Alnylam Pharmaceuticals (ALNY) 10-K 12 Feb 16 2015 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($)	12 Months Ended
	Dec. 31, 2015	Jan. 29, 2016	Jun. 30, 2015
Document Information [Line Items]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2015
Document Fiscal Year Focus	2,015
Document Fiscal Period Focus	FY
Trading Symbol	ALNY
Entity Registrant Name	ALNYLAM PHARMACEUTICALS, INC.
Entity Central Index Key	1,178,670
Current Fiscal Year End Date	--12-31
Entity Well-known Seasoned Issuer	Yes
Entity Current Reporting Status	Yes
Entity Voluntary Filers	No
Entity Filer Category	Large Accelerated Filer
Entity Common Stock, Shares Outstanding		85,138,602
Entity Public Float			$ 10,043,526,713

CONSOLIDATED BALANCE SHEETS

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Current assets:
Cash and cash equivalents	$ 180,895	$ 75,179
Marketable securities	848,217	526,929
Investment in equity securities of Regulus Therapeutics Inc.	51,419	94,583
Billed and unbilled collaboration receivables	8,298	39,937
Prepaid expenses and other current assets	16,559	9,739
Total current assets	1,105,388	746,367
Marketable securities	251,839	279,821
Deferred tax assets		31,667
Property and equipment, net	27,812	21,740
Other assets	1,471
Total assets	1,386,510	1,079,595
Current liabilities:
Accounts payable	16,787	15,111
Accrued expenses	28,798	23,680
Deferred tax liabilities		31,667
Deferred rent	1,162	1,005
Deferred revenue	15,352	23,871
Total current liabilities	62,099	95,334
Deferred rent, net of current portion	5,431	5,011
Deferred revenue, net of current portion	52,965	42,983
Other liabilities	1,301
Total liabilities	$ 121,796	$ 143,328
Commitments and contingencies (Note 7)
Stockholders' equity:
Preferred stock, $0.01 par value per share, 5,000,000 shares authorized and no shares issued and outstanding at December 31, 2015 and 2014
Common stock, $0.01 par value per share, 125,000,000 shares authorized; 85,090,968 shares issued and outstanding at December 31, 2015; 77,202,753 shares issued and outstanding at December 31, 2014	$ 851	$ 772
Additional paid-in capital	2,506,197	1,843,362
Accumulated other comprehensive income	4,369	48,763
Accumulated deficit	(1,246,703)	(956,630)
Total stockholders' equity	1,264,714	936,267
Total liabilities and stockholders' equity	$ 1,386,510	$ 1,079,595

CONSOLIDATED BALANCE SHEETS (Pa

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2015	Dec. 31, 2014
Preferred stock, par value	$ 0.01	$ 0.01
Preferred stock, shares authorized	5,000,000	5,000,000
Preferred stock, shares issued	0	0
Preferred stock, shares outstanding	0	0
Common stock, par value	$ 0.01	$ 0.01
Common stock, shares authorized	125,000,000	125,000,000
Common stock, shares issued	85,090,968	77,202,753
Common stock, shares outstanding	85,090,968	77,202,753

CONSOLIDATED STATEMENTS OF COMP

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) shares in Thousands, $ in Thousands		12 Months Ended
		Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Net revenues from collaborators		$ 41,097	$ 50,561	$ 47,167
Operating expenses:
Research and development	[1]	276,495	190,249	112,957
In-process research and development			220,766
General and administrative	[1]	60,610	44,526	27,152
Total operating expenses		337,105	455,541	140,109
Loss from operations		(296,008)	(404,980)	(92,942)
Other income (expense):
Interest income		5,859	2,559	1,069
Other income (expense)		76	1,817	(47)
Total other income		5,935	4,376	1,022
Loss before income taxes		(290,073)	(400,604)	(91,920)
Benefit from income taxes			40,209	2,695
Net loss		$ (290,073)	$ (360,395)	$ (89,225)
Net loss per common share - basic and diluted		$ (3.45)	$ (4.85)	$ (1.45)
Weighted-average common shares used to compute basic and diluted net loss per common share		83,992	74,278	61,551
Comprehensive income (loss):
Net loss		$ (290,073)	$ (360,395)	$ (89,225)
Unrealized (loss) gain on marketable securities, net of tax		(44,394)	31,127	4,055
Reclassification adjustment for realized gain on marketable securities included in net loss			(2,081)
Comprehensive loss		$ (334,467)	$ (331,349)	$ (85,170)
[1]	Non-cash stock-based compensation expenses included in operating expenses are as follows: Research and development $ 27,086 $ 18,233 $ 14,369 General and administrative 18,697 14,828 6,334

CONSOLIDATED STATEMENTS OF COM5

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS (Parenthetical) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Non-cash stock-based compensation expenses included in operating expenses are as follows:
Non-cash stock-based compensation	$ 45,783	$ 33,061	$ 20,703
Research and Development
Non-cash stock-based compensation expenses included in operating expenses are as follows:
Non-cash stock-based compensation	27,086	18,233	14,369
General and Administrative
Non-cash stock-based compensation expenses included in operating expenses are as follows:
Non-cash stock-based compensation	$ 18,697	$ 14,828	$ 6,334

CONSOLIDATED STATEMENTS OF STOC

CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($) $ in Thousands	Total	Sanofi Genzyme	Common Stock	Common StockSanofi Genzyme	Additional Paid-in Capital	Additional Paid-in CapitalSanofi Genzyme	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit
Balance (in shares) at Dec. 31, 2012			52,489,936
Balance at Dec. 31, 2012	$ 134,053		$ 525		$ 624,876		$ 15,662	$ (507,010)
Exercise of common stock options (in shares)			2,031,916
Exercise of common stock options	27,994		$ 20		27,974
Issuance of common stock under other types of equity plans (in shares)			60,180
Issuance of common stock under other types of equity plans	1,184		$ 1		1,183
Tax withholdings and cancellations of restricted stock, net of issuances of new awards, shares			(40,459)
Tax withholdings and cancellations of restricted stock, net of issuances of new awards	(1,989)		$ (1)		(1,988)
Issuance of common stock, net of offering costs (in shares)			9,200,000
Issuance of common stock, net of offering costs	173,572		$ 92		173,480
Stock-based compensation expense	20,703				20,703
Other comprehensive income (loss) before reclassifications, net of tax	4,055						4,055
Net loss	(89,225)							(89,225)
Balance (in shares) at Dec. 31, 2013			63,741,573
Balance at Dec. 31, 2013	270,347		$ 637		846,228		19,717	(596,235)
Exercise of common stock options (in shares)			1,972,204
Exercise of common stock options	28,449		$ 20		28,429
Issuance of common stock under other types of equity plans (in shares)			31,122
Issuance of common stock under other types of equity plans	1,581		$ 1		1,580
Tax withholdings and cancellations of restricted stock, net of issuances of new awards, shares			(172,976)
Tax withholdings and cancellations of restricted stock, net of issuances of new awards	(15,392)		$ (2)		(15,390)
Issuance of common stock, net of offering costs (in shares)				9,110,786
Issuance of common stock, net of offering costs		$ 774,487		$ 91		$ 774,396
Issuance of common stock in connection with an asset acquisition (in shares)			2,520,044
Issuance of common stock in connection with an asset acquisition	195,766		$ 25		195,741
Stock-based compensation expense	33,061				33,061
Tax provision associated with intraperiod tax allocation	(20,683)				(20,683)
Other comprehensive income (loss) before reclassifications, net of tax	31,127						31,127
Reclassification adjustment for realized gain on marketable securities included in net loss	(2,081)						(2,081)
Net loss	(360,395)							(360,395)
Balance (in shares) at Dec. 31, 2014			77,202,753
Balance at Dec. 31, 2014	936,267		$ 772		1,843,362		48,763	(956,630)
Exercise of common stock options (in shares)			1,461,237
Exercise of common stock options	29,425		$ 15		29,410
Issuance of common stock under other types of equity plans (in shares)			32,427
Issuance of common stock under other types of equity plans	2,666		$ 1		2,665
Tax withholdings and cancellations of restricted stock, net of issuances of new awards, shares			6,366
Tax withholdings and cancellations of restricted stock, net of issuances of new awards	(378)				(378)
Issuance of common stock, net of offering costs (in shares)			5,447,368	940,817
Issuance of common stock, net of offering costs	496,400	$ 89,018	$ 54	$ 9	496,346	$ 89,009
Stock-based compensation expense	45,783				45,783
Other comprehensive income (loss) before reclassifications, net of tax	(44,394)						(44,394)
Net loss	(290,073)							(290,073)
Balance (in shares) at Dec. 31, 2015			85,090,968
Balance at Dec. 31, 2015	$ 1,264,714		$ 851		$ 2,506,197		$ 4,369	$ (1,246,703)

CONSOLIDATED STATEMENTS OF CASH

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Cash flows from operating activities:
Net loss	$ (290,073)	$ (360,395)	$ (89,225)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization	19,050	11,926	10,229
Non-cash stock-based compensation	45,783	33,061	20,703
Charge for 401(k) company stock match	984	692	449
Realized gain on sale of marketable securities	0	(2,081)
Benefit from intraperiod tax allocation		(40,209)	(2,695)
In-process research and development		220,766
Changes in operating assets and liabilities:
Proceeds from landlord tenant improvements	374	1,941	204
Billed and unbilled collaboration receivables	31,639	(35,689)	(4,144)
Prepaid expenses and other assets	(6,820)	(5,829)	(1,356)
Accounts payable	1,676	8,840	1,832
Accrued expenses and other	6,343	9,122	1,547
Deferred revenue	1,904	(7,786)	(6,201)
Net cash used in operating activities	(189,140)	(165,641)	(68,657)
Cash flows from investing activities:
Purchases of property and equipment	(12,950)	(8,961)	(4,006)
Increase in restricted cash	(1,471)
Purchases of marketable securities	(1,033,843)	(977,775)	(364,305)
Sales and maturities of marketable securities	726,943	462,922	237,806
Payment for asset acquisition		(25,000)
Net cash used in investing activities	(321,321)	(548,814)	(130,505)
Cash flows from financing activities:
Proceeds from exercise of stock options and other types of equity	31,137	29,420	28,743
Proceeds from issuance of common stock, net of offering costs	496,400		173,572
Proceeds from issuance of common stock to Sanofi Genzyme	89,018	723,037
Payments for repurchase of common stock for employee tax withholding	(378)	(15,992)	(1,389)
Net cash provided by financing activities	616,177	736,465	200,926
Net increase in cash and cash equivalents	105,716	22,010	1,764
Cash and cash equivalents, beginning of period	75,179	53,169	51,405
Cash and cash equivalents, end of period	180,895	75,179	53,169
Supplemental disclosure of cash flows:
Net (cash paid for income taxes) cash proceeds from income tax refunds	(66)	517	(11)
Supplemental disclosure of noncash investing and financing activities:
Fixed asset expenditures included in accounts payable and accrued expenses	1,333	1,526	161
Fair value of common stock issued for asset acquisition		195,766
Receipt of common stock for exercises of stock options	$ 686	1,219
Difference in fair value of common stock issued to Sanofi Genzyme less cash proceeds received		$ 51,450
Repurchase of common stock for employee tax withholding in accrued expenses			$ 600

NATURE OF BUSINESS

NATURE OF BUSINESS	12 Months Ended
	Dec. 31, 2015
NATURE OF BUSINESS	1. NATURE OF BUSINESS We commenced operations on June 14, 2002 as a biopharmaceutical company seeking to develop and commercialize novel therapeutics based on RNA interference, or RNAi. We are focused on discovering, developing and commercializing RNAi therapeutics by establishing strategic alliances with leading pharmaceutical and life sciences companies, establishing and maintaining a strong intellectual property position in the RNAi field, generating revenues through licensing agreements, and ultimately developing and commercializing RNAi therapeutics for our own account. We have devoted substantially all of our efforts to business planning, research and development, acquiring, filing and expanding intellectual property rights, recruiting management and technical staff, and raising capital.

SUMMARY OF SIGNIFICANT ACCOUNTI

SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES	12 Months Ended
	Dec. 31, 2015
SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES	2. SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES Basis of Presentation and Principles of Consolidation The accompanying consolidated financial statements reflect the operations of Alnylam and our wholly-owned subsidiaries. All intercompany accounts and transactions have been eliminated. Use of Estimates The preparation of financial statements in conformity with accounting principles generally accepted in the United States of America, or GAAP, requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the consolidated financial statements and the reported amounts of revenues and expenses during the reporting period. Actual results could differ from those estimates. Concentrations of Credit Risk and Significant Customers Financial instruments that potentially expose us to concentrations of credit risk consist primarily of cash, cash equivalents and fixed income marketable securities. At December 31, 2015 and 2014, substantially all of our cash, cash equivalents and fixed income marketable securities were invested in money market funds, certificates of deposit, commercial paper, corporate notes, municipal debt securities, U.S. government-sponsored enterprise securities and U.S. treasury securities through highly rated financial institutions. Corporate notes also include foreign bonds denominated in U.S. dollars. Investments are restricted, in accordance with our investment policy, to a concentration limit per issuer. In recent periods, our revenues from collaborations have been generated primarily from Sanofi Genzyme, the specialty care global business unit of Sanofi, or Sanofi Genzyme, Takeda Pharmaceutical Company Limited, or Takeda, Monsanto Company, or Monsanto, The Medicines Company, or MDCO, and Cubist Pharmaceuticals, Inc., or Cubist (now a wholly-owned subsidiary of Merck & Co., Inc.). For the year ended December 31, 2015, our billed and unbilled collaboration receivables were composed primarily of amounts of expense reimbursement due from Sanofi Genzyme and certain milestones due from Ionis Pharmaceuticals, Inc., or Ionis (formerly Isis Pharmaceuticals, Inc.). For the year ended December 31, 2014, our billed and unbilled collaboration receivables were composed primarily of amounts due from Sanofi Genzyme and MDCO based upon the achievement of certain milestones and also, with respect to MDCO, expense reimbursement. The following table summarizes customers that represent greater than 10% of our net revenues from collaborators, for the periods indicated: Year Ended December 31, 2015 2014 2013 Sanofi Genzyme 27 % * * MDCO 25 % 21 % * Takeda 22 % 43 % 47 % Monsanto 14 % 30 % 12 % Cubist * * 21 % The following table summarizes customers with amounts due that represent greater than 10% of our billed and unbilled collaboration receivables balance, at the periods indicated: At December 31, 2015 2014 Sanofi Genzyme 88 % 63 % Ionis 12 % * MDCO * 37 % * Represents 10% or less Fair Value Measurements The fair value is the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. In general, fair values determined by Level 1 inputs utilize quoted prices (unadjusted) in active markets for identical assets or liabilities. Fair values determined by Level 2 inputs utilize data points that are observable, such as quoted prices (adjusted), interest rates and yield curves. Fair values determined by Level 3 inputs utilize unobservable data points for the asset or liability, and include situations where there is little, if any, market activity for the asset or liability. The fair value hierarchy level is determined by the lowest level of significant input. Investments in Marketable Securities We invest our excess cash balances in short-term and long-term marketable debt and equity securities. We classify our investments in marketable debt securities as either held-to-maturity or available-for-sale based on facts and circumstances present at the time we purchased the securities. At each balance sheet date presented, we classified all of our investments in debt and equity securities as available-for-sale. We report available-for-sale investments at fair value at each balance sheet date and include any unrealized holding gains and losses (the adjustment to fair value) in accumulated other comprehensive income (loss), a component of stockholders’ equity. At December 31, 2015, the balance in our accumulated other comprehensive income was composed solely of activity related to our available-for-sale marketable securities, including our investment in equity securities of Regulus Therapeutics Inc., or Regulus. Realized gains and losses are determined using the specific identification method and are included in other income (expense). We did not recognize any realized gains or losses from sales of our available-for-sale securities during the year ended December 31, 2015 and, as a result, did not reclassify any amount out of accumulated other comprehensive income (loss) for the same period. If any adjustment to fair value reflects a decline in the value of the investment, we consider all available evidence to evaluate the extent to which the decline is “other than temporary,” including our intention to sell and, if so, mark the investment to market through a charge to our consolidated statements of comprehensive income (loss). We did not record any impairment charges related to our fixed income marketable securities during the years ended December 31, 2015, 2014 or 2013. Our marketable securities are classified as cash equivalents if the original maturity, from the date of purchase, is 90 days or less, and as marketable securities if the original maturity, from the date of purchase, is in excess of 90 days. Our cash equivalents are composed of commercial paper, corporate notes, U.S. government-sponsored enterprise securities and money market funds. We account for our investment in Regulus as an available-for-sale marketable security. Intraperiod tax allocation rules require us to allocate our provision for income taxes between continuing operations and other categories of earnings, such as other comprehensive income. In periods in which we have a year-to-date pre-tax loss from continuing operations and pre-tax income in other categories of earnings, such as other comprehensive income, we must allocate the tax provision to the other categories of earnings. We then record a related tax benefit in continuing operations. Upon sales of our available-for-sale marketable securities, we apply the aggregate portfolio approach to recognize the related tax provision or benefit into income (loss) from continuing operations. As a result, the disproportionate tax effect remains in accumulated other comprehensive income (loss) as long as we maintain an investment portfolio. Estimated Liability for Development Costs We record accrued liabilities related to expenses for which service providers have not yet billed us with respect to products we have received or services that we have incurred, specifically related to ongoing pre-clinical studies and clinical trials. These costs primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator fees. We have multiple product candidates in concurrent pre-clinical studies and clinical trials at multiple clinical sites throughout the world. In order to ensure that we have adequately provided for ongoing pre-clinical and clinical development costs during the period in which we incur such costs, we maintain an accrual to cover these expenses. We update the estimate for this accrual on at least a quarterly basis. The assessment of these costs is a subjective process that requires judgment. Upon settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual costs. Revenue Recognition We have entered into collaboration agreements with leading pharmaceutical and life sciences companies, including Novartis Pharma AG and one of its affiliates (which assigned its rights and obligations to Arrowhead Research Corporation, or Arrowhead, in early 2015), F. Hoffmann-La Roche Ltd (which assigned its rights and obligations to Arrowhead in 2011), Takeda, Kyowa Hakko Kirin Co., Ltd., or Kyowa Hakko Kirin, Cubist, Monsanto, Sanofi Genzyme and MDCO. The terms of our collaboration agreements typically include deliverables such as non-refundable license fees, funding of research and development, payments based upon achievement of clinical and pre-clinical development milestones, regulatory milestones, manufacturing services, sales milestones and royalties on product sales. These agreements are generally referred to as multiple element arrangements. We apply the accounting standard on revenue recognition for multiple element arrangements. The fair value of deliverables under the arrangement may be derived using a “best estimate of selling price” if vendor specific objective evidence and third-party evidence is not available. Deliverables under the arrangement will be separate units of accounting provided that (i) a delivered item has value to the customer on a standalone basis and (ii) if the arrangement includes a general right of return relative to the delivered item, delivery or performance of the undelivered item is considered probable and substantially in the control of the vendor. We recognize upfront license payments as revenue upon delivery of the license only if the license has standalone value of the undelivered performance obligations, typically including research and/or steering committee services, can be determined. If the fair value of the undelivered performance obligations can be determined, such obligations would then be accounted for separately as performed. If the license is considered to not have standalone value, the arrangement would then be accounted for as a single unit of accounting and the license payments and payments for performance obligations are recognized as revenue over the estimated period of when the performance obligations are performed or deferred indefinitely until the undelivered performance obligation can be determined. As a biotechnology entity with unique and specialized delivered and undelivered performance obligations, we have been unable to demonstrate standalone value in our multiple element arrangements. Whenever we determine that an arrangement should be accounted for as a single unit of accounting, we determine the period over which the performance obligations will be performed and revenue will be recognized. Revenue is recognized using either a proportional performance or straight-line method. We recognize revenue using the proportional performance method when the level of effort required to complete our performance obligations under an arrangement can be reasonably estimated and such performance obligations are provided on a best-efforts basis. Direct labor hours or full-time equivalents are typically used as the measure of performance. The amount of revenue recognized under the proportional performance method is determined by multiplying the total payments under the contract, excluding royalties and payments contingent upon achievement of milestones, by the ratio of level of effort incurred to date to estimated total level of effort required to complete our performance obligations under the arrangement. Revenue is limited to the lesser of the cumulative amount of payments received or the cumulative amount of revenue earned, as determined using the proportional performance method, as of the period ending date. If we cannot reasonably estimate the level of effort to complete our performance obligations under an arrangement, we recognize revenue under the arrangement on a straight-line basis over the period we are expected to complete our performance obligations. Revenue is limited to the lesser of the cumulative amount of payments received or the cumulative amount of revenue earned, as determined using the straight-line method, as of the period ending date. Significant management judgment is required in determining the level of effort required under an arrangement and the period over which we are expected to complete our performance obligations under an arrangement. Steering committee services that are not inconsequential or perfunctory and that are determined to be performance obligations are combined with other research services or performance obligations required under an arrangement, if any, in determining the level of effort required in an arrangement and the period over which we expect to complete our aggregate performance obligations. Many of our collaboration agreements entitle us to additional payments upon the achievement of performance-based milestones. These milestones are generally categorized into three types; development milestones which are generally based on the advancement of our pipeline and initiation of clinical trials, regulatory milestones which are generally based on the submission, filing or approval of regulatory applications such as a new drug application in the United States, and commercialization milestones which are generally based on meeting specific thresholds of sales in certain geographic areas. If the achievement of a milestone is considered probable at the inception of the collaboration, the related milestone payment is included with other collaboration consideration, such as upfront fees and research funding, in our revenue model. Milestones that are tied to regulatory approval are not considered probable of being achieved until such approval is received. Milestones tied to counter-party performance are not included in our revenue model until the performance conditions are met. Upfront and ongoing development milestones are not subject to refund if the development activities are not successful. We perform an assessment to determine whether a substantive milestone exists at the inception of our collaborative arrangements. In evaluating if a milestone is substantive, we consider whether uncertainty exists as to the achievement of the milestone event at the inception of the arrangement, the achievement of the milestone involves substantive effort and can only be achieved based in whole or part on the performance or the occurrence of a specific outcome resulting from our performance, the amount of the milestone payment appears reasonable either in relation to the effort expected to be expended or to the projected enhancement of the value of the delivered items, there is any future performance required to earn the milestone, and the consideration is reasonable relative to all deliverables and payment terms in the arrangement. When a substantive milestone is achieved, the accounting rules permit us to recognize revenue related to the milestone payment in its entirety. To date, we have not recorded any substantive milestones under our collaborations because we have not identified any milestones that meet the required criteria listed above. We have deferred recognition of payments for achievement of non-substantive milestones and recognized revenue over the estimated period of performance applicable to each collaborative arrangement. As these milestones are achieved, we will recognize as revenue a portion of the milestone payment, which is equal to the percentage of the performance period completed when the milestone is achieved, multiplied by the amount of the milestone payment, upon achievement of such milestone. We will recognize the remaining portion of the milestone payment over the remaining performance period under the proportional performance method or on a straight-line basis. For revenue generating arrangements where we, as a vendor, provide consideration to a licensor or collaborator, as a customer, we apply the accounting standard that governs such transactions. This standard addresses the accounting for revenue arrangements where both the vendor and the customer make cash payments to each other for services and/or products. A payment to a customer is presumed to be a reduction of the selling price unless we receive an identifiable benefit for the payment and it can reasonably estimate the fair value of the benefit received. Payments to a customer that are deemed a reduction of selling price are recorded first as a reduction of revenue, to the extent of both cumulative revenue recorded to date and probable future revenues, which include any unamortized deferred revenue balances, under all arrangements with such customer, and then as an expense. Payments that are not deemed to be a reduction of selling price are recorded as an expense. We evaluate our collaborative agreements for proper classification in our consolidated statements of comprehensive loss based on the nature of the underlying activity. Transactions between collaborators recorded in our consolidated statements of comprehensive loss are recorded on either a gross or net basis, depending on the characteristics of the collaborative relationship. We generally reflect amounts due under our collaborative agreements related to cost-sharing of development activities as revenue. Amounts received prior to satisfying the above revenue recognition criteria are recorded as deferred revenue in the accompanying consolidated balance sheets. Although we follow detailed guidelines in measuring revenue, certain judgments affect the application of our revenue policy. For example, in connection with our existing collaboration agreements, we have recorded on our consolidated balance sheet short-term and long-term deferred revenue based on our best estimate of when such revenue will be recognized. Short-term deferred revenue consists of amounts that are expected to be recognized as revenue in the next 12 months. Amounts that we expect will not be recognized within the next 12 months are classified as long-term deferred revenue. However, this estimate is based on our current operating plan and, if our operating plan should change in the future, we may recognize a different amount of deferred revenue over the next 12-month period. The estimate of deferred revenue also reflects management’s estimate of the periods of our involvement in certain of our collaborations. Our performance obligations under these collaborations consist of participation on steering committees and the performance of other research and development services. In certain instances, the timing of satisfying these obligations can be difficult to estimate. Accordingly, our estimates may change in the future. Such changes to estimates would result in a change in revenue recognition amounts. If these estimates and judgments change over the course of these agreements, it may affect the timing and amount of revenue that we recognize and record in future periods. At December 31, 2015, we had short-term and long-term deferred revenue of $15.4 million and $53.0 million, respectively, related to our collaborations. Income Taxes We use the asset and liability method of accounting for income taxes. Under the asset and liability method, deferred tax assets and liabilities reflect the impact of temporary differences between amounts of assets and liabilities for financial reporting purposes and such amounts as measured under enacted tax laws. A valuation allowance is required to offset any net deferred tax assets if, based upon the available evidence, it is more likely than not that some or all of the deferred tax asset will not be realized. We account for uncertain tax positions using a “more-likely-than-not” threshold for recognizing and resolving uncertain tax positions. The evaluation of uncertain tax positions is based on factors that include, but are 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. Our policy is to accrue interest and penalties related to unrecognized tax positions in income tax expense. As of December 31, 2015, we have not recorded significant interest and penalty expense related to uncertain tax positions. Research and Development Costs We expense research and development costs as incurred. Included in research and development costs are wages, benefits and other operating costs, facilities, supplies, external services, clinical trial and manufacturing costs, and overhead directly related to our research and development operations, as well as costs to acquire technology licenses. We have entered into several license agreements for rights to utilize certain technologies. The terms of the licenses may provide for upfront payments, annual maintenance payments, milestone payments based upon certain specified events being achieved and royalties on product sales. We charge costs to acquire and maintain licensed technology that has not reached technological feasibility and does not have alternative future use to research and development expense as incurred. During the years ended December 31, 2015, 2014 and 2013, we charged to research and development expense costs associated with license fees of $3.5 million, $12.1 million and $8.0 million, respectively. Accounting for Stock-Based Compensation We have stock incentive plans and an employee stock purchase plan under which we grant equity instruments. We account for all stock-based awards granted to employees at their fair value and generally recognize compensation expense over the vesting period of the award. Determining the amount of stock-based compensation to be recorded requires us to develop estimates of fair values of stock options as of the grant date. We calculate the grant date fair values using the Black-Scholes valuation model. Our expected stock price volatility assumption is based on the historical volatility of our publicly traded stock. For stock-based awards granted to non-employees, we generally recognize compensation expense over the vesting period of the award, which is generally the period during which services are rendered by such non-employees. At the end of each financial reporting period prior to vesting, we re-measure the value of these stock-based awards (as calculated using the Black-Scholes option-pricing model) using the then-current fair value of our common stock. Stock options granted by us to non-employees, other than members of our board of directors and scientific advisory board members, generally vest over the service period. The fair value of restricted stock awards granted to employees is based upon the quoted closing market price per share on the date of grant, adjusted for assumed forfeitures. Expense is recognized over the vesting period, commencing when we determine that it is probable that the awards will vest. For performance-based stock awards, expense is first recorded when we determine that the achievement of such performance conditions is deemed probable. This determination requires significant judgment by management. At the probable date, we record a cumulative expense catch-up, with remaining expense amortized over the remaining service period. Comprehensive Loss Comprehensive loss is comprised of net loss and certain changes in stockholders’ equity that are excluded from net loss. We include foreign currency translation adjustments in other comprehensive loss as the functional currency is not the United States dollar. We include unrealized gains and losses on certain marketable securities in other comprehensive loss. Net Loss Per Common Share We compute basic net loss per common share by dividing net loss by the weighted-average number of common shares outstanding. We compute diluted net loss per common share by dividing net loss by the weighted-average number of common shares and dilutive potential common share equivalents then outstanding. Potential common shares consist of shares issuable upon the exercise of stock options (using the treasury stock method), and unvested restricted stock awards. Because the inclusion of potential common shares would be anti-dilutive for all periods presented, diluted net loss per common share is the same as basic net loss per common share. The following table sets forth for the periods presented the potential common shares (prior to consideration of the treasury stock method) excluded from the calculation of net loss per common share because their inclusion would be anti-dilutive, in thousands: At December 31, 2015 2014 2013 Options to purchase common stock 9,960 8,169 8,713 Unvested restricted common stock 19 30 500 9,979 8,199 9,213 Segment Information We operate in a single reporting segment, the discovery, development and commercialization of RNAi therapeutics. Subsequent Events We did not have any material recognized subsequent events. However, we did have the following nonrecognized subsequent event, which is more fully described in Note 7: • On February 10, 2016, we entered into an agreement to purchase land in Norton, Massachusetts for the construction of a manufacturing facility. Recent Accounting Pronouncements In May 2014, the Financial Accounting Standards Board, or FASB, issued a new revenue recognition standard which amends revenue recognition principles and provides a single, comprehensive set of criteria for revenue recognition within and across all industries. The new standard provides a five step framework whereby revenue is recognized when promised goods or services are transferred to a customer at an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services. The standard also requires enhanced disclosures pertaining to revenue recognition in both interim and annual periods. In August 2015, the FASB deferred the effective date of the new revenue standard from January 1, 2017 to January 1, 2018. Early adoption is permitted any time after the original effective date, which for us is January 1, 2017. The standard allows for adoption using a full retrospective method or a modified retrospective method. We are currently evaluating the timing, method of adoption and the expected impact that the standard could have on our consolidated financial statements and related disclosures. In April 2015, the FASB amended its guidance on internal use software to clarify the accounting by customers for fees paid in a cloud computing arrangement. Under this guidance, if a cloud computing arrangement includes a software license, the software license element of the arrangement should be accounted for consistent with the customer’s accounting for other software licenses. If a cloud computing arrangement does not include a software license, the arrangement should be accounted for as a service contract. The new guidance became effective for us on January 1, 2016. The adoption of this guidance is not expected to have a material impact on our consolidated financial statements and related disclosures. In November 2015, the FASB issued final guidance that requires companies to classify all deferred tax assets and liabilities as noncurrent on the balance sheet instead of separating deferred taxes into current and noncurrent amounts. This guidance allows for adoption on either a prospective or retrospective basis. This guidance will be effective on January 1, 2017. Early adoption is permitted. We have elected to early adopt this guidance on a prospective basis and, as a result, prior consolidated balance sheets were not retrospectively adjusted. The adoption of this guidance did not have a material impact on our consolidated financial statements and related disclosures. In January 2016, the FASB issued new guidance on recognition and measurement of financial assets and financial liabilities. The new guidance will impact the accounting for equity investments, financial liabilities under the fair value option, and the presentation and disclosure requirements for financial instruments. All equity investments in unconsolidated entities (other than those accounted for under the equity method of accounting) will generally be measured at fair value with changes in fair value recognized through earnings. There will no longer be an available-for-sale classification (changes in fair value reported in other comprehensive income (loss)) for equity securities with readily determinable fair values. In addition, the FASB clarified the need for a valuation allowance on deferred tax assets resulting from unrealized losses on available-for-sale debt securities. In general, the new guidance will require modified retrospective application to all outstanding instruments, with a cumulative effect adjustment recorded to opening retained earnings. This guidance will be effective for us on January 1, 2018. We are currently evaluating the expected impact that the standard could have on our consolidated financial statements and related disclosures.

SIGNIFICANT AGREEMENTS

SIGNIFICANT AGREEMENTS	12 Months Ended
	Dec. 31, 2015
SIGNIFICANT AGREEMENTS	3. SIGNIFICANT AGREEMENTS The following table summarizes our total consolidated net revenues from collaborators, for the periods indicated, in thousands: Year Ended December 31, 2015 2014 2013 Sanofi Genzyme $ 11,005 $ 369 $ — MDCO 10,301 10,753 4,604 Takeda 8,867 21,973 21,973 Monsanto 5,621 14,985 5,640 Cubist — — 9,721 Other 5,303 2,481 5,229 Total net revenues from collaborators $ 41,097 $ 50,561 $ 47,167 Product Alliances Sanofi Genzyme Collaboration In January 2014, we entered into a global, strategic collaboration with Sanofi Genzyme to discover, develop and commercialize RNAi therapeutics as Genetic Medicines to treat orphan diseases. The 2014 Sanofi Genzyme collaboration superseded and replaced the previous collaboration between us and Sanofi Genzyme entered into in October 2012 to develop and commercialize RNAi therapeutics targeting transthyretin, or TTR, for the treatment of TTR-mediated amyloidosis, or ATTR amyloidosis, including patisiran and revusiran, in Japan and the Asia-Pacific region. 2012 Sanofi Genzyme Agreement Under the 2012 Sanofi Genzyme agreement, Sanofi Genzyme paid us an upfront cash payment of $22.5 million. We were also entitled to receive certain milestone payments under the 2012 Sanofi Genzyme agreement. In the fourth quarter of 2013, we earned a milestone of $7.0 million based upon the completion of a successful patisiran Phase 2 clinical trial and a milestone of $4.0 million based upon the initiation of the Phase 3 clinical trial for patisiran. Under the 2012 Sanofi Genzyme agreement, the parties agreed to collaborate in the development and commercialization of licensed products, with Sanofi Genzyme assuming primary responsibility in the Sanofi Genzyme territory, which included Japan and the Asia-Pacific region, and us retaining primary responsibility in the rest of the world. We determined that the deliverables under the 2012 Sanofi Genzyme agreement included the license, a joint steering committee and any additional TTR-specific RNAi therapeutic compounds that comprised the ALN-TTR program. We also determined that, pursuant to the accounting guidance governing revenue recognition on multiple element arrangements, the license and undelivered joint steering committee and any additional TTR-specific RNAi therapeutic compounds did not have standalone value due to the specialized nature of the services to be provided by us. In addition, while Sanofi Genzyme had the ability to grant sublicenses, it could not sublicense all or substantially all of its rights under the 2012 Sanofi Genzyme agreement. The uniqueness of our services and the limited sublicense right were indicators that standalone value was not present in the arrangement. Therefore the deliverables were not separable and, accordingly, the license and undelivered services were treated as a single unit of accounting. We were unable to reasonably estimate the period of performance under the 2012 Sanofi Genzyme agreement, as we were unable to estimate the timeline of our deliverables related to the deliverable for any additional TTR-specific RNAi therapeutic compounds. Through December 31, 2013, we had deferred all revenue, or $33.5 million, under the 2012 Sanofi Genzyme agreement. 2014 Sanofi Genzyme Collaboration In January 2014, we entered into the 2014 Sanofi Genzyme collaboration. As noted above, the 2014 Sanofi Genzyme collaboration superseded and replaced the 2012 Sanofi Genzyme agreement. The 2014 Sanofi Genzyme collaboration is structured as an exclusive relationship for the worldwide development and commercialization of RNAi therapeutics in the field of Genetic Medicines, which includes our current and future Genetic Medicine programs that reach Human Proof-of-Principle Study Completion (as defined in the Sanofi Genzyme master agreement), or Human POP, by the end of 2019, subject to extension to the end of 2021 in various circumstances. We will retain product rights in North America and Western Europe, referred to as the Alnylam Territory, while Sanofi Genzyme will obtain exclusive rights to develop and commercialize collaboration products in the rest of the world, referred to as the Sanofi Genzyme Territory, together with certain broader co-development/co-promote or worldwide rights for certain products. Sanofi Genzyme’s rights, described in detail below, are structured as an opt-in that is triggered upon achievement of Human POP. We maintain development control for all programs prior to Sanofi Genzyme’s opt-in and maintain development and commercialization control after Sanofi Genzyme’s opt-in for all programs in the Alnylam Territory. Specifically, in addition to its regional rights for our current and future Genetic Medicine programs in the Sanofi Genzyme Territory, Sanofi Genzyme has the right to either (i) co-develop and co-promote fitusiran for the treatment of hemophilia and other rare bleeding disorders in the Alnylam Territory, with us maintaining development and commercialization control, or (ii) obtain a global license to ALN-AS1 for the treatment of hepatic porphyrias. Sanofi Genzyme may exercise this selection right upon the completion of Human POP for both the fitusiran and ALN-AS1 programs. Finally, Sanofi Genzyme has the right for a global license to a single, future Genetic Medicine program that was not one of our defined Genetic Medicine programs as of the effective date of the 2014 Sanofi Genzyme collaboration. We will retain global rights to any RNAi therapeutic Genetic Medicine program that does not reach Human POP by the end of 2019, subject to certain limited exceptions. We retain full rights to all current and future RNAi therapeutic programs outside of the field of Genetic Medicines, including the right to form new collaborations. Under the 2014 Sanofi Genzyme collaboration, Sanofi Genzyme’s specific license rights and the programs into which Sanofi Genzyme has opted include the following: • Regional license terms and programs — Upon opt-in, we will retain product rights in the Alnylam Territory, while Sanofi Genzyme will obtain exclusive rights to develop and commercialize the product in the Sanofi Genzyme Territory. Sanofi Genzyme can elect this license for any of our current and future Genetic Medicine programs that complete Human POP by the end of 2019, subject to limited extension. Development costs for products once Sanofi Genzyme exercises an option will be shared between Sanofi Genzyme and us, with Sanofi Genzyme responsible for twenty percent of the global development costs. Upon the effective date of the 2014 Sanofi Genzyme collaboration, Sanofi Genzyme expanded the scope of its regional license and collaboration for patisiran, an investigational RNAi therapeutic currently in a Phase 3 clinical trial, which was originally established under the 2012 Sanofi Genzyme agreement. In September 2015, Sanofi Genzyme elected to opt into our fitusiran clinical development program for the treatment of hemophilia and other rare bleeding disorders under the regional license terms. As described above, Sanofi Genzyme retains its future opt-in right to co-develop and co-promote fitusiran in the Alnylam Territory pursuant to the co-development/co-promote license terms described below. Cost-sharing for the fitusiran program began in January 2016. Sanofi Genzyme will be required to make payments totaling up to $50.0 million upon the achievement of certain patisiran development milestones. We could potentially earn the next patisiran milestone payment, ranging between $5.0 million and $20.0 million based on the geographic region, upon the achievement of specified events in connection with a regulatory filing or approval. In addition, Sanofi Genzyme will be required to make payments totaling up to $75.0 million per product other than patisiran, including fitusiran, consisting of up to $55.0 million in development milestones and $20.0 million in commercial milestones. We could potentially earn the first fitusiran milestone payment of $25.0 million based upon the initiation of the first global Phase 3 clinical trial for fitusiran. Sanofi Genzyme will also be required to pay tiered double-digit royalties up to twenty percent for each regional product based on annual net sales, if any, of such regional product by Sanofi Genzyme, its affiliates and sublicensees. • Co-development/co-promote license terms and programs — Upon opt-in, we will retain product rights in the Alnylam Territory, while Sanofi Genzyme will obtain exclusive rights to develop and commercialize the product in the Sanofi Genzyme Territory, and will co-promote the product in the Alnylam Territory. Upon the effective date of the 2014 Sanofi Genzyme collaboration, Sanofi Genzyme expanded its regional rights for revusiran, an investigational RNAi therapeutic currently in a Phase 3 clinical trial, which were originally granted under the 2012 Sanofi Genzyme agreement, to include a co-development/co-promote license and collaboration. As noted above, Sanofi Genzyme also has the right to elect a co-development/co-promote license and collaboration for fitusiran, if it does not elect a global license and collaboration for ALN-AS1. Development costs for co-development/co-promote products, once Sanofi Genzyme exercises an option, will be shared between Sanofi Genzyme and us, with Sanofi Genzyme responsible for fifty percent of the global development costs. Sanofi Genzyme will be required to make payments totaling up to $75.0 million in development milestones for revusiran and, if selected, fitusiran. In December 2014, we earned a development milestone payment of $25.0 million based upon the initiation of the first global Phase 3 clinical trial for revusiran. We could potentially earn the next revusiran milestone payment, ranging between $5.0 million and $25.0 million based on the geographic region, upon the achievement of specified events in connection with regulatory approval. Sanofi Genzyme will also be required to pay tiered double-digit royalties up to twenty percent for each co-development/co-promote product based on annual net sales, if any, in the Sanofi Genzyme Territory for such co-development/co-promote product by Sanofi Genzyme, its affiliates and sublicensees. The parties will share profits equally and we expect to book product sales in the Alnylam Territory. • Global license terms and programs — Upon opt-in, Sanofi Genzyme will obtain a worldwide license to develop and commercialize the product. Sanofi Genzyme can elect a global license for ALN-AS1, if it does not elect a co-development/co-promote license for fitusiran, as described above. Sanofi Genzyme will also have one right to a global license through 2019, subject to limited extension, for a future Genetic Medicine program that was not one of our defined Genetic Medicine programs as of the effective date of the 2014 Sanofi Genzyme collaboration. Sanofi Genzyme shall be responsible for one hundred percent of global development costs. Sanofi Genzyme will be required to make payments totaling up to $200.0 million per global product, including up to $60.0 million in development milestones and $140.0 million in commercial milestones. Sanofi Genzyme will also be required to pay tiered double-digit royalties up to twenty percent for each global product based on annual net sales, if any, of each global product by Sanofi Genzyme, its affiliates and sublicensees. Due to the uncertainty of pharmaceutical development and the high historical failure rates generally associated with drug development, we may not receive any additional milestone payments or any royalty payments from Sanofi Genzyme under the 2014 Sanofi Genzyme collaboration. Under the master agreement, the parties will collaborate in the development of option products, with us leading development for all programs prior to Sanofi Genzyme’s opt-in and also leading development and commercialization for all programs in the Alnylam Territory after Sanofi Genzyme’s opt-in. If Sanofi Genzyme does not exercise its option to license rights to a particular program, we will retain the exclusive right to develop and commercialize such program throughout the world, including the right to sublicense to third parties. The 2014 Sanofi Genzyme collaboration is governed by an alliance joint steering committee that is comprised of an equal number of representatives from each party. There are additional committees to manage various aspects of each regional, co-developed/co-promoted and global program. We and Sanofi Genzyme intend to enter into supply agreements to provide for supply of collaboration products to Sanofi Genzyme for clinical studies, and, at Sanofi Genzyme’s request, commercial sales. Sanofi Genzyme also has certain rights to manufacture collaboration products. Additionally, Sanofi Genzyme has certain limited opt-out rights, as specified in the master agreement, upon which products revert fully back to us with no further obligations to Sanofi Genzyme. The master agreement (including the license terms appended thereto) contains certain termination provisions, including for material breach by the other party. Unless terminated earlier pursuant to its terms, the master agreement will terminate upon the last to expire of any of the option periods under the master agreement or the license terms appended thereto. Upon the closing of the equity transaction in February 2014, we sold to Sanofi Genzyme 8,766,338 shares of our common stock and Sanofi Genzyme paid $700.0 million in aggregate cash consideration to us. As a condition to the closing of the equity transaction, Sanofi Genzyme entered into an investor agreement with us. Under the investor agreement, until the earlier of the fifth anniversary of the expiration or earlier termination of the 2014 Sanofi Genzyme collaboration and the date on which Sanofi Genzyme and its affiliates cease to beneficially own at least 5% of our outstanding common stock, Sanofi Genzyme and its affiliates are bound by certain “standstill” provisions. The standstill provisions include agreements not to acquire more than 30% of our outstanding common stock, call stockholder meetings, nominate directors other than those approved by our board of directors, subject to certain limited exceptions, or propose or support a proposal to acquire us. Further, Sanofi Genzyme has agreed to vote, and cause its affiliates to vote, all shares of our voting securities they are entitled to vote, up to a maximum of 20% of our outstanding common stock, in a manner either as recommended by our board of directors or proportionally with the votes cast by our other stockholders, except with respect to certain change of control transactions or our liquidation or dissolution. Until Sanofi Genzyme owns less than 7.5% of our outstanding common stock, subject to Sanofi Genzyme’s limited right to maintain its ownership percentage as described below, if we issue common stock or securities convertible into or exercisable for common stock to a third party that holds at least 30% of our outstanding common stock or, in connection with a collaboration or license transaction, to a third party that will initially hold at least the percentage of our outstanding common stock represented by the shares purchased by Sanofi Genzyme at the closing of the equity transaction, we will offer Sanofi Genzyme an opportunity to amend the standstill and voting provisions in the investor agreement to be consistent with the terms provided to such third party. Under the investor agreement, Sanofi Genzyme has also agreed not to dispose of any shares of common stock beneficially owned by it immediately after the closing of the stock purchase until the earlier of (i) December 31, 2019 (subject to extension by up to two years if Sanofi Genzyme’s option to select additional compounds under the master agreement is extended beyond December 31, 2019) and (ii) six months after the expiration or earlier valid termination of the collaboration, in each case subject to earlier termination in the event certain clinical activities under the collaboration fail to occur. Following the expiration of this lock-up period, Sanofi Genzyme will be permitted to sell such shares of common stock subject to certain limitations, including volume and manner of sale restrictions. Notwithstanding the foregoing, following the two-year anniversary of the closing of the stock purchase, in the event that the market price per share of our common stock is at least 100% higher than the market price per share of our common stock at closing of the stock purchase (in each case based upon a ten-day trailing average), Sanofi Genzyme may sell up to 25% of its initial shares, subject to certain restrictions on post-lock-up period dispositions as described above. Under the investor agreement, following the lock-up period, Sanofi Genzyme will have three demand rights to require us to conduct a registered underwritten public offering with respect to the shares of common stock beneficially owned by Sanofi Genzyme immediately after the closing of the stock purchase, subject to certain conditions. In addition, following the lock-up period, subject to certain conditions, Sanofi Genzyme will be entitled to participate in registered underwritten public offerings by us if other selling stockholders are included in the registration. The investor agreement provides that, until Sanofi Genzyme owns less than 7.5% of our outstanding common stock, subject to Sanofi Genzyme’s limited right to maintain its ownership percentage as described herein, in connection with new issuances of common stock, subject to certain exceptions, Sanofi Genzyme will be entitled to a right of first offer to participate proportionally to maintain its then-current ownership percentage of our common stock. If Sanofi Genzyme is not entitled to a right of first offer with respect to a new issuance, Sanofi Genzyme will have the opportunity, on a post-transaction basis, to purchase additional shares sufficient to maintain its pre-transaction ownership percentage of our common stock (subject to the same 7.5% ownership threshold). Finally, in the event Sanofi Genzyme and its affiliates acquire at least 20% or more of our outstanding common stock, Sanofi Genzyme will be entitled to appoint one individual to our board of directors. Sanofi Genzyme will also be entitled to certain information rights, including with respect to financial information in the event Sanofi Genzyme or its affiliates require such information for its own financial reporting purposes. The rights and restrictions under the investor agreement are subject to termination upon the occurrence of certain events. We recorded the issuance of 8,766,338 shares of our common stock under the stock purchase agreement using the price of our common stock on the date the shares were issued to Sanofi Genzyme. Based on the common stock price of $85.72, the fair value of the shares issued was $751.5 million, which was $51.5 million in excess of the proceeds received from Sanofi Genzyme for the issuance of our common stock. This $51.5 million is being amortized on a straight-line basis over the performance period, which is currently approximately six years as described below. In addition, due to intraperiod tax allocation rules, upon closing of the equity transaction we recorded a benefit from income taxes of $15.2 million due to the Sanofi Genzyme equity purchase being recorded in additional paid-in capital, net of tax. For the year ended December 31, 2014, we recorded a cumulative benefit from income taxes of $20.7 million. In accordance with the investor agreement, as a result of our issuance of shares in connection with our acquisition of Sirna Therapeutics, Inc., or Sirna, in March 2014, Sanofi Genzyme exercised its right to purchase an additional 344,448 shares of our common stock for $23.0 million. In addition, in January 2015, in connection with our public offering, Sanofi Genzyme exercised its right to purchase directly from us, in concurrent private placements, 744,566 shares of common stock at the public offering price resulting in $70.7 million in proceeds to us. The sales of common stock to Sanofi Genzyme were not registered as part of the public offering, though they were consummated simultaneously with the public offering. Sanofi Genzyme also has the right at the beginning of each year to purchase a number of shares of our common stock based on the number of shares we issued during the previous year for compensation-related purposes. Sanofi Genzyme exercised this right to purchase directly from us 196,251 shares of our common stock on January 22, 2015 for $18.3 million and 205,030 shares of our common stock on February 1, 2016 for $14.3 million. The sales of these shares to Sanofi Genzyme were consummated as private placements. In each instance, the purchase by Sanofi Genzyme described above allowed Sanofi Genzyme to maintain its ownership level of our common stock of approximately 12%. We determined that the deliverables for the programs on which Sanofi Genzyme was collaborating with us upon initiation of the 2014 collaboration included the licenses to our patisiran and revusiran clinical programs, which licenses were delivered to Sanofi Genzyme upon the closing date of the transaction, and the associated development activities, joint steering committee participation and information exchange for these clinical programs. We also determined that, pursuant to the accounting guidance governing revenue recognition on multiple element arrangements, the license and associated undelivered development activities, joint steering committee participation and information exchange activities did not have standalone value due to the specialized nature of the services to be provided by us. In addition, while Sanofi Genzyme has the ability to grant sublicenses, it cannot sublicense all or substantially all of its rights under the 2014 Sanofi Genzyme collaboration. The uniqueness of our services and the limited sublicense rights are indicators that standalone value is not present in the arrangement. Therefore the deliverables are not separable and, accordingly, the license and undelivered services were treated as a single unit of accounting. When multiple deliverables are accounted for as a single unit of accounting, we base our revenue recognition model on the final deliverable. Under the 2014 Sanofi Genzyme collaboration, the last deliverables for patisiran and revusiran are expected to be completed within approximately six years from the closing date of the transaction. We determined that the total cash received from Sanofi Genzyme under the now superseded 2012 Sanofi Genzyme agreement reflects consideration for certain of the performance obligations for ALN-TTR programs included in the 2014 Sanofi Genzyme collaboration. Therefore we are recognizing the $33.5 million of deferred revenue under the 2012 Sanofi Genzyme agreement on a straight-line basis over the period of performance of the ALN-TTR programs, which, as noted above, is currently approximately six years. In addition, during the fourth quarter of 2014, we recognized as revenue a portion of the $25.0 million milestone payment earned in December 2014 equal to the percentage of the performance period completed when the milestone was earned. During the year ended December 31, 2015, we also recognized as revenue a portion of the expense reimbursement of $33.9 million due to us under the terms of the 2014 Sanofi Genzyme collaboration equal to the percentage of the performance period completed to date. As future consideration is achieved, including any milestones or reimbursement for development activities, we will recognize as revenue a portion of these payments equal to the percentage of the performance period completed when the milestone or activities have been satisfied, multiplied by the amount of the payment. We will recognize the remaining portion of consideration received over the remaining performance period on a straight-line basis. At December 31, 2015, deferred revenue under the 2014 Sanofi Genzyme collaboration was $29.5 million. We determined that the opt-in rights that Sanofi Genzyme has for future Genetic Medicine programs represent separate and additional deliverables that Sanofi Genzyme may receive from us in future periods. Upon each opt-in by Sanofi Genzyme, we have determined that each program and the related activities will represent a single unit of accounting and, consistent with our accounting policies, we will base our revenue recognition period on the final deliverable associated with each future opt-in, including fitusiran, where we began earning revenue, including cost reimbursement and potential milestones, in January 2016. The Medicines Company Alliance In February 2013, we and MDCO entered into a license and collaboration agreement pursuant to which we granted to MDCO an exclusive, worldwide license to develop, manufacture and commercialize RNAi therapeutics targeting PCSK9 for the treatment of hypercholesterolemia and other human diseases, including ALN-PCSsc. MDCO paid us an upfront cash payment of $25.0 million. Upon achievement of certain events, we will be entitled to receive milestone payments, up to an aggregate of $180.0 million, including up to $30.0 million in specified development milestones, $50.0 million in specified regulatory milestones and $100.0 million in specified commercialization milestones. In addition, we will be entitled to royalties ranging from the low- to high- teens based on annual worldwide net sales, if any, of licensed products by MDCO, its affiliates and sublicensees, subject to reduction under specified circumstances. In December 2014, we earned a development milestone payment of $10.0 million under the MDCO agreement based upon the initiation of our Phase 1 clinical trial for ALN-PCSsc. In addition, in 2015 and 2014, we were reimbursed $3.8 million and $4.8 million, respectively, for costs incurred for certain development activities. We could potentially earn the next development milestone payment of $20.0 million based upon the initiation of a pivotal study for ALN-PCSsc. Due to the uncertainty of pharmaceutical development and the high historical failure rates generally associated with drug development, we may not receive any additional milestone payments or any royalty payments from MDCO. Under the MDCO agreement, we and MDCO will collaborate in the further development of ALN-PCSsc. We had responsibility for the development of ALN-PCSsc until Phase 1 Completion, as defined in the MDCO agreement, at our cost, up to an agreed upon initial development cost cap. In late 2015, MDCO assumed responsibility for all development and commercialization of ALN-PCSsc, at its sole cost. The collaboration between us and MDCO is governed by a joint steering committee comprised of an equal number of representatives from each party. We were solely responsible for obtaining supply of finished product reasonably required for the conduct of our obligations under the initial development plan through Phase 1 Completion, and are responsible for supplying MDCO with finished product reasonably required for the first Phase 2 clinical trial of ALN-PCSsc conducted by MDCO, at our expense, provided such costs do not exceed the development costs cap, subject to certain exceptions. After such time, MDCO will have the sole right and responsibility to manufacture and supply ALN-PCSsc for development and commercialization under the MDCO development plan, subject to the terms of the MDCO agreement. We and MDCO intend to enter into a supply and technical transfer agreement to provide for supply of ALN-PCSsc to MDCO. Unless terminated earlier in accordance with the terms of the agreement, the MDCO Agreement expires on a licensed product-by-licensed product and country-by-country basis upon expiration of the last royalty term for any licensed product in any country, where a royalty term is defined as the latest to occur of (1) the expiration of the last valid claim of patent rights covering a licensed product, (2) the expiration of the Regulatory Exclusivity, as defined in the MDCO Agreement, and (3) the twelfth anniversary of the first commercial sale of the licensed product in such country. We estimate that our fundamental RNAi patents covering licensed products under the MDCO Agreement will expire both in and outside of the United States generally between 2016 and 2028. We also estimate that our ALN-PCS product-specific patents covering licensed products under the MDCO Agreement in the United States and elsewhere will expire at the end of 2033. These patent rights are subject to potential patent term extensions and/or supplemental protection certificates extending such terms in countries where such extensions may become available. In addition, more patent filings relating to the collaboration may be made in the future. Either party may terminate the MDCO Agreement in the event the other party fails to cure a material breach or upon patent-related challenges by the other party. In addition, MDCO has the right to terminate the agreement without cause at any time upon four months’ prior written notice. During the term of the MDCO agreement, neither party will, alone or with an affiliate or third party, research, develop or commercialize, or grant a license to any third party to research, develop or commercialize, in any country, any product directed to the PCSK9 gene, other than a licensed product, without the prior written agreement of the other party, subject to the terms of the MDCO agreement. We have determined that the significant deliverables under the MDCO agreement include the license, the joint steering committee, technology transfer obligations, development activities through Phase 1 Completion and supply of product for a Phase 2 clinical trial. We also determined that, pursuant to the accounting guidance governing revenue recognition on multiple element arrangements, the license and collective undelivered activities and services do not have standalone value due to the specialized nature of the activities and services to be provided by us. In addition, while MDCO has the ability to grant sublicenses, it must receive our prior written consent to sublicense all or substantially all of its rights. The uniqueness of our services and the limited sublicense right are indicators that standalone value is not present in the arrangement. Therefore the deliverables are not separable and, accordingly, the license and undelivered services are being treated as a single unit of accounting. When multiple deliverables are accounted for as a single unit of accounting, we base our revenue recognition pattern on the final deliverable. Under the MDCO agreement, all deliverables are expected to be completed within five years. We are recognizing revenue under the MDCO agreement on a straight-line basis over five years. We are not utilizing a proportional performance model since we are unable to reasonably estimate the level of effort to fulfill these obligations, primarily because the effort required under the development activities is largely unknown. We received the upfront payment of $25.0 million from MDCO in February 2013, which was initially recorded as deferred revenue. During the fourth quarter of 2014, we recognized as revenue a portion of the $10.0 million milestone payment earned in December 2014 equal to the percentage of the performance period completed when the milestone was earned. During 2015 and 2014, we also recognized as revenue a portion of the $3.8 million and $4.8 million, respectively, of expense reimbursement due to us under the terms of the MDCO agreement equal to the percentage of the performance period completed upon the invoice date. As future consideration, including any milestones or reimbursement for development activities, are earned, we will recognize as revenue a portion of these payments equal to the percentage of the performance period completed when the milestone is achieved or service has been provided, multiplied by the amount of the payment. We will recognize the remaining portion of consideration received over the remaining performance period on a straight-line basis. At December 31, 2015, deferred revenue under the MDCO agreement was $18.3 million. Platform Alliances Monsanto Alliance In August 2012, we and Monsanto entered into a license and collaboration agreement, pursuant to which we granted to Monsanto a worldwide, exclusive, royalty bearing right and license, including the right to grant sublicenses, to our RNAi platform technology and intellectual property controlled by us as of the date of the Monsanto agreement o

FAIR VALUE MEASUREMENTS

FAIR VALUE MEASUREMENTS	12 Months Ended
	Dec. 31, 2015
FAIR VALUE MEASUREMENTS	4. FAIR VALUE MEASUREMENTS The following tables present information about our assets that are measured at fair value on a recurring basis at December 31, 2015 and 2014, and indicate the fair value hierarchy of the valuation techniques we utilized to determine such fair value, in thousands: Description At December 31, 2015 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Commercial paper $ 3,998 $ — $ 3,998 $ — Corporate notes 4,843 — 4,843 — U.S. government-sponsored enterprise securities 10,000 — 10,000 — Money market funds 148,612 148,612 — — Marketable securities (fixed income): Certificates of deposit 10,498 — 10,498 — Commercial paper 38,110 — 38,110 — Corporate notes 904,909 — 904,909 — Municipal debt securities 9,000 — 9,000 — U.S. government-sponsored enterprise securities 61,396 — 61,396 — U.S. treasury securities 76,143 — 76,143 — Marketable securities (Regulus equity holdings) 51,419 51,419 — — Restricted cash (money market funds) 1,471 1,471 — — Total $ 1,320,399 $ 201,502 $ 1,118,897 $ — Description At December 31, 2014 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Money market funds $ 56,203 $ 56,203 $ — $ — Marketable securities (fixed income): Certificates of deposit 24,300 — 24,300 — Commercial paper 40,796 — 40,796 — Corporate notes 662,545 — 662,545 — Municipal debt securities 9,005 — 9,005 — U.S. government-sponsored enterprise securities 64,856 — 64,856 — U.S. treasury securities 5,248 — 5,248 — Marketable securities (Regulus equity holdings) 94,583 94,583 — — Total $ 957,536 $ 150,786 $ 806,750 $ — For the years ended December 31, 2015 and 2014, there were no transfers between Level 1 and Level 2 financial assets. The carrying amounts reflected in our consolidated balance sheets for cash, billed and unbilled collaboration receivables, other current assets, accounts payable and accrued expenses approximate fair value due to their short-term maturities.

MARKETABLE SECURITIES

MARKETABLE SECURITIES	12 Months Ended
	Dec. 31, 2015
MARKETABLE SECURITIES	5. MARKETABLE SECURITIES The following tables summarize the fair value, accumulated other comprehensive income (loss) and intraperiod tax allocation regarding our investment in Regulus available-for-sale marketable securities at December 31, 2015 and 2014, and for the activity recorded in the year, in thousands: Description At December 31, 2014 Sales of Regulus Shares During Year December 31, 2015 All Other Activity During Year December 31, 2015 Balance at December 31, 2015 Carrying value $ 11,935 $ — $ — $ 11,935 Accumulated other comprehensive income (loss), before tax 82,648 — (43,164 ) 39,484 Investment in equity securities of Regulus Therapeutics Inc., as reported $ 94,583 $ — $ (43,164 ) $ 51,419 Accumulated other comprehensive income (loss), before tax $ 82,648 $ — $ (43,164 ) $ 39,484 Intraperiod tax allocation recorded as a benefit from income taxes (32,792 ) — — (32,792 ) Accumulated other comprehensive income (loss), net of tax $ 49,856 $ — $ (43,164 ) $ 6,692 Description At December 31, 2013 Sales of Regulus Shares During Year December 31, 2014 All Other Activity During Year December 31, 2014 Balance at December 31, 2014 Carrying value $ 12,449 $ (514 ) $ — $ 11,935 Accumulated other comprehensive income (loss), before tax 33,003 (2,081 ) 51,726 82,648 Investment in equity securities of Regulus Therapeutics Inc., as reported $ 45,452 $ (2,595 ) $ 51,726 $ 94,583 Accumulated other comprehensive income (loss), before tax $ 33,003 $ (2,081 ) $ 51,726 $ 82,648 Intraperiod tax allocation recorded as a benefit from income taxes (13,267 ) — (19,525 ) (32,792 ) Accumulated other comprehensive income (loss), net of tax $ 19,736 $ (2,081 ) $ 32,201 $ 49,856 We obtain fair value measurement data for our marketable securities from independent pricing services. We perform validation procedures to ensure the reasonableness of this data. This includes meeting with the independent pricing services to understand the methods and data sources used. Additionally, we perform our own review of prices received from the independent pricing services by comparing these prices to other sources and confirming those securities are trading in active markets. The following tables summarize our marketable securities, other than our holdings in Regulus noted above, at December 31, 2015 and 2014, in thousands: At December 31, 2015 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 10,498 $ — $ — $ 10,498 Commercial paper 38,113 — (3 ) 38,110 Corporate notes 907,119 4 (2,214 ) 904,909 Municipal debt securities 9,000 — — 9,000 U.S. government-sponsored enterprise securities 61,463 24 (91 ) 61,396 U.S. treasury securities 76,186 4 (47 ) 76,143 Total $ 1,102,379 $ 32 $ (2,355 ) $ 1,100,056 At December 31, 2014 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 24,300 $ — $ — $ 24,300 Commercial paper 40,785 11 — 40,796 Corporate notes 663,554 14 (1,023 ) 662,545 Municipal debt securities 9,002 3 — 9,005 U.S. government-sponsored enterprise securities 64,948 — (92 ) 64,856 U.S. treasury securities 5,254 — (6 ) 5,248 Total $ 807,843 $ 28 $ (1,121 ) $ 806,750 We classify our debt security investments based on their contractual maturity dates. The following table summarizes our available-for-sale debt securities by contractual maturity, at December 31, 2015, in thousands: At December 31, 2015 Amortized Cost Fair Value Less than one year $ 849,288 $ 848,217 Greater than one year but less than two years 253,091 251,839 Total $ 1,102,379 $ 1,100,056

PROPERTY AND EQUIPMENT, NET

PROPERTY AND EQUIPMENT, NET	12 Months Ended
	Dec. 31, 2015
PROPERTY AND EQUIPMENT, NET	6. PROPERTY AND EQUIPMENT, NET Property and equipment consist of the following at December 31, 2015 and 2014, in thousands: At December 31, Useful Life 2015 2014 Laboratory equipment 5 years $ 33,558 $ 28,559 Computer equipment and software 3 years 5,732 4,440 Furniture and fixtures 5 years 2,906 1,999 Leasehold improvements * 35,825 30,853 Construction in progress — 1,285 1,982 79,306 67,833 Less: accumulated depreciation (51,494 ) (46,093 ) $ 27,812 $ 21,740 * Shorter of asset life or lease term During the years ended December 31, 2015, 2014 and 2013, we recorded $6.7 million, $5.0 million and $6.1 million, respectively, of depreciation expense related to our property and equipment.

COMMITMENTS AND CONTINGENCIES

COMMITMENTS AND CONTINGENCIES	12 Months Ended
	Dec. 31, 2015
COMMITMENTS AND CONTINGENCIES	7. COMMITMENTS AND CONTINGENCIES Purchase Commitments We have future purchase commitments totaling $150.2 million at December 31, 2015, of which $87.5 million is expected to be incurred in 2016 and $62.7 million is expected to be incurred past 2016. These commitments are related to purchase orders, clinical and pre-clinical agreements, and other purchase commitments for goods or services that we are likely to continue, regardless of the fact that they were cancelable at December 31, 2015. Technology License Commitments We have licensed from third parties the rights to use certain technologies in our research processes as well as in any products we may develop including these licensed technologies. In accordance with the related license agreements, we are required to make certain fixed payments to the licensor or a designee of the licensor over various agreement terms. Many of these agreement terms are consistent with the remaining lives of the underlying intellectual property that we have licensed. At December 31, 2015, we were committed to make the following fixed, estimated and cancelable payments under existing license agreements, in thousands: Year Ending December 31, 2016 $ 8,734 2017 741 2018 751 2019 761 2020 761 Thereafter 7,819 Total $ 19,567 We in-license technology from a number of sources, including Ionis and Merck. Pursuant to these in-license agreements, we will be required to make additional payments if and when we achieve specified development, regulatory and commercialization milestones. To the extent we are unable to reasonably predict the likelihood, timing or amount of such payments, we have excluded them from the table above. Facility Leases 300 Third Street We lease office and laboratory space located at 300 Third Street, Cambridge, Massachusetts, for our corporate headquarters and primary research facility under a non-cancelable real property lease agreement, or the Third Street Lease, with ARE-MA Region No. 28 LLC, or the Landlord. Under the Third Street Lease, we lease a total of approximately 129,000 square feet of office and laboratory space. The term of the Third Street Lease was set to expire in September 2016. In March 2014, we and the Landlord amended the Third Street Lease to extend the term for an additional five years, through September 30, 2021. Under the amended Third Street Lease, we have the option to extend the term for one additional five-year period. 665 Concord Avenue On February 10, 2012, we entered into a non-cancelable real property lease agreement, or the BMR-665 Concord Avenue Lease, with BMR-Fresh Pond Research Park LLC for our manufacturing facility for patisiran formulated bulk drug product. Under the BMR-665 Concord Avenue Lease, we lease approximately 15,000 square feet of office and laboratory space located at 665 Concord Avenue, Cambridge, Massachusetts. The term of the BMR Lease expires August 31, 2017. We have the option to extend the BMR-665 Concord Avenue Lease for two successive five-year periods. 675 West Kendall Street In April 2015, we entered into a non-cancelable real property lease, or the BMR-675 West Kendall lease, with BMR-675 West Kendall Street, LLC, or BMR, for laboratory and office space located at 675 West Kendall Street, Cambridge, Massachusetts. We intend to move our corporate headquarters to this location in early 2019. Under the terms of the BMR-675 West Kendall lease, we will lease approximately 295,000 square feet of laboratory and office space. The term of the BMR-675 West Kendall lease will commence on May 1, 2018 and rent payments will become due commencing upon substantial completion of the building improvements, which is currently expected to be on or around February 1, 2019, and will continue for 15 years from the rent commencement date, with options to renew for two terms of five years each, subject to the terms of the BMR-675 West Kendall lease. Annual rent under the BMR-675 West Kendall lease, exclusive of operating expenses and real property taxes, will be $19.8 million for the first year, with annual increases of 3% thereafter. Under the terms of the BMR-675 West Kendall lease, BMR will contribute a total of $56.1 million toward the cost of base building and tenant improvements. Under the terms of the BMR-675 West Kendall lease, for so long as we lease and occupy 70% or more of the rentable area of the leased premises and there are at least ten years remaining on the term of the BMR-675 West Kendall lease, we have a one-time right of first offer as to all of the rentable space in the building at 500 Kendall Street, Cambridge, Massachusetts, that is available for lease after the lease for such space that is currently in effect expires or terminates. 101 Main Street In May 2015, we entered into a non-cancelable real property lease agreement with RREEF America REIT II CORP. PPP, or RREEF, for office space located on several floors at 101 Main Street, Cambridge, Massachusetts. This lease supplements the initial lease entered into in March 2015 between us and RREEF for office space on a separate floor at the 101 Main Street location. Under the terms of the 101 Main Street leases, we will lease approximately 72,000 square feet of office space at the 101 Main Street location. The terms of the initial 101 Main Street lease and the additional 101 Main Street lease commenced in March 2015 and January 2016, and continue for four years, with an option to renew for one five-year term, and five and a half years, with an option to renew for one five-year term, respectively. Initial annual rent for the initial lease and the additional lease, exclusive of operating expenses and real property taxes, will be $1.7 million and $3.5 million, respectively, with annual increases of $1/square foot under each lease thereafter. Rent payments commenced in May 2015 under the initial lease and we expect rent payments to commence in May 2016 under the additional lease. We received $0.4 million, $1.9 million and $0.2 million in leasehold improvement incentives during the years ended December 31, 2015, 2014 and 2013, respectively. These leasehold improvement incentives are being accounted for as a reduction in rent expense ratably over the lease term. The balance from these leasehold improvement incentives is included in current portion of deferred rent and deferred rent, net of current portion, in the consolidated balance sheets at December 31, 2015 and 2014. We had $1.5 million in restricted cash that is recorded in long-term other assets as of December 31, 2015 in connection with an irrevocable standby letter of credit with RREEF. Our facility leases described above generally contain customary provisions allowing the landlords to terminate the leases if we fail to remedy a breach of any of our obligations under any such lease within specified time periods, or upon our bankruptcy or insolvency. Total rent expense, including operating expenses, under our real property leases was $10.5 million, $8.9 million and $4.9 million for the years ended December 31, 2015, 2014 and 2013, respectively. Future minimum payments under our non-cancelable facility leases are approximately as follows, in thousands: Year Ending December 31, 2016 $ 11,521 2017 13,152 2018 13,055 2019 30,955 2020 33,035 Thereafter 350,148 Total $ 451,866 Other On February 10, 2016, we entered into an agreement with 20 Commerce LLC to purchase 12 acres of undeveloped land in Norton, Massachusetts for an aggregate of approximately $8.0 million in cash payable for the land and related acquisition costs. We anticipate constructing a manufacturing facility at this site for clinical and commercial drug products. The closing of the transaction is subject to the completion of due diligence on the property and the satisfaction or waiver of other customary closing conditions. We expect the transaction to close in the first quarter of 2016. Litigation University of Utah Litigation On March 22, 2011, The University of Utah, or Utah, filed a civil complaint in the United States District Court for the District of Massachusetts, or the MA District Court, against us, Max Planck Gesellschaft Zur Foerderung Der Wissenschaften e.V. and Max Planck Innovation GmbH, together, Max Planck, the Whitehead Institute for Biomedical Research, or Whitehead, the Massachusetts Institute of Technology, or MIT, and the University of Massachusetts, or UMass, claiming a professor at Utah is the sole inventor or, in the alternative, a joint inventor, of the Tuschl patents. Utah was seeking changes to the inventorship of the Tuschl patents, unspecified damages and other relief. On October 31, 2011, we, Max Planck, Whitehead, MIT and UMass filed a motion to dismiss. Also on October 31, 2011, UMass filed a motion to dismiss on separate grounds, which we, Max Planck, Whitehead and MIT joined. On December 31, 2011, Utah filed a second amended complaint dropping UMass as a defendant and adding as defendants several UMass officials. In June 2012, the MA District Court denied both motions to dismiss. We, Max Planck, Whitehead, MIT and UMass filed an appeal of the MA District Court’s ruling on the motion to dismiss for lack of jurisdiction and a motion requesting that the MA District Court stay the case pending the outcome of the appeal. In July 2012, the MA District Court stayed discovery in the case pending the outcome of the defendants’ appeal. In August 2013, the United States Court of Appeals for the Federal Circuit, or CAFC, affirmed the lower court’s ruling, in a split decision. In September 2013, we filed a petition with the CAFC for rehearing or rehearing en banc. In November 2013, the CAFC denied our petition for rehearing or rehearing en banc and remanded the case back to the MA District Court. In February 2014, we filed a petition for writ of certiorari from the Supreme Court and a motion to stay the lower court proceedings pending a decision from the Supreme Court on our petition. The MA District Court granted our motion to stay the proceedings, however, in June 2014 the Supreme Court denied our petition for certiorari and remanded the case back to the MA District Court for trial, which was scheduled to begin in November 2015. On March 30, 2015, Utah voluntarily dismissed its sole inventorship claims leaving joint inventorship and state law damages claims pending. Utah subsequently clarified that such dismissal was with prejudice. On March 31, 2015, we filed motions for summary judgment seeking dismissal of all remaining claims. An oral hearing on these motions was held on July 13, 2015. On September 28, 2015, the MA District Court granted both of our motions for summary judgment, finding that there was no collaboration between Dr. Bass and Dr. Tuschl, which is a pre-requisite for co-inventorship, and dismissing Utah’s state law damages claims as well. On October 28, 2015, Utah filed a notice of appeal to the CAFC. On December 18, 2015, the CAFC for the Federal Circuit entered an order dismissing Utah’s appeal following a joint motion filed by us and Utah seeking dismissal of the appeal with prejudice. This disposed of Utah’s inventorship claims and its state law claims for damages. On October 14, 2015, we filed a motion with the MA District Court seeking reimbursement of costs and fees associated with defending this action in the amount of approximately $8.0 million. On November 30, 2015, the MA District Court dismissed our motion and on December 15, 2015, we filed a notice of appeal of this ruling with the CAFC. While we believe a fee award is merited in this case, such awards are made at the discretion of the court. We anticipate a ruling on this motion in mid-2016, however, the timing will be determined by the court. Dicerna Litigation On June 10, 2015, we filed a trade secret misappropriation lawsuit against Dicerna Pharmaceuticals, Inc., or Dicerna, in the Superior Court of Middlesex County, Massachusetts, seeking to stop misappropriation by Dicerna of our confidential, proprietary and trade secret information related to the RNAi assets we purchased from Merck, including certain GalNAc conjugate technology. In addition to permanent injunctive relief, we are also seeking monetary damages from Dicerna. On July 10, 2015, Dicerna filed its answer to our complaint, in which it denied our claims, along with initial discovery requests, to which we responded in a timely fashion. On July 27, 2015, Dicerna filed a motion seeking removal of the case to the Business Litigation Session of the Superior Court of Suffolk County, which we opposed. On August 31, 2015, the Court denied Dicerna’s motion. A protective order has been agreed to by us and Dicerna and was entered by the Court on November 12, 2015. Discovery is ongoing with us and Dicerna. We intend to request a scheduling conference with the Court in the first quarter of 2016 to set a discovery schedule and trial date. Although we believe we have meritorious claims in this matter, litigation is subject to inherent uncertainty and a court could ultimately rule against us. In addition, litigation and related matters are costly and may divert the attention of our management and other resources that would otherwise be engaged in other activities. Our accounting policy for accrual of legal costs is to recognize such expenses as incurred. Arbutus Settlement Agreement On November 12, 2012, we, Arbutus Biopharma Corporation, or ABC (formerly Tekmira Pharmaceuticals Corporation), Protiva Biotherapeutics, Inc., a wholly owned subsidiary of ABC, and together with ABC, referred to as Arbutus, and Acuitas Therapeutics Inc., or Acuitas (formerly AlCana Technologies, Inc.), entered into a settlement agreement and general release resolving all ongoing litigation, as well as a patent interference proceeding between us and Arbutus. The terms of the settlement agreement include mutual releases and dismissal with prejudice of all claims and counterclaims between the parties. In addition, as part of the settlement agreement, the parties agreed to a covenant not to sue one another in the future on matters released under the settlement agreement, as well as substantial liquidated damages to be paid by any party that breaches such covenant. The parties also agreed to resolve any future disputes that may arise over the three years following the settlement through binding arbitration. Pursuant to the settlement agreement, we and Arbutus also agreed to resolve the interference proceeding declared by the United States Board of Patent Appeals and Interferences between us and Arbutus, captioned Protiva Biotherapeutics, Inc. v. Alnylam Pharmaceuticals, Inc., Patent Interference No. 105792. Contemporaneously with the execution of the settlement agreement, we and Arbutus restructured our contractual relationship and entered into a cross-license agreement that superseded the prior license and manufacturing agreements among us, ABC and Arbutus. In connection with this restructuring, we incurred a $65.0 million charge to operating expenses for the year ended December 31, 2012. Specifically, we made a one-time payment of $30.0 million to Arbutus for the termination of, and our release from, all of our obligations under the manufacturing agreement with ABC, including without limitation the obligations to obtain materials and/or services from ABC. Further, we elected to buy-down certain future potential milestone and royalty payments due to Arbutus for certain of our RNAi therapeutics, formulated using lipid nanoparticle, or LNP, technology. Specifically, pursuant to the cross-license agreement, we made a one-time payment of $35.0 million to Arbutus, which amount constituted payment for the termination of the 2008 license agreements with ABC and Arbutus and the parties’ rights and obligations thereunder, as well as the buy-down of certain milestone payments and the significant reduction of royalty rates for ALN-VSP, ALN-PCS02 and patisiran. In addition, under the 2012 cross-license agreement, we were obligated to pay ABC an aggregate of $10.0 million in contingent milestone payments related to advancement of ALN-VSP and patisiran, which now represent the only potential milestones due to Arbutus for ALN-VSP, ALN-PCS02 and patisiran LNP-based RNAi therapeutics. In the fourth quarter of 2013, we paid ABC $5.0 million in connection with the initiation of the patisiran Phase 3 clinical trial. With respect to the second $5.0 million milestone, in August 2013, we initiated binding arbitration proceedings to resolve a disagreement with ABC regarding the achievement by ABC of this milestone under the parties cross-license agreement relating to the manufacture of ALN-VSP clinical trial material for use in China. The Arbutus arbitration hearing was held in May 2015 and we now expect a decision from the arbitration panel during the first quarter of 2016. We have not recorded the expense of $5.0 million for this milestone because we do not believe it has been achieved. Our policy is to expense these potential milestones when incurred and record them as research and development expense. Indemnifications Licensor indemnification — In connection with our license agreements with Max Planck relating to the Tuschl I and Tuschl II patent applications, we are required to indemnify Max Planck for certain damages arising in connection with the intellectual property rights licensed under the agreements. Under the Max Planck indemnification agreement, we are responsible for paying the costs of any litigation relating to the license agreements or the underlying intellectual property rights, including the costs associated with certain litigation regarding the Tuschl patents, which was settled during 2011, as well as certain costs associated with defending the University of Utah litigation described above. In connection with the settlement of the litigation regarding the Tuschl patents, we also agreed to indemnify Whitehead, MIT and UMass for certain costs associated with defending the University of Utah litigation. In connection with our research agreement with Acuitas, we agreed to indemnify Acuitas for certain legal costs, subject to certain exceptions and limitations, associated with the Arbutus litigation described above. These indemnification costs were charged to general and administrative expense. We are also a party to a number of agreements entered into in the ordinary course of business, which contain typical provisions that obligate us to indemnify the other parties to such agreements upon the occurrence of certain events. Such indemnification obligations are usually in effect from the date of execution of the applicable agreement for a period equal to the applicable statute of limitations. Our maximum potential future liability under any such indemnification provisions is uncertain. However, to date, other than certain costs associated with certain previously settled litigation related to the Tuschl patents and the Arbutus litigation described above, and certain defense costs related to the University of Utah litigation also described above, we have not incurred material costs to defend lawsuits or settle claims related to these indemnification provisions. We have determined that the estimated aggregate fair value of our potential liabilities under all such indemnification provisions is minimal and have not recorded any liability related to such indemnification provisions at December 31, 2015 or 2014.

STOCKHOLDERS' EQUITY

STOCKHOLDERS' EQUITY	12 Months Ended
	Dec. 31, 2015
STOCKHOLDERS' EQUITY	8. STOCKHOLDERS’ EQUITY Preferred Stock We have authorized up to 5,000,000 shares of preferred stock, $0.01 par value per share, for issuance. The preferred stock will have such rights, preferences, privileges and restrictions, including voting rights, dividend rights, conversion rights, redemption privileges and liquidation preferences, as shall be determined by our board of directors upon its issuance. At December 31, 2015 and 2014, there were no shares of preferred stock outstanding. Public Offerings In January 2015, we sold an aggregate of 5,447,368 shares of our common stock through an underwritten public offering at a price to the public of $95.00 per share. As a result of the offering, which included the full exercise of the underwriters’ option to purchase additional shares, we received aggregate net proceeds of $496.4 million, after deducting underwriting discounts and commissions and other estimated offering expenses of $21.1 million. In January 2013, we sold an aggregate of 9,200,000 shares of our common stock through an underwritten public offering at a price to the public of $20.13 per share. As a result of this offering, we received aggregate net proceeds of $173.6 million, after deducting underwriting discounts and commissions and other estimated offering expenses of $11.6 million.

STOCK INCENTIVE PLANS

STOCK INCENTIVE PLANS	12 Months Ended
	Dec. 31, 2015
STOCK INCENTIVE PLANS	9. STOCK INCENTIVE PLANS Stock Plans In June 2009, our stockholders approved an amendment and restatement of our 2004 Stock Incentive Plan, or the Amended and Restated 2004 Plan, which replaced our 2004 Stock Incentive Plan, as amended, or the 2004 Plan. At December 31, 2015, the Amended and Restated 2004 Plan provided for the granting of stock options to purchase up to 12,366,485 shares of common stock. Prior to the adoption of the Amended and Restated 2004 Plan, we were authorized to grant both stock options and restricted stock awards under the 2004 Plan. As of the effective date of the Amended and Restated 2004 Plan, we may only grant stock options under the Amended and Restated 2004 Plan, provided that the terms and conditions of any restricted stock awards outstanding under the 2004 Plan will continue to be governed by the Amended and Restated 2004 Plan. In June 2009, our stockholders also approved our 2009 Stock Incentive Plan. In May 2015, our stockholders approved an amendment and restatement of the 2009 Stock Incentive Plan, or the Amended and Restated 2009 Plan, which increased the number of shares of common stock authorized for issuance from 5,900,000 to 11,700,000. The Amended and Restated 2009 Plan provides for the granting of stock options, restricted stock awards and units, stock appreciation rights and other stock-based awards. The Amended and Restated 2009 Plan has a fungible share pool. Any award that is not a full value award is counted against the authorized share limits specified in the Amended and Restated 2009 Plan as one share for each share of common stock subject to the award, and all full value awards, defined in the Amended and Restated 2009 Plan as restricted stock awards or other stock-based awards, are counted as one and a half shares for each one share of common stock subject to such full value award. At December 31, 2015, an aggregate of 13,626,583 shares of common stock were reserved for issuance under our stock plans, including outstanding stock options to purchase 9,959,512 shares of common stock, 3,482,679 of common stock available for additional equity awards and 184,392 shares available for future grant under our 2004 Employee Stock Purchase Plan, or the 2004 ESPP. Each stock option shall expire within ten years of issuance. Time vested stock options granted by us to employees generally vest as to 25% of the shares on the first anniversary of the grant date and 6.25% of the shares at the end of each successive three-month period until fully vested. Performance-based stock options granted to employees in 2015 vest as to one-fourth of the shares upon the achievement of each of four specific clinical development or commercial events, as approved by our compensation committee. Performance-based stock options granted to employees in 2013 and 2014 each vest as to one-third of the shares upon the achievement of each of three specific clinical development or regulatory events, as approved by our compensation committee. Stock-Based Compensation The following table summarizes stock-based compensation expense by type of award during the three years ended December 31, 2015, in thousands: 2015 2014 2013 Stock-based compensation expense by type of award: Stock options $ 43,078 $ 24,603 $ 13,839 Performance-based stock options — 4,960 — Restricted stock awards 555 1,068 3,420 ESPP share issuances 694 392 261 Non-employee stock options 1,456 2,038 3,183 $ 45,783 $ 33,061 $ 20,703 The following table summarizes our unrecognized stock-based compensation expense, net of estimated forfeitures, at December 31, 2015 by type of awards and the weighted-average period over which that expense is expected to be recognized: At December 31, 2015 Unrecognized Expense, Net of Estimated Forfeitures Weighted-average Recognition Period (in thousands) (in years) Type of award: Time-based stock options $ 128,073 2.87 Performance-based stock options 62,000 * Restricted stock awards 1,108 2.54 ESPP share issuances 350 0.33 * Performance-based stock options are recorded as expense when vesting events are determined to be probable. Valuation Assumptions for Stock Options The fair value of stock options, at date of grant, based on the following assumptions, was estimated using the Black-Scholes option-pricing model. Our expected stock-price volatility assumption is based on the historical volatility of our publicly traded stock. The expected life assumption is based on our historical data. The dividend yield assumption is based on the fact that we have never paid cash dividends and have no present intention to pay cash dividends. The risk-free interest rate used for each grant is equal to the zero coupon rate for instruments with a similar expected life. 2015 2014 2013 Risk-free interest rate 1.0-2.0 % 1.7-2.3 % 1.0-2.0 % Expected dividend yield — — — Expected option life 3.5-7.5 years 5.5-7.5 years 5.6 years Expected volatility 53-60 % 53-57 % 55-56 % Stock Option Activity The following table summarizes the activity of our stock option plans, excluding performance-based stock options: Number of Options (in thousands) Weighted- Exercise Price Weighted- average Remaining Contractual Term (in Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2014 7,530 $ 33.46 Granted 2,403 99.20 Exercised (1,438 ) 19.64 Cancelled (177 ) 70.67 Outstanding, December 31, 2015 8,318 $ 54.05 6.85 $ 352,646 Exercisable at December 31, 2015 4,699 $ 30.61 5.31 $ 299,365 Vested or expected to vest at December 31, 2015 8,048 $ 52.89 6.78 $ 349,933 The weighted-average fair value of stock options granted was $51.28, $39.08 and $26.33 per share for the years ended December 31, 2015, 2014 and 2013, respectively. The intrinsic value of stock options exercised was $130.0 million, $126.5 million and $57.9 million for the years ended December 31, 2015, 2014 and 2013, respectively. We satisfy stock option exercises with newly issued shares of our common stock. Performance-Based Stock Options We grant performance-based stock options to employees that vest as to one-fourth of the shares upon the achievement of each of four specific clinical development or commercial events, as approved by our compensation committee, for 2015 grants, and that vest as to one-third of the shares upon the achievement of each of three specific clinical development or regulatory events, as approved by our compensation committee, for 2013 and 2014 grants. The following table summarizes the activity of our performance-based stock options: Number of Options (in thousands) Weighted- Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2014 639 $ 73.15 Granted 1,072 91.07 Exercised (29 ) 63.00 Cancelled (40 ) 77.64 Outstanding, December 31, 2015 1,642 $ 84.92 9.15 $ 16,244 Exercisable at December 31, 2015 120 $ 63.00 7.84 $ 3,741 On December 12, 2014, we achieved the first performance criteria of the December 18, 2013 grant of performance-based stock options and each stock option award granted was vested as to one-third of the performance-based portion of the award. The weighted-average grant date fair value of the first tranche of the December 18, 2013 performance-based stock option awards was $32.26 per share. During the fourth quarter of 2014, we determined the first performance criteria of the December 18, 2013 grant was probable and began to record expense, which was recognized in full as of December 12, 2014. The intrinsic value of performance-based stock options exercised was $1.4 million and $0.1 million for the years ended December 31, 2015 and 2014, respectively. We satisfy performance-based stock option exercises with newly issued shares of our common stock. As of the grant date and December 31, 2015, we had determined that the remaining performance criteria of all outstanding performance-based stock options reflected in the table above were not probable. As a result, we had not recorded stock-based compensation expense for these performance-based stock options as of December 31, 2015. On February 1, 2016, we achieved the first performance criteria of the December 17, 2014 grant of performance-based stock options upon the completion of patient enrollment in our Phase 3 APOLLO study and the stock option was vested as to one-third of the performance-based portion of the grant. As a result, in the first quarter of 2016, we expect to record stock-based compensation expense of approximately $8.0 million related to these 159,122 vested options. Contingent Stock Option Awards On December 17, 2014, the compensation committee of our board of directors approved the grant of stock options to purchase 612,085 shares of our common stock, at an exercise price of $96.45 per share, to members of our management team. These stock option grants were approved subject to and contingent upon approval by our stockholders at our 2015 annual meeting of the Amended and Restated 2009 Plan, to, among other things, increase the shares authorized for issuance thereunder, which approval was obtained in May 2015. One-half of the contingent stock options granted are time-based stock options and one-half are performance-based stock options. The grant-date fair value of the contingent stock options is based on a Black-Scholes valuation model based on the fair market value of the stock May 1, 2015, the date of such stockholder approval. We began recording stock-based compensation expense relating to this contingent stock option grant on May 1, 2015. Restricted Stock Awards In October 2010, we granted 113,370 shares of our restricted stock to certain employees. These restricted stock awards were valued at $1.4 million on the grant date. These restricted stock awards vested ratably over an approximate three-year period. In May 2011, we granted an aggregate of 229,806 shares of performance-based restricted stock awards to our employees, excluding our leadership team. These restricted stock awards were valued at $2.3 million on the grant date and had a contractual term of five years. The vesting of these awards was predicated on our achievement of certain clinical development goals. These awards have vested in full due to the achievement of these goals in 2011 and 2013. In January 2012, as part of our post-restructuring retention program, we granted an aggregate of 508,928 shares of restricted stock to our retained employees, excluding our chief executive officer and president and chief operating officer. These restricted stock awards were valued at $5.3 million on the grant date and vested in full on the second anniversary of the grant date. The total fair value of restricted stock awards that vested during the years ended December 31, 2015, 2014 and 2013 (measured on the date of vesting) was $1.2 million, $44.4 million and $5.8 million, respectively. At December 31, 2015 and 2014, there were 19,271 and 30,149 unvested restricted stock awards, including restricted stock and restricted stock units, respectively. The weighted-average grant date fair value of these unvested restricted stock awards was approximately $70. Employee Stock Purchase Plan In 2004, we adopted the 2004 ESPP with 315,789 shares authorized for issuance. In June 2010, our stockholders approved an amendment to the 2004 ESPP, which increased the shares authorized for issuance from 315,789 shares to 715,789 shares. Under the 2004 ESPP, each offering period is six months, at the end of which employees may purchase shares of common stock through payroll deductions made over the term of the offering. The per-share purchase price at the end of each offering period is equal to the lesser of 85% of the closing price of our common stock at the beginning or end of the offering period. We issued 22,639, 21,938 and 45,141 shares during the years ended December 31, 2015, 2014 and 2013, respectively, and at December 31, 2015, 184,392 shares were available for issuance under the 2004 ESPP. The weighted-average fair value of stock purchase rights granted as part of the 2004 ESPP was $29.96, $17.03 and $11.49 per share for the years ended December 31, 2015, 2014 and 2013, respectively. The fair value was estimated using the Black-Scholes option-pricing model. During the three years ended December 31, 2015, we used a weighted-average stock-price volatility of approximately 55%, expected option life assumption of six months and a risk-free interest rate of 0.1%.

INCOME TAXES

INCOME TAXES	12 Months Ended
	Dec. 31, 2015
INCOME TAXES	10. INCOME TAXES The domestic and foreign components of loss before income taxes are as follows, in thousands: 2015 2014 2013 Domestic $ (245,681 ) $ (372,137 ) $ (81,109 ) Foreign (44,392 ) (28,467 ) (10,811 ) Loss before income taxes $ (290,073 ) $ (400,604 ) $ (91,920 ) Deferred income taxes reflect the tax effects of temporary differences between the carrying amounts of assets and liabilities for financial reporting and income tax purposes. We establish a valuation allowance when uncertainty exists as to whether all or a portion of the net deferred tax assets will be realized. As of December 31, 2015, we elected to early adopt new guidance issued by the FASB in November 2015, which simplifies the presentation of deferred income taxes by eliminating the need for entities to separate deferred income tax liabilities and assets into current and noncurrent amounts in a classified statement of financial position. We adopted this guidance prospectively and, as a result, prior consolidated balance sheets were not retrospectively adjusted. As of December 31, 2014, we allocated the valuation allowance between current and noncurrent deferred tax assets and liabilities. As a result of this allocation, we had recorded a long-term deferred tax asset of $31.7 million and a corresponding short-term deferred tax liability of $31.7 million on the balance sheet. Components of the net deferred tax (liability) asset at December 31, 2015 and 2014 are as follows, in thousands: 2015 2014 Deferred tax assets: Net operating loss carryforwards $ 253,908 $ 176,789 Research and development credits 61,424 38,204 AMT credits 788 788 Foreign tax credits 3,196 3,196 Capitalized research and development and start-up costs 19,075 19,246 Deferred revenue 17,279 14,273 Deferred compensation 33,397 24,516 Intangible assets 16,181 17,637 Partnership interest 689 689 Other 6,508 5,871 Total deferred tax assets 412,445 301,209 Deferred tax liabilities: Unrealized gain on available-for-sale securities (14,947 ) (32,793 ) Deferred tax asset valuation allowance (397,498 ) (268,416 ) Net deferred tax liability $ — $ — The benefit from income taxes for the years ended December 31, 2015, 2014 and 2013 is as follows, in thousands: 2015 2014 2013 U.S.: Current $ — $ — $ 34 Deferred — (40,209 ) (2,695 ) Total U.S. — (40,209 ) (2,661 ) Foreign: Current — — — Deferred — — (34 ) Total Foreign — — (34 ) Benefit from income taxes $ — $ (40,209 ) $ (2,695 ) Our effective income tax rate differs from the statutory federal income tax rate as follows for the years ended December 31, 2015, 2014 and 2013: 2015 2014 2013 At U.S. federal statutory rate 35.0 % 35.0 % 35.0 % State taxes, net of federal effect 4.0 1.8 4.3 Stock-based compensation (1.1 ) (0.2 ) 0.8 Tax credits 8.0 3.5 8.5 Orphan drug credit (2.0 ) (0.6 ) (2.7 ) Other permanent items (0.1 ) — (0.3 ) Foreign rate differential (5.4 ) (2.5 ) (4.1 ) In-process research and development — (19.4 ) — Tax basis in intangible assets as a result of Sirna transaction — 4.2 — Valuation allowance (38.4 ) (11.8 ) (38.5 ) Effective income tax rate — % 10.0 % 3.0 % We have evaluated the positive and negative evidence bearing upon the realizability of our deferred tax assets. We have concluded, in accordance with the applicable accounting standards, that it is more likely than not that we may not realize the benefit of all of our deferred tax assets. Accordingly, we have recorded a valuation allowance against the deferred tax assets that management believes will not be realized. We reevaluate the positive and negative evidence on a quarterly basis. The valuation allowance increased by $129.1 million, $46.0 million and $29.7 million for the years ended December 31, 2015, 2014 and 2013, respectively, due primarily to additional operating losses and research and development credits. In 2014, increases to the valuation allowance were partially offset by decreases related to the recognition of deferred revenue. For the years ended December 31, 2015, 2014 and 2013, we recorded a tax benefit of zero, $40.2 million and $2.7 million, respectively. For the years ended December 31, 2014 and 2013, we recorded unrealized gains on our investments in available-for-sale securities in other comprehensive income and additional paid-in capital. We recorded a benefit of $19.5 million and $2.7 million for the years ended December 31, 2014 and 2013, respectively, due to the recognition of corresponding income tax expense associated with the increase in the value of our investment in Regulus that we carried at fair market value during the same period. In addition, for the year ended December 31, 2014, we recorded a benefit of $20.7 million due to the difference between the fair value of stock and the cash proceeds received from Sanofi Genzyme for the issuance of our common stock calculated at the closing date of the transaction. The corresponding income tax expense has been recorded in other comprehensive income and additional paid-in capital, respectively. Intraperiod tax allocation rules require us to allocate our provision for income taxes between continuing operations and other categories of earnings, such as other comprehensive income and additional paid-in capital. In periods in which we have a year-to-date pre-tax loss from continuing operations and pre-tax income in other categories of earnings, such as other comprehensive income and additional paid-in capital, we must allocate the tax provision to the other categories of earnings. We then record a related tax benefit in continuing operations. The deferred tax assets above exclude $123.6 million of net operating losses and $0.4 million of federal and state research and development credits related to tax deductions from the exercise of stock options subsequent to the adoption of the 2006 accounting standard on stock-based compensation. This amount represents excess tax benefits and has not been included in the gross deferred tax assets since, if subsequently recognized, these tax benefits would be credited directly to contributed capital. At December 31, 2015, we had federal and state net operating loss carryforwards of $931.2 million and $991.5 million, respectively. These amounts will reduce future taxable income that will expire at various dates through 2035. At December 31, 2015, federal and state research and development credit carryforwards were $53.2 million and $13.3 million, respectively, available to reduce future tax liabilities that expire at various dates through 2035. At December 31, 2015, foreign tax credit carryforwards were $3.2 million available to reduce future tax liabilities that expire in 2017. At December 31, 2015, alternative minimum tax credits of $0.8 million are available to reduce future regular tax liabilities to the extent such regular tax less other non-refundable credits exceeds the tentative minimum tax. Ownership changes, as defined in the Internal Revenue Code, including those resulting from the issuance of common stock in connection with our public offerings, may limit the amount of net operating loss that can be utilized to offset future taxable income or tax liability. At December 31, 2015, 2014 and 2013, we had no unrecognized tax benefits that, if recognized, would favorably impact our effective income tax rate in future periods. The tax years 2010 through 2015 remain open to examination by major taxing jurisdictions to which we are subject, which are primarily in the United States, as carryforward attributes generated in years past may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if they have or will be used in a future period. We have not recorded any interest and penalties on any unrecognized tax benefits since its inception.

ACCRUED EXPENSES

ACCRUED EXPENSES	12 Months Ended
	Dec. 31, 2015
ACCRUED EXPENSES	11. ACCRUED EXPENSES Accrued expenses consist of the following at December 31, 2015 and 2014, in thousands: At December 31, 2015 2014 Compensation and related $ 11,157 $ 7,357 Clinical trial and manufacturing 10,885 5,548 Consulting and professional services 892 3,886 Pre-clinical 899 3,081 Other 4,965 3,808 $ 28,798 $ 23,680

QUARTERLY FINANCIAL DATA (UNAUD

QUARTERLY FINANCIAL DATA (UNAUDITED)	12 Months Ended
	Dec. 31, 2015
QUARTERLY FINANCIAL DATA (UNAUDITED)	12. QUARTERLY FINANCIAL DATA (UNAUDITED) The following information has been derived from unaudited consolidated financial statements that, in the opinion of management, include all recurring adjustments necessary for a fair statement of such information. Three Months Ended March 31, 2015 June 30, 2015 September 30, 2015 December 31, 2015 (In thousands, except per share data) Revenues $ 18,537 $ 8,685 $ 6,324 $ 7,551 Operating expenses 70,759 81,629 84,654 100,063 Net loss $ (50,777 ) $ (71,783 ) $ (76,792 ) $ (90,721 ) Net loss per common share — basic and diluted $ (0.62 ) $ (0.85 ) $ (0.91 ) $ (1.07 ) Weighted-average common shares — basic and diluted 82,074 84,353 84,633 84,871 Three Months Ended March 31, 2014 June 30, 2014 September 30, 2014 December 31, 2014 (In thousands, except per share data) Revenues $ 8,275 $ 7,295 $ 10,972 $ 24,019 Operating expenses 277,339 52,300 56,171 69,731 Net loss $ (250,943 ) $ (44,074 ) $ (43,989 ) $ (21,389 ) Net loss per common share — basic and diluted $ (3.70 ) $ (0.58 ) $ (0.58 ) $ (0.28 ) Weighted-average common shares — basic and diluted 67,786 75,835 76,408 76,957 Operating expenses for the three months ended March 31, 2014 include a $224.7 million charge to in-process research and development expense in connection with the purchase of the Sirna RNAi assets from Merck. During the three months ended June 30, 2014, we recorded a credit of $3.9 million to in-process research and development expense, resulting in $220.8 million in-process research and development expense recorded for the year ended December 31, 2014 as a result of this asset acquisition. See Note 3, “Significant Agreements,” for further information.

SUMMARY OF SIGNIFICANT ACCOUN20

SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES (Policies)	12 Months Ended
	Dec. 31, 2015
Basis of Presentation and Principles of Consolidation	Basis of Presentation and Principles of Consolidation The accompanying consolidated financial statements reflect the operations of Alnylam and our wholly-owned subsidiaries. All intercompany accounts and transactions have been eliminated.
Use of Estimates	Use of Estimates The preparation of financial statements in conformity with accounting principles generally accepted in the United States of America, or GAAP, requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the consolidated financial statements and the reported amounts of revenues and expenses during the reporting period. Actual results could differ from those estimates.
Concentrations of Credit Risk and Significant Customers	Concentrations of Credit Risk and Significant Customers Financial instruments that potentially expose us to concentrations of credit risk consist primarily of cash, cash equivalents and fixed income marketable securities. At December 31, 2015 and 2014, substantially all of our cash, cash equivalents and fixed income marketable securities were invested in money market funds, certificates of deposit, commercial paper, corporate notes, municipal debt securities, U.S. government-sponsored enterprise securities and U.S. treasury securities through highly rated financial institutions. Corporate notes also include foreign bonds denominated in U.S. dollars. Investments are restricted, in accordance with our investment policy, to a concentration limit per issuer. In recent periods, our revenues from collaborations have been generated primarily from Sanofi Genzyme, the specialty care global business unit of Sanofi, or Sanofi Genzyme, Takeda Pharmaceutical Company Limited, or Takeda, Monsanto Company, or Monsanto, The Medicines Company, or MDCO, and Cubist Pharmaceuticals, Inc., or Cubist (now a wholly-owned subsidiary of Merck & Co., Inc.). For the year ended December 31, 2015, our billed and unbilled collaboration receivables were composed primarily of amounts of expense reimbursement due from Sanofi Genzyme and certain milestones due from Ionis Pharmaceuticals, Inc., or Ionis (formerly Isis Pharmaceuticals, Inc.). For the year ended December 31, 2014, our billed and unbilled collaboration receivables were composed primarily of amounts due from Sanofi Genzyme and MDCO based upon the achievement of certain milestones and also, with respect to MDCO, expense reimbursement. The following table summarizes customers that represent greater than 10% of our net revenues from collaborators, for the periods indicated: Year Ended December 31, 2015 2014 2013 Sanofi Genzyme 27 % * * MDCO 25 % 21 % * Takeda 22 % 43 % 47 % Monsanto 14 % 30 % 12 % Cubist * * 21 % The following table summarizes customers with amounts due that represent greater than 10% of our billed and unbilled collaboration receivables balance, at the periods indicated: At December 31, 2015 2014 Sanofi Genzyme 88 % 63 % Ionis 12 % * MDCO * 37 % * Represents 10% or less
Fair Value Measurements	Fair Value Measurements The fair value is the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. In general, fair values determined by Level 1 inputs utilize quoted prices (unadjusted) in active markets for identical assets or liabilities. Fair values determined by Level 2 inputs utilize data points that are observable, such as quoted prices (adjusted), interest rates and yield curves. Fair values determined by Level 3 inputs utilize unobservable data points for the asset or liability, and include situations where there is little, if any, market activity for the asset or liability. The fair value hierarchy level is determined by the lowest level of significant input.
Investments in Marketable Securities	Investments in Marketable Securities We invest our excess cash balances in short-term and long-term marketable debt and equity securities. We classify our investments in marketable debt securities as either held-to-maturity or available-for-sale based on facts and circumstances present at the time we purchased the securities. At each balance sheet date presented, we classified all of our investments in debt and equity securities as available-for-sale. We report available-for-sale investments at fair value at each balance sheet date and include any unrealized holding gains and losses (the adjustment to fair value) in accumulated other comprehensive income (loss), a component of stockholders’ equity. At December 31, 2015, the balance in our accumulated other comprehensive income was composed solely of activity related to our available-for-sale marketable securities, including our investment in equity securities of Regulus Therapeutics Inc., or Regulus. Realized gains and losses are determined using the specific identification method and are included in other income (expense). We did not recognize any realized gains or losses from sales of our available-for-sale securities during the year ended December 31, 2015 and, as a result, did not reclassify any amount out of accumulated other comprehensive income (loss) for the same period. If any adjustment to fair value reflects a decline in the value of the investment, we consider all available evidence to evaluate the extent to which the decline is “other than temporary,” including our intention to sell and, if so, mark the investment to market through a charge to our consolidated statements of comprehensive income (loss). We did not record any impairment charges related to our fixed income marketable securities during the years ended December 31, 2015, 2014 or 2013. Our marketable securities are classified as cash equivalents if the original maturity, from the date of purchase, is 90 days or less, and as marketable securities if the original maturity, from the date of purchase, is in excess of 90 days. Our cash equivalents are composed of commercial paper, corporate notes, U.S. government-sponsored enterprise securities and money market funds. We account for our investment in Regulus as an available-for-sale marketable security. Intraperiod tax allocation rules require us to allocate our provision for income taxes between continuing operations and other categories of earnings, such as other comprehensive income. In periods in which we have a year-to-date pre-tax loss from continuing operations and pre-tax income in other categories of earnings, such as other comprehensive income, we must allocate the tax provision to the other categories of earnings. We then record a related tax benefit in continuing operations. Upon sales of our available-for-sale marketable securities, we apply the aggregate portfolio approach to recognize the related tax provision or benefit into income (loss) from continuing operations. As a result, the disproportionate tax effect remains in accumulated other comprehensive income (loss) as long as we maintain an investment portfolio.
Estimated Liability for Development Costs	Estimated Liability for Development Costs We record accrued liabilities related to expenses for which service providers have not yet billed us with respect to products we have received or services that we have incurred, specifically related to ongoing pre-clinical studies and clinical trials. These costs primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator fees. We have multiple product candidates in concurrent pre-clinical studies and clinical trials at multiple clinical sites throughout the world. In order to ensure that we have adequately provided for ongoing pre-clinical and clinical development costs during the period in which we incur such costs, we maintain an accrual to cover these expenses. We update the estimate for this accrual on at least a quarterly basis. The assessment of these costs is a subjective process that requires judgment. Upon settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual costs.
Revenue Recognition	Revenue Recognition We have entered into collaboration agreements with leading pharmaceutical and life sciences companies, including Novartis Pharma AG and one of its affiliates (which assigned its rights and obligations to Arrowhead Research Corporation, or Arrowhead, in early 2015), F. Hoffmann-La Roche Ltd (which assigned its rights and obligations to Arrowhead in 2011), Takeda, Kyowa Hakko Kirin Co., Ltd., or Kyowa Hakko Kirin, Cubist, Monsanto, Sanofi Genzyme and MDCO. The terms of our collaboration agreements typically include deliverables such as non-refundable license fees, funding of research and development, payments based upon achievement of clinical and pre-clinical development milestones, regulatory milestones, manufacturing services, sales milestones and royalties on product sales. These agreements are generally referred to as multiple element arrangements. We apply the accounting standard on revenue recognition for multiple element arrangements. The fair value of deliverables under the arrangement may be derived using a “best estimate of selling price” if vendor specific objective evidence and third-party evidence is not available. Deliverables under the arrangement will be separate units of accounting provided that (i) a delivered item has value to the customer on a standalone basis and (ii) if the arrangement includes a general right of return relative to the delivered item, delivery or performance of the undelivered item is considered probable and substantially in the control of the vendor. We recognize upfront license payments as revenue upon delivery of the license only if the license has standalone value of the undelivered performance obligations, typically including research and/or steering committee services, can be determined. If the fair value of the undelivered performance obligations can be determined, such obligations would then be accounted for separately as performed. If the license is considered to not have standalone value, the arrangement would then be accounted for as a single unit of accounting and the license payments and payments for performance obligations are recognized as revenue over the estimated period of when the performance obligations are performed or deferred indefinitely until the undelivered performance obligation can be determined. As a biotechnology entity with unique and specialized delivered and undelivered performance obligations, we have been unable to demonstrate standalone value in our multiple element arrangements. Whenever we determine that an arrangement should be accounted for as a single unit of accounting, we determine the period over which the performance obligations will be performed and revenue will be recognized. Revenue is recognized using either a proportional performance or straight-line method. We recognize revenue using the proportional performance method when the level of effort required to complete our performance obligations under an arrangement can be reasonably estimated and such performance obligations are provided on a best-efforts basis. Direct labor hours or full-time equivalents are typically used as the measure of performance. The amount of revenue recognized under the proportional performance method is determined by multiplying the total payments under the contract, excluding royalties and payments contingent upon achievement of milestones, by the ratio of level of effort incurred to date to estimated total level of effort required to complete our performance obligations under the arrangement. Revenue is limited to the lesser of the cumulative amount of payments received or the cumulative amount of revenue earned, as determined using the proportional performance method, as of the period ending date. If we cannot reasonably estimate the level of effort to complete our performance obligations under an arrangement, we recognize revenue under the arrangement on a straight-line basis over the period we are expected to complete our performance obligations. Revenue is limited to the lesser of the cumulative amount of payments received or the cumulative amount of revenue earned, as determined using the straight-line method, as of the period ending date. Significant management judgment is required in determining the level of effort required under an arrangement and the period over which we are expected to complete our performance obligations under an arrangement. Steering committee services that are not inconsequential or perfunctory and that are determined to be performance obligations are combined with other research services or performance obligations required under an arrangement, if any, in determining the level of effort required in an arrangement and the period over which we expect to complete our aggregate performance obligations. Many of our collaboration agreements entitle us to additional payments upon the achievement of performance-based milestones. These milestones are generally categorized into three types; development milestones which are generally based on the advancement of our pipeline and initiation of clinical trials, regulatory milestones which are generally based on the submission, filing or approval of regulatory applications such as a new drug application in the United States, and commercialization milestones which are generally based on meeting specific thresholds of sales in certain geographic areas. If the achievement of a milestone is considered probable at the inception of the collaboration, the related milestone payment is included with other collaboration consideration, such as upfront fees and research funding, in our revenue model. Milestones that are tied to regulatory approval are not considered probable of being achieved until such approval is received. Milestones tied to counter-party performance are not included in our revenue model until the performance conditions are met. Upfront and ongoing development milestones are not subject to refund if the development activities are not successful. We perform an assessment to determine whether a substantive milestone exists at the inception of our collaborative arrangements. In evaluating if a milestone is substantive, we consider whether uncertainty exists as to the achievement of the milestone event at the inception of the arrangement, the achievement of the milestone involves substantive effort and can only be achieved based in whole or part on the performance or the occurrence of a specific outcome resulting from our performance, the amount of the milestone payment appears reasonable either in relation to the effort expected to be expended or to the projected enhancement of the value of the delivered items, there is any future performance required to earn the milestone, and the consideration is reasonable relative to all deliverables and payment terms in the arrangement. When a substantive milestone is achieved, the accounting rules permit us to recognize revenue related to the milestone payment in its entirety. To date, we have not recorded any substantive milestones under our collaborations because we have not identified any milestones that meet the required criteria listed above. We have deferred recognition of payments for achievement of non-substantive milestones and recognized revenue over the estimated period of performance applicable to each collaborative arrangement. As these milestones are achieved, we will recognize as revenue a portion of the milestone payment, which is equal to the percentage of the performance period completed when the milestone is achieved, multiplied by the amount of the milestone payment, upon achievement of such milestone. We will recognize the remaining portion of the milestone payment over the remaining performance period under the proportional performance method or on a straight-line basis. For revenue generating arrangements where we, as a vendor, provide consideration to a licensor or collaborator, as a customer, we apply the accounting standard that governs such transactions. This standard addresses the accounting for revenue arrangements where both the vendor and the customer make cash payments to each other for services and/or products. A payment to a customer is presumed to be a reduction of the selling price unless we receive an identifiable benefit for the payment and it can reasonably estimate the fair value of the benefit received. Payments to a customer that are deemed a reduction of selling price are recorded first as a reduction of revenue, to the extent of both cumulative revenue recorded to date and probable future revenues, which include any unamortized deferred revenue balances, under all arrangements with such customer, and then as an expense. Payments that are not deemed to be a reduction of selling price are recorded as an expense. We evaluate our collaborative agreements for proper classification in our consolidated statements of comprehensive loss based on the nature of the underlying activity. Transactions between collaborators recorded in our consolidated statements of comprehensive loss are recorded on either a gross or net basis, depending on the characteristics of the collaborative relationship. We generally reflect amounts due under our collaborative agreements related to cost-sharing of development activities as revenue. Amounts received prior to satisfying the above revenue recognition criteria are recorded as deferred revenue in the accompanying consolidated balance sheets. Although we follow detailed guidelines in measuring revenue, certain judgments affect the application of our revenue policy. For example, in connection with our existing collaboration agreements, we have recorded on our consolidated balance sheet short-term and long-term deferred revenue based on our best estimate of when such revenue will be recognized. Short-term deferred revenue consists of amounts that are expected to be recognized as revenue in the next 12 months. Amounts that we expect will not be recognized within the next 12 months are classified as long-term deferred revenue. However, this estimate is based on our current operating plan and, if our operating plan should change in the future, we may recognize a different amount of deferred revenue over the next 12-month period. The estimate of deferred revenue also reflects management’s estimate of the periods of our involvement in certain of our collaborations. Our performance obligations under these collaborations consist of participation on steering committees and the performance of other research and development services. In certain instances, the timing of satisfying these obligations can be difficult to estimate. Accordingly, our estimates may change in the future. Such changes to estimates would result in a change in revenue recognition amounts. If these estimates and judgments change over the course of these agreements, it may affect the timing and amount of revenue that we recognize and record in future periods. At December 31, 2015, we had short-term and long-term deferred revenue of $15.4 million and $53.0 million, respectively, related to our collaborations.
Income Taxes	Income Taxes We use the asset and liability method of accounting for income taxes. Under the asset and liability method, deferred tax assets and liabilities reflect the impact of temporary differences between amounts of assets and liabilities for financial reporting purposes and such amounts as measured under enacted tax laws. A valuation allowance is required to offset any net deferred tax assets if, based upon the available evidence, it is more likely than not that some or all of the deferred tax asset will not be realized. We account for uncertain tax positions using a “more-likely-than-not” threshold for recognizing and resolving uncertain tax positions. The evaluation of uncertain tax positions is based on factors that include, but are 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. Our policy is to accrue interest and penalties related to unrecognized tax positions in income tax expense. As of December 31, 2015, we have not recorded significant interest and penalty expense related to uncertain tax positions.
Research and Development Costs	Research and Development Costs We expense research and development costs as incurred. Included in research and development costs are wages, benefits and other operating costs, facilities, supplies, external services, clinical trial and manufacturing costs, and overhead directly related to our research and development operations, as well as costs to acquire technology licenses. We have entered into several license agreements for rights to utilize certain technologies. The terms of the licenses may provide for upfront payments, annual maintenance payments, milestone payments based upon certain specified events being achieved and royalties on product sales. We charge costs to acquire and maintain licensed technology that has not reached technological feasibility and does not have alternative future use to research and development expense as incurred. During the years ended December 31, 2015, 2014 and 2013, we charged to research and development expense costs associated with license fees of $3.5 million, $12.1 million and $8.0 million, respectively.
Accounting for Stock-Based Compensation	Accounting for Stock-Based Compensation We have stock incentive plans and an employee stock purchase plan under which we grant equity instruments. We account for all stock-based awards granted to employees at their fair value and generally recognize compensation expense over the vesting period of the award. Determining the amount of stock-based compensation to be recorded requires us to develop estimates of fair values of stock options as of the grant date. We calculate the grant date fair values using the Black-Scholes valuation model. Our expected stock price volatility assumption is based on the historical volatility of our publicly traded stock. For stock-based awards granted to non-employees, we generally recognize compensation expense over the vesting period of the award, which is generally the period during which services are rendered by such non-employees. At the end of each financial reporting period prior to vesting, we re-measure the value of these stock-based awards (as calculated using the Black-Scholes option-pricing model) using the then-current fair value of our common stock. Stock options granted by us to non-employees, other than members of our board of directors and scientific advisory board members, generally vest over the service period. The fair value of restricted stock awards granted to employees is based upon the quoted closing market price per share on the date of grant, adjusted for assumed forfeitures. Expense is recognized over the vesting period, commencing when we determine that it is probable that the awards will vest. For performance-based stock awards, expense is first recorded when we determine that the achievement of such performance conditions is deemed probable. This determination requires significant judgment by management. At the probable date, we record a cumulative expense catch-up, with remaining expense amortized over the remaining service period.
Comprehensive Loss	Comprehensive Loss Comprehensive loss is comprised of net loss and certain changes in stockholders’ equity that are excluded from net loss. We include foreign currency translation adjustments in other comprehensive loss as the functional currency is not the United States dollar. We include unrealized gains and losses on certain marketable securities in other comprehensive loss.
Net Loss Per Common Share	Net Loss Per Common Share We compute basic net loss per common share by dividing net loss by the weighted-average number of common shares outstanding. We compute diluted net loss per common share by dividing net loss by the weighted-average number of common shares and dilutive potential common share equivalents then outstanding. Potential common shares consist of shares issuable upon the exercise of stock options (using the treasury stock method), and unvested restricted stock awards. Because the inclusion of potential common shares would be anti-dilutive for all periods presented, diluted net loss per common share is the same as basic net loss per common share. The following table sets forth for the periods presented the potential common shares (prior to consideration of the treasury stock method) excluded from the calculation of net loss per common share because their inclusion would be anti-dilutive, in thousands: At December 31, 2015 2014 2013 Options to purchase common stock 9,960 8,169 8,713 Unvested restricted common stock 19 30 500 9,979 8,199 9,213
Segment Information	Segment Information We operate in a single reporting segment, the discovery, development and commercialization of RNAi therapeutics.
Subsequent Events	Subsequent Events We did not have any material recognized subsequent events. However, we did have the following nonrecognized subsequent event, which is more fully described in Note 7: • On February 10, 2016, we entered into an agreement to purchase land in Norton, Massachusetts for the construction of a manufacturing facility.
Recent Accounting Pronouncements	Recent Accounting Pronouncements In May 2014, the Financial Accounting Standards Board, or FASB, issued a new revenue recognition standard which amends revenue recognition principles and provides a single, comprehensive set of criteria for revenue recognition within and across all industries. The new standard provides a five step framework whereby revenue is recognized when promised goods or services are transferred to a customer at an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services. The standard also requires enhanced disclosures pertaining to revenue recognition in both interim and annual periods. In August 2015, the FASB deferred the effective date of the new revenue standard from January 1, 2017 to January 1, 2018. Early adoption is permitted any time after the original effective date, which for us is January 1, 2017. The standard allows for adoption using a full retrospective method or a modified retrospective method. We are currently evaluating the timing, method of adoption and the expected impact that the standard could have on our consolidated financial statements and related disclosures. In April 2015, the FASB amended its guidance on internal use software to clarify the accounting by customers for fees paid in a cloud computing arrangement. Under this guidance, if a cloud computing arrangement includes a software license, the software license element of the arrangement should be accounted for consistent with the customer’s accounting for other software licenses. If a cloud computing arrangement does not include a software license, the arrangement should be accounted for as a service contract. The new guidance became effective for us on January 1, 2016. The adoption of this guidance is not expected to have a material impact on our consolidated financial statements and related disclosures. In November 2015, the FASB issued final guidance that requires companies to classify all deferred tax assets and liabilities as noncurrent on the balance sheet instead of separating deferred taxes into current and noncurrent amounts. This guidance allows for adoption on either a prospective or retrospective basis. This guidance will be effective on January 1, 2017. Early adoption is permitted. We have elected to early adopt this guidance on a prospective basis and, as a result, prior consolidated balance sheets were not retrospectively adjusted. The adoption of this guidance did not have a material impact on our consolidated financial statements and related disclosures. In January 2016, the FASB issued new guidance on recognition and measurement of financial assets and financial liabilities. The new guidance will impact the accounting for equity investments, financial liabilities under the fair value option, and the presentation and disclosure requirements for financial instruments. All equity investments in unconsolidated entities (other than those accounted for under the equity method of accounting) will generally be measured at fair value with changes in fair value recognized through earnings. There will no longer be an available-for-sale classification (changes in fair value reported in other comprehensive income (loss)) for equity securities with readily determinable fair values. In addition, the FASB clarified the need for a valuation allowance on deferred tax assets resulting from unrealized losses on available-for-sale debt securities. In general, the new guidance will require modified retrospective application to all outstanding instruments, with a cumulative effect adjustment recorded to opening retained earnings. This guidance will be effective for us on January 1, 2018. We are currently evaluating the expected impact that the standard could have on our consolidated financial statements and related disclosures.

SUMMARY OF SIGNIFICANT ACCOUN21

SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES (Tables)	12 Months Ended
	Dec. 31, 2015
Concentrations of Credit Risk and Significant Customers	The following table summarizes customers that represent greater than 10% of our net revenues from collaborators, for the periods indicated: Year Ended December 31, 2015 2014 2013 Sanofi Genzyme 27 % * * MDCO 25 % 21 % * Takeda 22 % 43 % 47 % Monsanto 14 % 30 % 12 % Cubist * * 21 % The following table summarizes customers with amounts due that represent greater than 10% of our billed and unbilled collaboration receivables balance, at the periods indicated: At December 31, 2015 2014 Sanofi Genzyme 88 % 63 % Ionis 12 % * MDCO * 37 % * Represents 10% or less
Common Shares Excluded from the Calculation of Net Loss Per Common Share	The following table sets forth for the periods presented the potential common shares (prior to consideration of the treasury stock method) excluded from the calculation of net loss per common share because their inclusion would be anti-dilutive, in thousands: At December 31, 2015 2014 2013 Options to purchase common stock 9,960 8,169 8,713 Unvested restricted common stock 19 30 500 9,979 8,199 9,213

SIGNIFICANT AGREEMENTS (Tables)

SIGNIFICANT AGREEMENTS (Tables)	12 Months Ended
	Dec. 31, 2015
Revenue from Collaborators	The following table summarizes our total consolidated net revenues from collaborators, for the periods indicated, in thousands: Year Ended December 31, 2015 2014 2013 Sanofi Genzyme $ 11,005 $ 369 $ — MDCO 10,301 10,753 4,604 Takeda 8,867 21,973 21,973 Monsanto 5,621 14,985 5,640 Cubist — — 9,721 Other 5,303 2,481 5,229 Total net revenues from collaborators $ 41,097 $ 50,561 $ 47,167

FAIR VALUE MEASUREMENTS (Tables

FAIR VALUE MEASUREMENTS (Tables)	12 Months Ended
	Dec. 31, 2015
Fair Value of Assets Measured on a Recurring Basis	The following tables present information about our assets that are measured at fair value on a recurring basis at December 31, 2015 and 2014, and indicate the fair value hierarchy of the valuation techniques we utilized to determine such fair value, in thousands: Description At December 31, 2015 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Commercial paper $ 3,998 $ — $ 3,998 $ — Corporate notes 4,843 — 4,843 — U.S. government-sponsored enterprise securities 10,000 — 10,000 — Money market funds 148,612 148,612 — — Marketable securities (fixed income): Certificates of deposit 10,498 — 10,498 — Commercial paper 38,110 — 38,110 — Corporate notes 904,909 — 904,909 — Municipal debt securities 9,000 — 9,000 — U.S. government-sponsored enterprise securities 61,396 — 61,396 — U.S. treasury securities 76,143 — 76,143 — Marketable securities (Regulus equity holdings) 51,419 51,419 — — Restricted cash (money market funds) 1,471 1,471 — — Total $ 1,320,399 $ 201,502 $ 1,118,897 $ — Description At December 31, 2014 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Money market funds $ 56,203 $ 56,203 $ — $ — Marketable securities (fixed income): Certificates of deposit 24,300 — 24,300 — Commercial paper 40,796 — 40,796 — Corporate notes 662,545 — 662,545 — Municipal debt securities 9,005 — 9,005 — U.S. government-sponsored enterprise securities 64,856 — 64,856 — U.S. treasury securities 5,248 — 5,248 — Marketable securities (Regulus equity holdings) 94,583 94,583 — — Total $ 957,536 $ 150,786 $ 806,750 $ —

MARKETABLE SECURITIES (Tables)

MARKETABLE SECURITIES (Tables)	12 Months Ended
	Dec. 31, 2015
Summary of Fair Value Accumulated Other Comprehensive Income (Loss) and Intraperiod Tax Allocation in Regulus Available-for-Sale Marketable Securities	The following tables summarize the fair value, accumulated other comprehensive income (loss) and intraperiod tax allocation regarding our investment in Regulus available-for-sale marketable securities at December 31, 2015 and 2014, and for the activity recorded in the year, in thousands: Description At December 31, 2014 Sales of Regulus Shares During Year December 31, 2015 All Other Activity During Year December 31, 2015 Balance at December 31, 2015 Carrying value $ 11,935 $ — $ — $ 11,935 Accumulated other comprehensive income (loss), before tax 82,648 — (43,164 ) 39,484 Investment in equity securities of Regulus Therapeutics Inc., as reported $ 94,583 $ — $ (43,164 ) $ 51,419 Accumulated other comprehensive income (loss), before tax $ 82,648 $ — $ (43,164 ) $ 39,484 Intraperiod tax allocation recorded as a benefit from income taxes (32,792 ) — — (32,792 ) Accumulated other comprehensive income (loss), net of tax $ 49,856 $ — $ (43,164 ) $ 6,692 Description At December 31, 2013 Sales of Regulus Shares During Year December 31, 2014 All Other Activity During Year December 31, 2014 Balance at December 31, 2014 Carrying value $ 12,449 $ (514 ) $ — $ 11,935 Accumulated other comprehensive income (loss), before tax 33,003 (2,081 ) 51,726 82,648 Investment in equity securities of Regulus Therapeutics Inc., as reported $ 45,452 $ (2,595 ) $ 51,726 $ 94,583 Accumulated other comprehensive income (loss), before tax $ 33,003 $ (2,081 ) $ 51,726 $ 82,648 Intraperiod tax allocation recorded as a benefit from income taxes (13,267 ) — (19,525 ) (32,792 ) Accumulated other comprehensive income (loss), net of tax $ 19,736 $ (2,081 ) $ 32,201 $ 49,856
Summary of Company's Marketable Securities Excluding Regulus	The following tables summarize our marketable securities, other than our holdings in Regulus noted above, at December 31, 2015 and 2014, in thousands: At December 31, 2015 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 10,498 $ — $ — $ 10,498 Commercial paper 38,113 — (3 ) 38,110 Corporate notes 907,119 4 (2,214 ) 904,909 Municipal debt securities 9,000 — — 9,000 U.S. government-sponsored enterprise securities 61,463 24 (91 ) 61,396 U.S. treasury securities 76,186 4 (47 ) 76,143 Total $ 1,102,379 $ 32 $ (2,355 ) $ 1,100,056 At December 31, 2014 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 24,300 $ — $ — $ 24,300 Commercial paper 40,785 11 — 40,796 Corporate notes 663,554 14 (1,023 ) 662,545 Municipal debt securities 9,002 3 — 9,005 U.S. government-sponsored enterprise securities 64,948 — (92 ) 64,856 U.S. treasury securities 5,254 — (6 ) 5,248 Total $ 807,843 $ 28 $ (1,121 ) $ 806,750
Summary of Available-For-Sale Debt Securities by Contractual Maturity	The following table summarizes our available-for-sale debt securities by contractual maturity, at December 31, 2015, in thousands: At December 31, 2015 Amortized Cost Fair Value Less than one year $ 849,288 $ 848,217 Greater than one year but less than two years 253,091 251,839 Total $ 1,102,379 $ 1,100,056

PROPERTY AND EQUIPMENT, NET (Ta

PROPERTY AND EQUIPMENT, NET (Tables)	12 Months Ended
	Dec. 31, 2015
Property and Equipment, Net	Property and equipment consist of the following at December 31, 2015 and 2014, in thousands: At December 31, Useful Life 2015 2014 Laboratory equipment 5 years $ 33,558 $ 28,559 Computer equipment and software 3 years 5,732 4,440 Furniture and fixtures 5 years 2,906 1,999 Leasehold improvements * 35,825 30,853 Construction in progress — 1,285 1,982 79,306 67,833 Less: accumulated depreciation (51,494 ) (46,093 ) $ 27,812 $ 21,740 * Shorter of asset life or lease term

COMMITMENTS AND CONTINGENCIES (

COMMITMENTS AND CONTINGENCIES (Tables)	12 Months Ended
	Dec. 31, 2015
Fixed, Estimated and Cancelable Payments under Existing License Agreements	At December 31, 2015, we were committed to make the following fixed, estimated and cancelable payments under existing license agreements, in thousands: Year Ending December 31, 2016 $ 8,734 2017 741 2018 751 2019 761 2020 761 Thereafter 7,819 Total $ 19,567
Future Minimum Payments Under Non-cancelable Leases	Future minimum payments under our non-cancelable facility leases are approximately as follows, in thousands: Year Ending December 31, 2016 $ 11,521 2017 13,152 2018 13,055 2019 30,955 2020 33,035 Thereafter 350,148 Total $ 451,866

STOCK INCENTIVE PLANS (Tables)

STOCK INCENTIVE PLANS (Tables)	12 Months Ended
	Dec. 31, 2015
Summary of Stock-Based Compensation Expense by Type of Award	The following table summarizes stock-based compensation expense by type of award during the three years ended December 31, 2015, in thousands: 2015 2014 2013 Stock-based compensation expense by type of award: Stock options $ 43,078 $ 24,603 $ 13,839 Performance-based stock options — 4,960 — Restricted stock awards 555 1,068 3,420 ESPP share issuances 694 392 261 Non-employee stock options 1,456 2,038 3,183 $ 45,783 $ 33,061 $ 20,703
Summary of Unrecognized Stock-Based Compensation Expense, Net of Estimated Forfeitures	The following table summarizes our unrecognized stock-based compensation expense, net of estimated forfeitures, at December 31, 2015 by type of awards and the weighted-average period over which that expense is expected to be recognized: At December 31, 2015 Unrecognized Expense, Net of Estimated Forfeitures Weighted-average Recognition Period (in thousands) (in years) Type of award: Time-based stock options $ 128,073 2.87 Performance-based stock options 62,000 * Restricted stock awards 1,108 2.54 ESPP share issuances 350 0.33 * Performance-based stock options are recorded as expense when vesting events are determined to be probable.
Valuation Assumptions for Stock Options	2015 2014 2013 Risk-free interest rate 1.0-2.0 % 1.7-2.3 % 1.0-2.0 % Expected dividend yield — — — Expected option life 3.5-7.5 years 5.5-7.5 years 5.6 years Expected volatility 53-60 % 53-57 % 55-56 %
Stock Option Activity	The following table summarizes the activity of our stock option plans, excluding performance-based stock options: Number of Options (in thousands) Weighted- Exercise Price Weighted- average Remaining Contractual Term (in Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2014 7,530 $ 33.46 Granted 2,403 99.20 Exercised (1,438 ) 19.64 Cancelled (177 ) 70.67 Outstanding, December 31, 2015 8,318 $ 54.05 6.85 $ 352,646 Exercisable at December 31, 2015 4,699 $ 30.61 5.31 $ 299,365 Vested or expected to vest at December 31, 2015 8,048 $ 52.89 6.78 $ 349,933
Performance-based Stock Options
Stock Option Activity	The following table summarizes the activity of our performance-based stock options: Number of Options (in thousands) Weighted- Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2014 639 $ 73.15 Granted 1,072 91.07 Exercised (29 ) 63.00 Cancelled (40 ) 77.64 Outstanding, December 31, 2015 1,642 $ 84.92 9.15 $ 16,244 Exercisable at December 31, 2015 120 $ 63.00 7.84 $ 3,741

INCOME TAXES (Tables)

INCOME TAXES (Tables)	12 Months Ended
	Dec. 31, 2015
Components of Loss before Income Tax, Domestic and Foreign	The domestic and foreign components of loss before income taxes are as follows, in thousands: 2015 2014 2013 Domestic $ (245,681 ) $ (372,137 ) $ (81,109 ) Foreign (44,392 ) (28,467 ) (10,811 ) Loss before income taxes $ (290,073 ) $ (400,604 ) $ (91,920 )
Schedule of Deferred Tax Assets and Liabilities	Components of the net deferred tax (liability) asset at December 31, 2015 and 2014 are as follows, in thousands: 2015 2014 Deferred tax assets: Net operating loss carryforwards $ 253,908 $ 176,789 Research and development credits 61,424 38,204 AMT credits 788 788 Foreign tax credits 3,196 3,196 Capitalized research and development and start-up costs 19,075 19,246 Deferred revenue 17,279 14,273 Deferred compensation 33,397 24,516 Intangible assets 16,181 17,637 Partnership interest 689 689 Other 6,508 5,871 Total deferred tax assets 412,445 301,209 Deferred tax liabilities: Unrealized gain on available-for-sale securities (14,947 ) (32,793 ) Deferred tax asset valuation allowance (397,498 ) (268,416 ) Net deferred tax liability $ — $ —
Benefit from Income Taxes	The benefit from income taxes for the years ended December 31, 2015, 2014 and 2013 is as follows, in thousands: 2015 2014 2013 U.S.: Current $ — $ — $ 34 Deferred — (40,209 ) (2,695 ) Total U.S. — (40,209 ) (2,661 ) Foreign: Current — — — Deferred — — (34 ) Total Foreign — — (34 ) Benefit from income taxes $ — $ (40,209 ) $ (2,695 )
Effective Income Tax Rate	Our effective income tax rate differs from the statutory federal income tax rate as follows for the years ended December 31, 2015, 2014 and 2013: 2015 2014 2013 At U.S. federal statutory rate 35.0 % 35.0 % 35.0 % State taxes, net of federal effect 4.0 1.8 4.3 Stock-based compensation (1.1 ) (0.2 ) 0.8 Tax credits 8.0 3.5 8.5 Orphan drug credit (2.0 ) (0.6 ) (2.7 ) Other permanent items (0.1 ) — (0.3 ) Foreign rate differential (5.4 ) (2.5 ) (4.1 ) In-process research and development — (19.4 ) — Tax basis in intangible assets as a result of Sirna transaction — 4.2 — Valuation allowance (38.4 ) (11.8 ) (38.5 ) Effective income tax rate — % 10.0 % 3.0 %

ACCRUED EXPENSES (Tables)

ACCRUED EXPENSES (Tables)	12 Months Ended
	Dec. 31, 2015
Accrued Expenses	Accrued expenses consist of the following at December 31, 2015 and 2014, in thousands: At December 31, 2015 2014 Compensation and related $ 11,157 $ 7,357 Clinical trial and manufacturing 10,885 5,548 Consulting and professional services 892 3,886 Pre-clinical 899 3,081 Other 4,965 3,808 $ 28,798 $ 23,680

QUARTERLY FINANCIAL DATA (UNA30

QUARTERLY FINANCIAL DATA (UNAUDITED) (Tables)	12 Months Ended
	Dec. 31, 2015
Schedule of Quarterly Financial Information	The following information has been derived from unaudited consolidated financial statements that, in the opinion of management, include all recurring adjustments necessary for a fair statement of such information. Three Months Ended March 31, 2015 June 30, 2015 September 30, 2015 December 31, 2015 (In thousands, except per share data) Revenues $ 18,537 $ 8,685 $ 6,324 $ 7,551 Operating expenses 70,759 81,629 84,654 100,063 Net loss $ (50,777 ) $ (71,783 ) $ (76,792 ) $ (90,721 ) Net loss per common share — basic and diluted $ (0.62 ) $ (0.85 ) $ (0.91 ) $ (1.07 ) Weighted-average common shares — basic and diluted 82,074 84,353 84,633 84,871 Three Months Ended March 31, 2014 June 30, 2014 September 30, 2014 December 31, 2014 (In thousands, except per share data) Revenues $ 8,275 $ 7,295 $ 10,972 $ 24,019 Operating expenses 277,339 52,300 56,171 69,731 Net loss $ (250,943 ) $ (44,074 ) $ (43,989 ) $ (21,389 ) Net loss per common share — basic and diluted $ (3.70 ) $ (0.58 ) $ (0.58 ) $ (0.28 ) Weighted-average common shares — basic and diluted 67,786 75,835 76,408 76,957

Significant Agreements - Additi

Significant Agreements - Additional Information (Detail)

Feb. 01, 2016USD ($)shares

Jan. 22, 2015USD ($)shares

Mar. 05, 2014USD ($)$ / sharesshares

Jan. 14, 2014USD ($)

Oct. 31, 2012USD ($)

Jan. 31, 2015USD ($)$ / sharesshares

Sep. 30, 2014USD ($)

Mar. 31, 2014USD ($)shares

Feb. 28, 2014USD ($)Right$ / sharesshares

Jan. 31, 2014USD ($)

Feb. 28, 2013USD ($)

Jan. 31, 2013$ / sharesshares

Aug. 31, 2012USD ($)

Jun. 30, 2008USD ($)

Mar. 31, 2004USD ($)Licenses

Dec. 31, 2014USD ($)

Jun. 30, 2014USD ($)shares

Dec. 31, 2013USD ($)

Feb. 28, 2014$ / shares

Dec. 31, 2015USD ($)Program

Dec. 31, 2014USD ($)

Dec. 31, 2013USD ($)

Dec. 31, 2012

Mar. 31, 2015

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Issuance of common stock, net of offering costs (in shares) | shares

5,447,368

9,200,000

Proceeds from issuance of common stock to Genzyme

$ 89,018,000

$ 723,037,000

Common stock price | $ / shares

$ 95

$ 20.13

Provision for (Benefit from) income taxes

(40,209,000)

$ (2,695,000)

Asset acquisition cash consideration

25,000,000

Issuance of common stock in connection with an asset acquisition

195,766,000

Accrued liabilities, current

$ 23,680,000

28,798,000

23,680,000

In-process research and development

$ 199,300,000

220,766,000

In-process research and development credit

$ 3,900,000

Sanofi Genzyme Corporation

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Percentage ownership interest owned by noncontrolling owners

12.00%

Research and Development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

License fee

$ 3,500,000

12,100,000

8,000,000

Ionis

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative agreement termination notice period

90 days

Minimum | Monsanto Alliance

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Estimated range of expiration for fundamental patents

2,016

Maximum | Monsanto Alliance

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Estimated range of expiration for fundamental patents

2,025

Product Alliances | MDCO

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront fee received

$ 25,000,000

Maximum number of potential future milestones

180,000,000

Amount earned upon achievement of milestone

10,000,000

Next potential milestone payment

$ 20,000,000

Deferred revenue

18,300,000

Potential future payment for the achievement of certain development milestones

30,000,000

Potential future payment for the achievement of specified commercialization milestones

100,000,000

Potential future payment for the achievement of specified regulatory milestones

$ 50,000,000

Revenue recognizing period

5 years

Product Alliances | MDCO | Licensing Agreements

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Revenue from reimbursement due from collaborator

$ 3,800,000

4,800,000

Product Alliances | Minimum | MDCO

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Estimated range of expiration for fundamental patents

2,016

Product Alliances | Maximum | MDCO

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Estimated range of expiration for fundamental patents

2,028

Platform Alliances | Joint Technology Transfer Committee

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Maximum life of collaboration committee

7 years

Platform Alliances | Joint Delivery Collaboration Committee

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Maximum life of collaboration committee

7 years

Platform Alliances | Monsanto Alliance

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront fee received

$ 29,200,000

Maximum number of potential future milestones

5,000,000

Amount earned upon achievement of milestone

$ 4,000,000

Final required milestone payment cancelled

$ 1,000,000

Next potential milestone payment

0

Deferred revenue

$ 5,000,000

Revenue recognizing period

5 years

Period of exclusivity in the collaboration

10 years

Deferred revenue, potential refundable amount

$ 5,000,000

Period for services under contract

5 years

Contractual agreement obligation period

30 months

Platform Alliances | Monsanto Alliance | Amended Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Deferred revenue

$ 16,800,000

Platform Alliances | Takeda

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront fee received

100,000,000

Maximum number of potential future milestones

171,000,000

Next potential milestone payment

2,000,000

Deferred revenue

0

Potential future payment for the achievement of certain development milestones

26,000,000

Potential future payment for the achievement of specified commercialization milestones

105,000,000

Potential future payment for the achievement of specified regulatory milestones

$ 40,000,000

Granted period of royalty bearing license

5 years

Milestone fees to company upon achievement of specified technology transfer milestones

$ 50,000,000

$ 50,000,000

License and collaborations agreements, prior written notice period before termination

180 days

Platform Alliances | Minimum | Takeda

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Estimated range of expiration for fundamental patents

2,016

Platform Alliances | Maximum | Takeda

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Estimated range of expiration for fundamental patents

2,025

Discovery and Development Alliances | Ionis

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of programs Providing exclusive RNA therapeutic license rights | Program

4

Potential future payment upon the occurrence of achievement of specified development and regulatory milestones

$ 3,400,000

Number of licensed products | Licenses

10

Additional number of licensed products | Licenses

1

Discovery and Development Alliances | Ionis | Research and Development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

License fee

$ 1,900,000

7,700,000

700,000

License fees incurred but not yet paid

200,000

Discovery and Development Alliances | Ionis | Up Front Payment | Research and Development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

License fee

$ 5,000,000

Discovery and Development Alliances | Ionis | Milestone Payments | Research and Development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

License fee

3,400,000

Discovery and Development Alliances | Ionis | Therapeutic target

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront fee received

$ 500,000

Sirna Therapeutics

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Common stock price | $ / shares

$ 81.36

Asset acquisition cash consideration

$ 25,000,000

Issuance of common stock in connection with an asset acquisition (in shares) | shares

2,142,037

378,007

Issuance of common stock in connection with an asset acquisition

$ 174,300,000

Asset acquisition consideration upon achievement of milestones

$ 105,000,000

Sirna Therapeutics | Intellectual Property

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Asset acquisition consideration upon achievement of milestones

10,000,000

Sirna Therapeutics | Clinical Development and Regulatory Milestone

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Asset acquisition consideration upon achievement of milestones

40,000,000

Sirna Therapeutics | Commercial Milestones

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Asset acquisition consideration upon achievement of milestones

$ 65,000,000

Sirna Therapeutics | Stock Issuance Obligations

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Accrued liabilities, current

$ 25,400,000

Sanofi Genzyme

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Amount earned upon achievement of milestone

$ 25,000,000

Issuance of common stock, net of offering costs (in shares) | shares

344,448

8,766,338

Proceeds from issuance of common stock to Genzyme

$ 23,000,000

$ 700,000,000

Voting percentage

20.00%

20.00%

Minimum percentage of ownership interest terminate

7.50%

Agreement lock-up period

6 months

Percentage of acquired outstanding common stock for Genzyme to appoint individual to board of directors

20.00%

Common stock price | $ / shares

$ 85.72

$ 85.72

Fair value of shares issued

$ 751,500,000

Excess of fair value over cash received for stock issuance

51,500,000

Provision for (Benefit from) income taxes

$ (15,200,000)

$ (20,700,000)

Revenue from reimbursement due from collaborator

33,900,000

Sanofi Genzyme | Minimum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Agreement to acquire outstanding shares of common stock percentage

5.00%

5.00%

Percentage of ownership interest

30.00%

Sanofi Genzyme | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Agreement to acquire outstanding shares of common stock percentage

30.00%

30.00%

Sanofi Genzyme | Extension on Lock-up Period

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Agreement lock-up period

2 years

Sanofi Genzyme | Product Alliances

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront fee received

$ 22,500,000

Deferred revenue

$ 33,500,000

$ 29,500,000

$ 33,500,000

Performance period

6 years

Sanofi Genzyme | Product Alliances | Phase Two Clinical Trial ALN-TTR

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Amount earned upon achievement of milestone

7,000,000

Sanofi Genzyme | Product Alliances | Phase Three Clinical Trial

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Amount earned upon achievement of milestone

$ 4,000,000

Sanofi Genzyme | Regional Collaboration Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Maximum number of potential future milestones

$ 75,000,000

Percentage of sharing in development cost

20.00%

Potential future payment for the achievement of certain development milestones

$ 55,000,000

Potential future payment for the achievement of specified commercialization milestones

$ 20,000,000

Royalty rate

20.00%

Sanofi Genzyme | Regional Collaboration Product | Patisiran

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Potential future payment for the achievement of certain development milestones

$ 50,000,000

Sanofi Genzyme | Regional Collaboration Product | Minimum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Potential milestone payments to be earned

5,000,000

Sanofi Genzyme | Regional Collaboration Product | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Potential milestone payments to be earned

20,000,000

Sanofi Genzyme | Regional Collaboration Product | Phase Three Clinical Trial

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Potential milestone payments to be earned

25,000,000

Sanofi Genzyme | Co-developed/ Co-promoted Collaboration Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Maximum number of potential future milestones

$ 75,000,000

Percentage of sharing in development cost

50.00%

Royalty rate

20.00%

Sanofi Genzyme | Co-developed/ Co-promoted Collaboration Product | Minimum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Potential milestone payments to be earned

$ 5,000,000

Sanofi Genzyme | Co-developed/ Co-promoted Collaboration Product | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Potential milestone payments to be earned

$ 25,000,000

Sanofi Genzyme | Global Collaboration Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Maximum number of potential future milestones

$ 200,000,000

Percentage of sharing in development cost

100.00%

Potential future payment for the achievement of certain development milestones

$ 60,000,000

Potential future payment for the achievement of specified commercialization milestones

$ 140,000,000

Royalty rate

20.00%

Sanofi Genzyme | Investors

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of demand rights to conduct registered underwritten public offering | Right

3

Sanofi Genzyme | Concurrent Private Placement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Issuance of common stock, net of offering costs (in shares) | shares

744,566

Proceeds from issuance of common stock to Genzyme

$ 70,700,000

Sanofi Genzyme | Compensatory Purposes

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Issuance of common stock, net of offering costs (in shares) | shares

196,251

Proceeds from issuance of common stock to Genzyme

$ 18,300,000

Sanofi Genzyme | Subsequent Event | Compensatory Purposes

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Issuance of common stock, net of offering costs (in shares) | shares

205,030

Proceeds from issuance of common stock to Genzyme

$ 14,300,000

Sanofi Genzyme | Following the two-year anniversary

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of trailing days on which average is calculated

10 days

Sanofi Genzyme | Following the two-year anniversary | Minimum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Percentage of market price per share of common stock compared to share of common stock at closing of stock purchase

100.00%

Sanofi Genzyme | Following the two-year anniversary | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Percentage of sale of initial shares

25.00%

25.00%

Customers that Represent Greate

Customers that Represent Greater than Ten Percent of Net Revenues from Collaborators (Detail) - Revenue from Rights Concentration Risk - Net Revenues	12 Months Ended
	Dec. 31, 2015		Dec. 31, 2014		Dec. 31, 2013
Takeda
Concentration Risk [Line Items]
Concentration risk percentage	22.00%		43.00%		47.00%
Monsanto
Concentration Risk [Line Items]
Concentration risk percentage	14.00%		30.00%		12.00%
MDCO
Concentration Risk [Line Items]
Concentration risk percentage	25.00%		21.00%			[1]
Cubist
Concentration Risk [Line Items]
Concentration risk percentage		[1]		[1]	21.00%
Sanofi Genzyme
Concentration Risk [Line Items]
Concentration risk percentage	27.00%			[1]		[1]
[1]	Represents 10% or less

Customers that Represent Grea33

Customers that Represent Greater than Ten Percent of Billed and Unbilled Collaboration Receivables (Detail) - Accounts Receivable - Credit Concentration Risk [Member]	12 Months Ended
	Dec. 31, 2015		Dec. 31, 2014
Sanofi Genzyme
Concentration Risk [Line Items]
Concentration risk percentage	88.00%		63.00%
MDCO
Concentration Risk [Line Items]
Concentration risk percentage		[1]	37.00%
Ionis
Concentration Risk [Line Items]
Concentration risk percentage	12.00%			[1]
[1]	Represents 10% or less

Summary of Significant Accoun34

Summary of Significant Accounting Policies - Additional Information (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Significant Accounting Policies [Line Items]
Gain on sale of available for sale securities	$ 0	$ 2,081
Marketable securities classified as cash equivalents, maximum original maturity	90 days
Policy for marketable securities	90 days
Deferred revenue, current	$ 15,352	23,871
Deferred revenue, net of current portion	52,965	42,983
Research and Development
Significant Accounting Policies [Line Items]
License fee	$ 3,500	$ 12,100	$ 8,000

Potential Common Shares Common

Potential Common Shares Common Shares Excluded from Calculation of Net Loss Per Common Share (Detail) - shares shares in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities excluded from computation of earnings per share	9,979	8,199	9,213
Employee Stock Option
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities excluded from computation of earnings per share	9,960	8,169	8,713
Restricted stock awards
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities excluded from computation of earnings per share	19	30	500

Revenue from Collaborators (Det

Revenue from Collaborators (Detail) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2015	Sep. 30, 2015	Jun. 30, 2015	Mar. 31, 2015	Dec. 31, 2014	Sep. 30, 2014	Jun. 30, 2014	Mar. 31, 2014	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators	$ 7,551	$ 6,324	$ 8,685	$ 18,537	$ 24,019	$ 10,972	$ 7,295	$ 8,275	$ 41,097	$ 50,561	$ 47,167
Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators									11,005	369
MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators									10,301	10,753	4,604
Takeda
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators									8,867	21,973	21,973
Monsanto
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators									5,621	14,985	5,640
Cubist
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators											9,721
Other
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators									$ 5,303	$ 2,481	$ 5,229

Fair Value Measured on Recurrin

Fair Value Measured on Recurring Basis (Detail) - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	$ 1,100,056	$ 806,750
Recurring
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale equity securities, Fair value disclosure	51,419	94,583
Restricted cash (money market funds)	1,471
Total	1,320,399	957,536
Recurring | Certificates of deposit
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	10,498	24,300
Recurring | Commercial paper
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	3,998
Available for sale debt securities, Fair value disclosure	38,110	40,796
Recurring | Corporate notes
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	4,843
Available for sale debt securities, Fair value disclosure	904,909	662,545
Recurring | Municipal debt securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	9,000	9,005
Recurring | U.S. government-sponsored enterprise securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	10,000
Available for sale debt securities, Fair value disclosure	61,396	64,856
Recurring | U.S. treasury securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	76,143	5,248
Recurring | Money Market Funds
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	148,612	56,203
Quoted Prices in Active Markets (Level 1) | Recurring
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale equity securities, Fair value disclosure	51,419	94,583
Restricted cash (money market funds)	1,471
Total	201,502	150,786
Quoted Prices in Active Markets (Level 1) | Recurring | Money Market Funds
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	148,612	56,203
Significant Observable Inputs (Level 2) | Recurring
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total	1,118,897	806,750
Significant Observable Inputs (Level 2) | Recurring | Certificates of deposit
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	10,498	24,300
Significant Observable Inputs (Level 2) | Recurring | Commercial paper
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	3,998
Available for sale debt securities, Fair value disclosure	38,110	40,796
Significant Observable Inputs (Level 2) | Recurring | Corporate notes
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	4,843
Available for sale debt securities, Fair value disclosure	904,909	662,545
Significant Observable Inputs (Level 2) | Recurring | Municipal debt securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	9,000	9,005
Significant Observable Inputs (Level 2) | Recurring | U.S. government-sponsored enterprise securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	10,000
Available for sale debt securities, Fair value disclosure	61,396	64,856
Significant Observable Inputs (Level 2) | Recurring | U.S. treasury securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	$ 76,143	$ 5,248

Summary of Fair Value Accumulat

Summary of Fair Value Accumulated Other Comprehensive Income (Loss) and Intraperiod Tax Allocation in Available-for-Sale Marketable Securities (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Schedule of Available-for-sale Securities [Line Items]
Intraperiod tax allocation recorded as a benefit from income taxes	$ (14,947)	$ (32,793)
Accumulated other comprehensive income (loss), net of tax	(44,394)	31,127	$ 4,055
Regulus Therapeutics Inc
Schedule of Available-for-sale Securities [Line Items]
Carrying value	11,935	11,935	12,449
Accumulated other comprehensive income (loss), before tax	39,484	82,648	33,003
Investment in equity securities of Regulus Therapeutics Inc., as reported	51,419	94,583	45,452
Accumulated other comprehensive income (loss), before tax	39,484	82,648	33,003
Intraperiod tax allocation recorded as a benefit from income taxes	(32,792)	(32,792)	(13,267)
Accumulated other comprehensive income (loss), net of tax	6,692	49,856	$ 19,736
Regulus Therapeutics Inc | Sales of Regulus Shares
Schedule of Available-for-sale Securities [Line Items]
Carrying value		(514)
Accumulated other comprehensive income (loss), before tax		(2,081)
Investment in equity securities of Regulus Therapeutics Inc., as reported		(2,595)
Accumulated other comprehensive income (loss), before tax		(2,081)
Accumulated other comprehensive income (loss), net of tax		(2,081)
Regulus Therapeutics Inc | All Other Activity
Schedule of Available-for-sale Securities [Line Items]
Accumulated other comprehensive income (loss), before tax	(43,164)	51,726
Investment in equity securities of Regulus Therapeutics Inc., as reported	(43,164)	51,726
Accumulated other comprehensive income (loss), before tax	(43,164)	51,726
Intraperiod tax allocation recorded as a benefit from income taxes		(19,525)
Accumulated other comprehensive income (loss), net of tax	$ (43,164)	$ 32,201

Summary of Company's Marketable

Summary of Company's Marketable Securities (Detail) - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	$ 1,102,379	$ 807,843
Gross Unrealized Gains	32	28
Gross Unrealized Losses	(2,355)	(1,121)
Fair Value	1,100,056	806,750
Certificates of deposit
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	10,498	24,300
Fair Value	10,498	24,300
Commercial paper
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	38,113	40,785
Gross Unrealized Gains		11
Gross Unrealized Losses	(3)
Fair Value	38,110	40,796
Corporate notes
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	907,119	663,554
Gross Unrealized Gains	4	14
Gross Unrealized Losses	(2,214)	(1,023)
Fair Value	904,909	662,545
Municipal debt securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	9,000	9,002
Gross Unrealized Gains		3
Fair Value	9,000	9,005
U.S. government-sponsored enterprise securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	61,463	64,948
Gross Unrealized Gains	24
Gross Unrealized Losses	(91)	(92)
Fair Value	61,396	64,856
U.S. treasury securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	76,186	5,254
Gross Unrealized Gains	4
Gross Unrealized Losses	(47)	(6)
Fair Value	$ 76,143	$ 5,248

Summary of Available-For-Sale D

Summary of Available-For-Sale Debt Securities by Contractual Maturity (Detail) - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Amortized Cost
Less than one year	$ 849,288
Greater than one year but less than two years	253,091
Amortized Cost	1,102,379	$ 807,843
Fair Value
Less than one year	848,217
Greater than one year but less than two years	251,839
Total	$ 1,100,056	$ 806,750

Property and Equipment (Detail)

Property and Equipment (Detail) - USD ($) $ in Thousands		12 Months Ended
		Dec. 31, 2015	Dec. 31, 2014
Property, Plant and Equipment [Line Items]
Laboratory equipment		$ 33,558	$ 28,559
Computer equipment and software		5,732	4,440
Furniture and fixtures		2,906	1,999
Leasehold improvements		35,825	30,853
Construction in progress		1,285	1,982
Property and Equipment Gross		79,306	67,833
Less: accumulated depreciation		(51,494)	(46,093)
Property and Equipment Net		$ 27,812	$ 21,740
Laboratory equipment
Property, Plant and Equipment [Line Items]
Property, and equipment, useful life		5 years
Computer equipment and software
Property, Plant and Equipment [Line Items]
Property, and equipment, useful life		3 years
Furniture and Fixtures
Property, Plant and Equipment [Line Items]
Property, and equipment, useful life		5 years
Leasehold improvements
Property, Plant and Equipment [Line Items]
Property, and equipment, useful life	[1]
[1]	Shorter of asset life or lease term

Property and Equipment Net - Ad

Property and Equipment Net - Additional Information (Detail) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Property, Plant and Equipment [Line Items]
Depreciation expense	$ 6.7	$ 5	$ 6.1

Commitments and Contingencies -

Commitments and Contingencies - Additional Information (Detail) $ in Thousands

Feb. 10, 2016USD ($)a

Oct. 14, 2015USD ($)

May. 31, 2015USD ($)ft²RenewalOptions$ / ft²

Apr. 30, 2015USD ($)ft²RenewalOptions

Mar. 31, 2014

Dec. 31, 2015USD ($)ft²

Sep. 30, 2015USD ($)

Jun. 30, 2015USD ($)

Mar. 31, 2015USD ($)

Dec. 31, 2014USD ($)

Sep. 30, 2014USD ($)

Jun. 30, 2014USD ($)

Mar. 31, 2014USD ($)

Dec. 31, 2013USD ($)

Dec. 31, 2015USD ($)ft²RenewalOptions

Dec. 31, 2014USD ($)

Dec. 31, 2013USD ($)

Dec. 31, 2012USD ($)

Commitments and Contingencies [Line Items]

Future purchase commitments

$ 150,200

$ 150,200

Future purchase commitments expected to be incurred in 2016

87,500

87,500

Future purchase commitments expected to be incurred past 2016

$ 62,700

$ 62,700

Lease extension period

5 years

Area of office and laboratory space held under operating lease | ft²

15,000

15,000

Lease expiration date

Aug. 31, 2017

Number of lease extension options | RenewalOptions

2

Lease incentive received

$ 400

$ 1,900

$ 200

$ 400

$ 1,900

$ 200

Rent expense

10,500

8,900

4,900

Litigation, motion filed for reimbursement of costs and fees

$ 8,000

Operating expenses

100,063

$ 84,654

$ 81,629

$ 70,759

$ 69,731

$ 56,171

$ 52,300

$ 277,339

337,105

$ 455,541

140,109

Other Assets

Commitments and Contingencies [Line Items]

Restricted cash

$ 1,500

$ 1,500

Tekmira Restructured Cross-License Agreement

Commitments and Contingencies [Line Items]

Operating expenses

$ 65,000

Future milestone payments

$ 5,000

Milestone paid

$ 5,000

Tekmira Restructured Cross-License Manufacturing Contracts and Service Agreement

Commitments and Contingencies [Line Items]

One time settlement payment

30,000

Tekmira Restructured Cross-License Buy-Down

Commitments and Contingencies [Line Items]

One time settlement payment

35,000

Contingent milestone payments

$ 10,000

Third Street

Commitments and Contingencies [Line Items]

Lease extension period

5 years

Lease extended expiration date

Sep. 30, 2021

Area of office and laboratory space held under operating lease | ft²

129,000

129,000

Lease expiration date

2016-09

Optional | Operating Lease Amendment | Third Street

Commitments and Contingencies [Line Items]

Lease extension period

5 years

BMR Six Seven Five West Kendall Lease

Commitments and Contingencies [Line Items]

Area of office and laboratory space held under operating lease | ft²

295,000

Number of lease extension options | RenewalOptions

2

Lease term

15 years

Lease renewal options period

5 years

Facility lease annual rent for the first year

$ 19,800

Facility lease percentage of annual rent increase after first year

3.00%

Cost of base building and tenant improvement

$ 56,100

Leased and occupied rentable area percentage

70.00%

BMR Six Seven Five West Kendall Lease | Minimum

Commitments and Contingencies [Line Items]

Remaining lease term

10 years

101 Main Street Leases

Commitments and Contingencies [Line Items]

Area of office and laboratory space held under operating lease | ft²

72,000

Operating lease annual rent for the first year

$ 1,700

Operating lease annual rent increase per square foot | $ / ft²

1

101 Main Street Leases | 10th Floor Lease

Commitments and Contingencies [Line Items]

Number of lease extension options | RenewalOptions

1

Operating lease term

4 years

Operating lease renewal options period

5 years

101 Main Street Leases | Additional Lease

Commitments and Contingencies [Line Items]

Number of lease extension options | RenewalOptions

1

Operating lease term

5 years 6 months

Operating lease renewal options period

5 years

Operating lease annual rent for the first year

$ 3,500

20 Commerce LLC | Subsequent Event

Commitments and Contingencies [Line Items]

Undeveloped land to be purchased as per agreement | a

12

Aggregate amount of cash payable to acquire land

$ 8,000

Future Minimum Payments Under N

Future Minimum Payments Under Non-cancelable Leases (Detail) $ in Thousands	Dec. 31, 2015USD ($)
Licenses Agreements [Line Items]
2,016	$ 8,734
2,017	741
2,018	751
2,019	761
2,020	761
Thereafter	7,819
Total	$ 19,567

Future Minimum Lease Payments u

Future Minimum Lease Payments under Non-Cancelable Lease (Detail) $ in Thousands	Dec. 31, 2015USD ($)
Leases Future Minimum Payments [Line Items]
2,016	$ 11,521
2,017	13,152
2,018	13,055
2,019	30,955
2,020	33,035
Thereafter	350,148
Total	$ 451,866

Stockholders Equity - Additiona

Stockholders Equity - Additional Information (Detail) - USD ($) $ / shares in Units, $ in Thousands	1 Months Ended		12 Months Ended
	Jan. 31, 2015	Jan. 31, 2013	Dec. 31, 2015	Dec. 31, 2013	Dec. 31, 2014
Stockholders Equity [Line Items]
Preferred stock, shares authorized			5,000,000		5,000,000
Preferred stock, par value			$ 0.01		$ 0.01
Preferred stock, shares outstanding			0		0
Issuance of common stock, net of offering costs (in shares)	5,447,368	9,200,000
Underwritten public offering amount per share	$ 95	$ 20.13
Issuance of common stock, net of offering costs	$ 496,400	$ 173,600	$ 496,400	$ 173,572
Underwriting discounts and commissions and other estimated offering expenses	$ 21,100	$ 11,600

Stock Incentive Plans - Additio

Stock Incentive Plans - Additional Information (Detail) - USD ($) $ / shares in Units, $ in Thousands	Dec. 17, 2014	Jan. 31, 2012	May. 31, 2011	Oct. 31, 2010	Mar. 31, 2016	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013	May. 31, 2015	Jun. 30, 2013	Jun. 30, 2010	Dec. 31, 2004
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares available for future grant						13,626,583
Option vesting percentage on the first anniversary of grant date						25.00%
Option vesting percentage at the end of each successive three-month period						6.25%
Stock-based compensation expense						$ 45,783	$ 33,061	$ 20,703
Fair value of equity awards granted			$ 2,300	$ 1,400
Employee stock purchase plan, offering period						6 months
Expected option life								5 years 7 months 6 days
Current Employees
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Fair value of equity awards granted		$ 5,300
Performance Contingent Options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock options granted	612,085
Stock options granted, exercise price	$ 96.45
Stock Incentive Plan 2004
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares authorized						12,366,485
Time-based stock option
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Weighted average fair value of stock options granted						$ 26.33	$ 26.33	$ 26.33
Aggregate intrinsic value of stock option exercised						$ 130,000	$ 126,500	$ 57,900
Stock options granted						2,403,000
Stock options granted, exercise price						$ 99.20
Restricted stock awards
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation expense						$ 555	1,068	3,420
Restricted Stock Awards Granted				113,370
Stock awards vesting period				3 years
Total fair value of restricted stock awards vested during period						$ 1,200	$ 44,400	5,800
Unvested restricted stock awards						19,271	30,149
Wighted-average grant date fair value						$ 70
Restricted stock awards | Current Employees
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted Stock Awards Granted		508,928
Stock awards vesting period		2 years
Performance Based Restricted Stock Awards
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Equity awards, term			5 years
Restricted Stock Awards Granted			229,806
Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares authorized											715,789	315,789
Stock incentive plan, shares available for future grant						184,392
Stock-based compensation expense						$ 694	$ 392	$ 261
Employee stock purchase plan, purchase price as a percentage of common stock closing price						85.00%
Employee stock purchase plan, shares issued						22,639	21,938	45,141
Weighted average fair value awards granted						$ 29.96	$ 17.03	$ 11.49
Expected volatility						53.00%	53.00%	53.00%
Expected option life						6 months	6 months	6 months
Risk-free interest rate						0.10%	0.10%	0.10%
Stock Incentive Plan 2009
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares authorized									11,700,000	5,900,000
Employee Stock Option
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares available for future grant						9,959,512
Equity awards, term						10 years
Stock-based compensation expense						$ 43,078	$ 24,603	$ 13,839
Additional Equity Awards
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares available for future grant						3,482,679
Performance-based Stock Options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Weighted average fair value of stock options granted								$ 32.26
Aggregate intrinsic value of stock option exercised						$ 1,400	100
Stock-based compensation expense							$ 4,960
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Vested in Period						159,122
Stock options granted						1,072,000
Stock options granted, exercise price						$ 91.07
Performance-based Stock Options | Scenario, Forecast [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation expense					$ 8,000

Summary of Stock-Based Compensa

Summary of Stock-Based Compensation Expense by Type of Award (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Non-cash stock-based compensation	$ 45,783	$ 33,061	$ 20,703
Employee Stock Option
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Non-cash stock-based compensation	43,078	24,603	13,839
Performance-based Stock Options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Non-cash stock-based compensation		4,960
Restricted stock awards
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Non-cash stock-based compensation	555	1,068	3,420
Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Non-cash stock-based compensation	694	392	261
Non Employee Stock Option
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Non-cash stock-based compensation	$ 1,456	$ 2,038	$ 3,183

Summary of Unrecognized Stock-B

Summary of Unrecognized Stock-Based Compensation Expense, Net of Estimated Forfeitures (Detail) $ in Thousands	12 Months Ended
	Dec. 31, 2015USD ($)
Time-based stock option
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 128,073
Weighted-average Recognition Period	2 years 10 months 13 days
Performance based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 62,000	[1]
Restricted stock awards
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 1,108
Weighted-average Recognition Period	2 years 6 months 15 days
Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 350
Weighted-average Recognition Period	3 months 29 days
[1]	Performance-based stock options are recorded as expense when vesting events are determined to be probable.

Valuation Assumptions for Stock

Valuation Assumptions for Stock Options (Detail)	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Risk-free interest rate, minimum	1.00%	1.70%	1.00%
Risk-free interest rate, maximum	2.00%	2.30%	2.00%
Expected option life			5 years 7 months 6 days
Expected volatility, minimum	53.00%	53.00%	55.00%
Expected volatility, maximum	60.00%	57.00%	56.00%
Minimum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected option life	3 years 6 months	5 years 6 months
Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected option life	7 years 6 months	7 years 6 months

Stock Option Activity (Detail)

Stock Option Activity (Detail) $ / shares in Units, shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2015USD ($)$ / sharesshares
Time-based stock option
Number of Options
Outstanding, beginning balance | shares	7,530
Granted | shares	2,403
Exercised | shares	(1,438)
Cancelled | shares	(177)
Outstanding, ending balance | shares	8,318
Exercisable at December 31, 2015 | shares	4,699
Vested or expected to vest at December 31, 2015 | shares	8,048
Weighted Average Exercise Price
Outstanding, beginning balance | $ / shares	$ 33.46
Granted | $ / shares	99.20
Exercised | $ / shares	19.64
Cancelled | $ / shares	70.67
Outstanding, ending balance | $ / shares	54.05
Exercisable at December 31, 2015 | $ / shares	30.61
Vested or expected to vest at December 31, 2015 | $ / shares	$ 52.89
Weighted Average Remaining Contractual Term
Outstanding, December 31, 2015	6 years 10 months 6 days
Exercisable at December 31, 2015	5 years 3 months 22 days
Vested or expected to vest at December 31, 2015	6 years 9 months 11 days
Aggregate Intrinsic Value
Outstanding, December 31, 2015 | $	$ 352,646
Exercisable at December 31, 2015 | $	299,365
Vested or expected to vest at December 31, 2015 | $	$ 349,933
Performance-based Stock Options
Number of Options
Outstanding, beginning balance | shares	639
Granted | shares	1,072
Exercised | shares	(29)
Cancelled | shares	(40)
Outstanding, ending balance | shares	1,642
Exercisable at December 31, 2015 | shares	120
Weighted Average Exercise Price
Outstanding, beginning balance | $ / shares	$ 73.15
Granted | $ / shares	91.07
Exercised | $ / shares	63
Cancelled | $ / shares	77.64
Outstanding, ending balance | $ / shares	84.92
Exercisable at December 31, 2015 | $ / shares	$ 63
Weighted Average Remaining Contractual Term
Outstanding, December 31, 2015	9 years 1 month 24 days
Exercisable at December 31, 2015	7 years 10 months 2 days
Aggregate Intrinsic Value
Outstanding, December 31, 2015 | $	$ 16,244
Exercisable at December 31, 2015 | $	$ 3,741

Components of Loss before Incom

Components of Loss before Income Tax, Domestic and Foreign (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Income (Loss) Before Income Tax
Domestic	$ (245,681)	$ (372,137)	$ (81,109)
Foreign	(44,392)	(28,467)	(10,811)
Loss before income taxes	$ (290,073)	$ (400,604)	$ (91,920)

Income Taxes - Additional Infor

Income Taxes - Additional Information (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Income Taxes [Line Items]
Deferred tax assets		$ 31,667
Deferred tax liabilities		31,667
Increase (decrease) in valuation allowance	$ 129,100	46,000	$ 29,700
(Benefit from) provision for income taxes	$ 0	(40,209)	(2,695)
Net operating loss carryforwards expiration year	2,035
Research and development tax credit
Income Taxes [Line Items]
Excess tax benefit from exercise of stock options	$ 400
Tax credit carryforwards expiration year	2,035
Alternative minimum tax
Income Taxes [Line Items]
Tax credit carryforwards	$ 800
Regulus Therapeutics Inc
Income Taxes [Line Items]
(Benefit from) provision for income taxes		(19,500)	$ (2,700)
Sanofi Genzyme
Income Taxes [Line Items]
(Benefit from) provision for income taxes		$ (20,700)
Net operating loss carryforwards
Income Taxes [Line Items]
Excess tax benefit from exercise of stock options	123,600
Federal
Income Taxes [Line Items]
Net operating loss carryforward	931,200
Federal | Research and development tax credit
Income Taxes [Line Items]
Tax credit carryforwards	53,200
State and local jurisdiction
Income Taxes [Line Items]
Net operating loss carryforward	991,500
State and local jurisdiction | Research and development tax credit
Income Taxes [Line Items]
Tax credit carryforwards	13,300
Foreign tax authority
Income Taxes [Line Items]
Tax credit carryforwards	$ 3,200
Tax credit carryforwards expiration year	2,017

Deferred Tax Assets and Liabili

Deferred Tax Assets and Liabilities (Detail) - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Deferred tax assets:
Net operating loss carryforwards	$ 253,908	$ 176,789
Research and development credits	61,424	38,204
AMT credits	788	788
Foreign tax credits	3,196	3,196
Capitalized research and development and start-up costs	19,075	19,246
Deferred revenue	17,279	14,273
Deferred compensation	33,397	24,516
Intangible assets	16,181	17,637
Partnership interest	689	689
Other	6,508	5,871
Total deferred tax assets	412,445	301,209
Deferred tax liabilities:
Unrealized gain on available-for-sale securities	(14,947)	(32,793)
Deferred tax asset valuation allowance	(397,498)	(268,416)
Net deferred tax liability	$ 0	$ 0

Benefit for Income Taxes (Detai

Benefit for Income Taxes (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Income Tax Expense (Benefit), Continuing Operations
Current			$ 34
Deferred		$ (40,209)	(2,695)
Total U.S.		(40,209)	(2,661)
Current	$ 0	0	0
Deferred			(34)
Total Foreign			(34)
Benefit from income taxes	$ 0	$ (40,209)	$ (2,695)

Effective Income Tax Rate (Deta

Effective Income Tax Rate (Detail)	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Effective Income Tax Rate Reconciliation, Percent
At U.S. federal statutory rate	35.00%	35.00%	35.00%
State taxes, net of federal effect	4.00%	1.80%	4.30%
Stock-based compensation	(1.10%)	(0.20%)	0.80%
Tax credits	8.00%	3.50%	8.50%
Orphan drug credit	(2.00%)	(0.60%)	(2.70%)
Other permanent items	(0.10%)		(0.30%)
Foreign rate differential	(5.40%)	(2.50%)	(4.10%)
In-process research and development		(19.40%)
Tax basis in intangible assets as a result of Sirna transaction		4.20%
Valuation allowance	(38.40%)	(11.80%)	(38.50%)
Effective income tax rate		10.00%	3.00%

Accrued Expenses (Detail)

Accrued Expenses (Detail) - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Schedule of Accrued Liabilities [Line Items]
Compensation and related	$ 11,157	$ 7,357
Clinical trial and manufacturing	10,885	5,548
Consulting and professional services	892	3,886
Pre-clinical	899	3,081
Other	4,965	3,808
Accrued expenses	$ 28,798	$ 23,680

Quarterly Financial Data (Detai

Quarterly Financial Data (Detail) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2015	Sep. 30, 2015	Jun. 30, 2015	Mar. 31, 2015	Dec. 31, 2014	Sep. 30, 2014	Jun. 30, 2014	Mar. 31, 2014	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Selected Quarterly Financial Information [Abstract]
Revenues	$ 7,551	$ 6,324	$ 8,685	$ 18,537	$ 24,019	$ 10,972	$ 7,295	$ 8,275	$ 41,097	$ 50,561	$ 47,167
Operating expenses	100,063	84,654	81,629	70,759	69,731	56,171	52,300	277,339	337,105	455,541	140,109
Net loss	$ (90,721)	$ (76,792)	$ (71,783)	$ (50,777)	$ (21,389)	$ (43,989)	$ (44,074)	$ (250,943)	$ (290,073)	$ (360,395)	$ (89,225)
Net loss per common share - basic and diluted	$ (1.07)	$ (0.91)	$ (0.85)	$ (0.62)	$ (0.28)	$ (0.58)	$ (0.58)	$ (3.70)	$ (3.45)	$ (4.85)	$ (1.45)
Weighted-average common shares - basic and diluted	84,871	84,633	84,353	82,074	76,957	76,408	75,835	67,786	83,992	74,278	61,551

Quarterly Financial Data - Addi

Quarterly Financial Data - Additional Information (Detail) - USD ($) $ in Thousands	Mar. 05, 2014	Jun. 30, 2014	Mar. 31, 2014	Dec. 31, 2014
Quarterly Financial Information [Line Items]
In-process research and development	$ 199,300			$ 220,766
In-process research and development credit		$ 3,900
Sirna Therapeutics
Quarterly Financial Information [Line Items]
In-process research and development			$ 224,700	$ 220,800
In-process research and development credit		$ 3,900