UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORMFORM 10-K

For the fiscal year ended December 31, 20152018

OR

For the transition period from                      to                     

Commission File Number000-14656

REPLIGEN CORPORATION

(Exact name of registrant as specified in its charter)

Registrant’s telephone number, including area code:(781) 250-0111

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

Title of Each Class

Common Stock, $0.01 Par Value Per Share

Name of Exchange on Which Registered

The NASDAQ Stock Market LLC

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  ¨☒    No  x.☐.

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act.    Yes  ¨☐    No  x.☒.

Indicate by checkmark 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 such filing requirements for the past 90 days.    Yes  x☒    No  ¨.☐.

Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Website, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of RegulationS-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  x☒    No  ¨.☐.

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of RegulationS-K (§229.405 of this chapter) is not contained herein, and will not be contained, to the best of registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form10-K or any amendment to this Form10-K.    x☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, anon-accelerated filer, or a smaller reporting company. See the definitions of “large accelerated filer,” “accelerated filer” andfiler,” “smaller reporting company” and “emerging growth company” in Rule12b-2 of the Exchange Act. (Check one):

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.    Yes  ☐    No  ☐.

Indicate by check mark whether the registrant is a shell company (as defined in Rule12b-2 of the Act).    Yes  ¨☐    No  x.☒.

The aggregate market value of the voting andnon-voting common equity held bynon-affiliates as of June 30, 2015,29, 2018, the last business day of the registrant’s most recently completed second fiscal quarter, was $1,348,697,533.$1,569,493,598.

The number of shares of the registrant’s common stock outstanding as of February 18, 201622, 2019 was 33,031,533.43,921,488.

Documents Incorporated By Reference

The registrant intends to file a proxy statement pursuant to Regulation 14A within 120 days of the end of the fiscal year ended December 31, 2015.2018. Portions of such proxy statement are incorporated by reference into Part III of this Annual Report on Form10-K.

Table of Contents

FORWARD-LOOKING STATEMENTS

This Annual Report on Form10-K (“Form10-K”) contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). The forward-looking statements in this Form10-K do not constitute guarantees of future performance. Investors are cautioned that express or implied statements in this Form10-K that are not strictly historical statements, including, without limitation, statements regarding current or future financial performance, potential impairment of future earnings, management’s strategy, plans and objectives for future operations or acquisitions, product development and sales, research and development, selling, general and administrative expenditures, intellectual property and adequacy of capital resources and financing plans constitute forward-looking statements. Such forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated, including, without limitation, the risks identified under the caption “Risk Factors” and other risks detailed in this Form10-K and our other filings with the Securities and Exchange Commission. We assume no obligation to update any forward-looking information contained in this Form10-K, except as required by law.

PART I

The following discussion of our business contains forward-looking statements that involve risks and uncertainties. When used in this report, the words “intend,” “anticipate,” “believe,” “estimate,” “plan” and “expect” and similar expressions as they relate to us are included to identify forward-looking statements. Our actual results could differ materially from those anticipated in these forward-looking statements and are a result of certain factors, including those set forth under “Risk Factors” and elsewhere in this Annual Report onForm 10-K.

References throughout this Annual Report on Form10-K to “Repligen”, “we”, “us”, “our”, or the “Company” refer to Repligen Corporation and its subsidiaries, taken as a whole, unless the context otherwise indicates.

Overview

Repligen Corporation (“Repligen,” the “Company” or “we”) is a leading provider of advanced bioprocessing company focused on the development, productiontechnologies and commercialization of innovative productssolutions used in the process of manufacturing biologic drugs. Our products are made to substantially increase biopharmaceutical manufacturing efficiencies and flexibility. As the global biologics market continues to experience strong growth and expansion, our customers – primarily large biopharmaceutical companies and contract manufacturing organizations – face critical production cost, capacity, quality and time pressures that our products are made to address. Our commitment to bioprocessing is helping to set new standards for the way our customers manufacture biologic drugs, including monoclonal antibodies (“bioprocessing”mAb”). Biologic, recombinant proteins, vaccines and gene therapies. We are dedicated to inspiring advances in bioprocessing as a trusted partner in the production of biologic drugs that improve human health worldwide.

We currently operate as one bioprocessing business, with a comprehensive suite of products to serve both upstream and downstream processes in biologic drug manufacturing. Building on over 35 years of industry expertise, we have developed a broad and diversified product portfolio that reflects our commitment to build abest-in-class bioprocessing technology company with a world-class direct sales and commercial organization.

We are committed to capitalizing on growth opportunities and maximizing the value of our product platform through both organic growth initiatives (internal innovation and commercial leverage) and targeted acquisitions.

Our Products

Our bioprocessing business is comprised of three main product lines – Chromatography, Filtration and Proteins.

Direct-to-Customer Products (Chromatography and Filtration)

Since 2012, we have significantly expanded ourdirect-to-customer presence through our Chromatography and Filtration product lines, which include monoclonaldifferentiated products and systems. We have diversified and grown ourdirect-to-customer product offering through internal innovation and through disciplined, accretive acquisitions of assets or businesses that leverage existing product lines and/or expand our customer and geographic scope.

To support our sales goals for ourdirect-to-consumer products, we have invested in our commercial organization. Our commercial and research and development teams work to effectively launch new products and applications, as well as build new markets for acquired technologies that increase flexibility and convenience while streamlining biomanufacturing workflow for our customers. In addition, to meet increased demand for our products, we continue to invest in increasing the volume and scale of manufacturing at our facilities in the United States, Sweden and Germany.

Chromatography

Our Chromatography product line includes a number of products used in the downstream purification and quality control of biological drugs. The main driver of growth in this portfolio is our lab and process-scale OPUS^®pre-packed chromatography (“PPC”) column line.

Our other products include chromatography resins (such as CaptivA^®) used in a small number of commercial drug processes and ELISA test kits used by quality control departments to detect and measure the presence of leached Protein A and/or growth factor in the final product.

OPUS^®

Our Chromatography product line features PPC columns under our OPUS brand. OPUS columns, which we deliver to our customerspre-packed with their choice of chromatography resin, are single-campaign(“single-use”) disposable columns that replace the use of traditional and more permanent glass columns used in downstream purification processes. By designing OPUS to be a technologically advanced and flexible option for the purification of biologics from process development through clinical-scale and some commercial manufacturing, Repligen has become a leader in the PPC market. The customization andready-to-use nature of our OPUS columns makes them ideal for purification of antibodies, recombinant proteins and vaccinesvaccines. Biomanufacturers value the time savings, labor and represent a growing areautility cost savings, product consistency and the “plug and play” convenience of drug development. Our customers include leading life sciences companies, global biopharmaceutical companies,OPUS.

We launched our first production-scale OPUS columns in 2012 and contract manufacturers worldwide. The high-value technologies thathave since added larger diameter options such as OPUS 45 and OPUS 60. Early in 2018, we provide enable biologics manufacturers to cost-effectively increase drug production yields while retainingintroduced OPUS 80 R, the highest quality and safety standards.

Repligen is a longtime global market leader in the manufacture of Protein A ligands, sold to life sciences companies under long term supply agreements. Protein A is a critical reagent used to purify monoclonal antibodies (“mAbs”)largest available PPC on the market, (over 50)for use in late-stage clinical or select commercial purification processes. We have also introduced next-generation features such as a resin recovery port on our larger columns. This allows our customers to reuse the recovered resin in development (over 300). In December 2011, we strengthenedother applications. The unpacking port feature was made available in the first quarter of 2017 on our Protein A market leadership with thelargest production-scale OPUS columns.

Through our acquisition of Novozymes’s bioprocessing business (“Novozymes”)Atoll GmbH in Lund, Sweden (the “Novozymes Acquisition”).2016, we established a customer-facing center in Europe and expanded our portfolio to include our smaller-scale columns, named OPUS PD, that are used in high-throughput process development screening, viral validation studies and scale down validation of chromatography processes. We maintain a broad and customizable PPC product line to meet our customers’ diverse needs.

We establishedOther Chromatography

Also included in our Chromatography portfolio are ELISA kits, which are analytical test kits to detect the presence of proteins and have executed ongrowth factors, and chromatography resins, including our CaptivA^® brand. In addition, following our acquisition of Spectrum in 2017, we sell Spectra/Chrom^® liquid chromatography products as part of our Chromatography product line.

Filtration

XCell^™ ATF

Our Filtration products offer a diversification strategy to selectively expand the number of bioprocessing products that we sell directlyadvantages to end users. With the Novozymes Acquisition, we gained a portfolio of growth factors, led by LONG^® R3 IGF-1, which is used in cell culture media to increase productivity. LONG^®R3 IGF-1 is sold in collaboration with MilliporeSigma (formerly Sigma Aldrich), our exclusive distributor for the product. We also developed and directly market our OPUS^® process-scale line of pre-packed chromatography columns for the capture and purificationmanufacturers of biologic drugs inat volumes that span from pilot studies to clinical development. Most recently, in June 2014, we acquired the businessand commercial-scale production. We first established our Filtration product line through our acquisition of Refine Technology, including Refine’sXCell^™ Alternating Tangential Flow (“ATF”) System,assets from Refine Technology (“Refine”) in 2014. XCell ATF systems are used primarily in upstream perfusion, or “continuous manufacturing”, processes.

XCell ATF is a best-in-classtechnologically advanced filtration device used in upstream processes to generate extremely high cell concentrationscontinuously remove cellular metabolic waste products during the course of a fermentation step ofrun, freeing healthy cells to continue producing the biologic drug manufacturing process (the “Refine Business”of interest. XCell ATF was designed to both increase the density of cells in a bioreactor and extend the acquisitionproduction run. By continuously removing waste products from the fermenter, the XCell ATF System routinely increases cell densities to2- or3-times the levels achieved by standard batch fermentation. As a result, product yield is increased, which improves facility utilization and can reduce the size of a bioreactor required to manufacture a given volume of biologic drug product. This is important to biomanufacturers who seek to maximize output from their existing facilities. XCell ATF Systems are suitable for use in laboratory andscale-up all the way to production bioreactors as large as 2,000 liters.

Through internal innovation, we developed and in 2016 launchedsingle-use formats of the Refine Business,original stainless steel XCell ATF device to address increasing industry demand for“plug-and-play” technology. The XCell ATF device is now available to customers in both its original configuration (steel housing and replaceable filters) in all sizes (2, 4, 6 and 10), and/or as asingle-use device (disposable housing/filter combination) in most sizes (2, 6, and 10). The availability of XCell ATF in asingle-use format eliminates the “Refine Acquisition”pre-use workflow associated with autoclaving, leading to an 80% reduction in implementation time. Thesingle-use format also enables our customers to accelerate evaluations of the product with a lower initial overall cost of ownership. Based on strong demand, we have continued to expand thesingle-use XCell ATF offering.

In September 2018, we entered into a collaboration agreement with industry leader Sartorius Stedim Biotech (“SSB”). to integrate our XCell ATF controller technology into SSB’s BIOSTAT^® STR large-scale,single-use bioreactors, to create novel perfusion-enabled bioreactors.

SIUS^™ Tangential Flow Filters (TangenX)

In December 2016, we acquired TangenX Technology Corporation (“TangenX”), balancing our upstream XCell ATF offering with a downstream portfolio of flat-sheet tangential flow filters (“TFF”) and cassettes used in downstream biologic drug purification and formulation processes. The TangenX portfolio includes oursingle-use SIUS^™ TFF brand, providing customers with a high-performance,low-cost alternative to reusable TFF cassettes.

TFF is a rapid and efficient method for separation and purification of biomolecules that is widely used in laboratory, process development and process scale applications in biopharmaceutical manufacturing. SIUS is an innovativesingle-use TFF line of cassettes and hardware forlab-scale through large-scale biopharmaceutical manufacturing.Single-use SIUS TFF cassettes with enclosed flat sheet membranes are designed to provide a high performing membrane at significantly lower product and labor costs than reusable TFF products. Each disposable cassette is deliveredpre-sanitized, integrity tested and ready to be equilibrated and used for tangential flow diafiltration and ultrafiltration processing. Use of SIUS TFF cassettes eliminatesnon-value added steps of cleaning and flushing required in reusable TFF products. The cassettes are interchangeable with filter hardware from multiple manufacturers, simplifying customer trial and adoption of SIUS products.

KrosFlo^®, ProConnex^® (Spectrum Life Sciences LLC)

We marketacquired Spectrum Life Sciences LLC (“Spectrum”) and its subsidiaries in August 2017 to strengthen our filtration business with the addition of a leading portfolio of hollow-fiber (HF) filters and modules,single-use flow path connectors and TFF filtration systems. Spectrum products globallyare used inbench-top through acommercial-scale processes, primarily for the filtration, isolation, purification and concentration of biologics and diagnostic products. Our Spectrum filtration products offer both standard and customized solutions to bioprocessing customers, with particular strength in consumable andsingle-use offerings.

With the addition of Spectrum, we nowin-house manufacture hollow-fiber filters that can be used in our XCell ATF system. In addition, we increased our direct commercial organizationsales presence in the U.S., Europe and Asia, and we diversified our end markets beyond monoclonal antibodies to include vaccines, recombinant protein and gene therapies.

Our Spectrum filtration brands include the KrosFlo^® line of hollow-fiber cartridges and TFF systems, the Spectra/Por^® portfolio of laboratory and process dialysis products andPro-Connex^®single-use hollow-fiberModule-Bag-Tubing sets.

In 2018, we introduced our KONDUiT device to automate concentration and buffer exchange to be used in conjunction with our hollow fiber or flat sheet TFF filtration products.

OEM Products (Proteins)

Our OEM products are represented by our Protein A affinity ligands, which are a critical component of Protein A chromatography resins used in downstream purification, and cell culture growth factor products, which are a key component of cell culture media used upstream to increase cell density in a bioreactor and improve product yield.

Protein A/Ligands

We are a leading provider of Protein A affinity ligands to life sciences companies. Protein A ligands are an essential “binding” component of Protein A chromatography resins used in the purification of virtually all monoclonal antibody based drugs on the market or in development. We manufacture multiple forms of Protein A ligands under long-term supply agreements with major life sciences companies including GE Healthcare, MilliporeSigma and Purolite Life Sciences (“Purolite”), who in turn sell their Protein A chromatography resins to end users (“mAb manufacturers”). We have two manufacturing sites supporting overall global demand for our Protein A ligands: one in Lund, Sweden and another in Waltham, Massachusetts.

Protein A chromatography resins are considered the industry standard for purification of antibody-based therapeutics due to the ability of the Protein A ligand to very selectively bind to or “capture” antibodies from crude protein mixtures. Protein A resins are packed into the first chromatography column of typically three columns used in a mAb purification process. As a result of Protein A’s high affinity for antibodies, the mAb product is highly purified and concentrated within this first capture step before moving to polishing steps.

In June 2018, we entered into an agreement with Navigo Proteins GmbH (“Navigo”) for the exclusiveco-development of multiple affinity ligands for which Repligen holds commercialization rights. We are manufacturing and have agreed to supply the first of these ligands,NGL-Impact™ A, exclusively to Purolite, who will pair our high-performance ligand with Purolite’s agarose jetting base bead technology used in their Jetted A50 Protein A resin product. We also signed a long-term supply agreement with Purolite forNGL-Impact A and potential additional affinity ligands that may advance from our Navigo collaboration. The Navigo and Purolite agreements are supportive of our strategy to secure and reinforce our Proteins product line.

Growth Factors

Most biopharmaceuticals are produced through an upstream mammalian cell fermentation process. In order to stimulate increased cell growth and maximize overall yield from a bioreactor, manufacturers often add growth factors, such as insulin, to their cell culture fermentation media. As part of the Novozymes Acquisition in 2011, we gained several cell culture growth factor additives. Among those products is LONG^®R3 IGF-1, our insulin-like growth factor that has been shown to be up to 100 times more biologically potent than insulin (the industry standard), thereby increasing recombinant protein production in cell culture fermentation applications. LONGR3IGF-1 is sold through a distribution partnership with MilliporeSigma.

Corporate Information

We are a Delaware corporation with global headquarters in Waltham, Massachusetts. We were incorporated in 1981 and became a publicly traded company in 1986. Our common stock is listed on The Nasdaq Global Market

under the symbol “RGEN”. We have over 540 employees and operate globally with offices and manufacturing sites located at multiple locations in the United States, Europe and Asia. Our principal executive offices are located at 41 Seyon Street, Waltham, Massachusetts 02453, our website iswww.repligen.com and our telephone number is(781) 250-0111.

Our Market Opportunity

The global biologics drug market was estimated to be over $200 billion in 2017. This market includes therapeutic antibodies, recombinant proteins and vaccines. Antibody-based biologics alone accounted for over $115 billion of global biopharma revenue and represented a majority of the top 10 best-selling drugs across the pharmaceutical industry in 2017. Industry sources project the biologics market to grow at a rate of8%-10% annually over the next five years, driven by strength in the mAb class of biologics, as evidenced by the rate of new approvals, expanded labels for marketed antibodies and the emergence of biosimilar versions of originator mAbs.

In 2018, 13 mAbs (a record 11 originator mAbs and two biosimilars) were approved by the U.S. Food and Drug Administration (“FDA”) to treat a diverse range of diseases. Between 2016 and 2018, 36 mAbs were approved by the FDA, representing over 40% of all approved mAbs since the first therapeutic antibody was brought to market in 1986. There are currently more than 80 mAbs on the market and more than 400 in various stages of clinical development addressing a wide range of medical conditions including asthma, migraines and Alzheimer’s disease.

In addition to investments in the discovery and development of novel biologic drugs, there has been substantial investment infollow-on products (biosimilars) by generic and specialty pharmaceutical as well as large biopharmaceutical companies. Development offollow-on products has accelerated as the first major mAbs have come off patent in the European Union and United States. Due to the high cost of biologic drugs, many countries in the developing and emerging markets have been aggressively investing in biomanufacturing capabilities to supply lower cost biosimilars for the local markets. For both originator andfollow-on biologics manufacturing, Repligen products are well-positioned to enable greater manufacturing flexibility, production yields and lower costs through strategic partnersimproved process efficiencies.

Many of the products we manufacture are in select markets. In 2014the early stages of their adoption cycle, and 2015, we invested in expandingtogether with the expansion of our global commercial organization addingand strategic acquisitions, have contributed to product revenue growth from $47.5 million in 2013, to $193.9 million in 2018. While all product lines have grown over this period, our diversification strategy has resulted in a significant increase in direct product sales marketingas a percent of total product revenue, from 17% in 2012. By 2018, 72% of total bioprocessing revenue was attributable to direct product sales; 47% from our Filtration product line, 23% from our Chromatography product line and applications personnel who interact directly witha small percentage from other sources including sales of hospital products that we obtained through our end users. Our customer base comprisesacquisition of leading life sciences companies, major contract manufacturers and 20 of the top 25 biopharmaceutical companies.Spectrum.

Customers use our products to produce initial quantities of drug for clinical studies, and thenscale-up to larger volumes as the drug progresses to commercial production following regulatory approval. Detailed specifications for a drug’s manufacturing process are included in applications that must be approved by regulators, such as the U.S. Food and Drug AdministrationFDA, and the European Medicines Agency (“EMA”), throughout the clinical trial process and prior to final commercial approval. As a result, products that become part of the manufacturing specifications of a late-stage clinical or commercial process can be very “sticky” due tosensitive given the regulatory hurdles, costs and uncertainties associated with displacing them.

Many of our products are early in their adoption cycle, and together with the expansion of our commercial organization and strategic acquisitions, have contributed to product revenue expansion from $41.8 million in 2012 to $83.5 million in 2015. To meet increased demand for our products, we have increased the volume and scale of manufacturing at our two manufacturing facilities in the U.S. and Sweden.

We were incorporated in May 1981 under the laws of the State of Delaware. Our principal executive offices are located at 41 Seyon Street, Waltham, Massachusetts 02453 and our telephone number is (781) 250-0111. We conduct manufacturing in Waltham and at our facility in Lund, Sweden.

Our Market Opportunity

The global biologics drug market is estimated to be over $200 billion. This market includes mAbs, proteins and vaccines. mAb-based biologics alone accounted for approximately $80 billion of revenue, and represented six of the top 10 best-selling drugs across the pharmaceutical industry, in 2014. Industry sources project the biologics market to grow at approximately 8-10% annually over the next five years, driven by strength in the mAb class of biologics. This strength is evidenced by the rate of new approvals, expanded labels for marketed mAbs and the emergence of biosimilar versions of originator mAbs. In 2015, a record of nine therapeutic mAbs were approved by the U.S. Food and Drug Administration (FDA) to treat a diverse range of diseases, including the first-ever approvals of mAbs to control LDL or “bad cholesterol.” There are currently more than 300 mAbs in various stages of clinical development, addressing a wide range of medical conditions including asthma, migraines and Alzheimer’s disease.

In addition to investments in the discovery and development of novel biologic drugs, there has been substantial investment in follow-on products (biosimilars and biobetters) by generic and specialty pharmaceutical as well as large biopharmaceutical companies. We believe development of follow-on products is accelerating as the first major mAbs begin to come off patent in the EU and U.S. For example, there are at least 12 companies attempting to market the first Humira^® (adalimumab) biosimilar, which faces patent expiration in the U.S. at the end of 2016. Also, due to the high cost of biologic drugs, many countries in the developing and emerging markets have been aggressively investing in biomanufacturing capabilities to supply lower cost alternatives or biosimilars for the local markets We believe they are focused on innovative technologies that offer greater manufacturing flexibility, production yields and lower-costs through improved process efficiencies.

The Biologics Manufacturing Process

Manufacturing biologic drugs requires three fundamental steps. First, upstream manufacturing involves the production of the biologic by living cells that are grown in a bioreactor under controlled conditions. Methods of production vary with the industry standard beingfed-batch, where nutrients (media) are added to a bioreactor to

stimulate cell growth and productivity and then followed by a harvest step. The industry is increasingly adopting the perfusion (or continuous) method of production, which circulates nutrients into the bioreactor, while simultaneously harvesting the biologic drug product. Some manufacturers are embracing a hybrid approach combining bothfed-batch and perfusion methods. The cells being grown in a bioreactor are engineered to produce the biologic drugs of interest. These cells, or factories,tiny cell “factories” are highly sensitive to the conditions under which they grow, including the composition of the cell culture media and the growth factors used to stimulate increased cell growth and protein production, or titre. In the second downstream step, the biologic made upstream must be separated and purified, typically through various filtration and chromatography steps. In the third stage of the process,Finally, the purified biologic drug is concentrated and formulated and then quality controlled and packaged into its final injectable form.

Biologics are generally high value therapies. Given the inherent complexities of the process and the final drug product, we have observed that manufacturers are seeking and investing in innovative technologies that address pressure points in the production process in order to improve yields. We see that manufacturersManufacturers are also seeking technologies that reduce cost of goodscosts as the biologic drug moves through clinical stages and into commercial processes by adoptingsingle-use technologies as well as other products that confer moreyield increased flexibility and efficiency.

Our Products

Downstream Products

Protein AStrategy

We are focused on the leading providerdevelopment, production and commercialization of Protein A ligands, an essential component of Protein A chromatography resins (media) useddifferentiated, technology-leading solutions or products that address specific pressure points in the purification of virtually all monoclonal antibody-based drugs on the market (more than 50) or in development (more than 300). We manufacture multiple forms of Protein A ligands under long term supply agreements for major life sciences companies including GE Healthcarebiologics manufacturing process and MilliporeSigma, who in turn sell their Protein A chromatography media to end users (biopharmaceutical manufacturers). We have two manufacturing sites, one in Lund, Sweden and another in Waltham, MA, collectively supporting overall global demand for our Protein A ligands. On February 23, 2016, we amended our long term supply agreements with GE Healthcare to, among other things, extend the terms of the supply agreement relatingdeliver substantial value to our Lund, Sweden facility through 2019. The supply agreement relating to our Waltham, MA facility runs through 2021. This dual manufacturing capability gives us strong business continuity and reduces overall supply risk for our major customers.

Protein A chromatography media is considered the industry standard for purification of mAbs, due to the ability of Protein A to selectively bind to or “capture” mAbs from crude protein mixtures. Protein A media is packed into chromatography columns as the standard first step in a purification process. As a result of Protein A’s high affinity for antibodies, the mAb product is highly purified and concentrated within this first capture step before moving to polishing steps. The global Protein A media market that we supply generates annual revenues of $350-$400 million. We expect continued growth for our Protein A ligands as new drugs are approved and biosimilar manufacturing accelerates.

Chromatography products

Our chromatography portfolio includes a number of products used in the downstream purification and quality control of biological drugs. The main driver of growth in this portfolio is our OPUS^® pre-packed chromatography column line. Our other products include Protein A chromatography resins used in a small number of commercial drug processes and ELISA test kits used by quality control departments to detect and measure the presence of leached Protein A in the final product.

Chromatography columns, packed with chromatography media, are used in biomanufacturing to purify the contents of a bioreactor. For late-stage clinical and large commercial processes, stainless steel columns are standard, and are packed in-house by the biomanufacturer. For clinical stage manufacturing, biomanufacturers value the quick turnover, cost savings and convenience of using pre-packed columns such as OPUS^® versus traditional glass columns.

OPUS columns are pre-packed with purification media and are an efficient plug-and-play solution for our customers, and is a growing area of our business. As biomanufacturers have become acutely focused on improving the drug development process, they are moving towards flexible manufacturing and disposable solutions such as OPUS. Over the past three years we have observed customers moving away from in-house solutions (self-packed glass columns). They are starting to adopt the OPUS ready-to-use format due to convenience, flexibility and consistent product performance. OPUS columns save labor time, reduce overall costs and improve overall manufacturing efficiency, allowing biomanufacturers to reassign resources to higher value-add processes.

Our OPUS line is distinctly open platform, providing desirable opportunities for customization. For example, most biopharmaceutical manufacturers utilize three different chromatography media in a given process and our flexible columns are designed to meet these needs. We differentiate ourselves in the pre-packed column space by packing any brand of chromatography media in OPUS to any bed height, ensuring the most convenientincrease our customers’ product yield, and efficient process for end users. The plug-and-play nature of our OPUS columns make them ideal for purification of antibodies and recombinant proteins. With the launch of OPUS 45 cm diameter columns in 2014 and 60 cm columns in 2015, we have further differentiated ourselves from our competitors who offer a limited number of column diameter and resin (media) options. By offering these larger columns, we are making inroads in the glass column market whichcommitted to supporting our customers typically self-pack.

Pre-packed chromatography columns are at the early stages of adoption; we estimate that currently, we and our competitors collectively capture approximately 30% of a $165 million addressable market. As our sales force expands and we increase the number of call points, we are seeing more multi-site adoption of our OPUS^® prepacked columns, including increased use by contract manufacturers, where quick turnover of multiple production runs is critical to profitability. We expect continuedwith strong growth for this product line as we aim to expand geographically and provide best-in-classcustomer service and support.

Upstream Products

Growth factors

Most biopharmaceuticals are produced through a mammalian cell fermentation process. In order to stimulate increased cell growth and maximize overall yield from a bioreactor, manufacturers often add growth factors, such as insulin, to the cell culture fermentation media. As part of the Novozymes Acquisition, we acquired several cell culture growth factor additives. Among those products is LONG^®R3 IGF-1, our insulin-like growth factor that has been shown to be 100 times more biologically potent than insulin (the industry standard), thereby increasing recombinant protein production in cell culture fermentation applications. LONG^®R3 IGF-1 is currently used in the manufacture of several commercial biopharmaceutical products and is sold through a distribution partnership with MilliporeSigma. Our goal over the last few years with MilliporeSigma has been to focus on pipeline development and work with customers already familiar with the product to more broadly adopt LONG^®R3 IGF-1 as a platform product.

We estimate that the current market for cell culture growth factors is $75-$80 million. We are gaining share of this market as customers displace insulin with LONG^®R3 IGF-1. We anticipate continued growth for this product group as our pipeline of opportunities advances from early-stage clinical to late-stage clinical and commercial manufacturing processes.

ATF Systems

The ATF System is a technologically advanced filtration device used to continuously remove cellular metabolic waste products during the course of a fermentation run, freeing healthy cells to continue producing the biologic drug of interest. The ATF System is designed to both increase the density of cells in a bioreactor and extend the production run, resulting in significantly greater product yield of up to two- to three-fold as well as reduced costs. This is important to biomanufacturers who seek to maximize output from their existing facilities. ATF Systems consist of a stainless steel housing that contains a consumable filter and an associated pump and controller. We sell the ATF System in a variety of sizes suitable for use in laboratory and scale-up all the way to production bioreactors as large as 2,000 liters. ATF Systems are used in the production of several FDA-approved monoclonal antibodies.

Following our acquisition of the ATF System from Refine Technology in 2014, we integrated the production of ATF into our operations in Waltham, MA.applications expertise.

We estimate thatintend to build on our recent history of developing market-leading solutions and delivering strong financial performance through the current market for cell retention devices is approximately $125-150 million. Within this market, we expect continued growth for our ATF franchise over the next several years, as biologics manufacturing accelerates globally and as large pharmaceutical customers who have evaluated the system adopt the technology as platform. The ATF System strengthens our upstream fermentation business and significantly broadens our technology base.following strategies:

Research and Development

Our research activities are focused on developing new high-value bioprocessing products. Specifically, we plan to focus these efforts on expanding our product portfolio and applications for our OPUS PPC columns, XCell ATF OPUSsystems, SIUS TFF, KrosFlo^®, TFF systems and chromatography portfolio, includingother products, and developing next generation Protein A ligands. Research and development expenses totaled approximately $5.7 million, $5.6 million and $7.3 million for the years ended December 31, 2015, 2014 and 2013, respectively.

Licensing Agreements

HDAC Agreement with BioMarin

On January 21, 2014, we out-licensed our HDACi portfolio, which includes the Friedreich’s ataxia program, to BioMarin Pharmaceuticals Inc. Friedreich’s ataxia is an inherited disease that causes progressive damage to the nervous system resulting in symptoms ranging from impaired walking and speech problems to heart disease. Pursuant to the terms of the agreement, BioMarin agrees to use commercially reasonable efforts to commercialize HDACi portfolio product until the later of (i) the expiration of the last-to-expire valid claim of an issued and unexpired patent or pending patent application claiming a compound included in the agreement or (ii) 10 years. Under the terms of the agreement, Repligen received an upfront payment of $2 million in January 2014 from BioMarin and we have the potential to receive up to $160 million in future milestone payments for BioMarin’s development, regulatory approval and commercial sale of portfolio compounds included in the agreement. These potential milestone payments are approximately 37% related to clinical development and 63% related to initial commercial sales in specific geographies. In addition, Repligen is eligible to receive royalties on sales of qualified products developed. The royalty rates are tiered and begin in the mid-single-digits for the first HDACi portfolio product and for the first non-HDACi portfolio product with lesser amounts for any backup products developed under the agreement. Repligen’s receipt of these royalties is subject to customary offsets and deductions. There are no refund provisions in this agreement. Royalties under this agreement are paid on a country-by-country basis during the period beginning on the first commercial sale of a compound in such country, until the later of: (i) the expiration of exclusivity period granted by a governmental authority to prevent the entry of generic product into such country; (ii) the expiration of the last-to-expire valid claim of an issued and unexpired patent or pending patent application claiming such compound in such country; or (iii) ten years following the first commercial sale of such HDACi portfolio product in any country. Royalty payments on products derived from the compounds included in the agreement are calculated by multiplying net sales of such product for the calendar year by an applicable royalty rate based on incremental net sale amounts. We have no further obligations to BioMarin.

SMA Agreement with Pfizer

On December 28, 2012, we entered into an exclusive worldwide licensing agreement (the “License Agreement”) with Pfizer to advance the SMA program, which is led by RG3039 and also includes backup compounds and enabling technologies. Under the terms of the License Agreement, we received $5 million from Pfizer as an upfront payment on January 22, 2013, a $1 million milestone payment on September 4, 2013 and a $1 million milestone payment on December 28, 2014. On January 26, 2015, Pfizer notified us that they were terminating the License Agreement for convenience, effective as of April 26, 2015. We do not intend to invest additional resources to the development of the SMA program.

RG1068

Our clinical development portfolio previously included RG1068, a synthetic human hormone we had developed as a novel imaging agent for the improved detection of pancreatic duct abnormalities in combination with magnetic resonance imaging in patients with pancreatitis and potentially other pancreatic diseases. On December 23, 2014, Innovate Biopharmaceuticals, Inc. (“Innovate”) acquired our RG1068 program for a nominal amount. Innovate is solely responsible for future development and commercialization of RG1068. If Innovate gains marketing approval and successfully commercializes RG1068, Repligen is eligible to receive royalties through the latter of ten years after the first commercial sale or the entry of a generic equivalent into the U.S. market.

Sales and Marketing

Our sales and marketing strategy supports our objective of establishing Repligenstrengthening our position as a leading provider of products and services, addressing upstream, downstream and quality control needs of bioprocessing customers in

The following table represents the Company’s total revenue by geographic area (based on the location of the customer):

We currently have 44 patents owned or licensed by us orgranted (which expire over the failure ofnext 20 years) and 85 patents to issue on pending patent applications could create increased competition, with potential adverse effects on our business prospects.in countries including Australia, Canada, China, France, Germany, India, Japan, Korea, Sweden, United Kingdom and the United States.

Other forms of market protection, including trade secrets and know-how, are also considered important elements of our proprietary strategy. Our policy is to require each of our employees, consultants, business partners, potential collaborators and major customers to execute confidentiality agreements upon the commencement of an employment, consulting, business relationship, or product related audit with us. These agreements provide that all confidential information developed or made known to the other party during the course of the relationship with us is to be kept confidential and not disclosed to third parties except in specific circumstances. In the case of employees and consultants, the agreements generally provide that all inventions conceived by the individual in the course of rendering services to Repligen shall be our exclusive property.property and must be assigned to Repligen.

Protein A

We have developed proprietary technology, trade secrets, and know-how relating to the manufacture of recombinant Protein A atcurrently hold a scale and quality standard which is consistent with the requirements of the biopharmaceutical industry. In addition, in April 2010, we were granted U.S. Patent No. 7,691,608,patent for “Nucleic Acids Encoding Recombinant Protein A,” which claims a recombinant genean isolated nucleic acid molecule that encodes a Protein A molecule with an amino acid sequence identical to that of the natural Protein A, molecule, which has long been commercialized for bioprocessing applications. This U.S. patent with the term adjustment that was granted, will remain in effect until June 2028. Foreign equivalents of this patentWe also have been issuedtwo pending patents covering affinity ligands through our collaboration with Navigo GmbH.

Trademarks

We vigilantly protect our products and services’ branding by maintaining trademark registrations globally for the Repligen trademark and our key product brands. We have a comprehensive branding policy that includes trademark usage guidelines to ensure Repligen trademarks are used in Sweden, Netherlands, Great Britain, France, Germanya manner that provides the maximum protection.

We prioritize our “housemark” trademarks, (i.e., Repligen, Spectrum and Canada. The claims of U.S. Patent No. 7,691,608 cover compositions of matter including isolated nucleic acids, expression vectors, bacterial cells that include the nucleic acids,TangenX), and ensure they are sufficiently protected and registered in key countries or regions globally, such as well as methods of producing truncated Protein A polypeptides, methods of producing affinity chromatography resins, and methods of purifying proteins.

OPUS

In January 2012, Repligen filed a provisional patent application with the U.S. Patent and Trademark Office (“USPTO”) which covers certain unique features of our OPUS pre-packed columns. Pending claims that relate to these unique features cover the ease and flexibility of column packing, bed height adjustment and cleaning that is improved over existing pre-packed column designs. In January 2013, we filed an international patent cooperation treaty (“PCT”) application as well as a utility application with the USPTO on the basis of the provisional application. The OPUS pre-packed column patent application is pending in the United States, Australia, Canada, Europe Hong Kong, India, and Japan.China. We also have product trademarks, including OPUS, XCell ATF, KrosFlo, SIUS,Pro-Connex, Spectra/Por andNGL-Impact A, that provide valuable company recognition and goodwill with its customers.

ATF Systems

As part of the Refine Acquisition, Repligen acquired the exclusive rightsOur ability to an issued U.S. patent (US 6,544,424) covering the Alternating Tangential Flow (ATF) System and a process related to the filtration of biologic fluids from a bioreactor through hollow fiber filters by the action of a diaphragm pump which creates alternating tangential flow through the filter. The patent expires in 2020. Another patent has been issuedcompete effectively in the U.S. covering improvementsmarketplace is dependent in part on the original ATF design that include a screen filter module (US 9,050,547). This family of patents and applications has issued or is pending in Brazil, Canada, China, Europe, India, and Korea. Other additional improvements on the original ATF systems and methods are covered by patent applications pending in one or more of the US, Canada, China, Europe, India, Japan, and Korea.

Spinal Muscular Atrophy

In 2009, Repligen entered into an exclusive license agreement with a non-profit organization, FSMA, now called CureSMA, for worldwide rightsour ability to patent applications related to compositions and methods for the

treatment of spinal muscular atrophy. FSMA had funded the development of these compounds and identified a novel enzyme target (“DcpS”) that these compounds inhibit. In 2011, we were granted U.S. Patent Nos. 7,888,366 and 7,985,755, both entitled “2,4 Diaminoquinazolines for Spinal Muscular Atrophy,” with allowed composition claims that cover both the genus and the species of the chemical structures of the lead clinical candidates. The expiration date of U.S. Patent No. 7,888,366 (the ‘366 patent) is in 2028 with potential for patent term extension. The expiration date of U.S. Patent No. 7,985,755 (the ‘755 patent) is in 2027 with potential for patent term extension. U.S. Patent No. 9,067,897, which is a continuation of the ‘366 patent, was issued in 2015 and expires in 2027. Foreign equivalents of these U.S. patents have been issued and/or are pending in Australia, Canada, Europe, Hong Kong, Japan, and New Zealand.

Pursuant to the License Agreement, we licensed all ofprotect our intellectual property relatedrights, which includes protecting the trademarks we use in connection with our products and services. We rely on several registered and unregistered trademarks to SMA to Pfizer and Pfizer has assumed responsibility for maintaining existing intellectual property and prosecuting new intellectual property relating to this program. On January 26, 2015, Pfizer issued to us a notice of its termination of the License Agreement for convenience, effective as of April 26, 2015.protect our brand.

Histone Deacetylase InhibitorsLicensing Agreements

Repligen hasWe have entered into multiple licensing and collaboration relationships with third-party business partners in an exclusive license agreement with The Scripps Research Institute for worldwide rightseffort to a patent application claiming compoundsfully exploit our technology and methods for treating Friedreich’s ataxia with inhibitors of histone deacetylase. We have extended this original work and filed additional patent applications which claim both methods and compositions for treating Friedreich’s ataxia. We licensed all ofadvance our intellectual property related to HDAC to BioMarin and BioMarin has assumed responsibility for maintaining existing intellectual property and prosecuting new intellectual property relating to this program. On January 21, 2014, we out-licensed our HDAC Inhibitor (HDACi) portfolio to BioMarin Pharmaceuticals Inc. Our out-licensed HDACi portfolio included patent applications in the United States as well as patent applications in Europe, Canada, Japan and Australia. Patents, if any, that are granted in the U.S. based on these patent applications are expected to expire from 2029 to 2032.bioprocessing business strategy.

Competition

Our bioprocessing products compete on the basis of quality, performance, cost effectiveness, and application suitability with numerous established technologies. Additional products using new technologies that may be competitive with our products may also be introduced. Many of the companies selling or developing competitive products, which in some cases include GE Healthcare and MilliporeSigma, our two largest customers, have greater financial and human resources, research and development, manufacturing and marketing experience than we do. They may undertake their own development of products that are substantially similar to or compete with

our products and they may succeed in developing products that are more effective or less costly than any that we may develop. These competitors may also prove to be more successful in their production, marketing and commercialization activities. We cannot be certain that the research, development and commercialization efforts of our competitors will not render any of our existing or potential products obsolete.

Manufacturing

We manufacture seven commercial forms of Protein A, including “native” Protein A for life sciences companies, including GE Healthcare, MilliporeSigma and MilliporeSigmaPurolite, under long-term supply agreements which expire between 2019 and 2021.2023. Native Protein A is manufactured in Lund, Sweden, while the recombinant forms are manufactured in Waltham, Massachusetts or in both Waltham, Massachusetts and Lund, Sweden. We currently manufacture our growth factor products in Sweden and ourLund, Sweden. Our OPUS chromatography columns and XCell ATF System products are manufactured in Waltham, Massachusetts.

We generally purchase raw materials from more than one commercially established company Our OPUSPD columns are manufactured in Ravensburg, Germany, and believe thatour SIUS TFF products were manufactured in Shrewsbury, Massachusetts until December 31, 2018 before manufacturing of the necessary raw materialsSIUS TFF products shifted to our new facility in Marlborough, Massachusetts. Our KrosFlo, Spectra/Pro andPro-Connex lines of products are currently commercially availablemanufactured in sufficient quantities necessary to meet market demand. However, thereRancho Dominguez, California. Our operating room products are only a limited number of suppliers of materials related to the ATF Systemmanufactured in Irving, Texas, and our Spectra/Chrom products one of which is the primary supplier of materials used for consumable ATF System products.are manufactured in Houston, Texas.

We utilize our own facilities in Waltham, Massachusetts and Lund, Sweden as well as third partythird-party contract manufacturing organizations to carry out certain fermentation and recovery operations, while the purification, immobilization, packaging and quality control testing of our bioprocessing products are conducted at our facilities. Our U.S. facility,facilities located in Waltham, MassachusettsMassachusetts; Lund, Sweden; Ravensburg, Germany; and our Sweden facility, located in Lund,Rancho Dominguez, California are both ISO 90019001:2015 certified and maintain formal quality systems to maintain process control, traceability, and product conformance. Additionally, our facility in Irving, Texas is ISO 13485:2012 certified. We practice continuous improvement initiatives based on routine internal audits as well as external feedback and audits performed by our partners and customers. In addition, we maintain a business continuity management system which focuses on key areas such as contingency planning, security stocks andoff-site storage of raw materials and finished goods to ensure continuous supply of our products.

Available Information

We maintain a website with the address www.repligen.com.www.repligen.com. We are not including the information contained on our website as a part of, or incorporating it by reference into, this Annual Report on Form10-K. We make available free of charge through our website our Annual Reports on Form10-K, Quarterly Reports on Form10-Q and Current Reports on Form8-K, and amendments to these reports, as soon as reasonably practicable after we electronically file such materials with, or furnish such materials to, the Securities and Exchange Commission. Our Code of Business Conduct and Ethics is also available free of charge through our website.

In addition, the public may read and copy any materials that we file with the Securities and Exchange Commission at the Securities and Exchange Commission’s Public Reference Room at 100 F Street, NE, Washington, D.C. 20549. The public may obtain information on the operation of the Public Reference Room by calling the Securities and Exchange Commission at 1-800-SEC-0330. Also, ourOur filings with the Securities and Exchange Commission may be accessed through the Securities and Exchange Commission’s Electronic Data Gathering, Analysis and Retrieval (EDGAR) system at www.sec.gov.

This Annual Report on Form10-K contains forward looking statements that involve risks and uncertainties. Our actual results could differ materially from those anticipated in these forward lookingforward-looking statements as a result of certain factors, including the risks faced by us described below and elsewhere in this Annual Report onForm10-K.

We face competition from numerous competitors, most of whom have far greater resources than we have, which may make it more difficult for us to achieve significant market penetration.

The bioprocessing market is intensely competitive, subject to rapid change and significantly affected by new product introductions and other market activities of industry participants.

Many of our competitors are large, well-capitalized companies with significantly more market share and resources than we have. As a consequence, they are able to spend more aggressively on product development, marketing, sales and other product initiatives than we can. Many of these competitors have:

Our current and future competitors, or other companiesincluding certain of our customers, may at any time develop additional products that compete with our products. If an existing or future competitorany company develops products that compete with or are superior to our products, our revenue may decline. In addition, some of our competitors may compete by lowering the price of their products. If prices were to fall, we may not be able to improve our gross margins or sales growth sufficiently to maintain and grow our profitability.

We dependDespite our increasingly diversified client base, we have historically depended on, and expect to continue to depend on, a limited number of customers for a high percentage of our revenues.

The loss of, or a significant reduction in orders from, any of theseour large customers, including following any termination or failure to renew a long-term supply contract, would significantly reduce our revenues and harm our results of operations. If a large customer purchases fewer of our products, defers orders or fails to place additional orders with us for any other reason, including for business continuity purposes, our revenue could decline, and our operating results may not meet market expectations. Under our long-term supply agreements with GE Healthcare (“GE”), we supply Protein A ligands to GE from our manufacturing facilities in Lund, Sweden and Waltham, Massachusetts (the “Lund Agreement” and “Waltham Agreement,” respectively). The Lund Agreement runs pursuant to its terms, through 2019 and the Waltham Agreement runs, pursuant to its terms, through 2021. GE may elect, upon six months’ prior notice to us, to reduce its minimum purchase requirements under the Lund Agreement. Even if GE so elects, GE would still be required to continue to purchase at least 50% of its global demand pursuant to the Waltham Agreement through the expiration of this agreement pursuant to its terms on December 31, 2021.

In addition, if thoseour customers order our products, but fail to pay on time or at all, our liquidity and operating results could be materially and adversely affected. Furthermore, if any of our current or future products compete with those of any of our largest customers, these customers may place fewer orders with us or cease placing orders with us, which would negatively affect our revenues and operating results.

AsIf we evolve from a company dependent on othersare unable to commercialize our products to a company selling directly to end users, we may encounter difficulties in expandingexpand our product portfolio, and our commercial efforts.ability to generate revenue could be adversely affected.

In connection with the Company’s decision to focus our efforts on the growth of our core bioprocessing business, weWe are increasingly seeking to develop and commercialize our own portfolio of products. Our future financial performance will depend, in part, on our ability to successfully develop and acquire additional bioprocessing products. There is no guarantee that we will be able to successfully acquire or develop additional bioprocessing products, and the Company’s financial performance will likely suffer if we are unable to do so.

If intangible assets and goodwill that we recorded in connection with our acquisitions become impaired, we couldmay have to take significant charges against earnings.

In connection with the accounting for the Novozymes Acquisition,our completed acquisitions, we recorded a significant amount of intangible assets, including developed technology and customer relationships relating to the growth factor products. In addition, in connection with the accounting for the Refine Acquisition, we recorded a significant amount of intangible assets, including developed technologyacquired product lines, and customer relationships relating to the ATF system.goodwill. Under U.S. GAAP, we must assess, at least annually and potentially more frequently, whether the value of intangible assets and goodwill has been impaired. Intangible assets and goodwill will be assessed for impairment in the event of an impairment indicator. Any reduction or impairment of the value of intangible assets and goodwill will result in a charge against earnings, which could materially adversely affect our results of operations and shareholders’ equity in future periods.

Our exposure to political, economic and other risks that arise from operating a multinational business has and may continue to increase.

We operate on a global basis with offices or activities in Japan, South Korea, China, India, Europe and North America. Our operations and sales outside of the United States have increased as a result of the Novozymes Acquisition and the Refine Acquisitionour strategic acquisitions and the continued expansion of our commercial organization. Risks related to these increased foreign operations include:

Our business success depends in part on our ability to anticipate and effectively manage these and other.other related factors. We cannot assure you that these and other related factors will not materially adversely affect our international operations or business as a whole.

In addition, a deterioration in diplomatic relations between the United States and any country where we conduct business could adversely affect our future operations and lead to a decline in profitability.

We may be unable to efficiently manage efficiently having becomeour growth as a larger and more geographically diverse organization.

The Novozymes Acquisition, the Refine Acquisition,Our strategic acquisitions, the continued expansion of our commercial sales operations, and our organic growth have increased the scope and complexity of our business. WeAs a result, we will face

challenges inherent in efficiently managing a more complex business with an increased number of employees over large geographic distances, including the need to implement appropriate systems, policies, benefits and compliance programs. Our inability to manage successfully the geographically more diverse (including from a cultural perspective) and substantially larger combined organization could materially adversely affect our operating results and, as a result, the market price of our common stock.

Our business is subject to a number of environmental risks.

Our manufacturing business involves the controlled use of hazardous materials and chemicals and is therefore subject to numerous environmental and safety laws and regulations and to periodic inspections for possible violations of these laws and regulations. In addition to these hazardous materials and chemicals, our facility in Sweden also uses Staphylococcus aureus and toxins produced by Staphylococcus aureus in some of its manufacturing processes. Staphylococcus aureus and the toxins it produces, particularly enterotoxins, can cause severe illness in humans. The costs of compliance with environmental and safety laws and regulations are significant and have increased since we completed the acquisition of the Novozymes Biopharma Business.significant. Any violations, even if inadvertent or accidental, of current or future environmental and safety laws or regulations and the cost of compliance with any resulting order or fine could adversely affect our operations.

Our acquisitions expose us to risks that could adversely affect our business, and we may not achieve the anticipated benefits of acquisitions of businesses or technologies.

In addition to the Novozymes Acquisition and the Refine Acquisition, and asAs a part of our growth strategy, we may make selected acquisitions of complementary products and/or businesses. Any acquisition involves numerous risks and operational, financial, and managerial challenges, including the following, any of which could adversely affect our business, financial condition, or results of operations:

In addition, the successful integration of acquired businesses requires significant efforts and expense across all operational areas, including sales and marketing, research and development, manufacturing, finance, legal, and information technologies. There can be no assurance that any of the acquisitions we may make will be successful or will be, or will remain, profitable. Our failure to successfully address the foregoing risks may prevent us from achieving the anticipated benefits from any acquisition in a reasonable time frame, or at all.

Servicing our debt will require a significant amount of cash, and we may not have sufficient cash flow from our business to make payments on our debt.

We incurred significant indebtedness in the amount of $115.0 million in aggregate principal with additional accrued interest under our 2.125% Convertible Senior Notes due 2021 (the “Notes”). Our ability to make scheduled payments of the principal of, to pay interest on, or to refinance our indebtedness, including the Notes, depends on our future performance, which is subject to economic, financial, competitive and other factors that may be beyond our control. Our business may not generate cash flow from operations in the future sufficient to service our debt and make necessary capital expenditures. If we are unable to generate such cash flow, we may be required to adopt one or more alternatives, such as selling assets, restructuring debt or obtaining additional equity capital on terms that may be onerous or highly dilutive. Our ability to refinance our indebtedness will depend on the capital markets and our financial condition at such time. In addition, in the event of a fundamental change or a default under the Notes, the holders and/or the trustee under the indentures governing the Notes may accelerate the payment obligations or trigger the holders’ repurchase rights under the Notes. We may not be able to engage in any of these activities or engage in these activities on desirable terms, which could result in a default on our debt obligations, including the Notes.

If a make-whole fundamental change, such as an acquisition of our company, occurs prior to the maturity of the Notes, under certain circumstances, the conversion rate for the Notes will increase such that additional shares of our common stock will be issued upon conversion of the Notes in connection with such make-whole fundamental change. The ATF Systemincrease in the conversion rate will be determined based on the date on which the make-whole fundamental change occurs or becomes effective and the price paid (or deemed paid) per share of our common stock in such transaction. Upon conversion of the Notes, unless we elect to deliver solely shares of our common stock to settle such conversion (other than paying cash in lieu of delivering any fractional share), we will be required to make cash payments in respect of the Notes being converted. We may not have enough available cash or be able to obtain financing at the time we are required to make repurchases of Notes surrendered therefor or

notes being converted. Our failure to repurchase Notes at a time when the repurchase is required by the indenture or to pay any cash payable on future conversions of the Notes as required by the indenture would constitute a default under the indenture. If the repayment of the related indebtedness were to be accelerated after any applicable notice or grace periods, we may not have sufficient funds to repay the indebtedness and repurchase the notes or make cash payments upon conversions thereof.

In addition, our significant indebtedness, combined with our other financial obligations and contractual commitments, could have other important consequences. For example, it could:

Any of these factors could materially and adversely affect our business, financial condition and results of operations. In addition, if we incur additional indebtedness, the risks related to our business and our ability to service or repay our indebtedness would increase.

Future strategic transactions or acquisitions may require us to seek additional financing, which we may not be able to secure on favorable terms, if at all.

We plan to continue a strategy of growth and development for our bioprocessing business, and we actively evaluate various strategic transactions on an ongoing basis, including licensing or acquiring complementary products, technologies or businesses that would complement our existing portfolio of development programs. In order to complete such strategic transactions, we may need to seek additional financing to fund these investments and acquisitions. Should we need to do so, we may not be able to secure such financing, or obtain such financing on favorable terms because of the volatile nature of the biotechnology marketplace. In addition, future acquisitions may require the issuance or sale of additional equity or debt securities, which may result in additional dilution to our stockholders.

We rely on a limited number of suppliers or, in some cases,for certain of our products, one supplier, and we may not be able to find replacements or immediately transition to alternative suppliers, which could have a material adverse effect on the ATF System business and our financial condition, results of operations and reputation.

There are only a limited number of suppliers of materials related to the ATF System products, onefor certain of which is the primary supplier of materials used for consumable ATF Systemour products. An interruption in operations of the business related to these products could occur if we encounter delays or difficulties in securing thesethe required materials, or if we cannot then obtain an acceptable substitute. Any such interruption could significantly affect the business related to these products and our financial condition, results of operations and reputation.

WeFor example, we believe that only a small number of suppliers are currently qualified to supply materials for the XCell ATF system.System. The use of materials furnished by these replacement suppliers would require us to alter our operations related to the XCell ATF system.System. Transitioning to a new supplier for our products would be time consuming and expensive, may result in interruptions in our operations, could affect the performance specifications of the ATF systemour product lines or could require that we revalidate the materials. There can be no assurance that we will be able to secure alternative materials and bring such materials on line and revalidate them without experiencing interruptions in our workflow. If we should encounter delays or difficulties in securing, reconfiguring or revalidating the materials required for ATF Systemour products, our business related to these products and our financial condition, results of operations and reputation could be adversely affected.

As we evolve from a company dependent on sales of Orencia expired on December 31, 2013.

Our royalty agreement with Bristol provided for usothers to receive payments from Bristol based on their net sales of their Orencia^®commercialize our products to a company selling directly to end users, we may encounter difficulties in expanding our product in the United States through December 31, 2013. As a result, we no longer receive royalty payments under this agreement as of December 31, 2013.

Our license agreement with Pfizer expired on April 26, 2015.

Our licensing agreement with Pfizer provided for us to potentially receive payments from Pfizer based on milestones related to clinical developmentportfolio and initialour commercial sales in specific geographies, as well as royalty payments from Pfizer based on its future sales of RG3039 or any SMA compounds developed under the license agreement. On January 26, 2015, Pfizer issued to us a notice of its termination of the License Agreement for convenience, effective as of April 26, 2015. As a result, we no longer receive milestone payments under this agreement.

We have limited sales and marketing capabilities.

We have a small sales force and, historically,Prior to 2016, we have generated most of our revenues through sales of bioprocessing products to a limited number of life sciences companies, such as GE Healthcare, MilliporeSigma and through other individual distributors. However, due in part to the Refine Acquisition,our recent strategic acquisitions, an increasing amount of our revenue is attributable to our commercialization of bioprocessing products that we sell directly toend-users, such as including biopharmaceutical companies and contract manufacturing organizations. This has required and will continue to require us to invest additional resources in our sales and marketing capabilities. We may not be able to attract and retain additional sales and marketing professionals, and the cost of building the sales and marketing function may not generate our anticipated revenue growth. In addition, our sales and marketing efforts may be unsuccessful. Our failure to manage these risks may have a negative impact on our financial condition, or results of operations and may cause our stock price to decline.

If we are unable to obtain or maintain our intellectual property, we may not be able to succeed commercially.

We endeavor to obtain and maintain trade secrets and, to a lesser extent with respect to the products that currently account for a majority of our revenue, patent and trade secret protection for our products and processes when available in order to protect themour products and processes from unauthorized use and to produce a financial return consistent with the significant time and expense required to bring our products to market. Our success will depend, in part, on our ability to:

We consider trade secrets,know-how and other forms of market protection to be among the most important elements of our proprietary position, in particular, as it relates to the products that currently account for a majority of our revenue. We also own or have exclusive rights to a number of U.S. patents and U.S. pending patent applications as well as corresponding foreign patents and patent applications. We continue to actively and selectively pursue patent protection and seek to expand our patent estate, particularly for our products currently in development, and we cannot be sure that any patent applications relating to our products that we will file in the future or that any currently pending applications will issue on a timely basis, if ever. Since patent applications in the United States filed prior to November 2000 are maintained in secrecy until patents issue and since publication of discoveries in the scientific or patent literature often lag behind actual discoveries, weWe cannot be certain that we were the first to make the inventions covered by each of our pending patent applications or that we were the first to file patent applications for such inventions. Even if patents are issued, the degree of protection afforded by such patents will depend upon the:

The patent position of life sciences companies is often highly uncertain and usually involves complex legal and scientific questions. Patents which may be granted to us in certain foreign countries may be subject to opposition proceedings brought by third parties or result in suits by us, which may be costly and result in adverse consequences for us.

In some cases, litigation or other proceedings may be necessary to assert claims of infringement, to enforce patents issued to us or our licensors, to protect trade secrets,know-how or other intellectual property rights we own or to determine the scope and validity of the proprietary rights of third parties. Such litigation could result in

substantial cost to us and diversion of our resources. An adverse outcome in any such litigation or proceeding could have a material adverse effect on our business, financial condition and results of operations.

If our competitors prepare and file patent applications in the United States that claim technology also claimed by us, we may be required to participate in interference proceedings declared by the U.S. Patent and Trademark Office to determine priority of invention, which would result in substantial costs to us.

While one of our U.S. patents covering recombinant Protein A had its term adjusted to expire in 2028, our other U.S. patents covering recombinant Protein A have expired, and as a result, we may face increased competition, which could harm our results of operations, financial condition, cash flow and future prospects.

Other companies could begin manufacturing and selling native or some of the commercial forms of recombinant Protein A in the U.S.United States and may directly compete with us on certain Protein A products. This may induce us to sell Protein A at lower prices and may erode our market share, which could adversely affect our results of operations, financial condition, cash flow and future prospects.

Our freedom to develop our products may be challenged by others, and we may have to engage in litigation to determine the scope and validity of competitors’ patents and proprietary rights, which, if we do not prevail, could harm our business, results of operations, financial condition, cash flow and future prospects.

There has been substantial litigation and other proceedings regarding the complex patent and other intellectual property rights in the life sciences industry. We have been a party to, and in the future may become a party to, patent litigation or other proceedings regarding intellectual property rights.

Other types of situations in which we may become involved in patent litigation or other intellectual property proceedings include:

The cost to us of any patent litigation or other proceeding, even if resolved in our favor, could be substantial. Some of our competitors may be able to sustain the cost of such litigation or proceedings more effectively than we can because of their substantially greater financial resources. If a patent litigation or other intellectual property proceeding is resolved in a way that is unfavorable to us, we or our collaborative or strategic partners may be enjoined from manufacturing or selling our products and services without a license from the other party and be held liable for significant damages. The failure to obtain any required license on commercially acceptable terms or at all may harm our business, results of operations, financial condition, cash flow and future prospects.

Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a material adverse effect on our ability to compete in the marketplace. Patent litigation and other proceedings may also absorb significant management time, attention and resources.

We may become involved in litigation or other proceedings with collaborative partners, which may be time consuming, costly and could result in delays in our development and commercialization efforts.

In connection with the Company’s decision to focus its efforts on the growth of its core bioprocessing business, we will seeksought development and commercialization partnerships for our remaining portfolio of clinical stage assets. Any disputes with such partners such as BioMarin, that lead to litigation or similar proceedings may

result in us incurring legal expenses, as well as facing potential legal liability. Such disputes, litigation or other proceedings are also time consuming and may cause delays in our development and commercialization efforts. If we fail to resolve these disputes quickly and with terms that are no less favorable to us than the current terms of the arrangements, our business, results of operations, financial condition, cash flow and future prospects may be harmed.

If we are unable to continue to hire and retain skilled personnel, then we will have trouble developing and marketing our products.

Our success depends largely upon the continued service of our management and scientific staff and our ability to attract, retain and motivate highly skilled technical, scientific, management and marketing personnel. We also face significant competition in the hiring and retention of such personnel from other companies, research and academic institutions, government and other organizations who have superior funding and resources. The loss of key personnel or our inability to hire and retain skilled personnel could materially adversely affect our product development efforts and our business.

The market may not be receptive to our new bioprocessing products upon their introduction.

We expect a portion of our future revenue growth to come from introducing new bioprocessing products, such as a larger size version ofincluding line extensions and new features for our OPUS disposable chromatography products, thecolumns, our XCell ATF System, our SIUS TFF product line, our Spectrum hollow fiber modules and newTFF systems and our growth factors. The commercial success of all of our products will depend upon their acceptance by the life science and biopharmaceutical industries. Many of the bioprocessing products that we are developing are based upon new technologies or approaches. As a result, there can be no assurance that these new products, even if successfully developed and introduced, will be accepted by customers. If customers do not adopt our new products and technologies, our results of operations may suffer and, as a result, the market price of our common stock may decline.

If our newOur products do not achieve sufficient market acceptance, our resultsare subject to quality control requirements.

Whether a product is produced by us or purchased from outside suppliers, it is subjected to quality control procedures, including the verification of operationsporosity and competitive position could suffer.

There can be no assurance that unforeseen problems will not occur with respectcertain products, the complete validation for good manufacturing practices, U.S. Food and Drug Administration, CE and ISO 2001 compliance, prior to final packaging. Quality control is performed by a staff of technicians utilizing calibrated equipment. In the development, performance or market acceptance of new products or thatevent we, will otherwise be able to successfully develop and market new products. Failure of our new products to gain market acceptance or our failuremanufacturers, produce products that fail to successfully developcomply with required quality standards, it may incur delays in fulfilling orders, write-downs, damage to our reputation and market new products could reduce our margins, which would have an adverse effect on our business, financial condition and results of operations.damages resulting from product liability claims.

If our products do not perform as expected or the reliability of the technology on which our products are based is questioned, we could experience lost revenue, delayed or reduced market acceptance of our products, increased costs and damage to our reputation.

Our success depends on the market’s confidence that we can provide reliable, high-quality bioprocessing products. We believe that customers in our target markets are likely to be particularly sensitive to product defects and errors. Our reputation and the public image of our products and technologies may be impaired if our products fail to perform as expected. Although our products are tested prior to shipment, defects or errors could nonetheless occur in our products. Furthermore, the Protein A that we manufacture is subsequently incorporated into products that are sold by other life sciences companies and we have no control over the manufacture and

production of those products. In the future, if our products experience, or are perceived to experience, a material defect or error, this could result in loss or delay of revenues, delayed market acceptance, damaged reputation, diversion of development resources, legal claims, increased insurance costs or increased service and warranty costs, any of which could harm our business. Such defects or errors could also narrow the scope of the use of our products, which could hinder our success in the market. Even after any underlying concerns or problems are resolved, any lingering concerns in our target market regarding our technology or any manufacturing defects or

performance errors in our products could continue to result in lost revenue, delayed market acceptance, damaged reputation, increased service and warranty costs and claims against us.

If we are unable to manufacture our products in sufficient quantities and in a timely manner, our operating results will be harmed, our ability to generate revenue could be diminished and our gross margin may be negatively impacted.

Our revenues and other operating results will depend in large part on our ability to manufacture and assemble our products in sufficient quantities and in a timely manner. Any interruptions we experience in the manufacturing or shipping of our products could delay our ability to recognize revenues in a particular quarter. Manufacturing problems can and do arise, and as demand for our products increases, any such problems could have an increasingly significant impact on our operating results. While we have not generally experienced problems with, or delays in, our production capabilities that resulted in delays in our ability to ship finished products, there can be no assurance that we will not encounter such problems in the future. We may not be able to quickly ship products and recognize anticipated revenues for a given period if we experience significant delays in the manufacturing process. In addition, we must maintain sufficient production capacity in order to meet anticipated customer demand, which carries fixed costs that we may not be able to offset if orders slow, which would adversely affect our operating margins. If we are unable to manufacture our products consistently, in sufficient quantities, and on a timely basis, our bioprocessing revenue, gross margins and our other operating results will be materially and adversely affected.

Our operating results may fluctuate significantly, our customers’ future purchases are difficult to predict and any failure to meet financial expectations may result in a decline in our stock price.

Our quarterly operating results may fluctuate in the future as a result of many factors such as the impact of seasonal spending patterns, changes in overall spending levels in the life sciences industry, the inability of some of our customers to consummate anticipated purchases of our products due to changes inend-user demand, and other unpredictable factors that may affect ordering patterns. Because our revenue and operating results are difficult to predict, we believe thatperiod-to-period comparisons of our results of operations are not a good indicator of our future performance. Additionally, if revenue declines in a quarter, whether due to a delay in recognizing expected revenue, adverse economic conditions or otherwise, our results of operations will be harmed because many of our expenses are relatively fixed. In particular, a large portion of our manufacturing costs, our research and development, sales and marketing and general and administrative expenses are not significantly affected by variations in revenue. Further, our gross margins are dependent on product mix. A shift in sales mix away from our higher margin products to lower margin products will adversely affect our gross margins. If our quarterly operating results fail to meet investor expectations, the price of our common stock may decline.

Our future revenues pursuantSecurities or industry analysts may not publish favorable research or reports about our business or may publish no information, which could cause our stock price or trading volume to decline.

The trading market for our asset purchase agreement with BioMarincommon stock is influenced by the research and reports that industry or securities analysts publish about us and our business. We do not have any control over these analysts and we cannot provide any assurance that analysts will cover us or provide favorable coverage. If any of the analysts who cover us issue an adverse opinion regarding the HDACi program depends significantly on BioMarin’s development and commercialization activities, over which we have no control.our stock price, our business or stock price would likely decline. If BioMarin is unableone or determines not to further develop or commercialize the HDACi program, or experiences significant delays in doing so, we may see a delay in receiving any potential milestone or royalty paymentsmore of these analysts cease coverage of our company or fail to receive any additional financial benefits from the program.

We entered into an asset purchase agreement with BioMarin on January 21, 2014, related to the histone deacetylase inhibitor (“HDACi”) portfolio, which includes the Friedreich’s ataxia program. We are dependent on BioMarin for the future success of this development program. We have no control over the conduct and timing of development efforts with respect to the HDACi program. BioMarin’s failure to devote sufficient financial and other resources to the development plan may resultregularly publish reports covering us, we could lose visibility in the delayedmarket, which in turn could cause our stock price or unsuccessful development of the program, which could leadtrading volume to the non-payment or delay in payment of milestones under the asset purchase agreement and may preclude or delay commercialization of any product under the HDACi program and any royalties we could receive on future commercial sales. Our future financial results may be harmed if BioMarin does not commercialize the HDACi program successfully or on a timely basis prior to the achievement of any milestones or the payment of any royalties to us.decline.

Health care reform measures could adversely affect our business.

The efforts of governmental and third-party payors to contain or reduce the costs of health care may adversely affect the business and financial condition of pharmaceutical and biotechnology companies, including us.ours. Specifically, in both the United States and some foreign jurisdictions, there have been a number of legislative and regulatory proposals to change the health care system in ways that could affect our ability to sell our products profitably. The U.S. Congress passed the America Affordable Health Choices Act of 2009 andFor example, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and is considering a numberEducation Reconciliation Act of proposals that are intended to reduce or limit2010 (together, the growth of“Affordable Care Act”), was passed, which substantially changes the way health care costsis financed by both governmental and which couldprivate insurers and significantly transformimpacts the market for pharmaceuticals products. We expect furtherU.S. life sciences industry. The Affordable Care Act and other federal and state proposals and health care reforms to continue to be proposed by legislators, which could limit the prices that can be charged for the products we develop and may limit our commercial opportunity. In the United States, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, also called the Medicare Modernization Act (the “MMA”) changed the way Medicare covers and pays for pharmaceutical products. These cost reduction initiatives and other provisions of this legislation could decrease the coverage and price that we receive for any approved products and could seriously harm our business. While the MMA applies only to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policy and payment limitations in setting their own reimbursement rates, and any reduction in reimbursement that results from the MMA may result in a similar reduction in payments from private payors. The continuing efforts ofEfforts by the government and other third-party payors to contain or reduce the costs of health care through various means may limit our commercial opportunities and result in a decrease in the price of our common stock or limit our ability to raise capital.

Recent federal government efforts have been aimed at amending or repealing all or portions of existing health care reform legislation, including the Affordable Care Act. Changes in existing health care reform measures may result in uncertainty with respect to legislation, regulation and government policy that could significantly impact our business and the life sciences industry.

The enactment of legislation implementing changes in taxation of international business activities, the adoption of other corporate tax reform policies, or changes in tax legislation or policies could materially impact our financial position and results of operations.

Corporate tax reform, base-erosion efforts and tax transparency continue to be high priorities in many tax jurisdictions where we have business operations. As a result, policies regarding corporate income and other taxes in numerous jurisdictions are under heightened scrutiny and tax reform legislation is being proposed or enacted in a number of jurisdictions. For example, the Tax Cuts and Jobs Act (the “2017 Tax Reform Act”), adopting broad U.S. corporate income tax reform will, among other things, reduce the U.S. corporate income tax rate, but will impose base-erosion prevention measures on earnings ofnon-U.S. subsidiaries of U.S. entities as well as the transition tax on mandatory deemed repatriation of accumulatednon-U.S. earnings of U.S. controlled foreign corporations. There is no assurance that our actual income tax liability will not be materially different than what is reflected in our income tax provisions and accruals.

In addition, many countries are beginning to implement legislation and other guidance to align their international tax rules with the Organisation for EconomicCo-operation and Development’s Base Erosion and Profit Shifting recommendations and action plan that aim to standardize and modernize global corporate tax policy, including changes to cross-border tax, transfer pricing documentation rules, and nexus-based tax incentive practices. Because of the heightened scrutiny of corporate taxation policies, prior decisions by tax authorities regarding treatments and positions of corporate income taxes could be subject to enforcement activities, and legislative investigation and inquiry, which could also result in changes in tax policies or prior tax rulings. Any such changes in policies or rulings may also result in the taxes we previously paid being subject to change.

Due to the large scale of our international business activities, any substantial changes in international corporate tax policies, enforcement activities or legislative initiatives may materially adversely affect our business, the amount of taxes we are required to pay and our financial condition and results of operations generally.

We compete with life science, pharmaceutical and biotechnology companies who are capable of developing new approaches that could make our products and technology obsolete.

The market for therapeutic and commercial products is intensely competitive, rapidly evolving and subject to rapid technological change. LifeWe compete with several medium and small companies in each of our product categories as well as several large companies, including GE Healthcare, Danaher Corporation (Pall), Thermo Fisher Scientific Inc., MilliporeSigma and Sartorius. These competitors, as well as other life science, pharmaceutical and biotechnology companies may have substantially greater financial, manufacturing, marketing, and research and development resources than we have. Newhave, as well as stronger name recognition, longer operating histories and benefits derived from greater economies of scale. These factors, among others, may enable our competitors to market their products at lower prices or on terms more advantageous to customers than what we can offer. Competition may result in price reductions, reduced gross margins and loss of market share, any of which could have a material adverse effect on our business, financial condition and results of operations. Additionally, new approaches by these competitors may make our products and technologies obsolete or noncompetitive.

We may become subject to litigation, which could result in substantial costs and divert management’s attention and resources from our business.

From time to time, we may become involved in litigation or other legal proceedings relating to claims arising from the ordinary course of business. Litigation is subject to inherent risks and uncertainties that may cause actual results to differ materially from our expectations. If we receive an adverse judgment in any litigation, we could be required to pay substantial damages. With or without merit, litigation can be complex, can extend for a protracted period of time, can be very expensive and the expense can be unpredictable. Litigation initiated by us could also result in counter-claims against us, which could increase the costs associated with the litigation and result in our payment of damages or other judgments against us. In addition, litigation, and any related publicity, may divert the efforts and attention of some of our management and key personnel, which could adversely affect our business.

We may be exposed to liabilities under the Foreign Corrupt Practices Act, and any determination that we violated the Foreign Corrupt Practices Act could have a material adverse effect on our business.

We are subject to the Foreign Corrupt Practice Act (the “FCPA”) and other laws that prohibit improper payments or offers of payments to foreign governments and their officials and political parties by U.S. persons and issuers as defined by the statute for the purpose of obtaining or retaining business. We have operations and agreements with third parties and make sales in jurisdictions outside of the U.S.,United States, which may experience corruption. Our activities in jurisdictions outside of the U.S.United States create the risk of unauthorized payments or offers of payments by one of our employees, consultants, sales agents or distributors, because these parties are not always subject to our control. These risks have increased following the Novozymes Acquisition.our recent acquisitions of overseas operations and facilities. It is our policy to implement safeguards to discourage these practices by our employees. However, our existing safeguards and any future improvements may prove to be less than effective, and the employees, consultants, sales agents or distributors of our Company may engage in conduct for which we might be held responsible. Violations of the FCPA may result in severe criminal or civil sanctions, and we may be subject to other liabilities, which could negatively affect our business, operating results and financial condition. In addition, the government may seek to hold us liable for successor liability FCPA violations committed by any companies in which we invest or that we acquire.

Our stock price could be volatile, which could cause shareholders to lose part or all of their investment.

The market price of our common stock, like that of the common stock of many other companies with similar market capitalizations, is highly volatile. In addition, the stock market has experienced extreme price and volume

fluctuations. This volatility has significantly affected the market prices of securities of many life sciences,

biotechnology and pharmaceutical companies for reasons frequently unrelated to or disproportionate to the operating performance of the specific companies. These broad market fluctuations may adversely affect the market price of our common stock.

Our growth potential is changing as we evolve from an organization that was heavily involved in research and development to an organization with a strategic focus on our bioprocessing business.

In connection with the Company’s decision to focus its efforts on the growth of its core bioprocessing business, the Company has terminated its therapeutic product development activities. The core bioprocessing business on which the Company now focuses will provide growth opportunities that are different than those of a research and development oriented biotechnology company. As a result, the price of the Company’s common stock may behave differently than it has historically and, during the shift in our business, may behave in a manner not expected by securities analysts and investors. If the Company’s future business focused on bioprocessing generates results that fall below the revised expectations of securities analysts and investors, the trading price of the Company’s common stock could decline.

As a result of these risks, we may not be able to achieve the expected benefits of any such transaction or deliver the value thereof to our shareholders. If we are unsuccessful in consummating any such transaction, we may be required to reevaluate our business only after we have incurred substantial expenses and devoted significant management time and resources.

Anti-takeover provisions in our charter documents, certain of our contracts with third parties, and under Delaware law could make an acquisition of us, even one that may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.

Provisions in our certificate of incorporation andby-laws may delay or prevent an acquisition of us or a change in our management. These provisions include the ability of our board of directors to issue preferred stock without stockholder approval. In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which limits the ability of stockholders owning in excess of 15% of our outstanding voting stock to merge or combine with us. Although we believe these provisions collectively provide for an opportunity to obtain greater value for stockholders by requiring potential acquirers to negotiate with our board of directors, they would apply even if an offer rejected by our board were considered beneficial by some stockholders. Additionally, certain of our contracts with third parties allow for termination upon specified change of control transactions. Anti-takeover provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our board of directors, which is responsible for appointing the members of our management, and anti-takeover or change of control contract termination rights may frustrate or prevent any attempts by a third party to acquire or attempt to acquire the Company.

Changes in accounting standards and subjective assumptions, estimates, and judgments by management related to complex accounting matters could significantly affect our financial results or financial condition.

Generally accepted accounting principles and related accounting pronouncements, implementation guidelines, and interpretations with regard to a wide range of matters that are relevant to our business, such as revenue recognition, asset impairment and fair value determinations, inventories, business combinations and intangible asset valuations, leases, and litigation, are highly complex and involve many subjective assumptions, estimates, and judgments. Changes in these rules or their interpretation or changes in underlying assumptions, estimates, or judgments could significantly change our reported or expected financial performance or financial condition.

Our results of operations could be negatively affected by potential fluctuations in foreign currency exchange rates.

We conduct a large portion of our business in international markets. For the fiscal year ended December 31, 2015, 33%2018, 28% of our revenuerevenues and 23%15% of our costs and expenses were denominated in foreign currencies, primarily

the Swedish Kroner,Krona, the British pound sterling, and the Euro. We are exposed to the risk of an increase or decrease in the value of the foreign currencies relative to the U.S. Dollar, which could increase the value of our expenses and decrease the value of our revenue when measured in U.S. Dollars. As a result, our results of operation may be influenced by the effects of future exchange rate fluctuations and such effects may have an adverse impact on our common stock price.

Our ability to use net operating loss and tax credit carryforwards and certainbuilt-in losses to reduce future tax payments is limited by provisions of the Internal Revenue Code, and it is possible that certain transactions or a combination of certain transactions may result in material additional limitations on our ability to use our net operating loss and tax credit carryforwards.

Section 382 and 383 of the Internal Revenue Code of 1986, as amended, contain rules that limit the ability of a company that undergoes an ownership change, which is generally any change in ownership of more than 50% of its stock over a three-year period, to utilize its net operating loss and tax credit carryforwards and certainbuilt-in losses recognized in years after the ownership change. These rules generally operate by focusing on ownership

changes involving stockholders owning directly or indirectly 5% or more of the stock of a company and any change in ownership arising from a new issuance of stock by the company. Generally, if an ownership change occurs, the yearly taxable income limitation on the use of net operating loss and tax credit carryforwards and certainbuilt-in losses is equal to the product of the applicable long term tax exemptlong-term,tax-exempt rate and the value of the company’s stock immediately before the ownership change. We may be unable to offset our taxable income with losses, or our tax liability with credits, before such losses and credits expire and therefore would incur larger federal income tax liability. We have completed a number of financings sinceWhile our inception which may have resulted in a change in control as defined by Section 382 analysis completed during 2018 did not show any current exposure, future transactions or couldcombinations of future transactions may result in a change in control under Section 382 in the future.

If we fail to maintain an effective system of internal controls, we may not be able to accurately report financial results or prevent fraud. If we identify a material weaknessesweakness in our internal control over financial reporting, our ability to meet our reporting obligations and the trading price of our stock could be negatively affected.

A material weakness is a deficiency,Effective internal controls are necessary to provide reliable financial reports and to assist in the effective prevention of fraud. Any inability to provide reliable financial reports or a combination of deficiencies, in internal control over financial reporting, such that there is a reasonable possibility that a material misstatement ofprevent fraud could harm our annual or interim financial statements will not be prevented or detected on a timely basis. Accordingly, a material weakness increases the risk that the financial information we report contains material errors.

business. We regularly review and update our internal controls, disclosure controls and procedures, and corporate governance policies. In addition, we are required under the Sarbanes-Oxley Act of 2002 to report annually on our internal control over financial reporting. Any system of internal controls, however well designed and operated, is based in part on certain assumptions and can provide only reasonable, not absolute, assurances that the objectives of the system are met. For example, in 2012, we updated our internal controls to include our operations in Sweden. If we, or our independent registered public accounting firm, determine that our internal controls over financial reporting are not effective, or we discover areas that need improvement in the future or discover a material weakness, these shortcomings could have an adverse effect on our business and financial results, and the price of our common stock could be negatively affected. A material weakness is a deficiency, or a combination of deficiencies, in internal control over financial reporting, such that there is a reasonable possibility that a material misstatement of our annual or interim financial statements will not be prevented or detected on a timely basis. Accordingly, a material weakness increases the risk that the financial information we report contains material errors.

If we cannot conclude that we have effective internal control over our financial reporting, or if our independent registered public accounting firm is unable to provide an unqualified opinion regarding the effectiveness of our internal control over financial reporting, investors could lose confidence in the reliability of our financial statements, which could lead to a decline in our stock price. Failure to comply with reporting requirements could also subject us to sanctions and/or investigations by the SEC, The NASDAQNasdaq Stock Market or other regulatory authorities.

If we fail to maintain an effective system of internal controls, we may not be able to accurately report financial results or prevent fraud.

Effective internal controls are necessary to provide reliable financial reports and to assist in the effective prevention of fraud. Any inability to provide reliable financial reports or prevent fraud could harm our business.

We must annually evaluate our internal procedures to satisfy the requirements of Section 404 of the Sarbanes-Oxley Act of 2002, which requires management and our independent registered public accounting firm to assess the effectiveness of internal control over financial reporting.

We are implementing a new enterprise resource planning (“ERP”) system and have recentlypreviously implemented several significant ERP modules and expect to implement additional ERP modules in the future. The implementation of the ERP system represents a change in our internal control over financial reporting. Although we continue to monitor and assess our internal controls in the new ERP system environment as changes are made and new modules are implemented, and we have taken additional steps to modify and enhance the design and effectiveness of our internal control over financial reporting, there is a risk that deficiencies may occur that could constitute significant deficiencies or in the aggregate a material weakness.

If we fail to remedy any deficiencies or maintain the adequacy of our internal controls, we could be subject to regulatory scrutiny, civil or criminal penalties or shareholder litigation. In addition, failure to maintain adequate internal controls could result in financial statements that do not accurately reflect our operating results or financial condition.

Natural disasters, geopolitical unrest, war, terrorism, public health issues or other catastrophic events could disrupt the supply, delivery or demand of products, which could negatively affect our operations and performance.

We are subject to the risk of disruption by earthquakes, floods and other natural disasters, fire, power shortages, geopolitical unrest, war, terrorist attacks and other hostile acts, public health issues, epidemics or pandemics and other events beyond our control and the control of the third parties on which we depend. Any of these catastrophic events, whether in the United States or abroad, may have a strong negative impact on the global economy, our employees, facilities, partners, suppliers, distributors or customers, and could decrease demand for our products, create delays and inefficiencies in our supply chain and make it difficult or impossible for us to deliver products to our customers. A catastrophic event that results in the destruction or disruption of our data centers or our critical business or information technology systems would severely affect our ability to conduct normal business operations and, as a result, our operating results would be adversely affected.

Changes in laws and regulations governing the privacy and protection of data and personal information could adversely affect our business.

We are subject to data privacy and protection laws and regulations that apply to the collection, transmission, storage and use of proprietary information and personally-identifying information, which among other things, imposes certain requirements relating to the privacy, security and transmission of certain individually identifiable information. In addition, numerous other federal and state laws, including state security breach notification laws, state health information privacy laws and federal and state consumer protection laws, govern the collection, use, disclosure and security of personal information.

Various foreign countries also have, or are developing, laws governing the collection, use, disclosure, security, and cross-border transmission of personal information. The legislative and regulatory landscape for privacy and data protection continues to evolve, and there has been an increasing amount of focus on privacy and data protection issues with the potential to affect our business. For example, privacy requirements in the European Union (“EU”) govern the transfer of personal information from the European Economic Area to the United States. While we continue to address the implications of changes to the EU data privacy regulations, the area remains an evolving landscape with new regulations coming into effect and continued legal challenges and our efforts to comply with the evolving data protection rules may be unsuccessful. Failure to comply with laws regarding data protection would expose us to risk of enforcement actions taken by data protection authorities in the EU and the potential for significant penalties if we are found to benon-compliant. Similarly, failure to comply with federal and state laws in the United States regarding privacy and security of personal information could expose us to penalties under such laws. Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our business.

None.

We currently leaseOur material office and occupy approximately 76,000 square feet of space located in Waltham, Massachusetts which serves as our corporate headquarters. We also conduct manufacturing research and development, marketing and administrative operations at this facility. This lease expires on May 31, 2023. We also rent approximately 2,500 square feet at a second location in Waltham, Massachusetts to provide for expanded manufacturing operations. This facility is rented on a month-to-month basis. We also lease four adjacent buildings in Lund, Sweden totaling approximately 45,000 square feet of space used primarily for manufacturing and administrative operations. The lease for three buildings totaling approximately 41,000 square feet expires on June 30, 2017, while the lease for the fourth building with approximately 4,000 square feet of space expires on September 30, 2019.leases are detailed below:

During the fiscal year ended December 31, 2015,2018, we incurred total rental costs for all facilities of approximately $2,619,000.$4.4 million.

From time to time, we may be subject to legal proceedings and claims in the ordinary course of business. We are not currently aware of any such proceedings or claims that we believe will have, individually or in the aggregate, a material adverse effect on our business, financial condition or results of operations.

Not applicable.

PART II

Market Information

Our common stock is traded on the Nasdaq Global Market under the symbol “RGEN.” The quarterly high and low sales prices for our common stock are shown in the following tables.

COMPARISON OF 5 YEAR CUMULATIVE TOTAL RETURN*

Among Repligen Corporation, the NASDAQ Composite Index,

the NASDAQ Pharmaceutical Index and the NASDAQ Biotechnology Index

*$100 invested on 12/31/13 in stock or index, including reinvestment of dividends.

Fiscal year ending December 31.

The information contained in the performance graph shall not be deemed to be “soliciting material” or to be “filed” with the Securities and Exchange Commission, and such information shall not be incorporated by reference into any future filing under the Securities Act of 1933, as amended (the “Securities Act”) or the Securities Exchange Act of 1934, as amended (the “Exchange Act”), except to the extent that Repligen specifically incorporates it by reference into such filing.

The following selected consolidated financial data are derived from the audited financial statements of Repligen. The selected financial data set forth below should be read in conjunction with our financial statements and the related notes thereto and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included elsewhere in this Annual Report, and in our Annual Reports on Form10-K for the fiscal years ended December 31, 2014, 20132018, 2017, 2016, 2015 and 2012 and our Transition Report on Form 10-K for the nine months ended December 31, 2011.2014.

This Annual Report on Form 10-K contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933,Repligen and its subsidiaries, collectively doing business as amended, and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). The forward-looking statements in this Annual Report on Form 10-K do not constitute guarantees of future performance. Investors are cautioned that statements in this Annual Report on Form 10-K that are not strictly historical statements, including, without limitation, statements regarding current or future financial performance, potential impairment of future earnings, management’s strategy, plans and objectives for future operations or acquisitions, product development and sales, product candidate research and development, selling, general and administrative expenditures, intellectual property, development and manufacturing plans, availability of materials, and product and adequacy of capital resources and financing plans constitute forward-looking statements. Such forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated, including, without limitation, the risks identified under the caption ��Risk Factors” and other risks detailed in this Annual Report on Form 10-K and our other filings with the Securities and Exchange Commission. We assume no obligation to update any forward-looking information contained in this Annual Report on Form 10-K, except as required by law.

Repligen Corporation (“Repligen,” the “Company”Repligen”, “we”, “our”, or “we”“the Company”) is a leading provider of advanced bioprocessing company focused on the development, productiontechnology and commercialization of innovative productssolutions used in the process of manufacturing biologic drugs. Our products are made to substantially increase biopharmaceutical manufacturing efficiencies and flexibility. As the global biologics market continues to experience strong growth and expansion, our customers – primarily large biopharmaceutical companies and contract manufacturing organizations – face critical production cost, capacity, quality and time pressures that our products are made to address. Our commitment to bioprocessing is helping set new standards for the way our customers manufacture biologic drugs (“bioprocessing”). Biologic drugs include– including monoclonal antibodies, recombinant proteins, and vaccines and representgene therapies. We are dedicated to “inspiring advances in bioprocessing” as a growing area of drug development. Our customers include leading life sciences companies, global biopharmaceutical companies, and contract manufacturers worldwide. The high-value technologies that we provide enable biologics manufacturers to cost-effectively increase drug production yields while retaining the highest quality and safety standards.

Repligen is a longtime global market leadertrusted partner in the manufactureproduction of biologic drugs that improve human health worldwide.

Our Chromatography products featurepre-packed chromatography columns under our OPUS^® brand. OPUS columns, which we deliver to our customerspre-packed with their choice of chromatography resin, are single-campaign(“single-use”) disposable columns that replace the use of traditional (more permanent) glass columns used in downstream purification processes. By designing OPUS as an advanced and flexible option for the purification of biologics from process development through clinical-scale and some commercial manufacturing, Repligen has become a leader inpre-packed columns.

Our Filtration products offer a number of advantages to manufacturers of biologic drugs at volumes that span from pilot studies to clinical and commercial-scale production. XCell ATF^™ systems are used primarily in upstream perfusion (“continuous manufacturing”) processes to increase cell concentration and significantly improve biologic product yield from a bioreactor. To address increasing industry demand for“plug-and-play” technology, we developed and in 2016 launchedsingle-use formats of the original stainless steel XCell ATF device. In December 2016, we acquired TangenX Technology Corporation (“TangenX”), balancing our upstream XCell ATF offering with a downstream portfolio of flat-sheet filters and cassettes used in biologic drug purification and formulation processes. The TangenX portfolio includes thesingle-use SIUS^™ TFF brand, providing customers with a high-performance,low-cost alternative to reusable TFF products. In August 2017, we completed our acquisition of Spectrum. Spectrum brands include the KrosFlo^® family of products, ProConnex^® disposable flow-path products, TFF systems and others. The Spectrum acquisition significantly strengthened our Filtration product line and diversifies our end markets beyond mAbs to include vaccine, recombinant protein and gene therapies.

We are a leading OEM manufacturer and supplier of Protein A ligands sold to life sciences companies under long term supply agreements.companies. Protein A is a critical reagentligands are an essential “binding” component of Protein A chromatography resins used to purify therapeuticin the purification of virtually all monoclonal antibodiesantibody (“mAbs”mAb”) based drugs on the market (over 50) or in development (over 300). In December 2011, we strengthenedthat our Protein A market leadership with the acquisition of Novozymes’s bioprocessing business (“Novozymes”) in Lund, Sweden (the “Novozymes Acquisition”).

We established and have executed on a diversification strategy to selectively expand the number of bioprocessing products that wecustomers sell direct to end users. With the Novozymes Acquisition, we gained a portfoliousers (biopharmaceutical manufacturers) for use in downstream purification of mAbs. We also manufacture and sell growth factors, led by LONG^® R3 IGF-1, which isfactor products used into supplement cell culture media in order to increase productivity. LONG^®R3 IGF-1 is soldcell growth and productivity in collaboration with MilliporeSigma (formerly Sigma Aldrich), our exclusive distributor for the product. We also developed and directly market our OPUS^® process-scale line of pre-packed chromatography columns for the capture and purification of biologic drugs in clinical development. Most recently, in June 2014, we acquired the business of Refine Technology, including Refine’s Alternating Tangential Flow (“ATF”) System, a best-in-class device used to generate extremely high cell concentrations during the fermentation step of the biologic drug manufacturing process (the “Refine Business” and the acquisition of the Refine Business, the “Refine Acquisition”).

We market our products globally through a direct commercial organization in the U.S., Europe and Asia, as well as through strategic partners in select markets. In 2014 and 2015, we invested in expanding our global commercial organization, adding world-class sales, marketing and applications personnel who interact directly with our end users. Our customer base comprises of leading life sciences companies, major contract manufacturers and 20 of the top 25 biopharmaceutical companies.bioreactor.

Customers use our products to produce initial quantities of drug for clinical studies and thenscale-up to larger volumes as the drug progresses to commercial production following regulatory approval. Detailed specifications

for a drug’s manufacturing process are included in the applications that must be approved bybiopharmaceutical companies file for marketing approval with regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, throughout the clinical trial process and prior to final commercial approval. As a result, products that become part of the manufacturing specifications of a late-stage clinical or commercial process can be very “sticky” due tosensitive given the regulatory hurdles, costs and uncertainties associated with displacing them.

Critical Accounting Policies and together with the expansion of our commercial organization and strategic acquisitions, have contributed to product revenue expansion from $41.8 million in 2012 to $83.5 million in 2015. To meet increased demand for our products, we have increased the volume and scale of manufacturing at our two manufacturing facilities in the U.S. and Sweden.

CRITICAL ACCOUNTING POLICIES AND ESTIMATESEstimates

While our significant accounting policies are more fully described in the notes to our consolidated financial statements, we have identified the policies and estimates below as being critical to our business operations and the understanding of our results of operations. The impact of and any associated risks related to these policies on our business operations are discussed throughout “Management’s Discussion and Analysis of Financial Condition,” including in the “Results of Operations” section, where such policies affect our reported and expected financial results.

Revenue recognition

Product Sales

We generate revenue from the sale of bioprocessing products, equipment devices, and related consumables used with these equipment devices to customers in the life science and biopharmaceutical industries. On product sales to end customers, revenue is recognized, net of discounts, when both the title and risk of loss have transferred to the customer, as determined by the shipping terms provided there are no uncertainties regarding acceptance, and all obligations have been completed. Generally, our product arrangements for equipment sales are multiple element arrangements, and may include services, such as installation and training, and multiple products, such as consumables and spare parts. In accordanceUnder ASC 606, “Revenue from Contracts with ASC 605-25, based on terms and conditions of the product arrangements, the Company believes that these services and undelivered products can be accounted for separately from the delivered product element as the delivered products have value to our customers on a standalone basis. Accordingly, revenue for services not yet performed at the time of product shipment are deferred and recognized as such services are performed. The relative selling price of any undelivered products is also deferred at the time of shipment and recognized as revenue when these products are delivered. For product sales to distributors, the Company recognizes revenue for both equipment and consumables upon delivery to the distributors unless direct shipment to the end user’s is requested. In this case, revenue is recognized upon delivery to the end user’s location. In general, distributors are responsible for shipment to the end customer along with installation, training and acceptance of the equipment by the end customer. Shipments to distributors are not contingent upon resale of the product. We have a few longstanding customers who comprise the majority of revenue and have excellent payment histories and therefore we do not require collateral. We have had no significant write-offs of uncollectible invoices in the periods presented.

At the time of sale, we also evaluate the need to accrue for warranty and sales returns. The supply agreements we have with our customers and related purchase orders identify the terms and conditions of each sale and the price of the goods ordered. Due to the nature of the sales arrangements, inventory produced for sale is tested for quality specifications prior to shipment. Since the product is manufactured to order and in compliance with required specifications prior to shipment, the likelihood of sales return, warranty or other issues is largely diminished. Furthermore, there is no customer right of return in our sales agreements. Sales returns and warranty issues are infrequent and have not had a material impact on our financial statements historically.

Shipping and handling fees are recorded as a component of product revenue, with the associated costs recorded as a component of cost of product revenue.

Orencia RoyaltyCustomers,”

In April 2008, we settled our outstanding litigation with Bristol and began recognizing royalty revenue from that settlement in fiscal year 2009 for Bristol’s net sales in the United States of Orencia^®, which is used in the treatment of rheumatoid arthritis. Pursuant to the settlement with Bristol, we recognized royalty revenue of $17,881,000 for the fiscal year ended December 31, 2013. Revenue earned from Bristol royalties was recorded in the periods when it was earned based on royalty reports sent by Bristol to us. We have no continuing obligations to Bristol as a result of this settlement. Our royalty agreement with Bristol provided that we would receive such royalty payments on sales of Orencia^® by Bristol through December 31, 2013. These royalty payments have ceased.

Pfizer License Agreement

In December 2012, we entered into an exclusive worldwide licensing agreement (the “License Agreement”) with Pfizer to advance the SMA program, which is led by RG3039 and also includes backup compounds and enabling technologies. Under the terms of the License Agreement, we received $5 million from Pfizer as an upfront payment on January 22, 2013, a $1 million milestone payment on September 4, 2013 and a $1 million milestone payment on December 28, 2014. On January 26, 2015, Pfizer sent us a termination notice, and the License Agreement expired on April 25, 2015.

BioMarin License Agreement

On January 21, 2014, we out-licensed our histone deacetylase inhibitor (“HDACi”) portfolio, which includes the Friedreich’s ataxia program, to BioMarin Pharmaceuticals Inc., or BioMarin. Under the terms of the agreement, Repligen received an upfront payment of $2 million in January 2014 from BioMarin and a $125,675 payment in September 2014 upon tech transfer, and we have the potential to receive up to $160 million in future milestone payments for the development, regulatory approval and commercial sale of portfolio compounds included in the agreement. In addition, Repligen is eligible to receive royalties on sales of qualified products developed.

Research and Development Agreements

We did not recognize any revenue from sponsored research and development projects in the fiscal years ended December 31, 2015 and 2014. For the fiscal year ended December 31, 2013, we recognized $1,589,000 of revenue from sponsored research and development projects under agreements with the National Institutes of Health / Scripps Research Institute, the Muscular Dystrophy Association, GoFar and the European Friedrich’s Ataxia Consortium for Translational Studies.

Research revenue is recognized when, the expense has been incurred and services have been performed. Determination of which incurred costs qualify for reimbursementor as, obligations under the terms of our contractual agreementsa contract are satisfied, which occurs when control of the promised products or services is transferred to customers. Revenue is measured as the amount of consideration the Company expects to receive in exchange for transferring products or services to a customer (“transaction price”). To the extent the transaction price includes variable consideration, the Company estimates the amount of variable consideration that should be included in the transaction price utilizing the expected value method or the most likely amount method, depending on the facts and circumstances relative to the timingcontract. Variable consideration is included in the transaction price if, in the Company’s judgment, it is probable that a significant future reversal of when such costs were incurred involvescumulative revenue under the judgmentcontract will not occur. Estimates of management. Our calculationsvariable consideration and determination of whether to include estimated amounts in the transaction price are based uponlargely on an assessment of the agreed-upon termsCompany’s anticipated performance and all information (historical, current and forecasted) that is reasonably available. Sales, value add, and other taxes collected on behalf of third parties are excluded from revenue.

When determining the transaction price of a contract, an adjustment is made if payment from a customer occurs either significantly before or significantly after performance, resulting in a significant financing component. Applying the practical expedient in paragraph606-10-32-18, the Company does not assess whether a significant financing component exists if the period between when the Company performs its obligations under the contract and when the customer pays is one year or less. None of the Company’s contracts contained a significant financing component as stated inof December 31, 2018.

Contracts with customers may contain multiple performance obligations. For such arrangements, the arrangements. However, shouldtransaction price is allocated to each performance obligation based on the estimated calculations changerelative standalone selling prices of the promised products or be challenged by other partiesservices underlying each performance obligation. The Company determines standalone selling prices based on the price at which the performance obligation is sold separately. If the standalone selling price is not observable through past transactions, the Company estimates the standalone selling price taking into account available information such as market conditions and internally approved pricing guidelines related to the agreements, researchperformance obligations.

The Company recognizes product revenue may be adjustedunder the terms of each customer agreement upon transfer of control to the customer, which occurs at a point in subsequent periods. The calculations have not historically changed or been challenged, and we do not anticipate any significant subsequent change in revenue related to sponsored research and development projects.time.

There have been no material changes to our initial estimates related to revenue recognition in any periods presented in the accompanying consolidated financial statements.Inventories

Inventories

Inventories relate to our bioprocessing business. We value inventory at cost or, if lower, fair marketnet realizable value, using thefirst-in,first-out method. We review our inventory at least quarterly and record a provision for excess

and obsolete inventory based on our estimates of expected sales volume, production capacity and expiration dates of raw materials,work-in-process and finished products. Expected sales volumes are determined based on supply forecasts provided by key customers for the next three to 12 months. We write down inventory that has become obsolete, inventory that has a cost basis in excess of its expected net realizable value, and inventory in excess of expected requirements to cost of product revenue. Manufacturing of bioprocessing finished goods is done to order and tested for quality specifications prior to shipment.

A change in the estimated timing or amount of demand for our products could result in additional provisions for excess inventory quantities on hand. Any significant unanticipated changes in demand or unexpected quality failures could have a significant impact on the value of inventory and reported operating results. During all periods presented in the accompanying consolidated financial statements, there have been no material adjustments related to a revised estimate of inventory valuations.

Business combinations

Amounts paid for acquisitions are allocated to the assets acquired and liabilities assumed, if any, based on their fair values at the dates of acquisition. The fair value of identifiable intangible assets is based on detailed valuations that use information and assumptions determined by management. Any excess of purchase price over the fair value of the net tangible and intangible assets acquired is allocated to goodwill. The fair value of contingent consideration includes estimates and judgments made by management regarding the probability that future contingent payments will be made, the extent of royalties to be earned in excess of the defined minimum royalties, etc. Management updates these estimates and the related fair value of contingent consideration at each reporting period based on the estimated probability of achieving the earnout targets and applying a discount rate that captures the risk associated with the expected contingent payments. To the extent our estimates change in the future regarding the likelihood of achieving these targets we may need to record material adjustments to our accrued contingent consideration. Changes in the fair value of contingent consideration are recorded in our Statementconsolidated statement of Operations. The largestoperations and most judgmental component of our contingent consideration relates to the contingent consideration tied to Refine sales targets. The remaining maximum potential liability related to Refine’s sales based contingent consideration is $9.9 million, and we have accrued approximately $6.4 million as of December 31, 2015 as the estimated fair value. Fair value estimates are based on our projections of future Refine sales.comprehensive income.

We use the income approach to determine the fair value of certain identifiable intangible assets including customer relationships and developed technology. This approach determines fair value by estimatingafter-tax cash flows attributable to these assets over their respective useful lives and then discounting theseafter-tax cash flows back to a present value. We base our assumptions on estimates of future cash flows, expected growth rates, expected trends in technology, etc. We base the discount rates used to arrive at a present value as of the date of acquisition on the time value of money and certain industry-specific risk factors. We believe the estimated purchased customer relationships, developed technologies, trademark / tradename, patents, and in process research and development amounts so determined represent the fair value at the date of acquisition and do not exceed the amount a third party would pay for the assets.

Intangible assets and goodwill

Intangible Assetsassets

We amortize our intangible assets that have finite lives using the straight-line method. Amortization is recorded over the estimated useful lives ranging from 82 to 1520 years. We review our intangible assets subject to amortization to determine if any adverse conditions exist or a change in circumstances has occurred that would indicate impairment or a change in the remaining useful life. Further, we also review our indefinite-lived intangible assets not subject to amortization to determine if any adverse conditions exist or a change in circumstances occurred that would indicate an impairment. If the carrying value of an asset exceeds its estimated

undiscounted cash flows, we will write-down the carrying value of the intangible asset to its fair value in the period identified. In assessing fair value, we must make assumptions regarding estimated future cash flows and discount rates. If these estimates or related assumptions change in the future, we may be required to record impairment charges. We generally calculate fair value as the present value of estimated future cash flows to be generated by the asset using a risk-adjusted discount rate. If the estimate of an intangible asset’s remaining useful life is changed, we will amortize the remaining carrying value of the intangible asset prospectively over the revised remaining useful life.

Goodwill

We test goodwill for impairment on an annual basis and between annual tests if events and circumstances indicate it is more likely than not that the fair value of a reporting unit is less than its carrying value. Events that

would indicate impairment and trigger an interim impairment assessment include, but are not limited, to current economic and market conditions, including a decline in market capitalization, a significant adverse change in legal factors, business climate or operational performance of the business, and an adverse action or assessment by a regulator. Our annual impairment test date is the last day of our fiscal year, December 31 2015. The Company performed its^st. While we currently operate as one operating segment, we perform our annual impairment test over each of the Company’s onetwo reporting unitunits and concluded that goodwill was not impaired.

Accrued liabilities

We estimate accrued liabilities by identifying services performed on our behalf, estimating the level of service performed and determining the associated cost incurred for such service as of each balance sheet date. For example, we would accrue for professional and consulting fees incurred with law firms, audit and accounting service providers and other third partythird-party consultants. These expenses are determined by either requesting those service providers to estimate unbilled services at each reporting date for services incurred or tracking costs incurred by service providers under fixed fee arrangements.

We have processes in place to estimate the appropriate amounts to record for accrued liabilities, which principally involve the applicable personnel reviewing the services provided. In the event that we do not identify certain costs that have begun to be incurred or we under or over-estimate the level of services performed or the costs of such services, the reported expenses for that period may be too low or too high. The date on which certain services commence, the level of services performed on or before a given date, and the cost of such services often require the exercise of judgment. We make these judgments based upon the facts and circumstances known at the date of the financial statements.

A change in the estimated cost or volume of services provided could result in additional accrued liabilities. Any significant unanticipated changes in such estimates could have a significant impact on our accrued liabilities and reported operating results. There have been no material adjustments to our accrued liabilities in any of the periods presented in the accompanying consolidated financial statements.

Stock-based compensation

We use the Black-Scholes option pricing model to calculate the fair value of share-based awards on the grant date.

The expected term of options granted represents the period of time for which the options are expected to be outstanding and is derived from our historical stock option exercise experience and option expiration data. For purposes of estimating the expected term, we have aggregated all individual option awards into one group, as we do not expect substantial differences in exercise behavior among our employees. The expected volatility is a measure of the amount by which our stock price is expected to fluctuate during the expected term of options granted. We determined the expected volatility based upon the historical volatility of our common stock over a

period commensurate with the option’s expected term. The risk-free interest rate is the implied yield available on U.S. Treasuryzero-coupon issues with a remaining term equal to the option’s expected term on the grant date. We have never declared or paid any cash dividends on any of our capital stock and do not expect to do so in the foreseeable future. Accordingly, we use an expected dividend yield of zero to calculate the grant-date fair value of a stock option.

We recognize compensation expense on awards that vest based on service conditions on a straight-line basis over the requisite service period based upon the number of options that are ultimately expected to vest, and accordingly, such compensation expense has been adjusted by an amount of estimated forfeitures. We recognize compensation expense on awards that vest based on performance conditions based on our assessment of the probability that the performance condition will be achieved over the service period. Forfeitures represent only the unvested portion of a surrendered option. Forfeitures are estimated at the time of grant and revised, if necessary,

in subsequent periods if actual forfeitures differ from those estimates. Based on an analysis of historical data, we have calculated an 8% annual forfeiture rate fornon-executive level employees, a 3% annual forfeiture rate for executive level employees, and a 0% forfeiture rate fornon-employee members of the Board of Directors, which we believe are reasonable assumptions to estimate forfeitures. However, the estimation of forfeitures requires significant judgment and, to the extent actual results or updated estimates differ from our current estimates, such amounts will be recorded as a cumulative adjustment in the period estimates are revised.

For the fiscal years ended December 31, 2015, 20142018, 2017 and 2013,2016, we recorded stock-based compensation expense of approximately $3,598,000, $1,766,000$10.2 million, $6.7 million and $1,060,000,$4.6 million, respectively, for share-based awards granted under all of the Company’s stock plans.

As of December 31, 2015,2018, there was $6,547,000$27.1 million of total unrecognized compensation cost related to unvested share-based awards. This cost is expected to be recognized over a weighted average remaining requisite service period of 3.084.53 years. We expect 623,6521,195,236 unvested options and RSUs to vest over the next five years.

Income Taxestaxes

Deferred taxes are determined based on the difference between the financial statement and tax basis of assets and liabilities using enacted tax rates in effect in the years 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. We account for uncertain tax positions using a “more-likely-than-not”“more-likely-than-not” threshold for recognizing and resolving uncertain tax positions. The evaluation of uncertain tax positions is based on factors including, but not limited to, changes in tax law, the measurement of tax positions taken or expected to be taken in tax returns, the effective settlement of matters subject to audit, new audit activity and changes in facts or circumstances related to a tax position. We evaluate our tax position on a quarterly basis. We also accrue for potential interest and penalties related to unrecognized tax benefits in income tax expense.

RESULTS OF OPERATIONSResults of Operations

The following discussion of the financial condition and results of operations should be read in conjunction with the accompanying consolidated financial statements and the related footnotes thereto.

Revenues

Total revenues for fiscal years 2015, 2014,2018, 2017, and 20132016 were comprised of the following:

Product revenues were comprised of the following:

We recognized $2,126,000 of revenue for fiscal 2014 from the out-license of our HDACi portfolio to BioMarin on January 21, 2014. We also recognized $1,000,000 and $1,217,000 of revenue for fiscal 2014 and 2013, respectively, from the out-license of our Spinal Muscular Atrophy program to Pfizer on December 28, 2012. In fiscal 2013, we also recognized $1,589,000 of revenue from sponsored research and development projects under agreements with the National Institutes of Health / Scripps Research Institute, the Muscular Dystrophy Association, GoFar and the European Friedrich’s Ataxia Consortium for Translational Studies. We did not recognize any such revenue in fiscal 2015, and we do not expect to recognize any research and license revenue or to receive any incremental funding for our therapeutic development programs going forward.

Costs and operating expenses

Total costs and operating expenses for fiscal years 2015, 2014,2018, 2017 and 20132016 were comprised of the following: