
 589
Net exercise of warrants to purchase common stock
 
 
 
 
 20,182
 
 465
 
 
 465
Unrealized loss on available-for-sale securities
 
 
 
 
 
 
 
 
 (220) (220)
Net loss
 
 
 
 
 
 
 
 (63,894) 
 (63,894)
Balance at December 31, 2015
 $
 
 $
 $
 33,313,355
 $34
 $416,926
 $(307,477) $(220) $109,263

See accompanying notes to consolidated financial statements.



F-6



Acceleron Pharma Inc.

Consolidated Statements of Cash Flows

(amounts in thousands)


 Year Ended December 31, Year Ended December 31,

 2013 2012 2011 2015 2014 2013

Operating Activities

            

Net (loss) income

 $(21,898)$(32,582)$36,266 

Adjustments to reconcile net (loss) income to net cash (used in) provided by operating activities:

       
Net loss$(63,894) $(51,259) $(21,898)
Adjustments to reconcile net loss to net cash used in operating activities:     

Depreciation and amortization

 915 1,293 3,134 1,176
 1,118
 915

Loss on disposition of property and equipment

 32   34
 25
 32

Stock-based compensation

 2,196 1,206 1,427 12,075
 4,778
 2,196

Amortization of debt discount

  51 162 

Accretion of deferred interest

 342 335 271 
 (536) 342

Amortization of deferred debt issuance costs

 186 84 79 
 36
 186

Change in fair value of warrants

 26,875 2,258 481 3,528
 (5,037) 26,875

Gain on retirement of warrants

 (76)   
 
 (76)

Forgiveness of related party receivable

 237   
 
 237
Net amortization of premium on investments(406) 
 

Changes in assets and liabilities:

         

  

Prepaid expenses and other current assets

 (823) (594) 2,564 7
 (255) (823)

Collaboration receivables

 (840) (1,116) 1,836 (261) 249
 (840)

Related party receivable

 (4) (8) (6)
 
 (4)

Accounts payable

 (53) (1,272) 334 151
 (161) (53)

Accrued expenses

 709 1,640 (2,773)4,976
 (17) 709

Deferred revenue

 (26,949) (9,696) (35,130)(1,184) (1,673) (26,949)

Deferred rent

 (499) (482) 211 (519) (499) (499)

Restricted cash

  (1) 200 106
 11
 
       

Net cash (used in) provided by operating activities

 (19,650) (38,884) 9,056 
Net cash used in operating activities(44,211) (53,220) (19,650)

Investing Activities

         

  
Purchase of investments(134,697) 
 
Proceeds from maturities investments26,685
 
 

Purchases of property and equipment

 (307) (441) (27)(959) (514) (307)
       

Net cash used in investing activities

 (307) (441) (27)(108,971) (514) (307)

Financing Activities

            

Proceeds from issuance of redeemable convertible preferred stock, net of issuance costs

   30,378 

Proceeds from long-term debt, net of issuance costs

  19,935  

Proceeds from issuance of common stock from initial public offering, net of issuance costs

 86,825   
Proceeds from issuance of common stock from public offering, net of issuance costs(47) 129,174
 86,825

Proceeds from issuance of common stock from private placements

 10,000   
 
 10,000

Payments of long-term debt

 (3,669) (6,191) (9,476)
 (16,331) (3,669)

Payments made to repurchase redeemable convertible preferred stock, common stock and warrants to purchase common stock

 (300)   
 
 (300)
Proceeds from issuances of common stock related to employee stock purchase plan589
 
 

Proceeds from exercise of stock options and warrants to purchase common stock

 653 155 190 3,963
 4,188
 653
       

Net cash provided by financing activities

 93,509 13,899 21,092 4,505
 117,031
 93,509
       

Net increase (decrease) in cash and cash equivalents

 73,552 (25,426) 30,121 

Cash and cash equivalents at beginning of period

 39,611 65,037 34,916 
       

Cash and cash equivalents at end of period

 $113,163 $39,611 $65,037 
       
       
Net (decrease) increase in cash and cash equivalents(148,677) 63,297
 73,552
Cash and cash equivalents at beginning of year176,460
 113,163
 39,611
Cash and cash equivalents at end of year$27,783
 $176,460
 $113,163

Supplemental Disclosure of Cash Flow Information:

         

  

Cash paid for interest

 $1,657 $1,065 $1,461 $
 $1,574
 $1,657
       
       

Supplemental Disclosure of Non-Cash Investing and Financing Activities:

         

  

Accretion of dividends, interest, redemption value, and issuance costs on preferred stock

 $19,870 $27,061 $21,757 $
 $
 $19,870
       
       

Conversion of preferred stock into common stock

 $286,094 $ $ $
 $
 $286,094
       
       

Conversion of preferred stock warrants into common stock warrants

 $2,012 $ $ $
 $
 $2,012
       
       

Cashless exercise of warrants

 $678 $ $ 
       
       
Reclassification of warrant liability to additional paid-in capital$465
 $11,592
 $678

Capitalized follow-on public offering costs included in accrued expenses

 $74 $ $ $306
 $
 $74
       
       

Purchase of property and equipment included in accounts payable and accrued expenses

 $297 $ $ $270
 $11
 $297
       
       

See accompanying notes to consolidated financial statements.



F-7


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements

Years Ended December 31, 2013, 20122015, 2014 and 2011

2013



1. Nature of Business

Acceleron Pharma Inc. (Acceleron or the Company) was incorporated in the state of Delaware on June 13, 2003, as Phoenix Pharma, Inc. The Company subsequently changed its name to Acceleron Pharma Inc. and commenced operations in February 2004. The Company is a Cambridge, Massachusetts-based biopharmaceutical company focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases. The Company's research focusestherapeutic candidates that are based on the biology ofmechanisms that the Transforming Growth Factor-Beta (TGF-b) protein superfamily, a large and diverse group of molecules thathuman body uses to regulate the growth and repair of tissues throughoutits cells and tissues. The Company's research focuses on key natural regulators of cellular growth and repair, particularly the human body.Transforming Growth Factor-Beta (TGF-beta) protein superfamily. By couplingcombining its discovery and development expertise, including its proprietary knowledge of the TGF-bTGF-beta superfamily, withand its internal protein engineering and manufacturing capabilities, the Company has built a highly productive researchdiscovery and development platform that has generated numerous innovative protein therapeuticstherapeutic candidates with novel mechanisms of action. The Company has four internally discovered three protein therapeuticstherapeutic candidates that are currently being studied in 12 ongoing Phase 2 clinical trials, focused on the areas of cancer and rare diseases.

trials.

The Company is subject to risks common to companies in the biotechnology industry, including, but not limited to, risk that the Company never achieves profitability, the need for substantial additional financing, risk of relying on third parties, risks of clinical trial failures, dependence on key personnel, protection of proprietary technology and compliance with government regulations.

2. Summary of Significant Accounting Policies

The accompanying consolidated financial statements reflect the application of certain significant accounting policies as described below and elsewhere in these notes to the consolidated financial statements. The Company believes that a significant accounting policy is one that is both important to the portrayal of the Company's financial condition and results, and requires management's most difficult, subjective, or complex judgments, often as the result of the need to make estimates about the effect of matters that are inherently uncertain.

Principles of Consolidation

The accompanying consolidated financial statements include those of the Company and its wholly-owned subsidiary, Acceleron Pharma Security Corporation.Securities Corp. All significant intercompany balances and transactions have been eliminated in consolidation.

Basis of Presentation

The accompanying consolidated financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (GAAP). Any reference in these notes to applicable guidance is meant to refer to the authoritative United States generally accepted accounting principles as found in the Accounting Standards Codification (ASC) and Accounting Standards Update (ASU) of the Financial Accounting Standards Board (FASB).

Use of Estimates

The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

2. Summary of Significant Accounting Policies (Continued)

contingent assets and liabilities at the date of the financial statements, and the reported amounts expensed during the reporting period. Actual results could materially differ from those estimates.

Management considers many factors in selecting appropriate financial accounting policies and controls, and in developing the estimates and assumptions that are used in the preparation of these consolidated financial statements. Management must apply significant judgment in this process. In addition, other factors may affect estimates, including: expected business and operational changes, sensitivity and volatility associated with the assumptions used in developing estimates, and whether historical trends are expected to be representative of future trends. The estimation process often may yield a range of potentially reasonable estimates of the ultimate future outcomes and management must select an amount that falls within that range of reasonable estimates. This process may result in actual results differing materially from those estimated amounts used in the preparation of the consolidated financial statements if these results differ from historical experience, or other assumptions do not turn out to be substantially accurate, even if such assumptions are reasonable when made. In preparing these consolidated financial statements, management used significant estimates in the following areas, among others: revenue recognition, stock-based compensation expense, the determination of the fair value of stock-based awards, the fair value of liability-classified warrants, accrued expenses, and the recoverability of the Company's net deferred tax assets and related valuation allowance.

The Company utilized significant estimates and assumptions in determining the fair value of its common stock, prior to the completion of its IPO.initial public offering (IPO). The Company's board of directors (the Board) determined the estimated fair

F-8

Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


value of the Company's common stock based on a number of objective and subjective factors, including external market conditions affecting the biotechnology industry sector and the prices at which the Company sold shares of redeemable convertible preferred stock, the superior rights and preferences of securities senior to the Company's common stock at the time, and the likelihood of achieving a liquidity event, such as an IPO or sale of the Company.

Collaboration Receivable

Credit is extended to customers based upon an evaluation of the customer's financial condition. Collaboration receivables are recorded at net realizable value. The Company does not charge interest on past due balances. Collaboration receivables are determined to be past due when the payment due date is exceeded. The Company utilizes a specific identification accounts receivable reserve methodology based on a review of outstanding balances and previous activities to determine the allowance for doubtful accounts. The Company charges off uncollectible receivables at the time the Company determines the receivable is no longer collectible. The Company did not have an allowance for doubtful accounts at December 31, 20132015 or 2012.

Segment Information

Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision maker, or decision making group, in making decisions on how to allocate resources and assess performance. The Company's chief operating decision maker is the chief executive officer. The Company and the chief executive officer view the Company's operations and manage its business as one operating segment, which is the discovery, development and commercialization of novel protein therapeutics for cancer and


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

2. Summary of Significant Accounting Policies (Continued)

rare diseases. All material long-lived assets of the Company reside in the United States. The Company does use contract research organizations (CROs) and research institutions located outside the United States. Some of these expenses are subject to collaboration reimbursement which is presented as a component of cost sharing, net in the statementconsolidated statements of operations and comprehensive income (loss).

Cash and Cash Equivalents

and Restricted Cash

The Company considers all highly liquid investments purchased with original maturities of 90 days or less at acquisition to be cash equivalents. Cash and cash equivalents include cash held in banks and amounts held in interest-bearing money market accounts. Cash equivalents are carried at cost, which approximates their fair market value.

Concentrations of Credit Risk and Off-Balance Sheet Risk

The Company has no off-balance sheet risk, such as foreign exchange contracts, option contracts, or other foreign hedging arrangements. Financial instruments that potentially subject the Company to concentrations of credit risk are primarily cash, cash equivalents, restricted cash and accounts receivable.collaboration receivables. The Company maintains its cash and cash equivalent balances in the form of money market accounts with financial institutions that management believes are creditworthy. The Company's investment policy includes guidelines on the quality of the institutions and financial instruments and defines allowable investments that the Company believes minimizes the exposure to concentrationconcentrations of credit risk.

The Company routinely assesses the creditworthiness of its customers and collaboration partners. The Company has not experienced any material losses related to receivables from individual customers and collaboration partners, or groups of customers. The Company does not require collateral. Due to these factors, no additional credit risk beyond amounts provided for collection losses is believed by management to be probable in the Company's accounts receivable.

Disclosure of Fair Value of Financial Instruments

The carrying amounts of the Company's financial instruments, which include cash, cash equivalents, certificates of deposit, collaboration receivables, accounts payable, and accrued expenses, and notes payable, approximated their fair values at December 31, 2013 and 2012,2015 or 2014 due to the short-term nature of these instruments, and for the notes payable, the interest rates the Company believes it could obtain for borrowings with similar terms.instruments. See discussion below on the determination of the fair value of the Company's preferred and common stock warrants.

The Company has evaluated the estimated fair value of financial instruments using available market information and management's estimates. The use of different market assumptions and/or estimation methodologies could have a significant effect on the estimated fair value amounts.


F-9

Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


Fair Value Measurements

ASC Topic 820,Fair Value Measurement (ASC 820), establishes a fair value hierarchy for instruments measured at fair value that distinguishes between assumptions based on market data (observable inputs) and the Company's own assumptions (unobservable inputs). Observable inputs are


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

2. Summary of Significant Accounting Policies (Continued)

inputs that market participants would use in pricing the asset or liability based on market data obtained from sources independent of the Company. Unobservable inputs are inputs that reflect the Company's assumptions about the inputs that market participants would use in pricing the asset or liability, and are developed based on the best information available in the circumstances.

ASC 820 identifies fair value as the exchange price, or exit price, representing the amount that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants. As a basis for considering market participant assumptions in fair value measurements, ASC Topic 820 establishes a three-tier fair value hierarchy that distinguishes between the following:

Level 1—Quoted market prices in active markets for identical assets or liabilities.

Level 2—Inputs other than Level 1 inputs that are either directly or indirectly observable, such as quoted market prices, interest rates, and yield curves.

Level 3—Unobservable inputs developed using estimates of assumptions developed by the Company, which reflect those that a market participant would use.

To the extent that the valuation is based on models or inputs that are less observable or unobservable in the market, the determination of fair value requires more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is greatest for instruments categorized in Level 3. A financial instrument's level within the fair value hierarchy is based on the lowest level of any input that is significant to the fair value measurement.

Items measured at fair value on a recurring basis include warrants to purchase redeemable convertible preferred stock, which were outstanding until the closing of the IPO, and warrants to purchase common stock (Note 6)7). During the periods presented, the Company has not changed the manner in which it values assets and liabilities that are measured at fair value using Level 3 inputs.

The following tables set forth the Company's financial instruments carried at fair value using the lowest level of input applicable to each financial instrument as of December 31, 20132015 and 20122014 and (in thousands):


 December 31, 2013 December 31, 2015

 Quoted Prices
in Active Markets
for Identical Items
(Level 1)
 Significant Other
Observable
Inputs
(Level 2)
 Significant
Unobservable
Inputs
(Level 3)
 Total Quoted Prices
in Active Markets
for Identical Items
(Level 1)
 Significant Other
Observable
Inputs
(Level 2)
 Significant
Unobservable
Inputs
(Level 3)
 Total

Assets:

          
  
  
  

Money market funds

 $101,394 $ $ $101,394 $24,811
 $
 $
 $24,811
Corporate obligations
 67,706
 
 67,706
U.S. Treasury securities
 10,991
 
 10,991
Certificates of deposit
 16,776
 
 16,776
Mortgage and other asset backed securities
 13,228
 
 13,228

Restricted cash

 913   913 796
 
 
 796
         
         

Total assets

 $102,307 $ $ $102,307 $25,607
 $108,701
 $
 $134,308
         
         

Liabilities:

          
  
  
  

Warrants to purchase common stock

 $ $ $30,753 $30,753 $
 $
 $17,187
 $17,187
         

Total liabilities

 $ $ $30,753 $30,753 $
 $
 $17,187
 17,187
         
         


F-10


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 20122015, 2014 and 2011

2. Summary of Significant Accounting Policies (Continued)

2013



 
 December 31, 2012 
 
 Quoted Prices
in Active Markets
for Identical Items
(Level 1)
 Significant other
Observable
Inputs
(Level 2)
 Significant
Unobservable
Inputs
(Level 3)
 Total 

Assets:

             

Money market funds

 $36,847 $ $ $36,847 

Restricted cash

  913      913 
          
          

Total assets

 $37,760 $ $ $37,760 
          
          

Liabilities:

             

Warrants to purchase redeemable convertible preferred stock

 $ $ $1,422 $1,422 

Warrants to purchase common stock

      5,229  5,229 
          

Total liabilities

 $ $ $6,651 $6,651 
          
          
 December 31, 2014
 Quoted Prices
in Active Markets
for Identical Items
(Level 1)
 Significant Other
Observable
Inputs
(Level 2)
 Significant
Unobservable
Inputs
(Level 3)
 Total
Assets: 
  
  
  
Money market funds$169,679
 $
 $
 $169,679
Restricted cash902
 
 
 902
Total assets$170,581
 $
 $
 $170,581
Liabilities: 
  
  
  
Warrants to purchase common stock$
 $
 $14,124
 $14,124
Total liabilities$
 $
 $14,124
 $14,124


The following table sets forth a summary of changes in the fair value of the Company's preferred and common stock warrant liabilities, which represent a recurring measurement that is classified within Level 3 of the fair value hierarchy, wherein fair value is estimated using significant unobservable inputs (in thousands):


 Year Ended
December 31,
 
Year Ended
December 31,

 2013 2012 2015 2014

Beginning balance

 $6,651 $4,393 $14,124
 $30,753

Change in fair value

 26,875 2,258 3,528
 (5,037)

Exercises

 (678)  (465) (11,592)

Repurchases

 (83)  
 

Conversions

 (2,012)  
 
     

Ending balance

 $30,753 $6,651 $17,187
 $14,124
     
     

The money market funds noted above are included in cash and cash equivalents in the accompanying consolidated balance sheets. The Company recognizes transfers between levels of the fair value hierarchy as of the end of the reporting period. There were no transfers within the hierarchy during the years ended December 31, 2013 or 2012 except for the transfer out of the warrants to purchase redeemable convertible preferred stock as described below.

        During the year 2013, as a result of the closing of the IPO, the warrants to purchase preferred stock were converted to warrants to purchase common stock. The resulting warrants to purchase common stock meet the criteria to be classified as permanent equity2015 and are no longer required to be measured at fair value at each reporting period.

2014.

The fair value of the warrants to purchase preferredcommon stock that were classified as liabilities was estimated using the Black-Scholes option pricing model aton the date of issuance and on each re-measurement date. Thisdate for those warrants to purchase common stock classified as liabilities was estimated using either the Monte Carlo simulation framework, which incorporates future financing events over the remaining life of the warrants to purchase common stock, or for certain re-measurement dates including December 31, 2015 and 2014, due to the warrants being deeply in the money, the Black-Scholes option pricing model was used. The Black-Scholes method of valuation involves using inputs such as the fair value of the


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

2. Summary of Significant Accounting Policies (Continued)

Company's various classes of preferred stock, stock price volatility, the contractual term of the warrants, risk free interest rates, and dividend yields. At each reporting period the company evaluates the best valuation methodology. Due to the nature of these inputs, the valuation of the warrants is considered a Level 3 measurement.

See Note 67 for further discussions of the accounting for the warrants, as well as for a summary of the significant inputs and assumptions used to determine the fair value of the warrants.

        The fair value of warrants to purchase common stock that are classified as liabilities was estimated using a Monte Carlo model up until September 30, 2013. This method of valuation involves using inputs such as the fair value of a share of common stock, stock price volatility, and the contractual term of the warrants. Due to the warrants being deeply in the money as of December 31, 2013, the valuation method to estimate the warrants to purchase common stock was changed to the Black-Scholes option pricing model. Due to the nature of these inputs, the valuation of the warrants is considered a Level 3 measurement.

The Company measures eligible assets and liabilities at fair value, with changes in value recognized in earnings. Fair value treatment may be elected either upon initial recognition of an eligible asset or liability or, for an existing asset or liability, if an event triggers a new basis of accounting. The Company did not elect to remeasure any of its existing financial assets or liabilities, and did not elect the fair value option for any financial assets and liabilities transacted in the years ended December 31, 20132015 or 2012.

Property and Equipment

Property and equipment is stated at cost. Maintenance and repairs that do not improve or extend the lives of the respective assets are expensed to operations as incurred. Upon disposal, retirement or sale the related cost and accumulated depreciation is

F-11

Table of Contents
Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


removed from the accounts and any resulting gain or loss is included in the results of operations. Depreciation and amortization is calculated using the straight-line method over the estimated useful lives of the assets, which are as follows:

AssetEstimated Useful Life

Computer equipment and software

3 years

Office and laboratory equipment

3 years

Leasehold improvements

Shorter of the useful life or remaining lease term

The Company reviews long-lived assets when events or changes in circumstances indicate the carrying value of the assets may not be recoverable. Recoverability is measured by comparison of the book values of the assets to future net undiscounted cash flows that the assets are expected to generate. If such assets are considered to be impaired, the impairment to be recognized is measured by the amount by which the book value of the assets exceed their fair value, which is measured based on the projected discounted future net cash flows arising from the assets. No impairment losses have been recorded during the years ended December 31, 2013, 2012 or 2011.


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 20122015, 2014 and 2011

2. Summary of Significant Accounting Policies (Continued)

Revenue Recognition

The company has primarily generated revenue through collaboration, license and research arrangements with collaboration partners for the development and commercialization of protein therapeutics.

therapeutic candidates.

The Company recognizes revenue in accordance with FASB ASC Topic 605,Revenue Recognition. Accordingly, revenue is recognized for each unit of accounting when all of the following criteria are met: (1) persuasive evidence of an arrangement exists; (2) delivery has occurred or services have been rendered; (3) the fee is fixed or determinable; and (4) collectability is reasonably assured.

Amounts received prior to satisfying the revenue recognition criteria are recorded as deferred revenue in the Company's consolidated balance sheets. Amounts expected to be recognized as revenue within the 12 months following the balance sheet date are classified as deferred revenue, current portion. Amounts not expected to be recognized as revenue within the 12 months following the balance sheet date are classified as deferred revenue, net of current portion.

Multiple Element Revenue Arrangements

The Company enters into collaboration agreements from time to time, which are more fully described in Note 9.10. The arrangements generally contain multiple elements or deliverables, which may include (1) licenses, or options to obtain licenses, to the Company's technology, (2) research and development activities performed for the collaboration partner, (3) participation on Joint Development Committees, and (4) manufacturing clinical or preclinical material. Payments pursuant to these arrangements typically include non-refundable, up-front payments, milestone payments upon achieving significant development events, research and development reimbursements, sales milestones, and royalties on future product sales.

Effective January 1, 2011, the Company adopted ASU No. 2009-13,Multiple-Deliverable Revenue Arrangements (ASU 2009-13), which amends ASC Topic 605-25,Revenue Recognition—Multiple Element Arrangements (ASC 605-25). The Company applies this guidance to new arrangements as well as existing agreements that are significantly modified after January 1, 2011. For agreements that are significantly modified, the Company determines the estimated selling price for the remaining undelivered elements as of the date of the material modification and allocates arrangement consideration based upon the estimated selling price to the undelivered elements.

The application of the multiple element guidance requires subjective determinations, and requires management to make judgments about the individual deliverables, and whether such deliverables are separable from the other aspects of the contractual relationship. Deliverables are considered separate units of accounting provided that: (1) the delivered item(s) has value to the customer on a stand-alone basis and (2) if the arrangement includes a general right of return relative to the delivered item(s), delivery or performance of the undelivered item(s) is considered probable and substantially in the control of the Company. In determining the units of accounting, management evaluates certain criteria, including whether the deliverables have stand-alone value, based on the consideration of the relevant facts and circumstances for each arrangement, such as the research, manufacturing and commercialization capabilities of the collaboration partner and the availability of the associated expertise in the general marketplace. In addition, the Company considers whether the collaboration


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

2. Summary of Significant Accounting Policies (Continued)

partner can use the other deliverable(s) for their intended purpose without the receipt of the remaining element(s), whether the value of the deliverable is dependent on the undelivered item(s) and whether there are other vendors that can provide the undelivered element(s).


F-12

Table of Contents
Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


Arrangement consideration that is fixed or determinable is allocated among the separate units of accounting using the relative selling price method, and the applicable revenue recognition criteria, as described above, are applied to each of the separate units of accounting in determining the appropriate period or pattern of recognition.

The Company determines the estimated selling price for deliverables within each agreement using vendor-specific objective evidence (VSOE) of selling price, if available, third-party evidence (TPE) of selling price if VSOE is not available, or management's best estimate of selling price (BESP) if neither VSOE nor TPE is available. Subsequent to the adoption of ASU 2009-13, the Company typically uses BESP to estimate the selling price of the deliverables. Determining the BESP for a unit of accounting requires significant judgment. In developing the BESP for a unit of accounting, the Company considers applicable market conditions and relevant entity-specific factors, including factors that were contemplated in negotiating the agreement with the customer and estimated costs. The Company validates the BESP for units of accounting by evaluating whether changes in the key assumptions used to determine the BESP will have a significant effect on the allocation of arrangement consideration between multiple units of accounting.

The Company typically receives up-front, non-refundable payments when licensing its intellectual property in conjunction with a collaboration agreement. When management believes the license to its intellectual property does not have stand-alone value from the other deliverables to be provided in the arrangement, the Company generally recognizes revenue attributed to the license on a straight-line basis over the contractual or estimated performance period, which is typically the term of the Company's research and development or manufacturing obligations. The Company continually evaluates these periods, and will adjust the period of revenue recognition if circumstances change. When management believes the license to its intellectual property has stand-alone value, the Company generally recognizes revenue attributed to the license upon delivery.

Research and development funding is recognized as revenue in the period that the related services are performed. When the Company acts as the principal under its collaboration agreements, it records payments received for the reimbursement of research and development costs as cost-sharing revenue in the consolidated statements of operations and comprehensive income (loss).loss. To the extent that the Company reimburses the collaborator for costs incurred, the Company records these costs as a reduction of cost-sharing revenue.

The Company's agreements may contain options which provide the collaboration partner the right to obtain additional licenses. Options are considered substantive if, at the inception of the arrangement, the Company is at risk as to whether the collaboration partner will choose to exercise the option. Factors considered in evaluating whether an option is substantive include the overall objective of the arrangement, the benefit the collaborator might obtain from the arrangement without exercising the option, the cost to exercise the option and the likelihood that the option will be exercised. For arrangements under which an option is considered substantive, the Company does not consider the item underlying the option to be a deliverable at the inception of the arrangement and the associated option fees are not included in allocable arrangement consideration, assuming the option is not priced at a significant and incremental discount. Conversely, for arrangements under which an option is not


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

2. Summary of Significant Accounting Policies (Continued)

considered substantive or if an option is priced at a significant and incremental discount, the Company would consider the item underlying the option to be a deliverable at the inception of the arrangement and a corresponding amount would be included in allocable arrangement consideration.

Effective January 1, 2011, the Company adopted ASU No. 2010-17,Revenue Recognition—Milestone Method (ASU 2010-17). At the inception of each arrangement that includes milestone payments, the Company evaluates, with respect to each milestone, whether the milestone is substantive and at-risk. This evaluation includes an assessment of whether (a) the consideration is commensurate with either (1) the entity's performance to achieve the milestone, or (2) the enhancement of the value of the delivered item(s) as a result of a specific outcome resulting at least in part from the entity's performance to achieve the milestone, (b) the consideration relates solely to past performance, and (c) the consideration is reasonable relative to all of the deliverables and payment terms within the arrangement. The Company evaluates factors such as the scientific, regulatory, commercial, and other risks that must be overcome to achieve the respective milestone, the level of effort and investment required to achieve the respective milestone, and whether the milestone consideration is reasonable relative to all deliverables and payment terms in the arrangement in making this assessment. On the milestone achievement date, assuming all other revenue recognition criteria are met and the milestone is deemed substantive and at-risk, the Company recognizes the payment as license and milestone revenue. For milestones that are not deemed substantive and at-risk, where payment is reasonably assured, the Company recognizes the milestone payment over the remaining service period.

Sales and commercial milestones and royalties will be recognized when and if earned, provided collectability is reasonably assured.

        Contract manufacturing revenue is recognized upon delivery


F-13

Table of the product in accordance with the terms of the contract, which specifies when transfer of titleContents
Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and risk of loss occurs.



Research and Development Expenses

Research and development costs are charged to expense as costs are incurred in performing research and development activities. Research and development costs include all direct costs, including salaries, stock compensation and benefits for research and development personnel, outside consultants, costs of clinical trials, sponsored research, clinical trials insurance, other outside costs, depreciation and facility costs related to the development of drug candidates. The Company records up-front, non-refundable payments made to outside vendors, or other payments made in advance of services performed or goods being delivered, as prepaid expenses, which are expensed as services are performed or the goods are delivered.

Certain research and development projects are, or have been, partially funded by collaboration agreements, and the expenses related to these activities are included in research and development costs. The Company records the related reimbursement of research and development costs under these agreements as revenue, as more fully described above and in Note 9.

10.

Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

2. Summary of Significant Accounting Policies (Continued)

At December 31, 2013,2015, the Company had two stock-based compensation plans, which are more fully described in Note 10.11. The Company accounts for stock-based compensation in accordance with the provisions of ASC Topic 718,Compensation—Stock Compensation (ASC 718), which requires the recognition of expense related to the fair value of stock-based compensation awards in the consolidated statements of operations and comprehensive income (loss).loss.

For stock options issued to employees and members of the Board for their services on the Board, the Company estimates the grant date fair value of each option using the Black-Scholes option-pricing model. The use of the Black-Scholes option-pricing model requires management to make assumptions with respect to the expected term of the option, the expected volatility of the common stock consistent with the expected life of the option, risk-free interest rates and expected dividend yields of the common stock. For awards subject to service-based vesting conditions, the Company recognizes stock-based compensation expense, net of estimated forfeitures, equal to the grant date fair value of stock options on a straight-line basis over the requisite service period, which is generally the vesting term. For awards subject to both performance and service-based vesting conditions, the Company recognizes stock-based compensation expense using an accelerated recognition method when it is probable that the performance condition will be achieved. If achievement of the performance condition is not probable, but the award will vest based on the service condition, expense is recognized over the requisite service period. Forfeitures are required to be estimated at the time of grant and revised, if necessary, in subsequent periods if actual forfeitures differ from those estimates.

The Company expenses restricted stock unit awards to employees based on the fair value of the award on a straight-line basis over the associated service period of the award.
Share-based payments issued to non-employees are recorded at their fair values, and are periodically revalued as the equity instruments vest and are recognized as expense over the related service period in accordance with the provisions of ASC 718 and ASC Topic 505 (ASC 505), Equity. For stock-based awards granted to non-employees, the Company recognizes stock-based compensation expense using an accelerated recognition method.

See Note 1011 for a discussion of the assumptions used by the Company in determining the grant date fair value of options granted under the Black-Scholes option pricing model, as well as a summary of the stock option activity under the Company's stock-based compensation planplans for the year ended December 31, 2013.

Income Taxes

Income taxes are recorded in accordance with ASC Topic 740,Income Taxes (ASC 740), which provides for deferred taxes using an asset and liability approach. The Company recognizes deferred tax assets and liabilities for the expected future tax consequences of events that have been included in the financial statements or tax returns. Deferred tax assets and liabilities are determined based on the difference between the financial statement and tax bases of assets and liabilities using enacted tax rates in effect for the year in which the differences are expected to reverse. Valuation allowances are provided, if based upon the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized.

The Company accounts for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, the Company recognizes the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as



F-14


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 20122015, 2014 and 2011

2. Summary 2013



of Significant Accounting Policies (Continued)

the tax position as well as consideration of the available facts and circumstances. As of December 31, 2013 and 2012,2015 or 2014, the Company does not have any significant uncertain tax positions.

Net Income (Loss) Per Share

Net income (loss) per share information is determined using the two-class method, which includes the weighted-average number of shares of common stock outstanding during the period and other securities that participate in dividends (a participating security). The Company's redeemable convertible preferred stock are participating securities as defined by ASC 260-10,Earnings Per Share.

Under the two-class method, basic net income (loss) per share applicable to common stockholders is computed by dividing the net income (loss) applicable to common stockholders by the weighted-average number of common shares outstanding for the reporting period. Diluted net income (loss) per share is computed using the more dilutive of (1) the two-class method or (2) the if-converted method. The Company allocates net income first to preferred stockholders based on dividend rights under the Company's articles of incorporation and then to preferred and common stockholders based on ownership interests. Net losses are not allocated to preferred stockholders as they do not have an obligation to share in the Company's net losses.

Diluted net income (loss) per share gives effect to all potentially dilutive securities, including redeemable convertible preferred stock, and shares issuable upon the exercise of outstanding warrants and stock options, using the treasury stock method. For the years ended December 31, 20132015, 2014 and 2012,2013, the Company has excluded the effects of all potentially dilutive shares, which include redeemable convertible preferred stock, warrants for redeemable convertible preferred stock, warrants for common stock and outstanding common stock options, from the weighted-average number of common shares outstanding as their inclusion in the computation for these two years would be anti-dilutive due to net losses.

losses incurred.

The following is a summary of the common stock equivalents which were excluded from the calculation of diluted net income (loss)loss per share for the periods indicated because including them would have had an anti-dilutive effect (in thousands):


 Year Ended December 31, Year Ended December 31,

 2013 2012 2011 2015 2014 2013

Outstanding stock options

 3,709 3,730  3,191
 3,230
 3,709

Common stock warrants

 908 884 874 398
 422
 908
Shares issuable under employee stock purchase plan15
 14
 
Restricted stock units521
 
 

Preferred stock

 13,218 18,166  
 
 13,218

Preferred stock warrants

 114 248  
 
 114
       4,125
 3,666
 17,949

 17,949 23,028 874 
       
       

Comprehensive income (loss) is defined as the change in equity of a business enterprise during a period from transactions, other events, and circumstances from non-owner sources. Comprehensive income (loss)loss consists of net income (loss)loss and other comprehensive income (loss),loss, which includes certain changes in equity that are excluded from net income (loss).loss. Comprehensive income (loss)loss has


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

2. Summary of Significant Accounting Policies (Continued)

been disclosed in the accompanying consolidated statements of operations and comprehensive (loss) incomeloss. Accumulated other comprehensive loss is presented separately on the consolidated balance sheets and equals the Company's net income (loss) for all periods presented.

Subsequent Events

The Company considers events or transactions that occur after the balance sheet date but prior to the issuance of the financial statements to provide additional evidence relative to certain estimates or to identify matters that require additional disclosure. Subsequent events have been evaluated as required. The Company has evaluated all subsequent events and determined that there are no material recognized or unrecognized subsequent events, other than as disclosed within the notes to the consolidated financial statements. See Note 15.


F-15

Table of New or Revised Accounting Standards

        On April 5, 2012, the Jump-Start Our Business Startups Act (the JOBS Act) was signed into law. The JOBS Act contains provisions that, among other things, reduce certain reporting requirements for an "emerging growth company." As an emerging growth company the Company has electedContents

Acceleron Pharma Inc.
Notes to not take advantage of the extended transition period afforded by the JOBS Act for the implementation of new or revised accounting standards,Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and as a result, will comply with new or revised accounting standards on the relevant dates on which adoption of such standards is required for non-emerging growth companies.



Recently Adopted Accounting Pronouncements

From time to time, new accounting pronouncements are issued by the FASB or other standard setting bodies and adopted by the Company as of the specified effective date. Unless otherwise discussed, the Company believes that the impact of recently issued standards that are not yet effective will not have a material impact on its financial position or results of operations upon adoption.

In May 2014, the FASB issued ASU No. 2014-09, Revenue from Contracts with Customers (Topic 606), which supersedes all existing revenue recognition requirements, including most industry-specific guidance. The new standard requires a company to recognize revenue when it transfers goods or services to customers in an amount that reflects the consideration that the company expects to receive for those goods or services. The new standard will be effective for the Company on January 1, 2018. The Company is currently evaluating the method of adoption and the potential impact that Topic 606 may have on its financial position and results of operations.
In August 2014, the FASB issued ASU No. 2014-15, Presentation of Financial Statements—Going Concern (Subtopic 205-40). The ASU requires all entities to evaluate for the existence of conditions or events that raise substantial doubt about the entity’s ability to continue as a going concern within one year after the issuance date of the financial statements. The accounting standard is effective for interim and annual periods ending after December 15, 2016, and will not have a material impact on the consolidated financial statements, but may impact the Company’s footnote disclosures.
In February 2015, the FASB issued ASU 2015-02, Consolidation (Topic 810), Amendments to the Consolidation Analysis, which updated accounting guidance on consolidation requirements. This update changes the guidance with respect to the analysis that a reporting entity must perform to determine whether it should consolidate certain types of legal entities. This guidance is effective for annual periods, and interim periods within those annual periods, beginning after December 15, 2015, with early adoption permitted. We will adopt this standard on January 1, 2016 and the adoption is not expected to have a material impact on our consolidated financial statements.
In November 2015, the FASB issued ASU No. 2015-17, Income Taxes (Topic 740), Balance Sheet Classification of Deferred Taxes. The new standard requires that deferred tax assets and liabilities be classified as non-current in a classified statement of financial position. The new standard will be effective for the Company on January 1, 2017. The Company is currently evaluating the method of adoption and the potential impact that Topic 740 may have on its financial position and results of operations.
3. Property and Equipment, Net

Property and equipment, net, consists of the following (in thousands):


 December 31, December 31,

 2013 2012 2015 2014

Computer equipment and software

 $921 $919 $1,163
 $956

Office equipment

 205 179 260
 213

Laboratory equipment

 12,334 11,815 11,458
 11,311

Leasehold improvements

 9,930 10,088 9,990
 9,930

Construction in progress

  8 390
 11
     

Total property and equipment

 23,390 23,009 23,261
 22,421

Accumulated depreciation and amortization

 (19,685) (18,950)(20,155) (19,334)
     

Property and equipment, net

 $3,705 $4,059 $3,106
 $3,087
     
     

Depreciation and amortization expense was $0.9$1.2 million, $1.3$1.1 million and $3.1$0.9 million for the years ending December 31, 2015, 2014 and 2013 2012 and 2011, respectively.



F-16

Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 20122015, 2014 and 2011

2013



4. Restricted Cash

As of December 31, 20132015, and 2012,2014, the Company maintained letters of credit totaling $0.8 million and $0.9 million respectively, held in the form of a money market accountcertificates of deposit as collateral for the Company's facility lease obligations and its credit cards.


F-17

Table of Contents
Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


5. Cash, Cash Equivalents and Short-term and Long-term Investments
The Company considers all highly liquid investments purchased with original maturities of 90 days or less at acquisition to be cash equivalents. Cash and cash equivalents include cash held in banks and amounts held primarily in interest-bearing money market accounts. Cash equivalents are carried at cost, which approximates their fair market value.
5.The Company determines the appropriate classification of marketable securities at the time of purchase and reevaluates such designation at each balance sheet date. The Company has classified all of its marketable securities at December 31, 2015 as “available-for-sale” pursuant to ASC 320, Investments – Debt and Equity Securities. The Company records available-for-sale securities at fair value, with the unrealized gains and losses included in accumulated other comprehensive income (loss) in stockholders’ equity. There were no realized gains or losses on marketable securities for the years ended December 31, 2015, 2014 and 2013.
Investments not classified as cash equivalents are presented as either short-term or long-term investments based on both their maturities as well as the time period the Company intends to hold such securities.
The Company adjusts the cost of available-for-sale debt securities for amortization of premiums and accretion of discounts to maturity. The Company includes such amortization and accretion in interest income. The cost of securities sold is based on the specific identification method. The Company includes in interest income interest and dividends on securities classified as available-for-sale.
The Company reviews marketable securities for other-than-temporary impairment whenever the fair value of a marketable security is less than the amortized cost and evidence indicates that a marketable security’s carrying amount is not recoverable within a reasonable period of time. Other-than-temporary impairments of investments are recognized in the consolidated statements of operations if the Company has experienced a credit loss, has the intent to sell the marketable security, or if it is more likely than not that the Company will be required to sell the marketable security before recovery of the amortized cost basis. Evidence considered in this assessment includes reasons for the impairment, compliance with the Company’s investment policy, the severity and the duration of the impairment and changes in value subsequent to the end of the period.
The following is a summary of cash, cash equivalents and available-for-sale securities as of December 31, 2015 and December 31, 2014 (in thousands):
 December 31, 2015
 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Estimated Fair Value
Cash and cash equivalents due in 90 days or less$27,783
 $
 $
 $27,783
Available-for-sale securities:       
Corporate obligations due in one year or less53,243
 
 (81) 53,162
Corporate obligations due in more than one year14,112
 
 (72) 14,040
U.S. Treasury securities due in one year or less6,016
 
 (4) 6,012
U.S. Treasury securities due in more than one year4,995
 
 (15) 4,980
Certificates of deposit due in one year or less11,890
 
 
 11,890
Certificates of deposit due in more than one year4,886
 
 
 4,886
Mortgage and other asset backed securities due in one year or less6,010
 
 (10) 6,000
Mortgage and other asset backed securities due in more than one year7,266
 
 (38) 7,228
Total available-for-sale securities$108,418
 $
 $(220) $108,198
Total cash, cash equivalents and available-for-sale securities$136,201
 $
 $(220) $135,981
 December 31, 2014
 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Estimated Fair Value
Cash and cash equivalents due in 90 days or less$176,460
 $
 $
 $176,460
Total cash and cash equivalents$176,460
 $
 $
 $176,460

F-18

Table of Contents
Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


6. Accrued Expenses

Accrued expenses consist of the following (in thousands):


 December 31, 

 2013 2012 December 31,

Collaboration expense

 $ $1,000 
2015 2014

Research and development related

 1,330 1,282 $4,938
 $2,291

Employee compensation

 2,930 2,448 3,551
 3,050

Professional services

 1,017 607 1,198
 426

Other

 1,650 816 2,713
 1,081
     $12,400
 $6,848

 $6,927 $6,153 
     
     

6.

7. Warrants

Below is a summary of the number of shares issuable upon exercise of outstanding warrants and the terms and accounting treatment for the outstanding warrants (in thousands, except per share data):

 Warrants as of      
     
Weighted-
Average
Exercise
   
Balance Sheet
Classification
 December 31, 2015 December 31, 2014 
Price Per
Share
 Expiration December 31, 2015 December 31, 2014
Warrants to purchase common stock393
 409
 5.88
 June 10, 2020 - July 9, 2020 Liability(2) Liability(2)
Warrants to purchase common stock5
 13
 4.00 - 7.40
 March 31, 2016 - December 31, 2017 Equity(1) (3) (4) Equity(1) (3) (4)
All warrants398
 422
 $5.88
      

 
 Warrants as of  
  
  
 
  
 Balance Sheet
Classification
 
  
  
 Weighted-
Average
Exercise
Price Per
Share
  
 
 December 31,  
 
  
 December 31,
2013
 December 31,
2012
 
 2013 2012 Expiration

Warrant to purchase Series A Preferred Stock

    107 $4.00 February 28, 2013 N/A(1) Liability

Warrants to purchase Series B Preferred Stock

    32  7.40 December 21, 2013 N/A(2)(4) Liability

Warrants to purchase Series C-1 Preferred Stock

    46  10.92 June 25, 2019 N/A(2) Liability

Warrants to purchase Series D-1 Preferred Stock

    64  12.56 March 18, 2020 N/A(2) Liability

Warrants to purchase Common Stock

  46    10.92 June 25, 2019 Equity(2) N/A

Warrants to purchase Common Stock

  64    12.56 March 18, 2020 Equity(2) N/A

Warrants to purchase Common stock

  857  872  5.88 June 10, 2020 - July 9, 2020 Liability Liability

Warrants to purchase Common stock

  13  13  4.00 - 7.40 March 31, 2015 - December 31, 2017 Equity(3) Equity
             

All warrants

  980  1,134 $6.53      
             
             


(1)
On February 6, 2013, the warrant holder exercised a warrant to purchase 107 shares of Series A Preferred Stock on a net basis, resulting in the issuance of 47 shares of Series A Preferred Stock.

(2)
Warrants to purchase Series B Preferred Stock, Series C-1 Preferred Stock, and Series D-1 Preferred Stock were converted to warrants to purchase common stock at the closing of the IPO on September 24, 2013.

(3)
Warrants to purchase common stock were issued in connection with various debt financing transactions that were consummated in periods prior to December 31, 2012. See discussion below for further details.

(4)
On December 19 and 20, 2013, the warrants holders exercised warrants to purchase 32 shares of Common Stock on a net basis, resulting in the issuance of 24 shares of Common Stock.
(1)
In March 2015, the warrant holders exercised warrants to purchase 5,029 shares of Common Stock on a net basis, resulting in the issuance of 4,519 shares of Common Stock.
(2)In May 2015, the warrant holders exercised warrants to purchase 16,665 shares of Common Stock on a net basis, resulting in the issuance of 13,588 shares of Common Stock.

Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

6. Warrants (Continued)

(3)
In August 2015, the warrant holders exercised warrants to purchase 2,399 shares of Common Stock on a net basis, resulting in the issuance of 2,075 shares of Common Stock.
(4)
Warrants to purchase common stock were issued in connection with various debt financing transactions that were consummated in periods prior to December 31, 2012. See discussion below for further details.

In connection with various financing transactions that were consummated in periods prior to December 31, 2012,2014, the Company issued warrants for the purchase of up to 106,500 shares of the Company's Series A redeemable convertible preferred stock (Series A Preferred Stock), 31,891 shares of the Company's Series B redeemable convertible preferred stock (Series B Preferred Stock), 45,786 shares of the Company's Series C-1 redeemable convertible preferred stock (Series C-1 Preferred Stock), and 63,693 shares of the Company's Series D-1 redeemable convertible preferred stock (Series D-1 Preferred Stock). Each warrant was immediately exercisable. The warrants to purchase Series A and Series B Preferred Stock expire seven years from the original date of issuance, while the warrants to purchase Series C-1 and Series D-1 Preferred Stock expire ten years from the original date of issuance. The warrants to purchase shares of the Company's preferred stock have an exercise price equal to the original issuance price of the underlying instrument. Each warrant is exercisable on either a physical settlement or net share settlement basis and the redemption provisions are outside the control of the Company. In connection with the closing of the Company's IPO on September 24, 2013, the outstanding warrants to purchase Series B Preferred Stock, Series C-1 Preferred Stock, and Series D-1 Preferred Stock were converted into warrants to purchase common stockstock. The exercise prices for each of these warrants remained unchanged.

The Company follows the provisions of ASC Topic 480,Issuer's Accounting for Freestanding Warrants and Other Similar Instruments on Shares that Are Redeemable, which requires that warrants to purchase redeemable preferred stock be

F-19

Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


classified as liabilities. In addition, the value of the warrants is remeasured to the then-current fair value at each reporting date. Changes in fair value are recorded to other income (expense), net. For the years ended December 31, 2013, 20122015 and 2011,2014, the Company remeasured the fair value of all of its outstanding warrants to purchase shares of the Company's preferred stock up until the conversion of such warrants on September 24, 2013, using current assumptions, resulting in an increase in fair value of $1.3 million, $0.4 million,zero, zero and $0.1$1.3 million, respectively, which was recorded in other expense net in the accompanying consolidated statementsstatement of operations and comprehensive (loss) income.loss. As a result of the closing of the IPO and the resulting conversion of the warrants to purchase preferred shares into warrants to purchase common stock, the fair value of the warrant liability at September 24, 2013 was reclassified to permanent equity and therefore, is no longer subject to remeasurement.

In December 2012, the Company modified the warrant to purchase 106,500 shares of Series A Preferred Stock and extended the expiration date from December 21, 2012 to February 28, 2013. During the year ended December 31, 2013, the holder of the warrant exercised the warrant on a net basis, resulting in the issuance of 46,668 shares of Series A Preferred Stock. Upon exercise, the Company re-measured the fair value of the warrant and recorded the resulting increase in fair value of $0.1 million as other expense in the accompanying statement of operations and comprehensive incomeloss for the year ended December 31, 2013.

In connection with the Series E redeemable convertible preferred stock (Series E Preferred Stock) financing transactions that took place in June 2010 and July 2010, the Company issued warrants to purchase up to 871,580 shares of common stock. Each warrant was immediately exercisable and expires ten years from the original date of issuance. The warrants to purchase shares of the Company's common stock have an exercise price equal to the estimated fair value of the underlying instrument as of the initial date such warrants were issued. Each warrant is exercisable on either a physical settlement


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

6. Warrants (Continued)

or net share settlement basis from the date of issuance. The warrant agreement contains a provision requiring an adjustment to the number of shares in the event the Company issues common stock, or securities convertible into or exercisable for common stock, at a price per share lower than the warrant exercise price. The Company concluded the anti-dilution feature required the warrants to be classified as liabilities under ASC Topic 815,Derivatives and Hedging—Contracts in Entity's Own Equity (ASC 815). The warrants are measured at fair value, with changes in fair value recognized as a gain or loss to other income (expense) in the consolidated statements of operations and comprehensive income (loss)loss for each reporting period thereafter. The fair value of the common stock warrants were recorded as a discount to the preferred stock issued of $3.0 million, and the preferred stock were being accreted to the redemption value. At the end of each reporting period, the Company remeasured the fair value of the outstanding warrants, using current assumptions, resulting in an increase (decrease) in fair value of $26.9$3.5 million, $1.9$(5.0) million and $0.3$26.9 million, respectively, which was recorded in other expenseincome (expense), net in the accompanying consolidated statements of operations and comprehensive (loss) incomeloss for the years ended December 31, 2013, 20122015, 2014 and 2011.2013. The Company will continue to re-measure the fair value of the liability associated with the warrants to purchase common stock at the end of each reporting period until the earlier of the exercise or the expiration of the applicable warrants. On March 31, 2013, the Company retired 13,994 warrants to purchase common stock as a consequence of a repurchase of shares from an investor. All remaining outstanding warrants were fully vested and exercisable as of December 31, 2013.2015.

In connection with various financing transactions that were consummated in periods prior to December 31, 2012,2015 the Company issued warrants to purchase up to 12,634 shares of common stock. The awards of warrants to purchase shares of common stock are accounted for as equity instruments. The warrants are exercisable at any time through their respective expiration dates. The fair value at issuance was calculated using the Black-Scholes option-pricing model, and was charged to interest expense during the periods the related debt was outstanding.

        The Company issued warrants to purchase up to 41,388 shares As of common stock in periods prior to December 31, 2012 in exchange for consulting services provided by2015, 5,206 warrants remain outstanding and expire a third party pursuant to stand-alone award agreements that are independent of an equity incentive plan. The warrants vested upon achievement of four milestones and were outstanding for approximately seven years from the date of issuance. During the year endedvarious dates through December 31, 2011, the holder exercised 41,388 warrants to purchase common stock on a net basis resulting in the issuance of 37,249 shares of common stock. There were no exercises, cancellations, or expirations of warrants during the years ended December 31, 2013 or 2012.

    2017.

Fair Value

The fair value of the warrants to purchase preferred stock on the date of issuance and on each re-measurement date was estimated using the Black-Scholes option pricing model. This method of valuation involves using inputs such as the fair value of the Company's various classes of preferred stock and common stock, stock price volatility, contractual term of the warrants, risk free interest rates, and dividend yields. The fair value of the warrants to purchase common stock on the date of issuance and on each re-measurement date for those warrants to purchase common stock classified as liabilities was estimated using either the Monte Carlo simulation framework, up until September 30, 2013, which


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

6. Warrants (Continued)

incorporated three incorporates future financing events over the remaining life of the warrants to purchase common stock. Duestock, or for certain re-measurement dates including December 31, 2015 and 2014, due to the warrants being deeply in the money, as of December 31, 2013, the valuation method to estimate the warrants to purchase common stock was changed to the Black-Scholes option pricing model. Due to the nature of these inputs and the valuation techniques utilized, the valuation of the warrants to purchase preferred stock and common stock are considered a Level 3 measurement (Note 2).

        The fair value of each warrant to purchase shares of the Company's Series A Preferred Stock was estimated using the Black-Scholes option pricing model withwas used. At each reporting period the following assumptions:

company evaluates the best valuation methodology.

 
 Year Ended December 31, 
 
 2013(2) 2012(1) 2011 

Fair value of underlying instrument

  n/a $9.24 $6.76 

Expected volatility

  n/a  69.1% 66.0%

Expected term (in years)

  n/a  0.16  1.16 

Risk-free interest rate

  n/a  0.04% 0.12%

Expected dividend yield

  n/a  % %
F-20

(1)
During December 2012, the expiration date of the warrant to purchase Series A Preferred Stock was extended from December 21, 2012 to February 28, 2013.

(2)
The warrant to purchase Series A Preferred Stock was exercised during the three months ended March 31, 2013.

        The fair value of each warrant to purchase shares of the Company's Series B Preferred Stock was estimated using the Black-Scholes option pricing model with the following assumptions:

 
 Year Ended December 31, 
 
 2013(1) 2012 2011 

Fair value of underlying instrument

 $20.03 $9.96 $7.56 

Expected volatility

  71.2% 69.1% 66.0%

Expected term (in years)

  0.24  0.97  1.98 

Risk-free interest rate

  0.04% 0.16% 0.25%

Expected dividend yield

  % % %

(1)
Warrants to purchase Series B Preferred Stock were converted to warrants to purchase common stock at the closing of the IPO on September 24, 2013.

Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 20122015, 2014 and 2011

6. Warrants (Continued)

        The fair value of each warrant to purchase shares of the Company's Series C-1 Preferred Stock was estimated using the Black-Scholes option pricing model with the following assumptions:

 
 Year Ended December 31, 
 
 2013(1) 2012 2011 

Fair value of underlying instrument

 $20.03 $11.04 $8.84 

Expected volatility

  71.2% 69.1% 66.0%

Expected term (in years)

  5.73  6.46  7.46 

Risk-free interest rate

  1.75% 0.95% 1.35%

Expected dividend yield

  % % %
2013

(1)
Warrants to purchase Series C-1 Preferred Stock were converted to warrants to purchase common stock at the closing of the IPO on September 24, 2013.

        The fair value of each warrant to purchase shares of the Company's Series D-1 Preferred Stock was estimated using the Black-Scholes option pricing model with the following assumptions:

 
 Year Ended December 31, 
 
 2013(1) 2012 2011 

Fair value of underlying instrument

 $20.03 $10.52 $8.84 

Expected volatility

  71.2% 69.1% 66.0%

Expected term (in years)

  6.48  7.22  8.22 

Risk-free interest rate

  1.75% 1.18% 1.62%

Expected dividend yield

  % % %

(1)
Warrants to purchase Series D-1 Preferred Stock were converted to warrants to purchase common stock at the closing of the IPO on September 24, 2013.

    Fair Value of Underlying Instrument

        The Company estimated the fair value of its shares of Series A Preferred Stock, Series B-1 Preferred Stock, Series C-1 Preferred Stock and Series D-1 Preferred Stock as of December 31, 2012 and 2011, and through the exercise or conversion of its Preferred stock warrants during 2013, using the PWERM (probability-weighted expected return method).

    Expected Volatility

        The Company estimated the expected volatility based on actual historical volatility of the stock price of similar companies with publicly-traded equity securities. The Company calculated the historical volatility of the selected companies by using daily closing prices over a period of the expected term of the associated award. The companies were selected based on their enterprise value, risk profiles, position within the industry, and with historical share price information sufficient to meet the expected term of the associated award. A decrease in the selected volatility would decrease the fair value of the underlying instrument.


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

6. Warrants (Continued)

        The Company based the expected term on the actual remaining contractual term of each respective warrant. A decrease in the expected term would decrease the fair value of the underlying instrument.

        The Company estimated the risk-free interest rate in reference to the yield on U.S. Treasury securities with a maturity date commensurate with the expected term of the associated award. A decrease in the selected risk-free rate would decrease the fair value of the underlying instrument.

        The Company estimated the expected dividend yield based on consideration of its historical dividend experience and future dividend expectations. The Company has not historically declared or paid dividends to stockholders. Moreover, it does not intend to pay dividends in the future, but instead expects to retain any earnings to invest in the continued growth of the business. Accordingly, the Company assumed an expected dividend yield of 0.0%.

7.

8. Commitments and Contingencies

Operating Leases

The Company leases its facilities under non-cancelable operating leases that expire at various dates through May 2018.March 2021. All of the Company's leases contain escalating rent clauses, which require higher rent payments in future years. The Company expenses rent on a straight-line basis over the term of the lease, including any rent-free periods. In addition, the Company received certain leasehold improvementlease incentives, and recorded these incentives as deferred rent, which is amortized as a reduction of rent expense over the life of the lease. Rent expense of approximately $3.5$3.4 million, $3.5$3.3 million and $3.6$3.5 million were incurred during the years ended December 31, 2015, 2014 and 2013, 2012 and 2011, respectively.

Future annual minimum lease payments as of December 31, 2013,2015, are as follows (in thousands):

2014

 $4,522 

2015

  4,106 

2016

  3,938 

2017

  3,938 

2018

  2,953 
    

Total

 $19,457 
    
    
20164,386
20174,547
20183,577
2019640
2020656
2021165
Total$13,971

        In February 2011,

On December 15, 2015, the Company entered into a subleasefive-year building lease for approximately 12,200 square feet of space located at 125 Sidney Street, Cambridge, Massachusetts. The lease commenced on January 1, 2016 when the lessor delivered the building to the Company. Rent will commence on April 1, 2016 and is approximately $0.6 million for the first year with annual rent escalations thereafter. The total operating lease obligation of for the term of this agreement foris $3.1 million. In addition, the lease provides a portioncontribution from the landlord towards the initial build-out of onethe space of up to $0.5 million. The Company has the option to extend this lease by an additional five years. In accordance with the lease, the Company will enter into a cash-collateralized irrevocable standby letter of credit in the amount of $0.2 million, naming the landlord as beneficiary.  
Legal Proceedings
Except as discussed below, the Company, from time to time, may be party to litigation arising in the ordinary course of its facility leases.business. The tenant will pay rent onCompany was not subject to any material legal proceedings during the lease from February 28, 2011 until May 30, 2015. Onyears ended December 31, 2015, 2014 and 2013, and, to the sublease agreement was expanded to include the remaining spacebest of that


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

7. Commitments and Contingencies (Continued)

facility. The expansion portion will be leased for one year, through December 31, 2014. The Company will continue to utilize the expansion portion of the leased property, once the sublease expires.

        Future annual minimum sublease proceeds as of December 31, 2013,its knowledge, no material legal proceedings are as follows (in thousands):

currently pending or threatened.

2014

 $832 

2015

  252 
    

Total

 $1,084 
    
    

    Legal Proceedings

On October 18, 2012, the Salk Institute for Biological Studies (Salk) filed a complaint in the Massachusetts Superior Court for Suffolk County, alleging that the Company breached one of the Company's two licensing agreements with Salk. The licensing agreement in dispute provides the Company with a license with respect to certain of Salk'sSalk’s U.S. patents related to the ActRIIB activin receptor proteins. Salk contendscontended that, under the licensing agreement, the Company owed Salk a greater share of the upfront payment that it received under its now-terminated agreement with Shire AG regarding ACE-031 and a share of the upfront payment and development milestone payments that the Company has received under its ongoing collaboration agreement with Celgene regarding ACE-536.luspatercept. Salk iswas seeking a total of approximately $10.5 million plus interest in payment and a 15% share of future development milestone payments received under the agreement with Celgene regarding ACE-536.luspatercept. The Company contendscontended that no additional amounts arewere due to Salk and that it hashad complied with all of its payment obligations under the applicable Salk license agreement.

The Company moved to dismiss the complaint on December 3, 2012. The Court denied the Company'sCompany’s motion on February 28, 2013. On March 14, 2013, Acceleron answered the complaint and asserted patent invalidity counterclaims. On the basis of those counterclaims, Acceleron removed the action on March 28, 2013 to the United States District Court for the District of Massachusetts. The parties have since reached an agreement on a stipulation as to certain patent issues raised in the action, and Acceleron hasthe Company dismissed its counterclaims. The Court held an initial scheduling conference on May 30, 2013, and the fact discovery is nowwas closed. The case is currently scheduled for trial in September 2014. The

On July 25, 2014, the Company intends to defend its position vigorously.

        The Company evaluated the suit under ASC Topic 450,Contingencies, as a loss contingency. The estimated loss from a loss contingency shall be accrued if information available before the financial statements are issued indicates that it is probable a liability had been incurred at the date of the financial statements, and the amount of loss can be reasonably estimated. BecauseSalk Institute for Biological Studies entered into an amendment (the Amendment) to that certain Exclusive License Agreement between Salk and the Company believes that the potential for an unfavorable outcome is not probable, it has not established a reserve with respect to the dispute as of December 31, 2013 or 2012.

        The Company's estimates can be affected by various factors. As of December 31, 2013regarding Activin Receptors (Type IIB) and 2012, management has determined a loss is reasonably possible. Although the Company believes it would successfully defend the lawsuit, the Company has in the past participated in settlement discussions with Salk. Accordingly, the Company has estimated the range of possible losses as of December 31, 2013 and 2012 to be between $0 and $10.5 million plus interest.



F-21

Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 20122015, 2014 and 2011

7. Commitments2013



Related Subject Matter for Therapeutic and Contingencies (Continued)

    Diagnostic Purposes, dated August 11, 2010 (the License Agreement). The License Agreement provides the Company with a license with respect to certain of Salk's U.S. patents related to the ActRIIB activin receptor proteins.


The Amendment was entered into as a condition to the settlement with Salk that provides for the release of all claims in the lawsuit. Pursuant to the settlement, the Company has made a one-time total payment of $5.0 million, inclusive of interest, to Salk and the Company has agreed to pay Salk 6% of future development milestone payments received under the agreement with Celgene relating to luspatercept. Finally, the Company and Salk have further agreed that the royalty percentage on net sales of luspatercept will remain at 1% as provided in the original license agreement with Salk, and that such royalty will be payable until June 2022.

The Company recorded the impact of the settlement as a charge to operations in the accompanying consolidated statement of operations and comprehensive loss for the year ended December 31, 2014.
Other

The Company is also party to various agreements, principally relating to licensed technology, that require future payments relating to milestones not met at December 31, 20132015 and 2012,2014, or royalties on future sales of specified products. No milestone or royalty payments under these agreements are expected to be payable in the immediate future. See Note 910 for discussion of these arrangements.

The Company enters into standard indemnification agreements in the ordinary course of business. Pursuant to the agreements, the Company indemnifies, holds harmless, and agrees to reimburse the indemnified party for losses suffered or incurred by the indemnified party, generally the Company's business partners or customers, in connection with any U.S. patent or any copyright or other intellectual property infringement claim by any third party with respect to the Company's products. The term of these indemnification agreements is generally perpetual any time after execution of the agreement. The maximum potential amount of future payments the Company could be required to make under these indemnification agreements is unlimited. The Company has never incurred costs to defend lawsuits or settle claims related to these indemnification agreements.

8. Redeemable Convertible Preferred Stock and

9. Stockholders' Equity

        As of December 31, 2012, the authorized capital stock of the Company was 104,013,161 shares of common stock, par value $0.001 per share and 74,077,227 shares of preferred stock, par value $0.001 per share, of which: (1) 26,069,980 shares have been designated as Series A Preferred Stock, (2) 16,944,378 shares have been designated as Series B Preferred Stock, (3) 11,923,077 shares have been designated as Series C redeemable convertible (Series C Preferred Stock), (4) 2,014,652 shares have been designated as Series C-1 Preferred Stock, (5) 955,414 shares have been designated as Series D redeemable convertible preferred stock (Series D Preferred Stock), (6) 2,802,548 shares have been designated as Series D-1 Preferred Stock, (7) 3,662,422 shares have been designated as Series E Preferred Stock, and (8) 9,704,756 shares have been designated as Series F redeemable convertible preferred stock (Series F Preferred Stock, and all collectively the Preferred Stock).

        On September 4, 2013, the Board and the stockholders of the Company approved a one-for-four reverse stock split of the Company's outstanding common stock, which was effected on September 5, 2013. Stockholders entitled to fractional shares as a result of the reverse stock split received a cash payment in lieu of receiving fractional shares. The Company's historical share and per share information have been retroactively adjusted to give effect to this reverse stock split. Shares of common stock underlying outstanding stock options and other equity instruments were proportionately reduced and the respective exercise prices, if applicable, were proportionately increased in accordance with the terms of the agreements governing such securities.

        On September 4, 2013, the Board also approved for filing immediately following the effectiveness of the Company's registration statement in connection with its IPO, the Restated Certificate of Incorporation to increase the authorized number of shares of common stock from 104,013,161 to 175,000,000, to authorize 25,000,000 shares of undesignated preferred stock, par value $0.001 per share, and to eliminate all references to the previously designated Series Preferred Stock. This Restated Certificate of Incorporation was approved by the stockholders on September 4, 2013.


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

8. Redeemable Convertible Preferred Stock and Stockholders' Equity (Continued)

On September 24, 2013, the Company completed its initial public offering (IPO)IPO whereby the Company sold 6,417,000 shares of common stock (including 837,000 shares of common stock sold by the Company pursuant to the full exercise of an overallotment option by the underwriters in connection with the offering) at a price of $15.00 per share. The shares began trading on The Nasdaq Global Market on September 19, 2013. The aggregate net proceeds received by the Company from the offering were $86.8 million, net of underwriting discounts and commissions and estimated offering expenses payable by the Company. Upon the closing of the IPO, all outstanding shares of convertible preferred stock converted into 18,516,993 shares of common stock and warrants exercisable for convertible preferred stock were automatically converted into warrants exercisable for 141,370 shares of common stock, resulting in the reclassification of the related convertible preferred stock warrant liability of $2.0 million to additional paid-in capital.

On September 24, 2013, the Company also completed the sale of a private placement of 666,667 shares of common stock to Celgene Corporation at the IPO price of $15.00 per share concurrent with and at the same offer price as the IPO. The aggregate net proceeds received by the Company from the concurrent private placement were $10.0 million.

On January 28, 2014, the Company completed its underwritten public offering of 2,760,000 shares of common stock, including 360,000 shares of common stock issued upon the exercise in full by the underwriters of their option to purchase additional shares, at a public offering price of $50.00 per share.  The aggregate net proceeds received by the Company, after underwriting discounts and commissions and other estimated offering expenses, were $129.2 million.
On January 11, 2016, the Company completed its underwritten public offering of 3,750,000 shares of common stock at a public offering price of $40.00 per share. The aggregate net proceeds received by the Company, after underwriting discounts and commissions and other estimated offering expenses, were approximately $140.4 million.
Preferred Stock

F-22


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 20122015, 2014 and 2011

8. Redeemable Convertible Preferred Stock and Stockholders' Equity (Continued)

Redeemable Convertible Preferred Stock

        Prior2013



The Company’s certificate of incorporation authorizes its board of directors to the closing of the initial public offering, at which time allissue 25,000,000 shares of Preferred Stock were converted into shares of commonpreferred stock the Company's Preferred Stock consisted of the following (in thousands, except share and per share data):

 
 December 31,
2012
 

Series A Preferred Stock, $0.001 par value: 26,069,980 shares authorized, 6,410,976 shares issued and outstanding at December 31, 2012, at redemption value

 $66,665 

Series B Preferred Stock, $0.001 par value: 16,944,378 shares authorized, 4,204,185 shares issued and outstanding at December 31, 2012, at redemption value

  67,044 

Series C Preferred Stock, $0.001 par value: 11,923,077 shares authorized, 2,978,062 shares issued, and outstanding at December 31, 2012, at redemption value

  59,909 

Series C-1 Preferred Stock, $0.001 par value: 2,014,652 shares authorized, 457,875 issued, and outstanding at December 31, 2012, at redemption value

  9,387 

Series D Preferred Stock, $0.001 par value: 955,414 shares authorized, 234,940 shares issued, and outstanding at December 31, 2012, at redemption value

  4,325 

Series D-1 Preferred Stock, $0.001 par value: 2,802,548 shares authorized, 636,942 issued and outstanding at December 31, 2012, at redemption value

  11,864 

Series E Preferred Stock, $0.001 par value: 3,662,422 shares authorized, 816,060 shares issued and outstanding at December 31, 2012, at redemption value

  13,393 

Series F Preferred Stock, $0.001 par value: 9,704,756 shares authorized, 2,426,171 issued and outstanding at December 31, 2012, at redemption value

  36,023 
    

Total redeemable convertible preferred stock

 $268,610 
    
    

from time to time in one or more series.  The holders of the Company's Preferred Stock had certain voting, dividend, and redemption rights, as well as liquidation preferences and conversion privileges. All rights, preferences, restrictions, qualifications and privileges associated withlimitations of such stock are determined by the Preferred Stock were terminated at the timeboard of the Company's IPO in conjunction with the conversiondirectors. As of all outstandingDecember 31, 2015 no shares of Preferred Stock into shares of common stock.

are issued or outstanding.

Common Stock

The holders of shares of common stock are entitled to one vote for each share of common stock held at all meetings of stockholders and written actions in lieu of meetings.

The holders of shares of common stock are entitled to receive dividends, if and when declared by the Board. No dividends have been declared or paid by the Company through December 31, 2013.

2015.

Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

8. Redeemable Convertible Preferred Stock and Stockholders' Equity (Continued)

Common Stock Reserved for Future Issuance

At December 31, 2013,2015, the Company has reserved for future issuance the following number of shares of common stock (in thousands):

2015

December 31,
2013

Outstanding stock options to purchase common stock

3,1913,942

Shares available for future issuance under stock option plan

1,890956

Warrants to purchase common stock

398980

Shares available for future issuance under the employee stock purchase plan

251
Additional shares reserved for unissued, but designated, Preferred Stock

25,000

Total shares of authorized common stock reserved for future issuance

30,73030,878

9.

10. Significant Agreements

Celgene

Overview

On February 20, 2008 the Company entered into a collaboration, license, and option agreement (the Sotatercept Agreement) with Celgene Corporation (Celgene) relating to sotatercept. On August 2, 2011, the Company entered into a second collaboration, license and option agreement with Celgene for ACE-536luspatercept (the ACE-536Luspatercept Agreement), and also amended certain terms of the Sotatercept Agreement. These agreements provide Celgene exclusive licenses for Sotaterceptsotatercept and ACE-536luspatercept in all indications, as well as exclusive rights to obtain a license to certain future compounds. Celgene is a global biopharmaceutical company primarily engaged in the discovery, development and commercialization of innovative therapies designed to treat cancer and immune-inflammatory related diseases.

Sotatercept Agreement

Under the terms of the Sotatercept Agreement, the Company and Celgene collaborate worldwide for the joint development and commercialization of sotatercept. The Company also granted Celgene an option to license three discovery stage compounds. Under the terms of the agreement, the Company and Celgene will jointly develop, manufacture and commercialize sotatercept. Celgene paid $45.0 million of nonrefundable, upfront license and option payments to the Company upon the closing of the Sotatercept Agreement.

The Company retained responsibility for research and development through the end of Phase 2a clinical trials, as well as manufacturing the clinical supplies for these trials. These activities were substantially completed in 2011. Celgene is conducting the ongoing Phase 2 trials for myelodysplastic syndromes (MDS), chronic kidney disease, andb-thalassemia beta-thalassemia and will be responsible for any Phase 3 clinical trials, as well as additional Phase 2 clinical trials, and will be responsible for overseeing the manufacture of Phase 3 and commercial supplies by third-party contract manufacturing organizations. Under the agreement, the Company was eligible to receive clinical milestones of up to $88.0 million, regulatory milestones of up to $272.0 million, and commercial milestones of up to $150.0 million for sotatercept. Clinical milestone payments are triggered upon initiation of a defined phase of clinical


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Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

9. Significant Agreements (Continued)

research for a producttherapeutic candidate. Regulatory milestone payments are triggered upon the acceptance of the marketing application and upon the approval to market a producttherapeutic candidate by the Food and Drug Administration


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Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


(FDA) or other global regulatory authorities. Commercial milestone payments are triggered when an approved pharmaceutical product reaches certain defined levels of net sales by Celgene in countries outside of North America. In addition, to the extent sotatercept is commercialized, the Company would be entitled to receive tiered royalty payments in the low-to-mid twenty percent range of net sales from sales generated from all geographies. Royalty payments are subject to certain reductions, including for entry of a generic product onto the market.

Additionally, for three named discovery-stage option programs the Company was eligible to receive option fees of up to $30.0 million, clinical milestones of up to $53.3 million, regulatory milestones of up to $204.0 million, and commercial milestones of up to $150.0 million for each option program. Clinical milestone payments are triggered upon initiation of a defined phase of clinical research for a producttherapeutic candidate. Regulatory milestone payments are triggered upon the acceptance of the marketing application and upon the approval to market a producttherapeutic candidate by the FDA or other global regulatory authorities. Commercial milestone payments are triggered when an approved pharmaceutical product reaches certain defined levels of net sales by Celgene in countries outside of North America. Option fee payments are triggered upon license of any of the option programs by Celgene. In addition, to the extent an option compound is commercialized, the Company would be entitled to receive tiered royalty payments in the low-to-mid twenty percent range of net sales from sales generated from all geographies. Royalty payments are subject to certain reductions, including for entry of a generic product onto the market. None of the three discovery stage programs has advanced to the stage to achieve payment of a milestone.

In connection with entering into the Sotatercept Agreement, Celgene purchased 457,875 shares of Series C-1 Preferred Stock at the aggregate purchase price of $5.0 million. The Series C-1 Preferred Stock was purchased at an amount that was deemed to represent fair value at the time of purchase.

Per our agreement and concurrent with the IPO, Celgene purchased 666,667 shares of Common Stock at the IPO offer price of $15.00 per share for $10.0 million.

Commensurate with the execution of the ACE-536Luspatercept Agreement described below, the Company and Celgene agreed to modify the terms of the Sotatercept Agreement. The modified terms included: (1) a change to the responsibility for development costs to align with the ACE-536Luspatercept Agreement, with Celgene responsible for more than half of the worldwide costs through December 31, 2012, and 100% of the development costs thereafter, (2) future contingent development milestones for sotatercept were amended to a two-category (oncology and non-oncology) structure with potential future clinical milestones of $27.0 million and regulatory milestones of $190.0 million from a four-category (various cancer indications) structure and, (3) future contingent development milestones for option compounds were amended to a two-category (oncology and non-oncology) structure with potential future clinical milestones of $25.5 million and regulatory milestones of $142.5 million from a four-category (various cancer indications) structure, and (4) an option to buy down tiered royalty payments on both Sotaterceptsotatercept and ACE-536luspatercept with a one-time $25.0 million payment on or prior to January 1, 2013. The potential commercial milestones remained unchanged. As of December 31, 2013,To date, the Company has received $41.6$43.0 million in research and development funding and milestone payments for sotatercept under the original and modified agreements, of which $7.0 million is a clinical milestone payment earned in December 2013 that resulted from Celgene's start of a Phase 2b clinical trial in chronic kidney disease.


Table The next likely clinical milestone payment would be $10.0 million and result from Celgene's start of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

9. Significant Agreements (Continued)

a Phase 3 study in chronic kidney disease.

The Sotatercept Agreement will expire on a country-by-country basis on the occurrence of both of the following: (1) the expiration of the royalty term with respect to all license products in such country, and (2) the exercise or forfeiture by Celgene of its option with regard to each option compound. The royalty term for each licensed product in each country outside North America is the period commencing with first commercial sale of the applicable licensed product in the applicable country and ending on the latest of expiration of specified patent coverage or a specified period of years. The royalty term for each licensed product in North America is the period commencing with the first commercial sale in North America and ending, on a licensed product and country-by-country basis on the date which commercialization of such licensed product has ceased. The term for each option compound runs for a specified period of years unless Celgene exercises its option, in which case the compound becomes a licensed product, or forfeits its option by failing to make certain payments following the achievement of certain milestones in early clinical development of the option compound.

Celgene has the right to terminate the agreement with respect to one or more licensed targets or in its entirety, upon 180 days' notice (or 45 days' notice if the licensed product has failed to meet certain end point criteria with respect to clinical trials or other development activities). The agreement may also be terminated in its entirety by either Celgene or the Company in the event of a material breach by the other party or in the event of a bankruptcy filing of the other party. There are no cancellation, termination or refund provisions in this arrangement that contain material financial consequences to the Company.

Luspatercept Agreement


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Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


Under the terms of the ACE-536Luspatercept Agreement, the Company and Celgene collaborate worldwide for the joint development and commercialization of ACE-536.luspatercept. The Company also granted Celgene an option for future products for which Acceleron files an Investigational New Drug application for the treatment of anemia. Celgene paid $25.0 million on the closing of the ACE-536Luspatercept Agreement in August, 2011.

        Under the terms of the ACE-536 Agreement the

The Company retains responsibility for research and development through the end of Phase 1 and initial Phase 2 clinical trials, as well as manufacturing the clinical supplies for these studies. Celgene will conduct subsequent Phase 2 and Phase 3 clinical studies. Acceleron will manufacture ACE-536luspatercept for the Phase 1 and Phase 2 clinical trials and Celgene will be responsible for overseeing the manufacture of Phase 3 and commercial supplies by third party contract manufacturing organizations. The Company is eligible to receive clinical milestones of up to $32.5 million, regulatory milestones of up to $105.0 million and commercial milestones of up to $80.0 million for ACE-536.luspatercept. The Company will receive additional, lower development, regulatory, and commercial milestones for any additional products for the treatment of anemia on which Celgene exercises an option. Clinical milestone payments are triggered upon initiation of a defined phase of clinical research for a producttherapeutic candidate. Regulatory milestone payments are triggered upon the acceptance of the marketing application and upon approval to market a protein therapeutic candidate by the FDA or other global regulatory authorities. Commercial milestone payments are triggered when an approved pharmaceutical product reaches certain defined levels of net sales by Celgene in countries outside of North America. In addition, to the extent ACE-536luspatercept is commercialized, the Company would be entitled to receive tiered royalty payments in the low-to-mid twenty percent range of net sales from


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

9. Significant Agreements (Continued)

sales generated from all geographies. Royalty payments are subject to certain reductions, including for entry of a generic product onto the market.

Through December 31, 2013,2015, the Company has received $31.9$60.3 million in research and development funding and milestone payments for ACE-536.luspatercept. The next likely clinical milestone payment would be $15.0 million and result from theCelgene's start of a Phase 3 study in MDS orb-thalassemia. beta-thalassemia. The Company has not yet identified additional compounds for the treatment of anemia. Accordingly, there is no assurance that the Company will generate future value from additional programs.

The ACE-536Luspatercept Agreement will expire on a country-by-country basis on the occurrence of both of the following: (1) the expiration of the royalty term with respect to all license products in such country, and (2) the end of the option term. The royalty term for each licensed product in each country outside North America is the period commencing with first commercial sale of the applicable licensed product in the applicable country and ending on the latest of expiration of specified patent coverage or a specified period of years. The royalty term for each licensed product in North America is the period commencing with the first commercial sale in North America and ending, on a licensed product and country-by-country basis on the date which commercialization of such licensed product has ceased. The option term runs until the later of (1) the date on which no development or commercialization activities are ongoing or are expected to commence for any licensed products under the ACE-536Luspatercept Agreement; (2) the date on which no development or commercialization activities are ongoing or are expected to commence for any licensed products under the Sotatercept Agreement and all option rights under the Sotatercept Agreement have been forfeited with respect to each option compound where Celgene has made a payment with respect to such compound; and (3) the royalty term for all licensed products under the ACE-536Luspatercept Agreement and the Sotatercept Agreement has ended; provided that if at the time the option term would otherwise end any option compounds under the ACE-536Luspatercept Agreement are in clinical development the option term shall continue until Celgene's rights to such compound are either exercised or forfeited.

Celgene has the right to terminate the ACE-536Luspatercept Agreement with respect to one or more licensed targets or in its entirety, upon 180 days' notice (or 45 days' notice if the licensed product has failed to meet certain end point criteria with respect to clinical trials or other development activities), provided that Celgene may not terminate the ACE-536Luspatercept Agreement prior to the completion of the on-going ACE-536b -thalassemialuspatercept beta-thalassemia and ACE-536luspatercept MDS Phase 2 clinical trials, except under certain conditions. The agreement may also be terminated in its entirety by either Celgene or the Company in the event of a material breach by the other party or in the event of a bankruptcy filing of the other party. There are no cancellation, termination or refund provisions in this arrangement that contain material financial consequences to the Company.

Both Agreements

The Company and Celgene shared development costs under the Sotatercept and ACE-536Luspatercept Agreements through December 31, 2012. As of January 1, 2013, Celgene ishas been responsible for paying 100% of the worldwide development costs under both agreements. Celgene will be responsible for all commercialization costs worldwide. The Company has the right to co-promote sotatercept, ACE-536luspatercept and future products under both agreements in North America. Celgene's option to buy down royalty rates for sotatercept and ACE-536luspatercept expired unexercised and, therefore, the Company will receive tiered



F-25


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 20122015, 2014 and 2011

9. Significant Agreements (Continued)

2013



royalties in the low-to-mid twenty percent range on net sales of sotatercept and ACE-536.luspatercept. The royalty schedules for sotatercept and ACE-536luspatercept are the same.

Accounting Analysis

Prior to 2011, the Company accounted for the Sotatercept Agreement, as a multiple element arrangement under ASC 605-25 (prior to the amendments of ASU 2009-13). The Company identified the following deliverables under the arrangement; (1)the license to the ActRIIA compound, (2) right to license option program compounds, (3) participation in the joint development committee, (4) participation in the joint commercialization committee and (5) research and development activities. Under the provisions of ASC 605- 25,605-25, applicable to the arrangement, since the Company could not establish VSOEvendor-specific objective evidence (VSOE) for the undelivered elements, the Company was required to recognize the initial consideration, consisting of the $45.0 million of nonrefundable upfront license and option payments, over the period the undelivered elements were to be delivered, which was initially estimated to be 15 years. As of the date of the modification of the agreement, there was approximately $34.7 million of deferred revenue under the arrangement.

As a result of the material modifications to the cost sharing obligations, milestone payments structure and royalty payment structure, the Company concluded the modification represented a significant modification under ASU 2009-13, which required the Company to apply the updated provisions of ASU 2009-13 subsequent to the modification.

Because the ACE-536Luspatercept Agreement and the amendment to the Sotatercept Agreement were negotiated in contemplation of each other, and the Company had not yet completed all of its obligations pursuant to the Sotatercept Agreement, the agreements were considered one arrangement for accounting purposes. The deliverables under the combined arrangement include: (1) licenses to develop and commercialize sotatercept and ACE-536,luspatercept, (2) performance of research and development services, (3) participation on the joint development committees, and (4) the performance of manufacturing services to provide clinical material to Celgene. The Company has determined the option to future products related to the treatment of anemia represents a substantive option. The Company is under no obligation to discover, develop or deliver any new compounds that modulate anemia and Celgene is not contractually obligated to exercise the option. As a result, the Company is at risk as to whether Celgene will exercise the option.

All of these deliverables identified in the arrangement were deemed to have stand-alone value and to meet the criteria to be accounted for as separate units of accounting under ASC 605-25. Factors considered in making this determination included, among other things, the subject of the licenses, the nature of the research and development services, and the capabilities of Celgene.

The total arrangement consideration of $77.7 million under the ACE-536Luspatercept Agreement and amended Sotatercept Agreement consisted of (1) the $25.0 million up-front payment for the license of ACE-536,luspatercept, (2) the remaining deferred revenue from the Sotatercept Agreement of $34.7 million, and (3) estimated payments for development activities and manufacturing services of $18.0 million. The Company used its BESPbest estimate of selling price (BESP) for each of the undelivered elements as the Company did not have VSOE or (third-party evidence) TPE of selling price for each deliverable. The Company's BESP considered its development plan for the compounds, expected manufacturing services, and reimbursement from Celgene (reimbursement of more than half


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

9. Significant Agreements (Continued)

of development expenses through December 31, 2012 and 100% thereafter). The Company determined its BESP for each of the undelivered elements under the arrangements as of the arrangement execution date as follows:

$18.8 million for research and development services

$2.9 million for the sotatercept joint development committee

$3.7 million for the ACE 536 joint development committee

$2.8 million for the manufacturing services

After determining the BESP of the undelivered elements, the remaining consideration of $49.5 million was recognized upon execution of the arrangements. The difference between the estimated payments of $18.0 million and the estimated selling prices which totaled $28.2 million, using BESP, for undelivered elements was $10.2 million. This amount was deferred at inception and will be recognized as the undelivered elements are delivered, using the proportional performance method, or ratably in the case of performance on the joint development committees.

Joint Development Committee.

As noted above, the total arrangement consideration includes estimated payments for development activities and manufacturing services identified at the outset of the ACE-536Luspatercept Agreement and amended Sotatercept Agreement. At the end of each reporting period, the Company reassesses the estimated payments to be received related to these services and the BESP

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Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


of the undelivered elements based upon the Company's current estimates. The Company accounts for such changes as a change in accounting estimate and the cumulative impact of any change is reflected in the period of change.

During 2011, the Company achieved a $7.5 million clinical milestone under its ACE-536Luspatercept Agreement, related to the dosing of the first patient in a multiple-dose clinical trial. The Company evaluated the milestone and determined that it was not substantive, as there was no significant uncertainty to achieving the milestone upon execution of the ACE-536Luspatercept Agreement. As such, the Company allocated the $7.5 million payment based on the allocation of arrangement consideration determined at the execution date of the ACE-536Luspatercept Agreement and amended Sotatercept Agreement. Based on this allocation, the Company recognized $4.8 million of the payment upon achievement, with the remaining $2.7 million recognized as revenue as the undelivered elements are delivered, consistent with the treatment of the up-front payment. During 2011, the Company achieved a $7.0 million clinical milestone under its Sotatercept Agreement, related to the dosing of the first patient for a Phase 2b clinical trial. The Company evaluated the milestone and deemed it to be substantive and consistent with the definition of a milestone included in ASU 2010-17 and, accordingly, recognized the $7.0 million payment in revenue during the year ended in December 31, 2011. During January 2013, the Company achieved a $10.0 million clinical milestone under its ACE-536Luspatercept Agreement, related to the dosing of the first patient for a Phase 2 clinical trial. The Company evaluated the milestone and deemed it to be substantive and consistent with the definition of a milestone included in ASU 2010-17 and, accordingly, recognized the $10.0 million payment in revenue during the year ended December 31, 2013. During December 2013, the Company achieved a $7.0 million clinical milestone under its Sotatercept Agreement, related to Celgene's start of a Phase 2b clinical trial in chronic kidney disease. The Company evaluated the milestone and deemed it to be substantive and consistent with the definition of a milestone included in ASU 2010-17 and, accordingly, recognized the $7.0 million payment in revenue during the year ended December 31, 2013.The remaining development milestones under the ACE-536Luspatercept and Sotatercept Agreements were deemed to be substantive and consistent with the definition of a milestone included in ASU 2010-17 and, accordingly, the Company will recognize payments related to the achievement of such milestones, if any, when such milestone is achieved. Factors considered in this determination included scientific and


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

9. Significant Agreements (Continued)

regulatory risks that must be overcome to achieve the milestones, the level of effort and investment required to achieve each milestone, and the monetary value attributed to each milestone. During the years ended December 31, 2013 20122015, 2014 and 2011,2013, the Company recognized $2.6$1.2 million, $2$1.7 million and $54.8$2.6 million, respectively, of the total deferred revenue as license and milestone revenue in the accompanying consolidated statements of operations and comprehensive loss.

As noted above, under the terms of the ACE-536Luspatercept Agreement the Company retains responsibility for certain research and development activities through the completion of Phase 1 and initial Phase 2 clinical trials, as well as manufacturing the clinical supplies for these studies. Celgene is responsible for the conduct of subsequent Phase 2 and Phase 3 clinical studies. In November, 2013, the Company agreed to conduct additional activities for the benefit of the ACE-536luspatercept program including certain clinical and non-clinical services such as multiple toxicology studies and associated assay development and sample testing, clinical extension studies, and market development work. These activities will be reimbursed under the same terms and rates of the existing Agreements. The Company evaluated the additional services to be provided and determined that as the Company is under no obligation to conduct these additional activities, these services do not represent a deliverable under or modification to the ACE-536Luspatercept Agreement, but rather, represent a separate services arrangement which should be accounted for as the services are delivered.

Pursuant to the terms of the agreement, Celgene and the Company share development costs, with Celgene responsible for substantially more than half of the costs for sotatercept and ACE-536luspatercept until December 31, 2012 and 100% of the costs from January 1, 2013 and thereafter. Payments from Celgene with respect to research and development costs incurred by the Company are recorded as cost-sharing revenue. Payments by the Company to Celgene for research and development costs incurred by Celgene are recorded as a reduction to cost-sharing revenue. During the years ended December 2013, 201231, 2015, 2014 and 2011,2013, the Company recorded net cost-sharing revenue of $16.9 million, $13.0 million and $12.7 million, $2.9 million and $(0.1) million, respectively, which includes payments to Celgene of $0, $2.8 million and $2.8 million, respectively, which were recorded as contra-revenue.

respectively.

Other Agreements

Shire License

In September 2010, the Company entered into a license and collaboration agreement granting Shire AG the exclusive right to develop, manufacture and commercialize ActRIIB compounds in territories outside North America. Shire also received the right to conduct research and manufacture commercial supplies in North America for ActRIIB compounds. The lead ActRIIB compound was designated ACE-031. Under the initial development plan, the companies share the costs associated with developing and commercializing ACE-031, in Duchenne Muscular Dystrophy. In September 2010, Shire made a nonrefundable, up-front license payment to the Company of $45.0 million. In accordance with the Company's revenue recognition policy prior to the adoption of ASU 2009-13, the up-front license payment of $45.0 million was deferred, and will be recognized as revenue ratably over three years, which represented the original period over which the Company expected to perform and deliver research and development and manufacturing services. On February 8, 2011, the FDA placed ACE-031 on clinical hold. The Company re-assessed the duration of its deliverables under the license agreement and estimated the new term

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Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


to be approximately five years. The adjustment was treated as a change in


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

9. Significant Agreements (Continued)

accounting estimate with the remaining deferred revenue of $38.8 million at February 8, 2011, recognized prospectively over the new period of research and development and manufacturing services. In April 2013, the Company and Shire determined not to further pursue development of ACE-031 and Shire sent the Company a notice of termination for the ACE-031 collaboration. The collaboration terminated effective June 30, 2013. At December 31, 2012, the Company had classified the remaining deferred revenue as current in the consolidated balance sheet. Upon the effectiveness of the termination of the Shire Agreement in the second quarter of 2013, the Company accelerated the recognition of $22.4 million of remaining deferred revenue from upfront non-refundable payments received under the Shire Agreement as it had no further obligation for deliverables under the Shire Agreement. During the yearsyear ended December 31, 2013, 2012 and 2011, the Company recognized $24.3 million $7.7 million and $8.4 million, respectively of the up-front, non-refundable payments as license and milestone revenue in the accompanying consolidated statements of operations and comprehensive loss.

No amounts were recognized subsequent to the June 30, 2013 termination.

The agreement also included contingent milestone payments, based on the achievement of development milestones totaling $223.8 million and commercial milestones of $228.8 million for ActRIIB compounds. The milestones under the Shire Agreement were deemed to be substantive and consistent with the definition of a milestone included in ASU 2010-17 and, accordingly, the Company recognized payments related to the achievement of such milestones, if any, when such milestone was achieved. Factors considered in this determination included scientific and regulatory risks that must be overcome to achieve the milestones, the level of effort and investment required to achieve each milestone, and the monetary value attributed to each milestone.

Pursuant to the terms of the agreement, Shire and the Company shared development costs, with Shire responsible for 65% of the costs for ACE-031 and 55% of the costs for licensed compounds other than ACE-031. Payments from Shire with respect to research and development costs incurred by the Company are recorded as cost-sharing revenue. Payments by the Company to Shire for research and development costs incurred by Shire are recorded as a reduction to cost-sharing revenue. During the yearsyear ended December 31, 2013, 2012 and 2011, the Company recorded net cost-sharing revenue of $0.6 million, $2.7 million and $4.1 million, respectively, which includes payments to Shire of $0.2 million, $0.7 million and $2.0 million, respectively, which are recorded as contra-revenue in the accompanying consolidated statements of operations and comprehensive loss.

        In December 2009, the Company entered into a Collaboration and License Agreement with Alkermes Inc. (Alkermes) relating to a proprietary technology platform for extending the circulating half-life of certain proteins. Under the terms of the agreement, Alkermes paid the Company an up-front cash payment of $2.0 million in December 2009, which was deferred and No amounts we recognized as license revenue ratably over the estimated research and development term. In addition, Alkermes purchased 636,942 shares of Series D-1 Preferred Stock at a per share price of $12.56, resulting in gross proceedssubsequent to the Company of $8.0 million. The Company determined thatJune 30, 2013 termination.

Other
In 2004, the price of $12.56 paid by Alkermes included a premium of $2.32 per share over the fair value of the Series D-1 Preferred Stock of $10.24 as calculated by the Company in its contemporaneous stock valuation. Accordingly, the Company has recognized the premium of $1.5 million as additional license revenue on a straight-line basis over the


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

9. Significant Agreements (Continued)

term discussed above. In October 2011, Alkermes discontinued development of the compounds being investigated under the license agreement, and as a result, the Company recognized the remaining $2.4 million of the up-front payment as revenue, as it had no further obligations under the arrangement, though the license continues.

        As the principal in the collaboration, Acceleron recognized cost-sharing revenue for reimbursement payments from Alkermes. During the year ended December 31, 2011, the Company recognized net cost-sharing revenue of $0.7 million. No amounts were recognized in subsequent periods.

        In October 2010, the Company entered into a Biopharmaceutical Services Agreement with ImmunoGen, Inc. Acceleron agreed to develop and manufacture an ImmunoGen product. The Company determined the arrangement should be accounted for as a service arrangement, using the proportional performance method. Accordingly, the Company recognized revenue as the underlying performance criteria were met. The costs associated with the services were charged to operations as incurred. As of December 31, 2011, the work was completed and the Company recorded revenue of $1.7 million for the year ended December 31, 2011.

        The Company entered into a license agreement with a non-profit institution for an exclusive, sublicensable, worldwide, royalty-bearing license to certain patents developed by the institution (Primary Licensed Products). In addition, the Company was granted a non-exclusive, non-sub- licensablenon-sub-licensable license for Secondary Licensed Products. As compensation for the licenses, the Company issued 62,500 shares of its common stock to the institution, the fair value of which was $25,000, and was expensed during 2004, to research and development expense. The Company also agreed to pay specified development milestone payments totaling up to $2.0 million for sotatercept and $0.7 million for ACE-536.luspatercept. In addition, the Company is obligated to pay milestone fees based on the Company's research and development progress, and U.S. sublicensing revenue ranging from 10%-25%, as well as a royalty ranging from 1.0%-3.5% of net sales on any products developed under the licenses. During the years ended December 31, 2013, 20122015, 2014 and 2011,2013, the Company paid and expensed milestones and fees defined under the agreement totaling $0.5$0.1 million, $0$0.1 million and $0.5 million, respectively.

        Therespectively, which is recorded as research and development expense.

In 2004, the Company entered into another license agreement with certain individuals for an exclusive, sublicensable, worldwide, royalty-bearing license to certain patents developed by the individuals. WeThe Company agreed to pay specified development and sales milestone payments aggregating up to $1.0 million relating to the development and commercialization of dalantercept. In addition, we arethe Company is required to pay royalties in the low single-digits on worldwide net product sales of dalantercept, with royalty obligations continuing at a 50% reduced rate for a period of time after patent expiration. If we sublicense ourthe Company sublicenses its patent rights, weit will owe a percentage of sublicensing revenue, excluding payments based on the level of sales, profits or other levels of commercialization. During the years ended December 31, 2013, 20122015, 2014 and 2011,2013, the Company did not reach any milestones defined under the agreement and, therefore, no amounts have been paid or expensed.


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

9. Significant Agreements (Continued)

During 2012, the Company executed a license agreement with a research institution for an exclusive, sublicensable, worldwide, royalty-bearing license. The Company is obligated to pay development milestones and commercial milestone fees totaling up to $1.0 million. Under the agreement, if the Company uses the inventors in the clinical research, the development milestones are waived and commercial milestones shall change to $0.8 million plus any waived milestones. The Company will also pay $25,000 annually upon first commercial sale as well as royalties of 1.5% of net sales on any products developed under the patents. During the years ended December 31, 2015, 2014 and 2013, paid and 2012, the Company did not reach anyexpensed milestones and fees defined under the agreement totaling $0.0 million, zero and therefore, no amounts have beenzero, respectively, which is recorded as research and development expense.

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Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


In May 2014, the Company executed a collaboration agreement with a research technology company. The Company paid or expensed.

10.an upfront and research fee of $0.3 million upon execution of the agreement and the Company is obligated to pay additional research fees of approximately $0.6 million over approximately the next year, depending on the success of the research program. The Company also received an option to obtain a commercial license to the molecules developed during the collaboration. During the year ended December 31, 2015 and December 31, 2014 the Company expensed milestones and fees of $1.4 million and $0.6 million, which is recorded as research and development expense.


11. Stock-Based Compensation

At December 31, 2013,2015, the Company had two stock-based compensations plans, which are more fully described below.

The Company's 2003 Stock Option and Restricted Stock Plan (the 2003 Plan) provides for the issuance of stock options, restricted stock awards, and restricted stock to employees, officers, directors, consultants and key personnel of the Company as determined by the Board. In conjunction with the effectiveness of the 2013 Equity Incentive Plan (the 2013 Plan) described below, the Company determined that no further stock options or other equity-based awards may be granted under the 2003 Plan.

On September 4, 2013, the Board and stockholders approved the adoption of the 2013 Equity Incentive Plan (the 2013 Plan). The Company has reserved for issuance an aggregate of 1,500,000 shares of common stock under the 2013 Plan which is comprised of (i) the remaining 155,884 shares reserved for issuance under the 2003 Plan and (ii) an additional 1,344,116 shares. The 2013 Plan provides that the number of shares reserved and available for issuance under the plan will automatically increase each January 1, beginning in 2014, by the lesser of (i) 3,150,000 shares, or (ii) 4% of the outstanding number of shares of the Company's common stock on the immediately preceding December 31st. This number is subject to adjustment in the event of a stock split, stock dividend or other change in the Company's capitalization. The number of options available for future grant was 956,0001,889,730 at December 31, 2013.

2015.

The Company has not granted unrestricted stock awards under the 2003 Plan andor the 2013 Plan since its inception. Stock options carry an exercise price equal to the estimated fair value of the Company's common stock on the date of grant. Options generally expire ten10 years following the date of grant. Stock options and restricted stock awards typically vest over four4 years, but vesting provisions can vary based on the discretion of the Board.

Shares of the Company's common stock underlying any awards that are forfeited, canceled, withheld upon exercise of an option, or settlement of an award to cover the exercise price or tax withholding, reacquired by the Company prior to vesting, satisfied without the issuance of shares of the Company's common stock, or otherwise terminated other than by exercise will be added back to the shares of common stock available for issuance under the 2013 Plan. Shares available for issuance under the 2013 Plan may be authorized but unissued shares of the Company's common stock or shares of the Company's common stock that have been reacquired by the Company.


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

10. Stock-Based Compensation (Continued)

Additionally, on September 4, 2013, the Company's board of directorsBoard and stockholders approved the adoption of the 2013 Employee Stock Purchase Plan (the 2013 ESPP). Under the 2013 ESPP, 275,000 shares of the Company's common stock will be available for issuance andto eligible employeesemployees. The per-share purchase price at the end of the Company may purchase shares of common stock during pre-specified purchase periods at a priceeach offering period is equal to the lesser of 85% of the fair market valueclosing price of aone share of itsthe Company’s common stock at the beginning of the purchase period or 85% of the fair market value of a share of its common stock at the end of the purchase period.offering period, whichever is lower, subject to Internal Revenue Service limits. The 2013 ESPP will terminate on September 4, 2023, the tenth anniversary of the initial adoption of the plan. The Board has not determined the dateinitial offering period commenced on whichSeptember 16, 2014 and the initial purchase period will commence underoccur on the 2013 ESPP. As6 month anniversary. The Company recorded $0.3 million, $0.1 million and zero of December 31, 2013, the initial purchase period under the 2013 ESPP has not yet commenced.

        During 2010, the Company modified the awards of three employees that left the Company. The modifications all related to the term of vested options post termination. The changes ranged from 3.5 years to the remaining life of the option. Awards were reviewed under ASC 718, and the fair value of the unvested options that were modified will be re-measured and thestock-based compensation expense adjusted at each reporting period. During theduring years ended December 31, 2015, 2014 and 2013, 2012 and 2011 non-employee stock compensation expense of $3,000, $36,000, and $0.2 million respectively, was recorded.

respectively.

The Company recognized stock-based compensation expense under the various Plans totaling $2.2$12.1 million, $1.2$4.8 million and $1.4$2.2 million during the years ended December 31, 2015, 2014 and 2013, 2012 and 2011, respectively.

Total compensation cost recognized for all stock-based compensation awards in the consolidated statements of operations and comprehensive (loss) incomeloss is as follows (in thousands):


F-29

Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


 
 Year Ended December 31, 
 
 2013 2012 2011 

Research and development

 $659 $514 $686 

General and administrative

  1,537  692  741 
        

 $2,196 $1,206 $1,427 
        
        
 Year Ended December 31,
 2015 2014 2013
Research and development$4,852
 $2,065
 $659
General and administrative7,223
 2,713
 1,537
 $12,075
 $4,778
 $2,196

The fair value of each option issued to employees was estimated on the date of grant using the Black-Scholes option pricing model with the following weighted-average assumptions:


 Year Ended December 31, Year Ended December 31,

 2013 2012 2011 2015 2014 2013

Expected volatility

 71.5% 69.0% 66.0%67.0% 70.9% 71.5%

Expected term (in years)

 6.0 6.0 6.0 6.0
 6.0
 6.0

Risk-free interest rate

 1.85% 0.9% 1.1%1.67% 1.82% 1.85%

Expected dividend yield

 % % %% % %

        Thean active market for the Company’s common stock prior to the completion of the Company’s initial public offering (IPO) on September 19, 2013, the Board, the members of which the Company estimatesbelieves have extensive business, finance, and venture capital experience, were required to estimate the fair value of itsthe Company’s common stock at the time of each option grant. The Board considered numerous objective and subjective factors in determining the value of the Company’s common stock at each option grant date, including the following factors: (1) prices for the Company’s preferred stock, which the Company had sold to outside investors in arm’s-length transactions, and the rights, preferences, and privileges of the Company’s preferred stock and common stock; (2) valuations performed by an independent valuation specialist; (3) the Company’s stage of development and revenue growth; (4) the fact that the option grants involved illiquid securities in a private company; and (5) the likelihood of achieving a liquidity event for the shares of common stock underlying the options, such as an initial public offering or sale of the Company, given prevailing market conditions. The Company believes this to have been a reasonable methodology based upon the Company’s internal peer company analyses, and based on several arm’s-length transactions involving the Company’s preferred stock, supportive of the results produced by this valuation methodology. Prior to the Company’s common stock being actively traded, the determination of fair value involved assumptions, judgments and estimates. If different assumptions were made, stock-based awards to employeescompensation expense, net loss and consolidated net loss per share could have been significantly different.

The fair value of each option grant issued under the Company’s stock-based compensation plans was estimated using the Black-Scholes option pricingoption-pricing model.

As there was no public market for its common stock prior to September 19, 2013, the effective date of the Company’s IPO, and as the trading history of the Company’s common stock was limited through December 31, 2014, the Company determined the volatility for options granted based on an analysis of reported data for a peer group of companies that issued options with substantially similar terms. The expected volatility of options granted has been determined using an average of the historical volatility measures of this peer group of companies. During 2015 we began to estimate our volatility by using a blend of our stock price history, for the length of time we have market data for our stock and the historical volatility of similar public companies for the expected term of each grant. The expected life of options has been determined utilizing the “simplified method”. The simplified method is based on the average of the vesting tranches and the contractual life of each grant. The risk-free interest rate is based on a treasury instrument whose term is consistent with the expected life of the stock options. The Company has not paid, and does not anticipate paying, cash dividends on its common stock; therefore, the expected dividend yield is assumed to be zero. In addition, based on an analysis of the historical actual forfeitures, the Company applied an estimated forfeiture rate of approximately 4% for each of the years ended December 31, 2015, 2014 and 2013, respectively, in determining the expense recorded in the accompanying consolidated statements of operations and comprehensive loss.


F-30


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 20122015, 2014 and 2011

10. Stock-Based Compensation (Continued)

    Expected Volatility

        The Company estimated the expected volatility based on actual historical volatility of the stock price of similar companies with publicly-traded equity securities. The Company calculated the historical volatility of the selected companies by using daily closing prices over a period of the expected term of the associated award. The companies were selected based on their enterprise value, risk profiles, position within the industry, and with historical share price information sufficient to meet the expected term of the associated award. A decrease in the selected volatility would decrease the fair value of the underlying instrument.

    Expected Term

        The Company estimates the expected life of its employee stock options using the "simplified" method, as prescribed in Staff Accounting Bulletin (SAB) No. 107, whereby, the expected life equals the arithmetic average of the vesting term and the original contractual term of the option due to its lack of sufficient historical data.

    Risk-Free Interest Rate

        The Company estimated the risk-free interest rate in reference to the yield on U.S. Treasury securities with a maturity date commensurate with the expected term of the associated award. A decrease in the selected risk-free rate would decrease the fair value of the underlying instrument.

    Expected Dividend Yield

        The Company estimated the expected dividend yield based on consideration of its historical dividend experience and future dividend expectations. The Company has not historically declared or paid dividends to stockholders. Moreover, it does not intend to pay dividends in the future, but instead expects to retain any earnings to invest in the continued growth of the business. Accordingly, the Company assumed an expected dividend yield of 0.0%.

2013

Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

10. Stock-Based Compensation (Continued)

Stock Option Activity

The following table summarizes the stock option activity under the Company's stock option plans during the year ended December 31, 20132015 (in thousands, except per share amounts and years):

 Number
of Grants
 Weighted-
Average
Exercise
Price Per
Share
 
Weighted-
Average
Contractual
Life
(in years)
 Aggregate
Intrinsic
Value(1)
Outstanding at December 31, 20143,230
 $9.77
    
Granted870
 $40.01
    
Exercised(837) $4.73
    
Canceled or forfeited(72) $31.72
    
Outstanding at December 31, 20153,191
 $18.85
 6.31 $95,479,304
Exercisable at December 31, 20151,997
 $10.79
 4.98 $75,853,297
Vested and expected to vest at December 31, 2015(2)3,135
 $18.56
 6.26 $94,709,640

 
 Number
of Grants
 Weighted-
Average
Exercise
Price Per
Share
 Weighted-
Average
Contractual
Life (in years)
 Aggregate
Intrinsic
Value(1)
 

Outstanding at December 31, 2012

  3,730 $4.16  6.62 $13,946 

Granted

  553 $23.88       

Exercised

  (293)$2.24       

Canceled or forfeited

  (48)$4.39       
             

Outstanding at December 31, 2013

  3,942 $7.05  6.43 $128,334 

Exercisable at December 31, 2013

  2,544 $4.07  5.13 $90,401 
             
             

Vested and expected to vest at December 31, 2013(2)

  3,860 $6.89  6.37 $126,258 
             
             

(1)
(1)The aggregate intrinsic value is calculated as the difference between the exercise price of the underlying options and the estimated fair value of the common stock for the options that were in the money at December 31, 2015 and 2014.

(2)This represents the number of vested options at December 31, 2015, plus the number of unvested options expected to vest at December 31, 2015, based on the unvested options outstanding at December 31, 2015, adjusted for the estimated forfeiture rate.

During the years ended December 31, 2015, 2014 and 2013, the Company granted stock options to purchase an aggregate of 870,526, 203,550 and 552,750 shares of its common stock, respectively, with weighted-average grant date fair values of options granted of $24.29, $24.39 and $15.27, respectively.
During the years ended December 31, 2015, 2014 and 2013, current and former employees of the Company exercised a total of 837,361, 853,507 and 292,802 options and options, respectively, resulting in total proceeds of $4.0 million, $3.2 million and $0.7 million, respectively.

The aggregate intrinsic value of options exercised during the years ended December 31, 2015, 2014 and 2013, under the Company's stock option plans, was $25.2 million, $26.3 million and $7.0 million, respectively, calculated as the difference between the exercise price of the underlying options and the estimated fair value of the common stock for the options that were in the money at December 31, 2013 and 2012.

(2)
This represents the number of vested options at December 31, 2013, plus the number of unvested options expected to vest at December 31, 2013, based on the unvested options outstanding at December 31, 2013, adjusted for the estimated forfeiture rate.

        During the years ended December 31, 2013, 2012 and 2011, the Company granted stock options to purchase an aggregaterespective date of 552,750, 722,000 and 334,175 shares of its common stock, respectively, with a weighted-average grant date fair values of options granted of $15.27, $7.20, $5.12, respectively.

        During the years ended December 31, 2013, 2012 and 2011, current and former employees of the Company exercised a total of 292,802, 38,697 and 94,748 options, respectively, resulting in total proceeds of $0.7 million, $0.2 million, and $0.2 million, respectively.

        The aggregate intrinsic value of options exercised during the years ended December 31, 2013, 2012 and 2011, under the Company's stock option plans, was $7 million, $47,000 and $ 186,000, respectively.

exercise.


As of December 31, 2013,2015, there was $10.1$19.5 million of unrecognized compensation expense related to unvested stock options, under the Company's stock option plans, that is expected to be recognized over a weighted-average period of 2.662.31 years.

11.

Restricted Stock Units
The following table summarizes the restricted stock unit (RSU) activity under the 2013 Plan during the year ended December 31, 2015:

F-31

Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


 Number
of Grants
 Weighted-
Average
Grant Date Fair Value
Unvested balance at December 31, 2014
 $
Granted527
 $31.67
Vested
 $
Forfeited(6) $41.20
Unvested balance at December 31, 2015521
 $31.57
During the year ended December 31 2015 the Company issued 62,650 restricted stock units, or RSUs, to certain employees.  These RSUs are subject to time-based vesting. At December 31, 2015, there was approximately $1.7 million of unrecognized compensation cost related to the time-based RSUs, which the Company expects to recognize over a remaining weighted-average period of 2.39 years. 57,150 restricted stock units remained unvested and outstanding at December 31, 2015.
In September 2015, the Company issued 464,000 performance-based RSUs to certain employees. The vesting of these performance-based RSUs is accelerated upon the occurrence of certain milestone events, but otherwise these RSUs vest four years from grant date.  As a result, when deemed probable, compensation cost is recognized over the estimated period of achievement. If achievement is not considered probable the expense is recognized over the four year vesting period. At December 31, 2015, there was approximately $12.4 million of unrecognized compensation cost related to the time-based RSUs, which the Company expects to recognize over a remaining weighted-average period of 2.83 years. All 464,000 of these performance-based RSUs remained outstanding at December 31, 2015.
12. 401(k) Savings Plan

In 2004, the Company established a defined-contribution savings plan under Section 401(k) of the Internal Revenue Code (the 401(k) Plan). The 401(k) Plan covers all employees who meet defined minimum age and service requirements, and allows participants to defer a portion of their annual


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

11. 401(k) Savings Plan (Continued)

compensation on a pretax basis. The Company has not made anyFor the years 2015 and 2014 the Board approved matching contributions of up to $5,000 and $2,500 respectively, per eligible participant pursuant to the 401(k) Plan to date.

Savings Plan’s matching formula. All matching contributions and participant contributions vest immediately. Contributions totaled $0.3 million and $0.2 million for the year ended 12.December 31, 2015 and 2014 have been recorded in the consolidated statement of operations and comprehensive loss.

13. Income Taxes

The Company provides for income taxes under ASC 740. Under ASC 740, the liability method is used in accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on differences between financial reporting and tax bases of assets and liabilities, and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse.

For the years ended December 31, 2013, 20122015, 2014 and 2011,2013, the Company did not record a current or deferred income tax expense or benefit.

The Company's (loss) incomeloss before income taxes was $(21.9)$(63.9) million, $(32.6)$(51.3) million and $36.3$(21.9) million for the years ended December 31, 2013, 20122015, 2014 and 2011,2013, respectively, and was generated entirely in the United States.

Deferred taxes are recognized for temporary differences between the basis of assets and liabilities for financial statement and income tax purposes. The significant components of the Company's deferred tax assets are comprised of the following (in thousands):


F-32

Table of Contents
Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013



 Year Ended December 31, Year Ended December 31,

 2013 2012 2015 2014

Deferred tax assets:

        

U.S. and state net operating loss carryforwards

 $51,886 $35,584 $90,732
 $75,334

Research and development credits

 5,519 5,384 7,864
 6,704

Deferred revenue

 3,005 21,882 1,883
 2,348

Accruals and other temporary differences

 5,675 5,333 9,319
 5,416
     

Total deferred tax assets

 66,085 68,183 109,798
 89,802

Less valuation allowance

 (66,085) (68,183)(109,798) (89,802)
     

Net deferred tax assets

 $ $ $
 $
     
     

The Company has evaluated the positive and negative evidence bearing upon the realizability of its deferred tax assets. Based on the Company's history of operating losses, the Company has concluded that it is more likely than not that the benefit of its deferred tax assets will not be realized. Accordingly, the Company has provided a full valuation allowance for deferred tax assets as of December 31, 20132015 and 2012.2014. The valuation allowance decreasedincreased by $2.1$20.0 million during the year ended December 31, 2013, due primarily to the decrease in deferred revenue during the period. The valuation allowance increased by $11.2 million during the year ended December 31, 2012,2015, due primarily to the generation of net operating losses during the period.


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

12. Income Taxes (Continued)

A reconciliation of income tax expense computed at the statutory federal income tax rate to income taxes as reflected in the consolidated financial statements is as follows:


 Year Ended December 31, Year Ended December 31,

 2013 2012 2011 2015 2014 2013

Federal income tax expense at statutory rate

 34.0% 34.0% 34.0%34.0 % 34.0 % 34.0 %

State income tax, net of federal benefit

 (1.5)% 4.2% 5.0%4.6 % 4.1 % (1.5)%

Permanent differences

 (43.1)% (3.4)% 1.5%(8.3)% 2.0 % (43.1)%

Research and development credit

 0.7% % (1.0)%1.2 % 1.6 % 0.7 %

Other

 0.0% (0.4)% % % 4.6 %  %

Change in valuation allowance

 9.9% (34.4)% (39.5)%(31.5)% (46.3)% 9.9 %
       
       

Effective income tax rate

 0.0% 0.0% 0.0% %  %  %
       
       

As of December 31, 20132015 and 2012,2014, the Company had U.S. federal net operating loss carryforwards of $141.0$276.1 million and $93.3$211.2 million, respectively, which may be available to offset future income tax liabilities and expire at various dates through 2033.2035. As of December 31, 20132015 and 2012,2014, the Company also had U.S. state net operating loss carryforwards of $122.9$229.8 million and $75.4$165.0 million, respectively, which may be available to offset future income tax liabilities and expire at various dates through 2033.

2035. Included in the federal and state net operating loss carryforwards are approximately $38.9 million and $13.2 million, respectively, of deductions related to the exercise of stock options which represent an excess tax benefit which will be realized when it results in the reduction of cash income tax in accordance with ASC 718.

As of December 31, 20132015 and 2012,2014, the Company had federal research and development tax credit carryforwards of $3.9$5.5 million and $3.8$4.8 million, respectively, available to reduce future tax liabilities which expire at various dates through 2033.2035. As of December 31, 20132015 and 2012,2014, the Company had state research and development tax credit carryforwards of approximately $2.4$3.5 million and $2.4$2.9 million, respectively, available to reduce future tax liabilities which expire at various dates through 2028.

2030.

Under the provisions of the Internal Revenue Code, the net operating loss and tax credit carryforwards are subject to review and possible adjustment by the Internal Revenue Service and state tax authorities. Net operating loss and tax credit carryforwards may become subject to an annual limitation in the event of certain cumulative changes in the ownership interest of significant shareholders over a three-yearthree‑year period in excess of 50 percent, as defined under Sections 382 and 383 of the Internal Revenue Code, respectively, as well as similar state provisions. This could limit the amount of tax attributes that can be utilized annually to offset future taxable income or tax liabilities. The amount of the annual limitation is determined based on the value of the Company immediately prior to the ownership change. Subsequent ownership changes may further affect the limitation in future years. The Company has completed several financings since its inception which may have resulted in a change in control as defined by Sections 382 and 383 of the Internal Revenue Code, or could result in a change in control in the

F-33

Table of Contents
Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


future. TheThrough June 2014, the Company has not, as of yet, conducted a studycompleted an assessment to determine if any such changeswhether there may have occurredbeen a Section 382 ownership change and determined that could limit its ability to useit is more-likely-than-not that the Company’s net operating loss and tax credit carryforwards.

amounts as disclosed are not subject to any material Section 382 limitations.

The Company will recognize interest and penalties related to uncertain tax positions in income tax expense. As of December 31, 20132015 and 2012,2014, the Company had no accrued interest or penalties related to uncertain tax positions and no amounts have been recognized in the Company's consolidated statements of operations and comprehensive (loss) income.

loss.

Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

12. Income Taxes (Continued)

For all years through December 31, 2013,2015, the Company generated research credits but has not conducted a study to document the qualified activities. This study may result in an adjustment to the Company'sCompany’s research and development credit carryforwards; however, until a study is completed and any adjustment is known, no amounts are being presented as an uncertain tax position for these two years.the years ended December 31, 2015 and 2014. A full valuation allowance has been provided against the Company'sCompany’s research and development credits and, if an adjustment is required, this adjustment would be offset by an adjustment to the deferred tax asset established for the research and development credit carryforwards and the valuation allowance.

The Company files income tax returns in the United States, and various state jurisdictions. The federal and state income tax returns are generally subject to tax examinations for the tax years ended December 31, 20102012 through December 31, 2013.2015. To the extent the Company has tax attribute carryforwards, the tax years in which the attribute was generated may still be adjusted upon examination by the Internal Revenue Service, state or foreign tax authorities to the extent utilized in a future period.

13.

14. Long-Term Debt

On June 7, 2012, the Company entered into a loan and security agreement (the Loan Agreement) with three lenders, pursuant to which the Company received a loan in the aggregate principal amount of $20.0 million. The Company iswas required to repay the aggregate principal balance under the Loan Agreement in 42 months. The first 12 payments arewere interest only and the remaining 30 payments arewere equal monthly installments of principal plus interest. The Loan Agreement provided that the interest only period could be extended under certain circumstances. The Company did not trigger the requirements and began paying principal in July 2013.

Per annum interest iswas payable at the 8.5%. The Loan Agreement also included a closing fee of $0.2 million. The Company is amortizingamortized the cost over the 42 months of loan. The Loan Agreement iswas also subject to an additional deferred payment of $1.2 million due with the final payment. The Company is recordingrecorded the deferred payment to interest expense over the term of the Loan Agreement. The resulting effective interest rate iswas approximately 11.8%. The Loan Agreement iswas secured by a lien on all of the Company's personal property as of, or acquired after, the date of the Loan Agreement, except for intellectual property.

        The Loan Agreement defines events of default, including the occurrence of an event that results in a material adverse effect upon the Company's business operations, properties, assets or condition (financial or otherwise), its ability to perform its obligations under and in accordance with the terms of the Loan Agreement, or upon the ability of the lenders to enforce any of their rights or remedies with respect to such obligations, or upon the collateral under the Loan Agreement or upon the liens of the lenders on such collateral or upon the priority of such liens. The lenders also received a right, to purchase at fair value, up to $2.0 million of equity of the Company sold in any sale by the Company to third parties of equity securities resulting in at least $5.0 million in net cash proceeds to the Company, subject to certain exceptions. On December 30, 2013, in conjunction with the establishment of the Company's wholly owned subsidiary, Acceleron Security Corporation Inc., the Loan Agreement was modified to add a debt covenant that requires the Company to maintain a cash balance equal to 150% of the outstanding principal debt balance in a separate bank account, at all times. That bank account can be subject to the lender's exclusive control in the event of a default. As of December 31, 2013 and


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

13. Long-Term Debt (Continued)

2012, there have been no events of default under the loan and the Company was in compliance with all financial and nonfinancial covenants at December 31, 2013. As of December 31, 2013 and 2012, the principal balance outstanding was $16.3 million and $20.0 million, respectively.

On March 12, 2014, the Company paid offrepaid the remaining principal outstanding underbalance of the Loan Agreement. In accordance with ASC 470-10-45Intent and Ability to Refinance on A Long Term Basis,At the time of repayment the Company has classifiedrecognized interest expense related to the outstanding debt balanceremaining $0.6 million of the $1.2 million deferred payment due with the final payment. The Company also recognized $0.3 million in prepayment fees as a current liability as of December 31, 2013.

14.additional expense

15. Related Party Transactions

Celgene Corporation (Celgene)

In connection with its entry into the collaboration agreement with Celgene, on February 2008, the Company sold Celgene 457,875 shares of its Series C-1 Preferred Stock. As part of the Company's June 2010 Series E financing, Celgene purchased 36,496 shares of Series E Preferred Stock and received warrants to purchase 38,979 shares of common stock. As part of the Company's December 2011 Series F financing, Celgene purchased 1,990,446 shares of Series F Preferred Stock. In connection with the Company's IPO, Celgene purchased 666,667 shares of common stock. In connection with the Company's January 2014 public offering, Celgene purchased 300,000 shares of common stock. In May 2014, Celgene purchased 1,100,000 shares of common stock from five current shareholders of the Company. As a result of these transactions, Celgene owned 9.7%12.3% and 9.9%12.8% of the Company's fully diluted equity as of December 31, 20132015 and 2012,2014, respectively. Refer to Note 910 for additional information regarding this collaboration agreement.


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Table of Contents
Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


During the yearyears ended December 31, 2015, 2014 and 2013, the Company recognized $18.1 million, $14.6 million and $32.3 million, respectively, in collaboration revenue under the Celgene collaboration arrangement and, asarrangement. As of December 31, 2013,2015 and 2014, the Company had $7.7$4.8 million and $6.0 million, respectively, of deferred revenue related to the Celgene collaboration arrangement. During the year ended December 31, 2012, the Company recognized $4.9 million in collaboration revenue under the Celgene collaboration arrangement and, as of December 31, 2012, had $10.3 million of deferred revenue related to the Celgene collaboration arrangement. During the year ended December 31, 2011, the Company recognized $63.5 million in collaboration revenue under the Celgene collaboration arrangement.

The Company recognized revenue from Celgene during the years ended December 31, 2013, 20122015, 2014 and 20112013 as follows (in thousands):

 
 Year Ended December 31, 
 
 2013 2012 2011 

License and milestone

 $19,626 $2,035 $63,607 

Cost sharing, net

  12,658  2,879  (121)
        

 $32,284 $4,914 $63,486 
        
        
 Year Ended December 31,
 2015 2014 2013
License and milestone$1,184
 $1,673
 $19,626
Cost sharing, net16,913
 12,959
 12,658
 $18,097
 $14,632
 $32,284

Alkermes

        One of the Company's directors is also the Chairman, President, and Chief Executive Officer of Alkermes plc, the parent company of Alkermes, with which the Company entered into a collaboration agreement during 2009.


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

14. Related Party Transactions (Continued)

        As of December 31, 2013, Alkermes held 718,655 common shares of the Company's (upon conversion of its investment in the Company's Preferred stock) and warrants to purchase 42,624 shares of common stock. As of December 31, 2012, Alkermes held 695,250 shares of the Company's Preferred Stock and warrants to purchase 42,624 shares of common stock. Upon the closing of the IPO on September 24, 2013, all of the shares of the Company's preferred stock held by Alkermes were converted into 718,655 shares of common stock.

        For the year ended December 31, 2011, Alkermes paid the Company $0.7 million for research services. No such fees were paid to the Company during 2012 or 2013.

On January 28, 2008, the Company issued a secured promissory note (the Note Receivable) in the amount of $0.2 million to the current chief executive officer of the Company (the CEO). The Note Receivable bore interest at an annual interest rate of 3.11% and was initially repayable on the earlier of January 28, 2011, or the date prior to the date that the Company files a registration statement with the SEC, covering shares of its common stock. The Note Receivable was secured by shares of the Company's common stock owned by the CEO. On December 22, 2010, the term was extended until January 28, 2014, or the date prior to the date that the Company files a registration statement with the SEC covering shares of its common stock.

In November 2012, the Company further modified the terms of the Note Receivable, such that in the event that an acquisition event occurs or the Company files a registration statement with the SEC on or before the maturity date, the unpaid principal and interest will be forgiven. The Company evaluated the forgiveness provisions and determined that forgiveness was not probable as of December 31, 2012, and as such, continued to record the Note Receivable as an asset at December 31, 2012. As a result of the Company's filing of a registration statement with the SEC on August 6, 2013 which triggered the forgiveness of the Note Receivable, the Company expensed the unpaid principal and interest expense totaling $0.2 million as compensation expense during the year ended December 31, 2013.

15.

16. Subsequent Events

The Company considers events or transactions that occur after the balance sheet date but prior to the issuance of the financial statements to provide additional evidence relative to certain estimates or to identify matters that require additional disclosure. The Company has evaluated all subsequent events and determined that there are no material recognized or unrecognized subsequent events requiring disclosure, other the following:

disclosure:

On January 28, 2014,11, 2016, the Company completed a follow-onits underwritten public offering of its common stock and issued and sold 2,760,000 shares of our common stock, including 360,0003,750,000 shares of common stock sold pursuant to the underwriters' full exercise of their option to purchase additional shares at a public offering price of $50.00$40.00 per share, forshare. The aggregate net proceeds received by the Company, were $129.0 million, after deducting underwriting discounts of $8.3 million and commissions and other estimated offering expenses, totaling $0.7were approximately $140.4 million. All of the shares issued and sold in this follow-on public offering were registered under the Securities Act pursuant to a Registration Statement on Form S-1 (File No. 333-193252), which was


Table of Contents


Acceleron Pharma Inc.

Notes to Consolidated Financial Statements (Continued)

Years Ended December 31, 2013, 2012 and 2011

15. Subsequent Events (Continued)

declared effective by the SEC on January 22, 2014, and a registration statement filed pursuant to Rule 462(b) of the Securities Act.

        On March 12, 2014, the Company paid off the remaining principal outstanding under the Loan Agreement (see Note 13 Long-term Debt). Accordingly, the Company has classified the outstanding debt balance as a current liability as of December 31, 2013.

16.

17. Quarterly Financial Data (unaudited)

The following table presents certain unaudited quarterly financial information for the eight quarters in the period ended December 31, 2013.2015. This information has been prepared on the same basis as the audited financial statements and includes all adjustments (consisting only of normal recurring adjustments) necessary to present fairly the unaudited quarterly results of operations set forth herein. Net income (loss) per share for all periods presented have been retroactively adjusted to reflect the 1-for-4 reverse stock split effected on September 5, 2013.


 
 For the Three Months Ended(1) 
 
 March 31 June 30 September 30 December 31 
 
 (in thousands except per share data)
 

2013:

             

Total revenue

 $15,012 $26,427 $4,270 $11,521 

Total costs and expenses

  (11,876) (12,276) (11,154) (14,972)

Income (loss) from operations

  3,136  14,151  (6,884) (3,451)

Net income (loss)

  1,647  13,078  (18,513) (18,110)

Basic net income (loss) per share*

 $(0.24)$0.30 $(5.62)$(0.64)

Diluted net income (loss) per share*

 $(0.24)$0.28 $(5.62)$(0.64)

2012:

             

Total revenue

 $3,324 $4,040 $3,905 $3,985 

Total costs and expenses

  (10,257) (10,944) (10,763) (12,179)

Loss from operations

  (6,933) (6,904) (6,858) (8,194)

Net loss

  (7,588) (7,400) (7,215) (10,379)

Basic net loss per share*

 $(1.50)$(5.93)$(5.82)$(7.10)

Diluted net loss per share*

 $(1.50)$(5.93)$(5.82)$(7.10)
F-35

(1)
The amounts were computed independently for each quarter, and the sum of the quarters may not total the annual amounts.

*
Applicable to common stockholders

Table of Contents

Acceleron Pharma Inc.
Notes to Consolidated Financial Statements (Continued)
Years Ended December 31, 2015, 2014 and 2013


 For the Three Months Ended(1)
 March 31 June 30 September 30 December 31
 (in thousands except per share data)
2015       
Total revenue$4,420
 $5,717
 $4,155
 $3,804
Total costs and expenses19,479
 18,811
 18,768
 21,919
Loss from operations(15,059) (13,094) (14,613) (18,115)
Net loss(14,574) (10,383) (11,858) (27,082)
Basic net loss per share*$(0.45) $(0.32) $(0.36) $(0.81)
Diluted net loss per share*$(0.45) $(0.32) $(0.36) $(0.81)
2014 
  
  
  
Total revenue$3,307
 $4,078
 $3,508
 $3,739
Total costs and expenses15,515
 21,389
 14,899
 18,293
Loss from operations(12,208) (17,311) (11,391) (14,554)
Net loss(9,120) (16,550) (7,972) (17,617)
Basic net loss per share*$(0.30) $(0.52) $(0.25) $(0.55)
Diluted net loss per share*$(0.30) $(0.52) $(0.25) $(0.55)

Exhibits


(1)The amounts were computed independently for each quarter, and the sum of the quarters may not total the annual amounts.

*Applicable to common stockholders

F-36

Table of Contents

Exhibits
Number
Exhibit
number
Description of exhibit
 Exhibit Description
Filed
with this
Report
Incorporated by
Reference
herein from
Form or
Schedule
Filing Date
SEC File/Reg.
Number
3.1 Restated Certificate of Incorporation (incorporated by reference to exhibit 3.1 to the Company's Current Report on Form 8-K (001-36065), filed on September 24, 2013)(Exhibit 3.1)9/24/2013001-36065

3.2

3.2


Amended and Restated By-laws (incorporated by reference to exhibit 3.2 to the Company's Current Report on
Form 8-K (001-36065), filed on September 24, 2013)(Exhibit 3.2)9/24/2013001-36065

4.1

4.1


Form of Common Stock Certificate (incorporated by reference to exhibit 4.1 to the Company's Registration Statement on
Form S-1/A (333-190417), filed on September 6, 2013)S-1 (Exhibit 4.1)8/7/2013333-190417

4.2

4.2


Form of Amended and Restated Registration Rights Agreement (incorporated by reference to exhibit 4.2 to the Company's Registration Statement on
Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 4.2)8/7/2013333-190417

4.3

4.3


Form of Warrant to Purchase Stock, issued to Series E Investors as of June 10, 2010 and July 9, 2010 (incorporated by reference to exhibit 4.3 to the Company's Registration Statement on
Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 4.3)8/7/2013333-190417

4.4

4.4


Form of Common Stock Warrant Certificate, issued to General Electric Capital Corporation as of March 28, 2007 (incorporated by reference to exhibit 4.4 to the Company's Registration Statement on
Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 4.4)8/7/2013333-190417

10.1*

10.1


Form of Director Indemnification Agreement (incorporated by reference to exhibit 10.1 to the Company's Registration Statement on
Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 10.1)8/7/2013333-190417

10.2+

10.2


Form of Amended and Restated Voting Agreement (incorporated by reference to exhibit 10.2 to the Company's Registration Statement on Form S-1 (333-190417), filed on August 7, 2013)


10.3


Amended and Restated Right of First Refusal and Co-sale Agreement, dated as of December 22, 2011 (incorporated by reference to exhibit 10.3 to the Company's Registration Statement on Form S-1 (333-190417), filed on August 7, 2013)


10.4


Amended and Restated Investor Rights Agreement, dated as of December 22, 2011 (incorporated by reference to exhibit 10.4 to the Company's Registration Statement on Form S-1 (333-190417), filed on August 7, 2013)


10.5


Loan and Security Agreement, dated as of June 7, 2012, among Oxford Finance LLC, the Lenders listed on Schedule 1.1, Silicon Valley Bank, MidCap Financial SBIC, LP, and Acceleron Pharma Inc. (incorporated by reference to exhibit 10.5 to the Company's Registration Statement on Form S-1 (333-190417), filed on August 7, 2013)


10.6

+

Collaboration, License and Option Agreement between Acceleron Pharma Inc. and Celgene Corporation, dated as of February 20, 2008, and amended as of August 2, 2011 (incorporated by reference to exhibit 10.6 to the Company's Registration Statement on
Form S-1/A (333-190417), filed on September 6, 2013)(Exhibit 10.6)9/6/2013333-190417

10.3

10.7

+

Amended and Restated License Agreement between Acceleron Pharma Inc. and Ludwig Institute for Cancer Research Ltd., dated as of August 6, 2010 (incorporated by reference to exhibit 10.7 to the Company's Registration Statement on
Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 10.7)8/7/2013333-190417

10.4+

10.8

+

Exclusive License Agreement between Beth Israel Deaconess Medical Center and Acceleron Pharma Inc., dated as of June 21, 2012 (incorporated by reference to exhibit 10.8 to the Company's Registration Statement on
Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 10.8)8/7/2013333-190417

10.5+

10.9

+

Collaboration, License and Option Agreement between Acceleron Pharma Inc. and Celgene Corporation, dated as of August 2, 2011 (incorporated by reference to exhibit 10.9 to the Company's Registration Statement on
Form S-1/A (333-190417), filed on September 6, 2013)(Exhibit 10.9)

Table of Contents

Exhibit
number
Description of exhibit
 10.109/6/2013333-190417
10.6 Exclusive License Agreement between Salk Institute for Biological Studies and Acceleron Pharma Inc., dated as of August 10, 2010 (incorporated by reference to exhibit 10.10 to the Company's Registration Statement on Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 10.10)8/7/2013333-190417

10.7

10.11


Amended and Restated License Agreement between Salk Institute for Biological Studies and Acceleron Pharma Inc., dated as of August 11, 2010 (incorporated by reference to exhibit 10.11 to the Company's Registration Statement on
Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 10.11)8/7/2013333-190417

10.8

10.12

Amendment, dated as of July 25, 2014, to Amended and Restated License Agreement between Salk Institute for Biological Studies and Acceleron Pharma Inc. dated as of August 11, 2010

Form 10-Q (Exhibit 10.1)8/12/2014001-36065
10.9Indenture of Lease between Massachusetts Institute of Technology and Acceleron Pharma Inc., dated as of May 20, 2008 (incorporated by reference to exhibit 10.12 to the Company's Registration Statement on Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 10.12)8/7/2013333-190417

10.10*

10.13


Acceleron Pharma Inc. 2013 Equity Incentive Plan (incorporated by reference to exhibit 4.4 to the Company's Registration Statement on
Form S-8 (333-192789), filed on December 12, 2013)(Exhibit 4.4)12/12/2013333-192789

10.11*

10.14


Form of Acceleron Pharma Inc. Cash Incentive Plan (incorporated by reference to exhibit 10.14 to the Company's Registration Statement on
Form S-1/A (333-190417), filed on August 19, 2013)(Exhibit 10.14)8/19/2013333-190417

10.12*

10.15


Acceleron Pharma Inc. 2003 Stock Option and Restricted Stock Plan (incorporated by reference to exhibit 10.15 to the Company's Registration Statement on
Form S-1 (333-190417), filed on August 7, 2013)(Exhibit 10.15)8/7/2013333-190417

10.13*

10.16


Promissory Note by and between Acceleron Pharma Inc. and John Knopf, dated as of January 28, 2008, and amended November 13, 2012 (incorporated by reference to exhibit 10.16 to the Company's Registration Statement on Form S-1 (333-190417), filed on August 7, 2013)


10.17


Form of Amended and Restated Employment Agreement between John Knopf and Acceleron Pharma Inc. (incorporated by reference to exhibit 10.17 to the Company's Registration Statement on , dated as of August 26, 2013
Form S-1/A (333-190417), filed on August 19, 2013)10-K
(Exhibit 10.13)
3/2/2015001-36065

10.14*

10.18


Form of Amended and Restated Employment Agreement between Matthew L. Sherman and Acceleron Pharma Inc. (incorporated by reference to exhibit 10.18 to the Company's Registration Statement on , dated as of August 26, 2013
Form S-1/A (333-190417), filed on August 19, 2013)10-K
(Exhibit 10.14)
3/2/2015001-36065


Table of Contents



10.19


Exhibit
Number
Exhibit Description
Filed
with this
Report
Incorporated by
Reference
herein from
Form of or
Schedule
Filing Date
SEC File/Reg.
Number
10.15*Amended and Restated Employment Agreement between John D. Quisel and Acceleron Pharma Inc. (incorporated by reference to exhibit 10.19 to the Company's Registration Statement on , dated as of August 26, 2013
Form S-1/A (333-190417), filed on August 19, 2013)10-K
(Exhibit 10.15)
3/2/2015001-36065

10.16*

10.20

Amended and Restated Employment Agreement between Kevin F. McLaughlin and Acceleron Pharma Inc. dated as of January 31, 2014

Form 10-K
(Exhibit 10.16)
3/2/2015001-36065
10.16.1*First Amendment to Amended and Restated Employment Agreement, by and between Kevin F. McLaughlin and Acceleron Pharma Inc., dated as of September 9, 2015
Form 8-K
(Exhibit 10.2)
9/11/2015001-36065
10.17*Amended and Restated Employment Agreement between Steven D. Ertel and Acceleron Pharma Inc. dated as of January 31, 2014
Form 10-K
(Exhibit 10.17)
3/2/2015001-36065
10.17.1*First Amendment to Amended and Restated Employment Agreement, by and between Steven D. Ertel and Acceleron Pharma Inc., dated as of September 9, 2015
Form 8-K
(Exhibit 10.1)
9/11/2015001-36065
10.18*Employee Stock Purchase Plan (incorporated by reference to exhibit 10.20 to the Company's Registration Statement on Form S-1/A (333-190417), filed on September 6, 2013)(Exhibit 10.20)9/6/2013333-190417

10.19*

10.21


Form of Non-statutoryNon-Statutory Stock Option Agreement under the 2013 Equity Incentive Plan (incorporated by reference to exhibit 10.21 to the Company's Registration Statement on
Form S-1/A (333-193252), filed on January 9, 2013)S-1 (Exhibit 10.21)1/9/2014333-193252

10.20*

10.22


Form of Incentive Stock Option Agreement under the 2013 Equity Incentive Plan (incorporated by reference to exhibit 10.22 to the Company's Registration Statement on
Form S-1/A (333-193252), filed on January 9, 2013)S-1 (Exhibit 10.22)1/9/2014333-193252

10.21*

21.1

Form of Restricted Stock Unit Award Agreement under the 2013 Equity Incentive Plan (2016)

X
10.22*Form of Restricted Stock Unit Award Agreement under the 2013 Equity Incentive Plan (Executives)
Form 8-K
(Exhibit 10.3)
9/11/2015001-36065
21.1List of SubsidiariesX

23.1

23.1


Consent of Ernst & Young LLP, Independent Registered Public Accounting Firm
X

31.1

31.1


Certification of Principal Executive Officer pursuant to Rule 13a-14(a) or Rule 15d-14(a) of the Securities Exchange Act of 1934, as adopted pursuant to Section 302 of Sarbanes Oxleythe Sarbanes-Oxley Act of 2002 by Chief Executive Officer
X

31.2

31.2


Certification of Principal Financial Officer pursuant to Rule 13a-14(a) or Rule 15d-14(a) of the Securities Exchange Act of 1934, as adopted pursuant to Section 302 of Sarbanes Oxleythe Sarbanes-Oxley Act of 2002 by Chief Financial Officer

Table of Contents

X
Exhibit
number
Description of exhibit
32.1 Certification of periodic financial reportPrincipal Executive Officer and Principal Financial Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of Sarbanes Oxleythe Sarbanes-Oxley Act of 2002

 

32.2X

 

Certification of periodic financial report pursuant to Section 906 of Sarbanes Oxley Act of 2002

101

101


The following financial information from the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 20132015 formatted in ExtensibleXBRL (eXtensible Business Reporting Language,Language): (i) the Consolidated Balance Sheets as of December 31, 2015 and December 31, 2014, (ii) the Consolidated Statements of Operations and Comprehensive Loss for the years ended December 31, 2015, 2014 and 2013, (iii) the Consolidated Statements of Comprehensive Income for the years ended December 31, 2015, 2014 and 2013, (iv) the Consolidated Statements of Redeemable Convertible Preferred Stock and Stockholders' Equity (Deficit), for the years ended December 31, 2015, 2014 and 2013, (v) the Consolidated Statements of Cash Flows for the years ended December 31, 2015, 2014 and 2013, and (vi) the Notes to the Consolidated Financial Statements
X

+
Portions of this exhibit (indicated by asterisks) have been omitted pursuant to a request for confidential treatment and this exhibit has been submitted separately.



Table of Contents


+Confidential treatment has been granted by, or is being requested from, the Securities and Exchange Commission as to certain portions of this Exhibit, which portions have been omitted and filed separately with the Securities and Exchange Commission as part of an application for confidential treatment pursuant to the Securities Act of 1933, as amended, and the Securities Exchange Act of 1934, as amended, as applicable.
*Management contract or compensatory plan or arrangement.





Signatures

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

 ACCELERON PHARMA INC.

Date: March 17, 2014February 25, 2016

By:

By:


/s/ JOHN L. KNOPF, PH.D.

John L. Knopf, Ph.D.
Chief Executive Officer, President and Director


Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, this report has been signed by the following persons on behalf of the registrant and in the capacities and on the dates indicated:

Signature
Title
Date


 

Title

 

Date
/s/ JOHN L. KNOPF, PH.D.

John L. Knopf, Ph.D.
 Chief Executive Officer, President and PresidentDirector (Principal Executive Officer) March 17, 2014
February 25, 2016


John L. Knopf, Ph.D.
/s/ KEVIN F. MCLAUGHLIN

Kevin F. McLaughlin

 

Senior Vice President, Chief Financial Officer and Treasurer (Principal Financial Officer and Principal Accounting Officer)

 
February 25, 2016

March 17, 2014
Kevin F. McLaughlin
/s/ FRANCOIS NADER, M.D.Chair of the Board of Directors
February 25, 2016

Francois Nader, M.D.
��
/s/ JEAN M. GEORGEDirector
February 25, 2016


Jean M. George
 

Director


March 17, 2014

/s/ GEORGE GOLUMBESKI, PH.D.Director
February 25, 2016


George Golumbeski, Ph.D.
 

Director


March 17, 2014

/s/ EDWIN M. KANIA, JR.

Edwin M. Kania, Jr.

 

Director

 

March 17, 2014
/s/ TERRENCE C. KEARNEYDirector
February 25, 2016

Terrence C. Kearney
/s/ TOM MANIATIS, PH.D.Director
February 25, 2016


Tom Maniatis, Ph.D.
 

Director


March 17, 2014

/s/ TERRANCE G. MCGUIREDirector
February 25, 2016


Terrance G. McGuire
 

Director


March 17, 2014

/s/ RICHARD F. POPSDirector
February 25, 2016


Richard F. Pops
 

Director


March 17, 2014

/s/ JOSEPH S. ZAKRZEWSKIDirector
February 25, 2016


Joseph S. Zakrzewski
 

Director


March 17, 2014