Alnylam Pharmaceuticals (ALNY) 10-K 15 Feb 18 2017 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($)	12 Months Ended
	Dec. 31, 2017	Jan. 31, 2018	Jun. 30, 2017
Document And Entity Information [Abstract]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2017
Document Fiscal Year Focus	2,017
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		99,867,820
Entity Public Float			$ 7,243,192,478

CONSOLIDATED BALANCE SHEETS

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Current assets:
Cash and cash equivalents	$ 645,361	$ 193,617
Marketable securities	1,045,257	424,185
Investment in equity securities of Regulus Therapeutics Inc.		8,997
Billed and unbilled collaboration receivables	34,002	23,334
Prepaid expenses and other current assets	40,120	21,744
Total current assets	1,764,740	671,877
Marketable securities	13,919	324,799
Property, plant and equipment, net	181,900	114,572
Restricted investments	30,000	150,000
Other assets	4,171	1,562
Total assets	1,994,730	1,262,810
Current liabilities:
Accounts payable	28,355	54,465
Accrued expenses	72,203	42,118
Deferred rent	1,988	1,576
Deferred revenue	41,705	33,540
Total current liabilities	144,251	131,699
Deferred rent, net of current portion	6,626	8,431
Deferred revenue, net of current portion	43,075	49,392
Long-term debt	30,000	150,000
Other liabilities	4,347	3,067
Total liabilities	228,299	342,589
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, 2017 and 2016
Common stock, $0.01 par value per share, 125,000,000 shares authorized; 99,666,549 shares issued and outstanding at December 31, 2017; 85,941,344 shares issued and outstanding at December 31, 2016	997	859
Additional paid-in capital	3,947,552	2,609,614
Accumulated other comprehensive loss	(34,433)	(33,441)
Accumulated deficit	(2,147,685)	(1,656,811)
Total stockholders’ equity	1,766,431	920,221
Total liabilities and stockholders’ equity	$ 1,994,730	$ 1,262,810

CONSOLIDATED BALANCE SHEETS (Pa

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2017	Dec. 31, 2016
Statement Of Financial Position [Abstract]
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	99,666,549	85,941,344
Common stock, shares outstanding	99,666,549	85,941,344

CONSOLIDATED STATEMENTS OF COMP

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) shares in Thousands, $ in Thousands		12 Months Ended
		Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Income Statement [Abstract]
Net revenues from collaborators		$ 89,912	$ 47,159	$ 41,097
Operating expenses:
Research and development	[1]	390,635	382,392	276,495
General and administrative	[1]	199,365	89,354	60,610
Total operating expenses		590,000	471,746	337,105
Loss from operations		(500,088)	(424,587)	(296,008)
Other income (expense):
Interest income		12,236	8,308	5,859
Other (expense) income		(3,022)	6,171	76
Total other income		9,214	14,479	5,935
Net loss		$ (490,874)	$ (410,108)	$ (290,073)
Net loss per common share — basic and diluted		$ (5.42)	$ (4.79)	$ (3.45)
Weighted-average common shares used to compute basic and diluted net loss per common share		90,554	85,596	83,992
Comprehensive loss:
Net loss		$ (490,874)	$ (410,108)	$ (290,073)
Unrealized loss on marketable securities, net of tax		(2,886)	(30,833)	(44,394)
Reclassification adjustment for realized loss (gain) on marketable securities included in net loss		1,894	(6,977)
Comprehensive loss		$ (491,866)	$ (447,918)	$ (334,467)
[1]	Stock-based compensation expenses included in operating expenses are as follows: Research and development $51,872 $42,946 $27,086 General and administrative 40,947 32,582 18,697

CONSOLIDATED STATEMENTS OF COM5

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS (Parenthetical) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Stock-based compensation	$ 92,819	$ 75,528	$ 45,783
Research and Development
Stock-based compensation	51,872	42,946	27,086
General and Administrative
Stock-based compensation	$ 40,947	$ 32,582	$ 18,697

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 at Dec. 31, 2014	$ 936,267		$ 772		$ 1,843,362		$ 48,763	$ (956,630)
Balance (in shares) at Dec. 31, 2014			77,202,753
Exercise of common stock options, net of tax withholdings	29,425		$ 15		29,410
Exercise of common stock options, net of tax withholdings (in shares)			1,461,237
Issuance of common stock under other types of equity plans	2,666		$ 1		2,665
Issuance of common stock under other types of equity plans (in shares)			32,427
Issuance of common stock under equity plans, net of tax withholdings	(378)				(378)
Issuance of common stock under equity plans, net of tax withholdings (in shares)			6,366
Issuance of common stock, net of offering costs	496,400	$ 89,018	$ 54	$ 9	496,346	$ 89,009
Issuance of common stock, net of offering costs (in shares)			5,447,368	940,817
Stock-based compensation expense related to equity-classified awards	45,783				45,783
Other comprehensive loss, net of tax	(44,394)						(44,394)
Net loss	(290,073)							(290,073)
Balance at Dec. 31, 2015	1,264,714		$ 851		2,506,197		4,369	(1,246,703)
Balance (in shares) at Dec. 31, 2015			85,090,968
Exercise of common stock options, net of tax withholdings	11,608		$ 5		11,603
Exercise of common stock options, net of tax withholdings (in shares)			559,344
Issuance of common stock under other types of equity plans	3,648		$ 1		3,647
Issuance of common stock under other types of equity plans (in shares)			75,453
Issuance of common stock under equity plans, net of tax withholdings	(314)				(314)
Issuance of common stock under equity plans, net of tax withholdings (in shares)			10,549
Issuance of common stock, net of offering costs		14,301		$ 2		14,299
Issuance of common stock, net of offering costs (in shares)				205,030
Stock-based compensation expense related to equity-classified awards	74,182				74,182
Other comprehensive loss, net of tax	(37,810)						(37,810)
Reclassification adjustment for realized (gain) loss on marketable securities included in net loss	(6,977)
Net loss	(410,108)							(410,108)
Balance at Dec. 31, 2016	$ 920,221		$ 859		2,609,614		(33,441)	(1,656,811)
Balance (in shares) at Dec. 31, 2016	85,941,344		85,941,344
Exercise of common stock options, net of tax withholdings	$ 80,546		$ 19		80,527
Exercise of common stock options, net of tax withholdings (in shares)			1,841,566
Issuance of common stock under other types of equity plans	5,907		$ 2		5,905
Issuance of common stock under other types of equity plans (in shares)			134,615
Issuance of common stock under equity plans, net of tax withholdings	(707)				(707)
Issuance of common stock under equity plans, net of tax withholdings (in shares)			11,523
Issuance of common stock, net of offering costs	1,139,625	$ 21,381	$ 114	$ 3	1,139,511	$ 21,378
Issuance of common stock, net of offering costs (in shares)			11,440,000	297,501
Stock-based compensation expense related to equity-classified awards	91,324				91,324
Other comprehensive loss, net of tax	(992)						(992)
Reclassification adjustment for realized (gain) loss on marketable securities included in net loss	1,894
Net loss	(490,874)							(490,874)
Balance at Dec. 31, 2017	$ 1,766,431		$ 997		$ 3,947,552		$ (34,433)	$ (2,147,685)
Balance (in shares) at Dec. 31, 2017	99,666,549		99,666,549

CONSOLIDATED STATEMENTS OF CASH

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Cash flows from operating activities:
Net loss	$ (490,874)	$ (410,108)	$ (290,073)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization	13,367	15,130	19,050
Stock-based compensation	92,819	75,528	45,783
Charge for 401(k) company stock match	2,302	1,507	984
Realized loss (gain) on sale of marketable equity securities	1,894	(6,977)
Other	608
Changes in operating assets and liabilities:
Proceeds from landlord tenant improvements		2,145	374
Billed and unbilled collaboration receivables	(10,668)	(15,036)	31,639
Prepaid expenses and other assets	(20,711)	(5,276)	(6,820)
Accounts payable	(4,939)	10,098	1,676
Accrued expenses and other	31,568	10,673	6,343
Deferred revenue	1,848	14,615	1,904
Net cash used in operating activities	(382,786)	(307,701)	(189,140)
Cash flows from investing activities:
Purchases of property, plant and equipment	(104,209)	(64,557)	(12,950)
Purchases of restricted investments and increase in restricted cash		(150,000)	(1,471)
Purchases of marketable securities	(903,457)	(759,310)	(1,033,843)
Sales and maturities of marketable securities	597,305	1,116,458	726,943
Sale of restricted investments	120,000
Net cash (used in) provided by investing activities	(290,361)	142,591	(321,321)
Cash flows from financing activities:
Proceeds from exercise of stock options and other types of equity	84,142	14,127	31,137
Proceeds from issuance of common stock, net of offering costs	1,139,625		496,400
Proceeds from issuance of common stock to Sanofi Genzyme	21,381	14,301	89,018
Proceeds from issuance of long-term debt		150,000
Repayment of long-term debt	(120,000)
Payments for repurchase of common stock for employee tax withholding	(257)	(596)	(378)
Net cash provided by financing activities	1,124,891	177,832	616,177
Net increase in cash and cash equivalents	451,744	12,722	105,716
Cash and cash equivalents, beginning of period	193,617	180,895	75,179
Cash and cash equivalents, end of period	645,361	193,617	180,895
Supplemental disclosure of cash flows:
Cash paid for interest	2,430	1,096
Cash paid for income taxes	114	111	66
Supplemental disclosure of noncash investing and financing activities:
Fixed asset expenditures included in accounts payable and accrued expenses	8,176	33,153	1,333
Fair value of common stock received for collaboration agreement in other assets	2,700
Receipt of common stock for exercises of stock options	653	$ 1,260	$ 686
Repurchase of common stock for employee tax withholding in accrued expenses	$ 450

NATURE OF BUSINESS

NATURE OF BUSINESS	12 Months Ended
	Dec. 31, 2017
Accounting Policies [Abstract]
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 globally. We have devoted substantially all of our efforts to business planning, research, development and early commercial efforts, acquiring, filing and expanding intellectual property rights, recruiting management and technical staff, and raising capital. In late 2017, we filed a new drug application, or NDA, and a marketing authorisation application, or MAA, seeking regulatory approval of our first product in the United States and Europe, respectively. If one or both of such applications is approved, we expect to begin commercializing and generating product revenues in 2018. We are subject to risks common to companies in our industry including, but not limited to, uncertainties relating to conducting clinical research and development, the manufacture and supply of products for clinical and commercial use, obtaining and maintaining regulatory approvals and pricing and reimbursement for our products, market acceptance, managing global growth and operating expenses, availability of additional capital, competition, obtaining and enforcing patents, stock price volatility, dependence on collaborative relationships and third-party service providers, dependence on key personnel, potential litigation, product liability claims and government investigations.

SUMMARY OF SIGNIFICANT ACCOUNTI

SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES	12 Months Ended
	Dec. 31, 2017
Accounting Policies [Abstract]
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, 2017 and 2016, 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, U.S. government-sponsored enterprise securities and U.S. treasury securities through highly rated financial institutions. Corporate notes may 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, The Medicines Company, or MDCO, Takeda Pharmaceutical Company Limited, or Takeda, and Monsanto Company, or Monsanto. For the year ended December 31, 2017, our billed and unbilled collaboration receivables were composed primarily of a milestone payment due from MDCO and expense reimbursement due from Sanofi Genzyme. For the year ended December 31, 2016, our billed and unbilled collaboration receivables were composed primarily of expense reimbursement due from Sanofi Genzyme. The following table summarizes customers that represent greater than 10 percent of our net revenues from collaborators, for the periods indicated: Year Ended December 31, 2017 2016 2015 Sanofi Genzyme 61 % 68 % 27 % MDCO 34 % 24 % 25 % Takeda * * 22 % Monsanto * * 14 % The following table summarizes customers with amounts due that represent greater than 10 percent of our billed and unbilled collaboration receivables balance, at the periods indicated: At December 31, 2017 2016 MDCO 59 % * Sanofi Genzyme 39 % 97 % * Represents 10 percent 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 and Cash Equivalents 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, 2017, the balance in our accumulated other comprehensive loss 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 recognized $1.9 million of realized losses and $7.0 million of realized gains from sales of our Regulus available-for-sale securities as other income (expense) in our consolidated statements of comprehensive loss during the years ended December 31, 2017 and 2016, respectively. 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 loss. We did not record any impairment charges related to our fixed income marketable securities during the years ended December 31, 2017, 2016 or 2015. 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, U.S. treasury securities and money market funds. During the second quarter of 2017, we sold all our remaining holdings in Regulus. We accounted 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. Property, Plant and Equipment Property, plant and equipment are stated at cost, net of accumulated depreciation. Depreciation expense is recorded on a straight-line basis over the estimated useful life of the asset. Leasehold improvements are amortized over the shorter of the asset’s estimated useful life or the lease term. Construction in progress reflects amounts incurred for construction or improvements of property, plant or equipment that have not been placed in service. The cost and accumulated depreciation of assets retired or sold are removed from the respective asset category, and any gain or loss is recognized in our consolidated statements of comprehensive loss. The estimated useful lives of property, plant and equipment are as follows: Asset Category Useful Life Laboratory equipment 5 years Computer equipment and software 3-10 years Furniture and fixtures 5 years Leasehold improvements Shorter of asset life or lease term Land — Construction in progress — 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 Takeda, Kyowa Hakko Kirin Co., Ltd., or Kyowa Hakko Kirin, 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, that 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 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 proportional performance or a 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 an NDA 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 per our collaboration agreements 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 with 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, 2017, we had short-term and long-term deferred revenue of $41.7 million and $43.1 million, respectively, related to our collaborations. The new accounting standard related to revenue recognition effective as of January 1, 2018, discussed below under the heading “Recent Accounting Pronouncements,” will have a material impact on our consolidated financial statements. 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, 2017, we have not recorded significant interest and penalty expense related to uncertain tax positions. Research and Development Expenses We record research and development expenses as incurred. Included in research and development expenses are wages, stock-based compensation expenses, 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, 2017, 2016 and 2015, we charged to research and development expense costs associated with license fees of $7.7 million, $2.4 million and $3.5 million, respectively. Stock-Based Compensation We have stock incentive plans and an employee stock purchase plan under which we grant equity instruments. We may also grant inducement stock grants outside of our stock incentive plans. 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 of stock options using the Black-Scholes valuation model. Our expected stock price volatility assumption is based on the historical volatility of our publicly traded stock. 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. Expense for time-based restricted stock awards is recognized over the vesting period. For performance-based stock option and restricted stock awards, we begin to recognize expense 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 if 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 (the proceeds of which are then assumed to have been used to repurchase outstanding shares using the treasury stock method). 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, 2017 2016 2015 Options to purchase common stock 11,239 12,270 9,960 Unvested restricted common stock 149 171 19 11,388 12,441 9,979 Segment Information We operate in a single reporting segment, the discovery, development and commercialization of RNAi therapeutics. 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 control of 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. In March 2016, the FASB issued amendments to clarify the implementation guidance on principal versus agent considerations. In April 2016, the FASB issued amendments to clarify the guidance on accounting for licenses of intellectual property and identifying performance obligations. In May 2016, the FASB issued amendments related to collectibility, non-cash consideration, the presentation of sales and other similar taxes collected from customers and transition. The standard allows for adoption using a full retrospective method or a modified retrospective method. On January 1, 2018, we adopted this standard using the modified retrospective method. Our implementation approach included performing a detailed review of our collaboration agreements. In addition, we designed internal controls to enable the preparation of financial information and have reached conclusions on key accounting assessments related to the new standard, including our assessment that the impact of accounting for costs incurred to obtain a contract is immaterial. We completed our assessment to quantify the expected impact that the new standard will have on our consolidated financial statements and related disclosures. We expect the adoption of the new standard to result in a cumulative reduction of $68.3 million of deferred revenue with a corresponding adjustment to the opening balance of accumulated deficit to be recorded in the first quarter of 2018. This adjustment is due primarily to the application of the new standard to our collaboration agreements with Sanofi Genzyme, MDCO and Kyowa Hakko Kirin. A substantial portion of the incremental $68.3 million adjustment is the result of the application of the new guidance regarding how entities should measure progress in satisfying performance obligations and the contract’s transaction price. In addition, as a result of the cumulative reduction in deferred revenue, our corresponding deferred tax asset will be reduced by approximately $13.6 million, which will be offset by a corresponding decrease to our valuation allowance. These offsetting adjustments will be recorded to accumulated deficit in the first quarter of 2018. We do not expect an impact to cash from or used in operating, financing or investing on our consolidated statement of cash flows as a result of the adoption of the new standard. 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 became effective for us on January 1, 2018. We currently do not expect this guidance to have a significant impact on our consolidated financial statements and related disclosures. In February 2016, the FASB issued a new leasing standard that requires that all lessees recognize the assets and liabilities that arise from leases on the consolidated balance sheet and disclose qualitative and quantitative information about its leasing arrangements. The new standard will be effective for us on January 1, 2019. Early adoption is permitted. We are currently evaluating the timing of our adoption and the expected impact that this standard could have on our consolidated financial statements and related disclosures. In October 2016, the FASB issued guidance that an entity should recognize the income tax consequences of an intra-entity transfer of an asset other than inventory when the transfer occurs instead of deferring the income tax effects. The new guidance became effective for us on a modified retrospective basis on January 1, 2018. The adoption of this guidance did not have an impact on our consolidated financial statements and related disclosures. In November 2016, the FASB issued guidance that requires restricted cash and restricted cash equivalents be included with cash and cash equivalents when reconciling the total beginning and ending amounts for the periods shown on the consolidated statement of cash flows. The new standard became effective for us on January 1, 2018 using a retrospective transition method for each period presented. For the years ended December 31, 2017 and 2016, our restricted cash and restricted cash equivalents were not significant. We currently do not expect this guidance to have a significant impact on our consolidated financial statements and related disclosures. In March 2017, the FASB issued guidance that amends the amortization period for certain purchased callable debt securities held at a premium by shortening the amortization period for the premium to the earliest call date. The new standard will be effective for us on January 1, 2019. Early adoption is permitted. We are currently evaluating the timing of our adoption and the expected impact that this standard could have on our consolidated financial statements and related disclosures. Subsequent Events We did not have any material recognized subsequent events. However, we did have a nonrecognized subsequent event with respect to our collaboration with Sanofi Genzyme, which is more fully described in Note 3.

SIGNIFICANT AGREEMENTS

SIGNIFICANT AGREEMENTS	12 Months Ended
	Dec. 31, 2017
Organization Consolidation And Presentation Of Financial Statements [Abstract]
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, Description 2017 2016 2015 Sanofi Genzyme $ 54,625 $ 32,015 $ 11,005 MDCO 30,217 11,220 10,301 Takeda — — 8,867 Monsanto 2,500 — 5,621 Other 2,570 3,924 5,303 Total net revenues from collaborators $ 89,912 $ 47,159 $ 41,097 The following table provides the research and development expenses incurred by type that are directly attributable to each significant agreement for the periods indicated, in thousands: Year Ended December 31, 2017 2016 2015 Sanofi Genzyme MDCO Ionis Sanofi Genzyme MDCO Ionis Sanofi Genzyme MDCO Ionis Research and development Clinical trial and manufacturing $ 174,901 $ 5,421 $ — $ 150,179 $ 1,211 $ — $ 108,903 $ 3,308 $ — External services 4,475 — 3,250 7,366 — — 3,151 770 — Other 5,327 106 — 3,035 64 525 3,714 497 3,300 Total research and development expenses $ 184,703 $ 5,527 $ 3,250 $ 160,580 $ 1,275 $ 525 $ 115,768 $ 4,575 $ 3,300 The research and development expenses incurred for each significant agreement consist of costs incurred for external development and manufacturing services for which we are reimbursed and licensing payments made to the counterparty to such agreement. In addition, these expenses include a reasonable estimate of compensation and related costs as billed to our counterparties. There were no material research and development expenses incurred for Monsanto or Takeda during the years ended December 31, 2017, 2016 and 2015. For the years ended December 31, 2017, 2016 and 2015, we did not incur material general and administrative expenses related to our significant agreements. 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, referred to as the 2014 Sanofi Genzyme collaboration. 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 hereditary ATTR amyloidosis, including patisiran and revusiran, in Japan and the Asia-Pacific region. On January 6, 2018, we and Sanofi Genzyme entered into an amendment to our 2014 Sanofi Genzyme collaboration. In connection and simultaneously with entering into the amendment to the 2014 Sanofi Genzyme collaboration, we and Sanofi Genzyme also entered into an Exclusive License Agreement with respect to all TTR products, including patisiran, ALN-TTRsc02 and any back-up products, referred to as the Exclusive TTR License, and the ALN-AT3 Global License Terms with respect to fitusiran and any back-up products, referred to as the AT3 License Terms. As a result, we will have the exclusive right to pursue the further global development and commercialization of all TTR products, including patisiran, ALN-TTRsc02 and any back-up products, and Sanofi Genzyme will have the exclusive right to pursue the further global development and commercialization of fitusiran and any back-up products. The January 2018 transaction is subject to customary closing conditions and clearances, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act. We expect the transaction to close during the first quarter of 2018. 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 $11.0 million in patisiran development milestones under the 2012 Sanofi Genzyme agreement. 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, as amended in January 2018 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 and was amended in January 2018, at which time we also entered into the Exclusive TTR License and the AT3 License Terms. 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 the United States, Canada 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 worldwide rights for one product. Sanofi Genzyme’s rights under the 2014 Sanofi Genzyme collaboration, 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. 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 which Sanofi Genzyme opted into prior to the 2018 amendment 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. Sanofi Genzyme will be required to make payments totaling up to $75.0 million per regional product, consisting of up to $55.0 million in development milestones and $20.0 million in commercial milestones. 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. Upon the effective date of the 2014 Sanofi Genzyme collaboration, Sanofi Genzyme expanded the scope of its regional license and collaboration for patisiran, 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. Cost-sharing for the fitusiran program began in January 2016 under the regional license terms. Sanofi Genzyme also had the right to elect to co-develop and co-commercialize fitusiran in the Alnylam Territory pursuant to the co-development/co-commercialize license terms described below. In November 2016, Sanofi Genzyme exercised this right and elected to co-develop and co-commercialize fitusiran in the Alnylam Territory. In addition, during 2016, Sanofi Genzyme elected not to opt into the development and commercialization of givosiran or cemdisiran in the Sanofi Genzyme Territory. Sanofi Genzyme’s rights with respect to patisiran and fitusiran will be modified in connection with the 2018 amendment, the Exclusive TTR License the AT3 License Terms, as described below. Sanofi • Co-development/co-commercialize license terms and programs — Upon opt-in, we retained product rights in the Alnylam Territory, while Sanofi Genzyme obtained exclusive rights to develop and commercialize the product in the Sanofi Genzyme Territory, and to co-commercialize the product in the Alnylam Territory. Upon the effective date of the 2014 Sanofi Genzyme collaboration, Sanofi Genzyme expanded its regional rights for revusiran, which were originally granted under the 2012 Sanofi Genzyme agreement, to include a co-development/co-commercialize license and collaboration. In October 2016, we decided to discontinue development of revusiran. In our TTR program, we are also developing ALN-TTRsc02. Sanofi Genzyme had a right to elect a co-development/co-commercialize license for ALN-TTRsc02. As noted above, in November 2016, Sanofi Genzyme exercised its right to elect a co-development/co-commercialize license for fitusiran. Development costs for co-development/co-commercialize products, once Sanofi Genzyme exercised an option, were shared between Sanofi Genzyme and us, with Sanofi Genzyme responsible for fifty percent of the global development costs. In connection with the exercise of its co-development/co-commercialize rights for fitusiran, Sanofi Genzyme paid us approximately $6.0 million in January 2017 for its incremental share of co-development costs incurred from January 2016 through September 2016. Sanofi Genzyme was required to make certain milestone payments for fitusiran, and, prior to the discontinuation of the revusiran program, was required to make certain milestone payments for revusiran. 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. Sanofi Genzyme was also obligated to pay us a milestone of $25.0 million upon the dosing of the first patient in our ATLAS Phase 3 program for fitusiran. In addition, Sanofi Genzyme was required to pay tiered double-digit royalties up to twenty percent for each co-development/co-commercialize product based on annual net sales, if any, in the Sanofi Genzyme Territory for such co-development/co-commercialize product by Sanofi Genzyme, its affiliates and sublicensees. The parties were to share profits equally and we expected to book product sales in the Alnylam Territory. In connection with the 2018 amendment, the Exclusive TTR License the AT3 License Terms, as described below • Global license terms and programs — Sanofi Genzyme continues to 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 could elect its global license for lumasiran. Sanofi Genzyme Exclusive TTR License and AT3 License Terms As noted above, the 2018 amendment, together with the Exclusive TTR License and the AT3 License Terms, revise the terms and conditions of the 2014 Sanofi Genzyme collaboration to (i) provide us the exclusive right to pursue the further global development and commercialization of all TTR products, including patisiran, ALN-TTRsc02 and any back-up products, (ii) provide Sanofi Genzyme the exclusive right to pursue the further global development and commercialization of fitusiran and any back-up products and (iii) terminate the previous co-development and co-commercialization rights related to revusiran, ALN-TTRsc02 and fitusiran under the 2014 Sanofi Genzyme collaboration. Going forward, we will fund all development and commercialization costs for patisiran and ALN-TTRsc02. We also will fund development and commercialization costs for fitusiran through the transition period, up to a cap of $50.0 million, after which Sanofi Genzyme will fund all development and commercialization costs for fitusiran. We expect to substantially complete the transition of the fitusiran program to Sanofi Genzyme by mid-2018. Each party will be responsible for its costs associated with the transfer of the respective program to the other party. Under the 2018 amendment and the Exclusive TTR License, Sanofi Genzyme will be eligible to receive (i) royalties up to twenty-five percent, increasing over time, based on annual net sales of patisiran in territories excluding the United States, Canada and Western Europe, provided royalties on annual net sales of patisiran in Japan will be twenty-five percent beginning as of the effective date of the Exclusive TTR License, (ii) tiered royalties of fifteen to thirty percent based on global annual net sales of ALN-TTRsc02 (consistent with the royalties due to us from Sanofi Genzyme on fitusiran), and (iii) tiered royalties of up to fifteen percent based on global annual net sales of any back-up products, in each case by us, our affiliates and our sublicensees. Except as described below, there will be no additional milestones due to either party with respect to patisiran, ALN-TTRsc02 or fitusiran. In consideration for the rights granted to Sanofi Genzyme under the 2018 amendment and the AT3 License Terms, Sanofi Genzyme is required to make one milestone payment of $50.0 million following the dosing of the first patient in the ATLAS Phase 3 program for fitusiran. In addition, we will be eligible to receive tiered royalties of fifteen to thirty percent based on global annual net sales of fitusiran and up to fifteen percent based on global annual net sales of any back-up products, in each case by Sanofi Genzyme, its affiliates and its sublicensees. We and Sanofi Genzyme intend to enter into a supply agreement to provide for the supply of fitusiran to Sanofi Genzyme for ongoing clinical studies, and, at Sanofi Genzyme’s request, commercial sales. Sanofi Genzyme also has the right to manufacture fitusiran. 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, as amended, or the AT3 License Terms. The 2014 Sanofi Genzyme collaboration, as amended, will continue to be 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 and global program and to oversee certain matters, including transition planning, that may arise under the Exclusive TTR License and the AT3 License Terms. The original master agreement (including the license terms appended thereto), as well as the Exclusive TTR License and the AT3 License Terms, contain certain termination provisions, including for material breach by the other party. In addition, we have the right to terminate Exclusive TTR License without cause with respect to any or all licensed products at any time upon six months’ prior written notice and Sanofi Genzyme has the right to terminate the AT3 License Terms without cause with respect to any particular licensed product at any time upon six months’ prior written notice. 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. The term of the Exclusive TTR License expires on a licensed product-by-licensed product and country-by-country basis upon expiration of the last royalty term to expire under the agreement, where a royalty term is defined as the latest to occur of (a) expiration of the last valid claim of patent rights covering a licensed product; (b) the expiration of Regulatory Exclusivity for a licensed product, as defined in the Exclusive TTR License; or (c) the twelfth anniversary of the first commercial sale of the licensed product in such country. The term of the AT3 License Terms expires on a licensed product-by-licensed product and country-by-country basis upon expiration of the last royalty term to expire under the agreement, where a royalty term is defined as the latest to occur of (x) the expiration of the last valid claim of patent rights covering a licensed product; (y) the expiration of Regulatory Exclusivity for a licensed product, as defined in the AT3 License Terms; or (z) the twelfth anniversary of the first commercial sale of the licensed product in such country. 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 percent 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 percent 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 percent 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 percent 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 percent 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, in the event that the market price per share of our common stock is at least 100 percent 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 percent 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 percent 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 percent ownership threshold). Finally, in the event Sanofi Genzyme and its affiliates acquire at least 20 percent 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 for the ALN-TTR programs. 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. 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 connection with our public offerings, Sanofi Genzyme exercised its right to purchase directly from us, in concurrent private placements, 744,566 shares of common stock in January 2015 at the public offering price resulting in $70.7 million in proceeds to us and 297,501 shares of common stock in May 2017 at the public offering price resulting in $21.4 million in proceeds to us. Sanofi Genzyme elected not to purchase shares in connection with our November 2017 offering. The sales of common stock to Sanofi Genzyme were not registered as part of these public offerings, though they were consummated simultaneously with such public offerings. 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. Sanofi Genzyme elected not to exercise its compensation-related right for 2016 or 2017. The sales of these shares to Sanofi Genzyme were consummated as private placements. Sanofi Genzyme currently holds approximately 11 percent of our outstanding common stock. We determined that the deliverables for the programs on which Sanofi Genzyme was collaborating with us upon initiation of the 2014 Sanofi Genzyme 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 were expected to be completed within approximately six years from the closing date of the transaction and the last deliverables for fitusiran were expected to be completed within approximately five years from the date Sanofi Genzyme elected to opt into our fitusiran program under the regional license terms. Our estimate regarding the performance period under the 2014 Sanofi Genzyme collaboration related to the license to our patisiran and revusiran clinical programs was adjusted in October 2016 due to our decision to discontinue development of revusiran. As a result, with respect to these programs, we currently expect the last deliverables to be completed within approximately five years from the closing date of the transaction as compared to an initial expectation of approximately six years. Our estimate regarding the performance period under the 2014 Sanofi Genzyme collaboration related to the license to our fitusiran program was adjusted in September 2017 due to our temporary suspension of dosing in all ongoing fitusiran studies. As a result, with respect to the fitusiran program, we currently expect the last deliverables to be completed within approximately six years from the date Sanofi Genzyme elected to opt into the program under the regional license terms as compared to an initial expectation of approximately five years. Beginning in September 2017, we are prospectively recognizing the remaining deferred revenue as of August 31, 2017 related to the license to our fitusiran program over this adjusted performance period. 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. As consideration is achieved, including any milestones or reimbursement for development activities, we 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 recognize the remaining portion of consideration received over the remaining performance period on a straight-line basis. The following table presents information related to the 2014 Sanofi Genzyme collaboration, in thousands: Excess of fair value of our common stock issued to Sanofi Genzyme in February 2014 $ (51,450 ) Deferred revenue remaining under the 2012 Sanofi Genzyme agreement upon execution of the 2014 Sanofi Genzyme collaboration 33,500 Milestone payment received: Year-ended December 31, 2014 25,000 Development expense reimbursement from Sanofi Genzyme: Year-ended December 31, 2015 33,949 Year-ended December 31, 2016 54,337 Year-ended December 31, 2017 51,846 Total consideration at December 31, 2017 $ 147,182 Cumulative revenue recognized at December 31, 2017 $ 98,014 Deferred revenue at December 31, 2017 $ 49,168 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 initial 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. 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 inclisiran. 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 inclisiran. In November 2017, we earned a development milestone payment of $20.0 million under the MDCO agreement based upon the initiation by MDCO of a pivotal study for inclisiran. In addition, in 2017, 2016 and 2015, we were reimbursed an aggregate of $12.2 million for costs incurred for certain development activities. We could potentially earn the next development milestone payment of $25.0 million based upon regulatory approval of an NDA for inclisiran in the United States. 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

FAIR VALUE MEASUREMENTS

FAIR VALUE MEASUREMENTS	12 Months Ended
	Dec. 31, 2017
Fair Value Disclosures [Abstract]
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, 2017 and 2016, and indicate the fair value hierarchy of the valuation techniques we utilized to determine such fair value, in thousands: Description At December 31, 2017 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Commercial paper $ 82,262 $ — $ 82,262 $ — Corporate notes 18,116 — 18,116 — U.S. government-sponsored enterprise securities 231,122 — 231,122 — U.S. treasury securities 62,855 — 62,855 — Money market funds 122,986 122,986 — — Marketable securities (fixed income): — Certificates of deposit 30,200 — 30,200 — Commercial paper 56,951 — 56,951 — Corporate notes 373,252 — 373,252 — U.S. government-sponsored enterprise securities 398,298 — 398,298 — U.S. treasury securities 200,475 — 200,475 — Restricted cash (Money market funds) 1,471 1,471 — — Total $ 1,577,988 $ 124,457 $ 1,453,531 $ — Description At December 31, 2016 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Commercial paper $ 17,199 $ — $ 17,199 $ — Money market funds 151,479 151,479 — — Marketable securities (fixed income): — Certificates of deposit 17,999 — 17,999 — Commercial paper 59,340 — 59,340 — Corporate notes 333,872 — 333,872 — U.S. government-sponsored enterprise securities 297,773 — 297,773 — U.S. treasury securities 40,000 — 40,000 — Marketable securities (Regulus equity holdings) 8,997 8,997 — — Restricted cash (Money market funds) 1,471 1,471 — — Total $ 928,130 $ 161,947 $ 766,183 $ — For the years ended December 31, 2017 and 2016, 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. The fair value of our long-term debt at December 31, 2017, computed pursuant to a discounted cash flow technique using a market interest rate, was $30.1 million and is considered a Level 3 fair value measurement. The effective interest rate reflects the current market rate.

MARKETABLE SECURITIES

MARKETABLE SECURITIES	12 Months Ended
	Dec. 31, 2017
Investments Debt And Equity Securities [Abstract]
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, 2017 and 2016, and for the activity recorded in each year, in thousands: Description At December 2016 Sales Regulus Shares During Year Ended December 31, 2017 All Other Activity During Year December 31, 2017 Balance at December 2017 Carrying value $ 8,093 $ (7,485 ) $ (608 ) $ — Accumulated other comprehensive income (loss), before tax 904 1,894 (2,798 ) — Investment in equity securities of Regulus Therapeutics Inc., as reported $ 8,997 $ (5,591 ) $ (3,406 ) $ — Accumulated other comprehensive income (loss), before tax $ 904 $ 1,894 $ (2,798 ) $ — Intraperiod tax allocation recorded as a benefit from income taxes (32,792 ) — — (32,792 ) Accumulated other comprehensive income (loss), net of tax $ (31,888 ) $ 1,894 $ (2,798 ) $ (32,792 ) Description At December 2015 Sales Regulus Shares During Year Ended December 31, 2016 All Other Activity During Year December 31, 2016 Balance at December 2016 Carrying value $ 11,935 $ (3,842 ) $ — $ 8,093 Accumulated other comprehensive income (loss), before tax 39,484 (6,977 ) (31,603 ) 904 Investment in equity securities of Regulus Therapeutics Inc., as reported $ 51,419 $ (10,819 ) $ (31,603 ) $ 8,997 Accumulated other comprehensive income (loss), before tax $ 39,484 $ (6,977 ) $ (31,603 ) $ 904 Intraperiod tax allocation recorded as a benefit from income taxes (32,792 ) — — (32,792 ) Accumulated other comprehensive income (loss), net of tax $ 6,692 $ (6,977 ) $ (31,603 ) $ (31,888 ) 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, 2017 and 2016, in thousands: At December 31, 2017 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 30,200 $ — $ — $ 30,200 Commercial paper 56,951 — — 56,951 Corporate notes 373,736 11 (495 ) 373,252 U.S. government-sponsored enterprise securities 399,281 — (983 ) 398,298 U.S. treasury securities 200,649 1 (175 ) 200,475 Total $ 1,060,817 $ 12 $ (1,653 ) $ 1,059,176 At December 31, 2016 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 17,999 $ — $ — $ 17,999 Commercial paper 59,340 — — 59,340 Corporate notes 334,266 47 (441 ) 333,872 U.S. government-sponsored enterprise securities 298,910 9 (1,146 ) 297,773 U.S. treasury securities 40,022 1 (23 ) 40,000 Total $ 750,537 $ 57 $ (1,610 ) $ 748,984 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, 2017, in thousands: At December 31, 2017 Amortized Cost Fair Value Less than one year $ 1,046,834 $ 1,045,257 Greater than one year but less than two years 13,983 13,919 Total $ 1,060,817 $ 1,059,176

PROPERTY, PLANT AND EQUIPMENT,

PROPERTY, PLANT AND EQUIPMENT, NET	12 Months Ended
	Dec. 31, 2017
Property Plant And Equipment [Abstract]
PROPERTY, PLANT AND EQUIPMENT, NET	6. PROPERTY, PLANT AND EQUIPMENT, NET Property, plant and equipment consist of the following at December 31, 2017 and 2016, in thousands: At December 31, 2017 2016 Laboratory equipment $ 40,462 $ 37,303 Computer equipment and software 9,608 9,650 Furniture and fixtures 5,844 6,002 Leasehold improvements 50,612 45,362 Land 9,080 9,080 Construction in progress 133,645 68,182 249,251 175,579 Less: accumulated depreciation (67,351 ) (61,007 ) $ 181,900 $ 114,572 During the years ended December 31, 2017, 2016 and 2015, we recorded $11.9 million, $9.6 million and $6.7 million, respectively, of depreciation expense related to our property, plant and equipment. Manufacturing Facility In April 2016, we purchased 12 acres of undeveloped land in Norton, Massachusetts. We are constructing a manufacturing facility at this site for drug substance, including small interfering RNAs, or siRNAs, and siRNA conjugates, for clinical and commercial use. At December 31, 2017 and 2016, property, plant and equipment, net, on our consolidated balance sheets reflects $140.5 million and $73.2 million, respectively, of land and associated costs related to the construction of our drug substance manufacturing facility.

COMMITMENTS AND CONTINGENCIES

COMMITMENTS AND CONTINGENCIES	12 Months Ended
	Dec. 31, 2017
Commitments And Contingencies Disclosure [Abstract]
COMMITMENTS AND CONTINGENCIES	7. COMMITMENTS AND CONTINGENCIES Technology License and Other Commitments We have licensed from third parties the rights to use certain technologies and information in our research processes as well as in any products that we may develop. In accordance with the related license or technology agreements, we are required to make certain fixed payments to the counterparty 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, 2017, we were committed to make the following fixed, estimated and cancelable payments under existing license agreements, in thousands: Year Ending December 31, 2018 $ 21,012 2019 12,277 2020 795 2021 795 2022 595 Thereafter 1,500 Total $ 36,974 At December 31, 2017, we were committed to make fixed, non-cancelable payments of $5.0 million in each of 2018 and 2019 under an agreement that will provide us access to information during this time that we can use in our future research and any products that we may develop. 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-665 Concord Avenue Lease was set to expire in August 2017. In August 2016, we and BMR-Fresh Pond Research Park LLC amended the BMR-665 Concord Avenue Lease to extend the term for an additional five years, through August 31, 2022. Under the amended BMR-665 Concord Avenue Lease, we have the option to extend the term for one additional five-year period. 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 and research facility 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 percent 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. 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 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, was $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 rent payments commenced in May 2016 under the additional lease. We have $1.5 million in restricted cash that is recorded in long-term other assets as of December 31, 2017 and 2016 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 $18.7 million, $15.9 million and $10.5 million for the years ended December 31, 2017, 2016 and 2015, respectively. In addition to the lease agreements described above, we also lease additional office space in several locations in and outside of the United States to support our operations and growth. Future minimum payments under our non-cancelable facility leases, including rent payments for the BMR-675 West Kendall Lease which are expected to commence in early 2019, are approximately as follows, in thousands: Year Ending December 31, 2018 $ 14,464 2019 32,446 2020 34,570 2021 30,928 2022 23,050 Thereafter 297,726 Total $ 433,184 Credit Agreements On April 29, 2016, we entered into (i) a Credit Agreement, or the BOA Credit Agreement, with Alnylam U.S., Inc., our wholly-owned subsidiary, as the borrower, us, as a guarantor, and Bank of America N.A., or BOA, as the lender and (ii) a Credit Agreement, or the Wells Credit Agreement, together with the BOA Credit Agreement, the Credit Agreements, by and among Alnylam U.S., Inc., as the borrower, us, as a guarantor, and Wells Fargo Bank, National Association, or Wells, as the lender. The Credit Agreements were entered into in connection with the planned build out of our new drug substance manufacturing facility. The BOA Credit Agreement provided for a $120.0 million term loan facility and was scheduled to mature on April 29, 2021. On December 27, 2017, we repaid in full the $120.0 million outstanding principal amount under the BOA Credit Agreement and the BOA Credit Agreement terminated in accordance with its terms upon repayment of the outstanding indebtedness. The Wells Credit Agreement provides for a $30.0 million term loan facility and matures on April 29, 2021. The proceeds of the borrowing under the BOA Credit Agreement were, and the Wells Credit Agreement are, to be used for working capital and general corporate purposes. Interest on borrowings under the BOA Credit Agreement was, and under the Wells Credit Agreement is calculated based on LIBOR plus 0.45 percent, except in the event of default. The borrower may prepay loans under the Wells Credit Agreement at any time, without premium or penalty, subject to certain notice requirements and LIBOR breakage costs. The obligations of the borrower and us under the BOA Credit Agreement were, and under the Wells Credit Agreement are secured by cash collateral in an amount equal to, at any given time, at least 100 percent of the principal amount of all term loans outstanding under such Credit Agreement at such time. At December 31, 2017 and 2016, we have recorded $30.0 million and $150.0 million, respectively, of cash collateral in connection with the Credit Agreements as restricted investments on our consolidated balance sheets. Wells and the borrower have agreed to consider the appropriateness of a change in the type of approved collateral on a periodic basis throughout the term of the Wells Credit Agreement; provided that any such change to the type of such approved collateral shall be made only upon each of the lender’s and the borrower’s consent. The Wells Credit Agreement contains limited representations and warranties and limited affirmative and negative covenants, including quarterly reporting obligations. The Wells Credit Agreement also contains certain customary events of default, including nonpayment of principal or interest, material inaccuracy of representations, failure to comply with covenants, cross-defaults to certain other indebtedness, invalidity of any loan document relating to such Credit Agreement, judgments having a material adverse effect, insolvency events and change of control. If an event of default occurs and is continuing under the Wells Credit Agreement, the entire outstanding balance may become immediately due and payable. Several of the lenders under each of the Credit Agreements, as well as their affiliates, have various relationships with us and our subsidiaries involving the provision of financial services, such as investment banking, commercial banking, advisory, cash management, custody and corporate credit card services for which they receive customary fees and may do so in the future. During the years ended December 31, 2017 and 2016, we recorded $0.8 million and $1.2 million, respectively, of interest expense related to the Credit Agreements that is reflected in other income (expense) on our consolidated statements of comprehensive loss. Litigation From time to time, we are a party to legal proceedings in the course of our business, including the matters described below. The claims and legal proceedings in which we could be involved include challenges to the scope, validity or enforceability of patents relating to our product candidates, and challenges by us to the scope, validity or enforceability of the patents held by others. These include claims by third parties that we infringe their patents. The outcome of any such legal proceedings, regardless of the merits, is inherently uncertain. 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. If we were unable to prevail in any such legal proceedings, our business, results of operations, liquidity and financial condition could be adversely affected Silence Litigation On October 17, 2017, Silence Therapeutics plc, or Silence, served its previously announced claim in the High Court of England and Wales, or the High Court, issued in the name of Silence Therapeutics GmbH against Alnylam UK Ltd., Alnylam Pharmaceuticals, Inc., and The Medicines Company UK Ltd, referred to collectively as the Defendants. The claim seeks a declaration that patisiran, fitusiran, givosiran and inclisiran, together, the Products, are protected by Silence’s European Patent No. 2 258 847, or the ‘847 patent, within the meaning of the Supplementary Protection Certificate, or SPC, Regulation of the European Union. The claim alleges that any marketing authorization for any of these Products granted to any of the Defendants is a valid authorization within the meaning of the SPC Regulation, to support an application for an SPC by Silence for each of the Products, allegedly allowing Silence to extend the expiration date of their ‘847 patent on a Product by Product basis, based on the amount of time in regulatory review for each of the Products, again on a Product by Product basis, up to a statutory maximum. In addition, Silence is seeking costs, interest and other unspecified relief. On October 31, 2017, the Defendants acknowledged service of the claim served by Silence contesting jurisdiction of the High Court. On November 30, 2017, the Defendants submitted substantive defenses to the claim. On October 27, 2017, we, through our affiliate Alnylam UK Ltd., and The Medicines Company UK Ltd filed and served a claim against Silence Therapeutics GmbH and Silence in the High Court seeking revocation of the ‘847 patent, as well as a declaration of non-infringement by each of the Products of the ‘847 patent, and costs and interest among other potential remedies. On November 14, 2017, Silence filed a defense to our claim along with counterclaims alleging infringement of the ‘847 patent by our Products. On December 11, 2017, we filed an answer and defense to the counter claims. The High Court has set a trial date of December 3, 2018 for all claims between Silence and the Defendants. Although we believe the ‘847 patent is invalid and not infringed by our Products and that, therefore, Silence would not be entitled to obtain an SPC based on any of our Products, litigation is subject to inherent uncertainty, as noted above, and a court could ultimately rule against us. 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, or the Court, 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 N-acetylgalactosamine, or 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, following which discovery proceeded. Fact discovery on our claims against Dicerna ended on August 16, 2017, and expert discovery on those claims is underway. In August 2017, Dicerna successfully added counterclaims against us in the trade secret lawsuit alleging that our lawsuit represented abuse of process and claiming tortious interference with its business. On September 27, 2017, we filed a motion to dismiss Dicerna’s counterclaims. The motion was denied on October 24, 2017, and we intend to vigorously defend against those claims. The trial for this lawsuit now is scheduled for April 23, 2018. In addition, on August 8, 2017, Dicerna filed a lawsuit against us in the United States District Court of Massachusetts alleging attempted monopolization by us under the Sherman Antitrust Act. Dicerna’s allegations related to its new claim largely overlap with its counterclaims in the state court action. We do not believe the claim is meritorious and on October 23, 2017, we filed a motion to dismiss the antitrust lawsuit. On November 20, 2017, Dicerna filed an amended complaint adding the fact that the motion to dismiss Dicerna’s counterclaims had been denied. On December 4, 2017, we filed a renewed motion to dismiss Dicerna’s complaint, which Dicerna has opposed. Although we believe we have meritorious claims against Dicerna and meritorious defenses and responses to the counterclaims and federal claim now being asserted by Dicerna, as noted above, litigation is subject to inherent uncertainty, we will incur significant costs in defending against such claims, and a court could ultimately rule against us. 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. After several years of court proceedings and discovery, 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 United States Court of Appeals for the Federal Circuit, or the CAFC. On December 18, 2015, the CAFC 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 denied our motion and on December 15, 2015, we filed a notice of appeal of this ruling with the CAFC. Oral arguments on our appeal were heard at the CAFC on January 12, 2017. On March 23, 2017, the CAFC denied our appeal and we decided not to appeal this ruling any further. Final judgment in our favor on the merits has been entered by the MA District Court. Indemnifications 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 Therapeutics Inc., or Acuitas (formerly AlCana Technologies, Inc.), we agreed to indemnify Acuitas for certain legal costs, subject to certain exceptions and limitations, associated with certain litigation with Arbutus Biopharma Corporation, or ABC (formerly Tekmira Pharmaceuticals Corporation), and Protiva Biotherapeutics, Inc., a wholly owned subsidiary of ABC, and together with ABC, Arbutus, which has been settled. 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 litigation with Arbutus referenced above, and certain defense costs related to the University of Utah litigation 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, 2017 or 2016.

STOCKHOLDERS' EQUITY

STOCKHOLDERS' EQUITY	12 Months Ended
	Dec. 31, 2017
Equity [Abstract]
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, 2017 and 2016, there were no shares of preferred stock outstanding. Public Offerings In November 2017, we sold an aggregate of 6,440,000 shares of our common stock through an underwritten public offering at a price to the public of $125.00 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 $784.5 million, after deducting underwriting discounts and commissions and other offering expenses of $20.5 million. In May 2017, we sold an aggregate of 5,000,000 shares of our common stock through an underwritten public offering at a price to the public of $71.87 per share. As a result of the offering, we received aggregate net proceeds of $355.2 million, after deducting underwriting discounts and commissions and other offering expenses of $4.2 million. 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 offering expenses of $21.1 million.

STOCK-BASED COMPENSATION

STOCK-BASED COMPENSATION	12 Months Ended
	Dec. 31, 2017
Disclosure Of Compensation Related Costs Sharebased Payments [Abstract]
STOCK-BASED COMPENSATION	9. STOCK-BASED COMPENSATION 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. At December 31, 2017, the Amended and Restated 2004 Plan provided for the granting of stock options to purchase up to 12,366,485 shares of common stock. 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, which increased the number of shares of common stock authorized for issuance from 5,900,000 to 11,700,000. In May 2017, our stockholders approved a second amendment and restatement of the 2009 Stock Incentive Plan, or the Second Amended and Restated 2009 Plan, which increased the number of shares of common stock authorized for issuance from 11,700,000 to 15,480,000. The Second Amended and Restated 2009 Plan provides for the granting of stock options, restricted stock and restricted stock units (together, restricted stock awards), stock appreciation rights and other stock-based awards. The Second 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 Second 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 Second 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, 2017, an aggregate of 15,556,526 shares of common stock were reserved for issuance under our stock plans, including outstanding stock options to purchase 11,239,128 shares of common stock, 148,670 outstanding restricted stock units, 3,641,501 of common stock available for additional equity awards and 527,227 shares available for future grant under our Amended and Restated 2004 Employee Stock Purchase Plan, or the Amended and Restated ESPP. Each stock option shall expire within ten years of issuance. Time-based stock options granted by us to employees generally vest as to 25 percent of the shares on the first anniversary of the grant date and 6.25 percent of the shares at the end of each successive three-month period thereafter until fully vested. Performance-based stock options granted to employees in 2015 and 2016 vest, with respect to each year, as to one-fourth of the shares upon the later of the one-year anniversary of the grant date and the achievement of each of four specific clinical development, regulatory or commercial events, as approved by our compensation committee. Performance-based stock options granted to employees in 2013 and 2014 vest, with respect to each year, 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. Historically, stock option awards to employees for annual performance, including performance-based stock option awards beginning in 2013, were approved for grant by the compensation committee of our board of directors at year-end. However, with respect to 2017 annual awards as well as future annual awards, our compensation committee intends to approve the grant of any such awards in the first quarter of the following year. Change in Control Agreements On November 7, 2017, we entered into a Change in Control, or CIC, Agreement with each member of our management board. If a member of our management board is terminated by us without Cause (as defined in the CIC Agreement) or if a management board member terminates his or her employment for Good Reason (as defined in the CIC Agreement), in either case, within 12 months following a CIC, such management board member will be entitled to receive certain benefits, including the immediate acceleration of all outstanding unvested stock options and other stock-based awards. In accordance with accounting guidance for stock-based compensation expense, we expect to record the modification date fair value for any equity grants that were not considered probable of vesting as of November 7, 2017 that ultimately vest. Inducement Equity Grants Effective as of each of May 8, 2017 and September 19, 2016, respectively, our compensation committee approved a grant to a newly hired executive of non-qualified stock options to purchase an aggregate of 150,000 shares of common stock. For each executive, time-vested options to purchase 125,000 shares of common stock will vest as to 25 percent of the shares on the first anniversary of the respective grant date and 6.25 percent of the shares at the end of each successive three-month period thereafter until fully vested. For each executive, performance-based stock options to purchase 25,000 shares of common stock will vest upon the later of the one-year anniversary of the respective grant date and the launch of our first internally developed product. In addition, effective as of February 6, 2017, our compensation committee approved a grant to a newly hired vice president level employee, of non-qualified stock options to purchase an aggregate of 50,000 shares of common stock. This time-vested option grant will vest as to 25 percent of the shares on the first anniversary of the grant date and 6.25 percent of the shares at the end of each successive three-month period thereafter until fully vested. Each of the May 8, 2017, February 6, 2017 and September 19, 2016 option grants was granted as an inducement grant outside of our stockholder approved stock plans in accordance with NASDAQ Listing Rule 5635(c)(4). These stock options have a ten-year term and an exercise price equal to the closing price of our common stock on the respective grant date. Stock-Based Compensation The following table summarizes stock-based compensation expense by type of award during the three years ended December 31, 2017, in thousands: 2017 2016 2015 Stock-based compensation expense by type of award: Time-based stock options $ 61,802 $ 62,800 $ 43,078 Performance-based stock options 23,260 8,337 — Restricted stock awards 541 497 555 ESPP share issuances 2,155 1,360 694 Other equity programs 1,946 1,846 — Non-employee stock options 3,115 688 1,456 $ 92,819 $ 75,528 $ 45,783 The following table summarizes our unrecognized stock-based compensation expense, net of estimated forfeitures, at December 31, 2017 by type of awards, and the weighted-average period over which that expense is expected to be recognized: At December 31, 2017 Unrecognized Expense, Net of Estimated Forfeitures Weighted- average Recognition Period (in thousands) (in years) Type of award: Time-based stock options $ 124,295 2.60 Performance-based stock options 59,416 * Performance-based restricted stock units 14,649 * ESPP share issuances 970 0.33 * Performance-based stock options and performance-based restricted stock units are recorded as expense beginning 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. 2017 2016 2015 Risk-free interest rate 1.9-2.3% 0.9-2.2% 1.0-2.0% Expected dividend yield — — — Expected option life 5.7-7.2 years 3.5-7.5 years 3.5-7.5 years Expected volatility 61-67% 55-65% 53-60% Stock Option Activity The following table summarizes the activity of our stock option plans and the inducement grants described above, excluding performance-based stock options: Number of Options (in Weighted- average Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2016 9,913 $ 56.05 Granted 1,664 75.66 Exercised (1,796 ) 42.81 Cancelled (680 ) 83.70 Outstanding, December 31, 2017 9,101 $ 60.18 6.92 $ 609,620 Exercisable at December 31, 2017 5,294 $ 51.54 5.59 $ 400,390 Vested or expected to vest at December 31, 2017 8,670 $ 59.64 6.82 $ 587,480 The weighted-average fair value of stock options granted was $44.76, $31.66 and $51.28 per share for the years ended December 31, 2017, 2016 and 2015, respectively. The intrinsic value of stock options exercised was $111.3 million, $22.0 million and $130.0 million for the years ended December 31, 2017, 2016 and 2015, respectively. We satisfy stock option exercises with newly issued shares of our common stock. Performance-Based Stock Options We granted performance-based stock options to employees that vest as to one-fourth of the shares upon the later of the one-year anniversary of the grant date and the achievement of each of four specific clinical development, regulatory or commercial events, as approved by our compensation committee, with respect to 2015 and 2016 grants, and that vest as to one-third of the shares upon the later of the one-year anniversary of the grant date and the achievement of each of three specific clinical development or regulatory events, as approved by our compensation committee, with respect to 2013 and 2014 grants. During each of the years ended December 31, 2017 and 2016, we also granted an option to purchase 25,000 shares of common stock to a newly hired executive that vests upon the later of the one-year anniversary of the grant date and the achievement of a commercial event. The following table summarizes the activity of our performance-based stock options granted under our equity plans and the performance-based portion of the inducement grants described above: Number of Options (in Weighted- average Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2016 2,357 $ 69.61 Granted 25 52.61 Exercised (54 ) 80.46 Cancelled (190 ) 69.59 Outstanding, December 31, 2017 2,138 $ 69.14 7.79 $ 123,795 Exercisable at December 31, 2017 813 $ 73.66 7.23 $ 43,416 During the years ended December 31, 2017 and 2016, there were 614,796 and 159,122 performance-based stock options that vested, respectively. There were no performance-based stock options that vested during the year ended December 31, 2015. The weighted-average grant-date fair value for the performance-based stock options that vested during the years ended December 31, 2017 and 2016 was $37.86 and $52.29 per share, respectively. The intrinsic value of performance-based stock options exercised was $1.8 million, $35,000 and $1.4 million for the years ended December 31, 2017, 2016 and 2015, respectively. We satisfy performance-based stock option exercises with newly issued shares of our common stock. During the three years ended December 31, 2017, each performance-based stock option that vested was determined to be probable of vesting, and we began to record expense, during the year the performance-based stock option vested based on achievement of the respective performance-criteria. As of the grant date and December 31, 2017, we had determined that the remaining performance criteria for all outstanding performance-based stock options reflected in the table above as of December 31, 2017 were not probable of being achieved. As a result, we have not recorded stock-based compensation expense for these performance-based stock options as of December 31, 2017. 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 on 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. Performance-Based Restricted Stock Units In January 2016, we granted 172,718 shares of performance-based restricted stock units to certain employees, excluding our chief executive officer and president. These performance-based restricted stock units were valued at $16.1 million on the grant date. The vesting of these performance-based restricted stock units is predicated on the launch of our first internally developed product. Employee Stock Purchase Plan In 2004, we adopted the 2004 Employee Stock Purchase Plan with 315,789 shares authorized for issuance. In June 2010, our stockholders approved an amendment to the 2004 Employee Stock Purchase Plan, which increased the shares authorized for issuance from 315,789 shares to 715,789 shares. In May 2017, our stockholders approved the Amended and Restated ESPP, which further increased the shares authorized for issuance from 715,789 shares to 1,215,789 shares. Under the Amended and Restated 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 percent of the closing price of our common stock at the beginning or end of the offering period. We issued 103,666, 53,499 and 22,639 shares during the years ended December 31, 2017, 2016 and 2015, respectively, and at December 31, 2017, 527,227 shares were available for issuance under the Amended and Restated ESPP. The weighted-average fair value of stock purchase rights granted as part of the Amended and Restated ESPP was $17.10, $24.90 and $29.96 per share for the years ended December 31, 2017, 2016 and 2015, respectively. The fair value was estimated using the Black-Scholes option-pricing model. During the year ended December 31, 2017, we used a weighted-average stock-price volatility of 91 percent, expected option life assumption of six months and a risk-free interest rate of 0.7 percent. During the years ended December 31, 2016 and 2015, we used a weighted-average stock-price volatility of approximately 55 percent, expected option life assumption of six months and a risk-free interest rate of approximately 0.1 percent.

INCOME TAXES

INCOME TAXES	12 Months Ended
	Dec. 31, 2017
Income Tax Disclosure [Abstract]
INCOME TAXES	10. INCOME TAXES The domestic and foreign components of loss before income taxes are as follows, in thousands: 2017 2016 2015 Domestic $ (378,293 ) $ (350,704 ) $ (245,681 ) Foreign (112,581 ) (59,404 ) (44,392 ) Loss before income taxes $ (490,874 ) $ (410,108 ) $ (290,073 ) 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. Components of the net deferred tax (liability) asset at December 31, 2017 and 2016 are as follows, in thousands: 2017 2016 Deferred tax assets: Net operating loss carryforwards $ 405,784 $ 346,965 Research and development credits 192,094 111,394 AMT credits 788 788 Foreign tax credits — 3,196 Capitalized research and development and start-up costs 13,163 18,138 Deferred revenue 13,576 20,853 Deferred compensation 42,990 51,355 Intangible assets 9,018 14,725 Partnership interest — 1,623 Other 11,608 7,845 Total deferred tax assets 689,021 576,882 Deferred tax liabilities: Unrealized gain on available-for-sale securities (765 ) (1,524 ) Deferred tax asset valuation allowance (688,256 ) (575,358 ) Net deferred tax liability $ — $ — Our effective income tax rate differs from the statutory federal income tax rate as follows for the years ended December 31, 2017, 2016 and 2015: 2017 2016 2015 At U.S. federal statutory rate 35.0 % 35.0 % 35.0 % State taxes, net of federal effect 3.8 3.7 4.0 Stock-based compensation 3.3 (1.4 ) (1.1 ) Tax credits 9.9 11.8 8.0 Orphan drug credit (3.4 ) (3.5 ) (2.0 ) Other permanent items (1.0 ) (0.4 ) (0.1 ) Foreign rate differential (8.1 ) (5.1 ) (5.4 ) Tax reform change (46.5 ) — — Other (0.9 ) — — Valuation allowance 7.9 (40.1 ) (38.4 ) Effective income tax rate — % — % — % 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 $112.9 million, $177.9 million and $129.1 million for the years ended December 31, 2017, 2016 and 2015, respectively, due primarily to additional operating losses. On December 22, 2017, the President of the United States signed into law the Tax Cuts and Jobs Act, or TCJA, tax reform legislation. The TCJA makes significant changes in U.S. tax law including a reduction in the corporate tax rates, changes to net operating loss carryforwards and carrybacks, and a repeal of the corporate alternative minimum tax. The TCJA reduced the U.S. corporate tax rate from the current rate of 35 percent down to 21 percent starting on January 1, 2018. As a result of the TCJA, we were required to revalue deferred tax assets and liabilities at 21 percent. This revaluation resulted in a provision of $227.9 million to income tax expense in continuing operations and a corresponding reduction in the valuation allowance. As a result, there was no impact to our consolidated statements of comprehensive loss as a result of the reduction in tax rates. The other provisions of the TCJA did not have a material impact on our consolidated financial statements. Our preliminary estimate of the TCJA and the remeasurement of our deferred tax assets and liabilities is subject to the finalization of management’s analysis related to certain matters, such as developing interpretations of the provisions of the TCJA, changes to certain estimates and the filing of our tax returns. U.S. Treasury regulations, administrative interpretations or court decisions interpreting the TJCA may require further adjustments and changes in our estimates. The final determination of the TCJA and the remeasurement of our deferred assets and liabilities will be completed as additional information becomes available, but no later than one year from the enactment of the TCJA. There was no benefit from income taxes recorded during the years ended December 31, 2017, 2016, and 2015. On January 1, 2017, we adopted new accounting guidance released in March 2016 that updates the accounting for certain aspects of share-based payments to employees, including the income tax consequences, classification of awards as either equity or liabilities and classification on the consolidated statement of cash flows. On January 1, 2017, the deferred tax assets associated with net operating losses increased by $122.2 million and the deferred tax asset associated with federal and state research credit increased by $30.8 million. These amounts were offset by a corresponding increase in the valuation allowance. The adoption of this standard did not impact our consolidated financial statements. At December 31, 2017, we had federal and state net operating loss carryforwards of $1.47 billion and $1.55 billion, respectively, to reduce future taxable income that will expire at various dates through 2037. At December 31, 2017, we had federal and state research and development and investment tax credit carryforwards of $180.0 million and $15.3 million, respectively, available to reduce future tax liabilities that expire at various dates through 2037. At December 31, 2017, we had alternative minimum tax credits of $0.8 million that will either be available to reduce future regular tax liabilities or be fully refundable in 2021. We have a valuation allowance against the net operating loss and credit deferred tax assets as it is unlikely that we will realize these assets. 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 and tax credit carryforwards that can be utilized to offset future taxable income or tax liability. The amount of the limitation is determined in accordance with Section 382 of the Internal Revenue Code. We have performed an analysis of ownership changes through December 31, 2017. Based on this analysis, we do not believe that any of our tax attributes will expire unutilized due to Section 382 limitations. At December 31, 2017, 2016 and 2015, we had no unrecognized tax benefits. The tax years 2014 through 2017 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. However, the statute of limitations remains open to the extent we utilize net operating losses or credits from earlier years. 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, 2017
Accrued Liabilities Current [Abstract]
ACCRUED EXPENSES	11. ACCRUED EXPENSES Accrued expenses consist of the following at December 31, 2017 and 2016, in thousands: At December 31, 2017 2016 Compensation and related $ 33,826 $ 13,689 Clinical trial and manufacturing 20,004 11,756 Consulting and professional services 7,276 2,788 Pre-clinical 239 1,257 Other 10,858 12,628 $ 72,203 $ 42,118

QUARTERLY FINANCIAL DATA (UNAUD

QUARTERLY FINANCIAL DATA (UNAUDITED)	12 Months Ended
	Dec. 31, 2017
Quarterly Financial Information Disclosure [Abstract]
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, 2017 June 30, 2017 September 30, 2017 December 31, 2017 (In thousands, except per share data) Revenues $ 18,960 $ 15,932 $ 17,096 $ 37,924 Operating expenses 125,471 136,406 142,896 $ 185,227 Net loss $ (107,290 ) $ (118,420 ) $ (122,937 ) $ (142,227 ) Net loss per common share — basic and diluted $ (1.25 ) $ (1.34 ) $ (1.34 ) $ (1.48 ) Weighted-average common shares — basic and diluted 86,027 88,098 91,828 96,139 Three Months Ended March 31, 2016 June 30, 2016 September 30, 2016 December 31, 2016 (In thousands, except per share data) Revenues $ 7,345 $ 8,709 $ 13,651 $ 17,454 Operating expenses 117,373 101,159 120,327 132,887 Net loss $ (102,974 ) $ (90,129 ) $ (104,071 ) $ (112,934 ) Net loss per common share — basic and diluted $ (1.21 ) $ (1.05 ) $ (1.21 ) $ (1.32 ) Weighted-average common shares — basic and diluted 85,277 85,545 85,716 85,843

SUMMARY OF SIGNIFICANT ACCOUN20

SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES (Policies)	12 Months Ended
	Dec. 31, 2017
Accounting Policies [Abstract]
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, 2017 and 2016, 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, U.S. government-sponsored enterprise securities and U.S. treasury securities through highly rated financial institutions. Corporate notes may 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, The Medicines Company, or MDCO, Takeda Pharmaceutical Company Limited, or Takeda, and Monsanto Company, or Monsanto. For the year ended December 31, 2017, our billed and unbilled collaboration receivables were composed primarily of a milestone payment due from MDCO and expense reimbursement due from Sanofi Genzyme. For the year ended December 31, 2016, our billed and unbilled collaboration receivables were composed primarily of expense reimbursement due from Sanofi Genzyme. The following table summarizes customers that represent greater than 10 percent of our net revenues from collaborators, for the periods indicated: Year Ended December 31, 2017 2016 2015 Sanofi Genzyme 61 % 68 % 27 % MDCO 34 % 24 % 25 % Takeda * * 22 % Monsanto * * 14 % The following table summarizes customers with amounts due that represent greater than 10 percent of our billed and unbilled collaboration receivables balance, at the periods indicated: At December 31, 2017 2016 MDCO 59 % * Sanofi Genzyme 39 % 97 % * Represents 10 percent 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 and Cash Equivalents	Investments in Marketable Securities and Cash Equivalents 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, 2017, the balance in our accumulated other comprehensive loss 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 recognized $1.9 million of realized losses and $7.0 million of realized gains from sales of our Regulus available-for-sale securities as other income (expense) in our consolidated statements of comprehensive loss during the years ended December 31, 2017 and 2016, respectively. 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 loss. We did not record any impairment charges related to our fixed income marketable securities during the years ended December 31, 2017, 2016 or 2015. 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, U.S. treasury securities and money market funds. During the second quarter of 2017, we sold all our remaining holdings in Regulus. We accounted 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.
Property, Plant and Equipment	Property, Plant and Equipment Property, plant and equipment are stated at cost, net of accumulated depreciation. Depreciation expense is recorded on a straight-line basis over the estimated useful life of the asset. Leasehold improvements are amortized over the shorter of the asset’s estimated useful life or the lease term. Construction in progress reflects amounts incurred for construction or improvements of property, plant or equipment that have not been placed in service. The cost and accumulated depreciation of assets retired or sold are removed from the respective asset category, and any gain or loss is recognized in our consolidated statements of comprehensive loss. The estimated useful lives of property, plant and equipment are as follows: Asset Category Useful Life Laboratory equipment 5 years Computer equipment and software 3-10 years Furniture and fixtures 5 years Leasehold improvements Shorter of asset life or lease term Land — Construction in progress —
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 Takeda, Kyowa Hakko Kirin Co., Ltd., or Kyowa Hakko Kirin, 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, that 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 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 proportional performance or a 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 an NDA 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 per our collaboration agreements 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 with 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, 2017, we had short-term and long-term deferred revenue of $41.7 million and $43.1 million, respectively, related to our collaborations. The new accounting standard related to revenue recognition effective as of January 1, 2018, discussed below under the heading “Recent Accounting Pronouncements,” will have a material impact on our consolidated financial statements.
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, 2017, we have not recorded significant interest and penalty expense related to uncertain tax positions.
Research and Development Expenses	Research and Development Expenses We record research and development expenses as incurred. Included in research and development expenses are wages, stock-based compensation expenses, 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, 2017, 2016 and 2015, we charged to research and development expense costs associated with license fees of $7.7 million, $2.4 million and $3.5 million, respectively.
Stock-Based Compensation	Stock-Based Compensation We have stock incentive plans and an employee stock purchase plan under which we grant equity instruments. We may also grant inducement stock grants outside of our stock incentive plans. 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 of stock options using the Black-Scholes valuation model. Our expected stock price volatility assumption is based on the historical volatility of our publicly traded stock. 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. Expense for time-based restricted stock awards is recognized over the vesting period. For performance-based stock option and restricted stock awards, we begin to recognize expense 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 if 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 (the proceeds of which are then assumed to have been used to repurchase outstanding shares using the treasury stock method). 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, 2017 2016 2015 Options to purchase common stock 11,239 12,270 9,960 Unvested restricted common stock 149 171 19 11,388 12,441 9,979
Segment Information	Segment Information We operate in a single reporting segment, the discovery, development and commercialization of RNAi therapeutics.
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 control of 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. In March 2016, the FASB issued amendments to clarify the implementation guidance on principal versus agent considerations. In April 2016, the FASB issued amendments to clarify the guidance on accounting for licenses of intellectual property and identifying performance obligations. In May 2016, the FASB issued amendments related to collectibility, non-cash consideration, the presentation of sales and other similar taxes collected from customers and transition. The standard allows for adoption using a full retrospective method or a modified retrospective method. On January 1, 2018, we adopted this standard using the modified retrospective method. Our implementation approach included performing a detailed review of our collaboration agreements. In addition, we designed internal controls to enable the preparation of financial information and have reached conclusions on key accounting assessments related to the new standard, including our assessment that the impact of accounting for costs incurred to obtain a contract is immaterial. We completed our assessment to quantify the expected impact that the new standard will have on our consolidated financial statements and related disclosures. We expect the adoption of the new standard to result in a cumulative reduction of $68.3 million of deferred revenue with a corresponding adjustment to the opening balance of accumulated deficit to be recorded in the first quarter of 2018. This adjustment is due primarily to the application of the new standard to our collaboration agreements with Sanofi Genzyme, MDCO and Kyowa Hakko Kirin. A substantial portion of the incremental $68.3 million adjustment is the result of the application of the new guidance regarding how entities should measure progress in satisfying performance obligations and the contract’s transaction price. In addition, as a result of the cumulative reduction in deferred revenue, our corresponding deferred tax asset will be reduced by approximately $13.6 million, which will be offset by a corresponding decrease to our valuation allowance. These offsetting adjustments will be recorded to accumulated deficit in the first quarter of 2018. We do not expect an impact to cash from or used in operating, financing or investing on our consolidated statement of cash flows as a result of the adoption of the new standard. 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 became effective for us on January 1, 2018. We currently do not expect this guidance to have a significant impact on our consolidated financial statements and related disclosures. In February 2016, the FASB issued a new leasing standard that requires that all lessees recognize the assets and liabilities that arise from leases on the consolidated balance sheet and disclose qualitative and quantitative information about its leasing arrangements. The new standard will be effective for us on January 1, 2019. Early adoption is permitted. We are currently evaluating the timing of our adoption and the expected impact that this standard could have on our consolidated financial statements and related disclosures. In October 2016, the FASB issued guidance that an entity should recognize the income tax consequences of an intra-entity transfer of an asset other than inventory when the transfer occurs instead of deferring the income tax effects. The new guidance became effective for us on a modified retrospective basis on January 1, 2018. The adoption of this guidance did not have an impact on our consolidated financial statements and related disclosures. In November 2016, the FASB issued guidance that requires restricted cash and restricted cash equivalents be included with cash and cash equivalents when reconciling the total beginning and ending amounts for the periods shown on the consolidated statement of cash flows. The new standard became effective for us on January 1, 2018 using a retrospective transition method for each period presented. For the years ended December 31, 2017 and 2016, our restricted cash and restricted cash equivalents were not significant. We currently do not expect this guidance to have a significant impact on our consolidated financial statements and related disclosures. In March 2017, the FASB issued guidance that amends the amortization period for certain purchased callable debt securities held at a premium by shortening the amortization period for the premium to the earliest call date. The new standard will be effective for us on January 1, 2019. Early adoption is permitted. We are currently evaluating the timing of our adoption and the expected impact that this standard could have on our consolidated financial statements and related disclosures.
Subsequent Events	Subsequent Events We did not have any material recognized subsequent events. However, we did have a nonrecognized subsequent event with respect to our collaboration with Sanofi Genzyme, which is more fully described in Note 3.

SUMMARY OF SIGNIFICANT ACCOUN21

SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES (Tables)	12 Months Ended
	Dec. 31, 2017
Accounting Policies [Abstract]
Concentrations of Credit Risk and Significant Customers	The following table summarizes customers that represent greater than 10 percent of our net revenues from collaborators, for the periods indicated: Year Ended December 31, 2017 2016 2015 Sanofi Genzyme 61 % 68 % 27 % MDCO 34 % 24 % 25 % Takeda * * 22 % Monsanto * * 14 % The following table summarizes customers with amounts due that represent greater than 10 percent of our billed and unbilled collaboration receivables balance, at the periods indicated: At December 31, 2017 2016 MDCO 59 % * Sanofi Genzyme 39 % 97 % * Represents 10 percent or less
Estimated Useful Lives of Property, Plant and Equipment	The estimated useful lives of property, plant and equipment are as follows: Asset Category Useful Life Laboratory equipment 5 years Computer equipment and software 3-10 years Furniture and fixtures 5 years Leasehold improvements Shorter of asset life or lease term Land — Construction in progress —
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, 2017 2016 2015 Options to purchase common stock 11,239 12,270 9,960 Unvested restricted common stock 149 171 19 11,388 12,441 9,979

SIGNIFICANT AGREEMENTS (Tables)

SIGNIFICANT AGREEMENTS (Tables)	12 Months Ended
	Dec. 31, 2017
Organization Consolidation And Presentation Of Financial Statements [Abstract]
Revenue from Collaborators	The following table summarizes our total consolidated net revenues from collaborators, for the periods indicated, in thousands: Year Ended December 31, Description 2017 2016 2015 Sanofi Genzyme $ 54,625 $ 32,015 $ 11,005 MDCO 30,217 11,220 10,301 Takeda — — 8,867 Monsanto 2,500 — 5,621 Other 2,570 3,924 5,303 Total net revenues from collaborators $ 89,912 $ 47,159 $ 41,097
Schedule of Research and Development Expenses Incurred by Type that are Directly Attributable to Each Significant Agreement	The following table provides the research and development expenses incurred by type that are directly attributable to each significant agreement for the periods indicated, in thousands: Year Ended December 31, 2017 2016 2015 Sanofi Genzyme MDCO Ionis Sanofi Genzyme MDCO Ionis Sanofi Genzyme MDCO Ionis Research and development Clinical trial and manufacturing $ 174,901 $ 5,421 $ — $ 150,179 $ 1,211 $ — $ 108,903 $ 3,308 $ — External services 4,475 — 3,250 7,366 — — 3,151 770 — Other 5,327 106 — 3,035 64 525 3,714 497 3,300 Total research and development expenses $ 184,703 $ 5,527 $ 3,250 $ 160,580 $ 1,275 $ 525 $ 115,768 $ 4,575 $ 3,300
Information Related to 2014 Sanofi Genzyme Collaboration	The following table presents information related to the 2014 Sanofi Genzyme collaboration, in thousands: Excess of fair value of our common stock issued to Sanofi Genzyme in February 2014 $ (51,450 ) Deferred revenue remaining under the 2012 Sanofi Genzyme agreement upon execution of the 2014 Sanofi Genzyme collaboration 33,500 Milestone payment received: Year-ended December 31, 2014 25,000 Development expense reimbursement from Sanofi Genzyme: Year-ended December 31, 2015 33,949 Year-ended December 31, 2016 54,337 Year-ended December 31, 2017 51,846 Total consideration at December 31, 2017 $ 147,182 Cumulative revenue recognized at December 31, 2017 $ 98,014 Deferred revenue at December 31, 2017 $ 49,168

FAIR VALUE MEASUREMENTS (Tables

FAIR VALUE MEASUREMENTS (Tables)	12 Months Ended
	Dec. 31, 2017
Fair Value Disclosures [Abstract]
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, 2017 and 2016, and indicate the fair value hierarchy of the valuation techniques we utilized to determine such fair value, in thousands: Description At December 31, 2017 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Commercial paper $ 82,262 $ — $ 82,262 $ — Corporate notes 18,116 — 18,116 — U.S. government-sponsored enterprise securities 231,122 — 231,122 — U.S. treasury securities 62,855 — 62,855 — Money market funds 122,986 122,986 — — Marketable securities (fixed income): — Certificates of deposit 30,200 — 30,200 — Commercial paper 56,951 — 56,951 — Corporate notes 373,252 — 373,252 — U.S. government-sponsored enterprise securities 398,298 — 398,298 — U.S. treasury securities 200,475 — 200,475 — Restricted cash (Money market funds) 1,471 1,471 — — Total $ 1,577,988 $ 124,457 $ 1,453,531 $ — Description At December 31, 2016 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Commercial paper $ 17,199 $ — $ 17,199 $ — Money market funds 151,479 151,479 — — Marketable securities (fixed income): — Certificates of deposit 17,999 — 17,999 — Commercial paper 59,340 — 59,340 — Corporate notes 333,872 — 333,872 — U.S. government-sponsored enterprise securities 297,773 — 297,773 — U.S. treasury securities 40,000 — 40,000 — Marketable securities (Regulus equity holdings) 8,997 8,997 — — Restricted cash (Money market funds) 1,471 1,471 — — Total $ 928,130 $ 161,947 $ 766,183 $ —

MARKETABLE SECURITIES (Tables)

MARKETABLE SECURITIES (Tables)	12 Months Ended
	Dec. 31, 2017
Investments Debt And Equity Securities [Abstract]
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, 2017 and 2016, and for the activity recorded in each year, in thousands: Description At December 2016 Sales Regulus Shares During Year Ended December 31, 2017 All Other Activity During Year December 31, 2017 Balance at December 2017 Carrying value $ 8,093 $ (7,485 ) $ (608 ) $ — Accumulated other comprehensive income (loss), before tax 904 1,894 (2,798 ) — Investment in equity securities of Regulus Therapeutics Inc., as reported $ 8,997 $ (5,591 ) $ (3,406 ) $ — Accumulated other comprehensive income (loss), before tax $ 904 $ 1,894 $ (2,798 ) $ — Intraperiod tax allocation recorded as a benefit from income taxes (32,792 ) — — (32,792 ) Accumulated other comprehensive income (loss), net of tax $ (31,888 ) $ 1,894 $ (2,798 ) $ (32,792 ) Description At December 2015 Sales Regulus Shares During Year Ended December 31, 2016 All Other Activity During Year December 31, 2016 Balance at December 2016 Carrying value $ 11,935 $ (3,842 ) $ — $ 8,093 Accumulated other comprehensive income (loss), before tax 39,484 (6,977 ) (31,603 ) 904 Investment in equity securities of Regulus Therapeutics Inc., as reported $ 51,419 $ (10,819 ) $ (31,603 ) $ 8,997 Accumulated other comprehensive income (loss), before tax $ 39,484 $ (6,977 ) $ (31,603 ) $ 904 Intraperiod tax allocation recorded as a benefit from income taxes (32,792 ) — — (32,792 ) Accumulated other comprehensive income (loss), net of tax $ 6,692 $ (6,977 ) $ (31,603 ) $ (31,888 )
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, 2017 and 2016, in thousands: At December 31, 2017 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 30,200 $ — $ — $ 30,200 Commercial paper 56,951 — — 56,951 Corporate notes 373,736 11 (495 ) 373,252 U.S. government-sponsored enterprise securities 399,281 — (983 ) 398,298 U.S. treasury securities 200,649 1 (175 ) 200,475 Total $ 1,060,817 $ 12 $ (1,653 ) $ 1,059,176 At December 31, 2016 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 17,999 $ — $ — $ 17,999 Commercial paper 59,340 — — 59,340 Corporate notes 334,266 47 (441 ) 333,872 U.S. government-sponsored enterprise securities 298,910 9 (1,146 ) 297,773 U.S. treasury securities 40,022 1 (23 ) 40,000 Total $ 750,537 $ 57 $ (1,610 ) $ 748,984
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, 2017, in thousands: At December 31, 2017 Amortized Cost Fair Value Less than one year $ 1,046,834 $ 1,045,257 Greater than one year but less than two years 13,983 13,919 Total $ 1,060,817 $ 1,059,176

PROPERTY, PLANT AND EQUIPMENT25

PROPERTY, PLANT AND EQUIPMENT, NET (Tables)	12 Months Ended
	Dec. 31, 2017
Property Plant And Equipment [Abstract]
Property, Plant and Equipment, Net	Property, plant and equipment consist of the following at December 31, 2017 and 2016, in thousands: At December 31, 2017 2016 Laboratory equipment $ 40,462 $ 37,303 Computer equipment and software 9,608 9,650 Furniture and fixtures 5,844 6,002 Leasehold improvements 50,612 45,362 Land 9,080 9,080 Construction in progress 133,645 68,182 249,251 175,579 Less: accumulated depreciation (67,351 ) (61,007 ) $ 181,900 $ 114,572

COMMITMENTS AND CONTINGENCIES (

COMMITMENTS AND CONTINGENCIES (Tables)	12 Months Ended
	Dec. 31, 2017
Commitments And Contingencies Disclosure [Abstract]
Fixed, Estimated and Cancelable Payments under Existing License and Other Technology Agreements	At December 31, 2017, we were committed to make the following fixed, estimated and cancelable payments under existing license agreements, in thousands: Year Ending December 31, 2018 $ 21,012 2019 12,277 2020 795 2021 795 2022 595 Thereafter 1,500 Total $ 36,974
Future Minimum Payments Under Non-cancelable Leases	Future minimum payments under our non-cancelable facility leases, including rent payments for the BMR-675 West Kendall Lease which are expected to commence in early 2019, are approximately as follows, in thousands: Year Ending December 31, 2018 $ 14,464 2019 32,446 2020 34,570 2021 30,928 2022 23,050 Thereafter 297,726 Total $ 433,184

STOCK-BASED COMPENSATION (Table

STOCK-BASED COMPENSATION (Tables)	12 Months Ended
	Dec. 31, 2017
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, 2017, in thousands: 2017 2016 2015 Stock-based compensation expense by type of award: Time-based stock options $ 61,802 $ 62,800 $ 43,078 Performance-based stock options 23,260 8,337 — Restricted stock awards 541 497 555 ESPP share issuances 2,155 1,360 694 Other equity programs 1,946 1,846 — Non-employee stock options 3,115 688 1,456 $ 92,819 $ 75,528 $ 45,783
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, 2017 by type of awards, and the weighted-average period over which that expense is expected to be recognized: At December 31, 2017 Unrecognized Expense, Net of Estimated Forfeitures Weighted- average Recognition Period (in thousands) (in years) Type of award: Time-based stock options $ 124,295 2.60 Performance-based stock options 59,416 * Performance-based restricted stock units 14,649 * ESPP share issuances 970 0.33 * Performance-based stock options and performance-based restricted stock units are recorded as expense beginning when vesting events are determined to be probable.
Valuation Assumptions for Stock Options	2017 2016 2015 Risk-free interest rate 1.9-2.3% 0.9-2.2% 1.0-2.0% Expected dividend yield — — — Expected option life 5.7-7.2 years 3.5-7.5 years 3.5-7.5 years Expected volatility 61-67% 55-65% 53-60%
Stock Option and Inducement Grant Activity	The following table summarizes the activity of our stock option plans and the inducement grants described above, excluding performance-based stock options: Number of Options (in Weighted- average Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2016 9,913 $ 56.05 Granted 1,664 75.66 Exercised (1,796 ) 42.81 Cancelled (680 ) 83.70 Outstanding, December 31, 2017 9,101 $ 60.18 6.92 $ 609,620 Exercisable at December 31, 2017 5,294 $ 51.54 5.59 $ 400,390 Vested or expected to vest at December 31, 2017 8,670 $ 59.64 6.82 $ 587,480
Performance-based stock options
Stock Option and Inducement Grant Activity	The following table summarizes the activity of our performance-based stock options granted under our equity plans and the performance-based portion of the inducement grants described above: Number of Options (in Weighted- average Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2016 2,357 $ 69.61 Granted 25 52.61 Exercised (54 ) 80.46 Cancelled (190 ) 69.59 Outstanding, December 31, 2017 2,138 $ 69.14 7.79 $ 123,795 Exercisable at December 31, 2017 813 $ 73.66 7.23 $ 43,416

INCOME TAXES (Tables)

INCOME TAXES (Tables)	12 Months Ended
	Dec. 31, 2017
Income Tax Disclosure [Abstract]
Schedule of Domestic and Foreign Components of Loss before Income Taxes	The domestic and foreign components of loss before income taxes are as follows, in thousands: 2017 2016 2015 Domestic $ (378,293 ) $ (350,704 ) $ (245,681 ) Foreign (112,581 ) (59,404 ) (44,392 ) Loss before income taxes $ (490,874 ) $ (410,108 ) $ (290,073 )
Schedule of Components of Net Deferred Tax (Liability) Asset	Components of the net deferred tax (liability) asset at December 31, 2017 and 2016 are as follows, in thousands: 2017 2016 Deferred tax assets: Net operating loss carryforwards $ 405,784 $ 346,965 Research and development credits 192,094 111,394 AMT credits 788 788 Foreign tax credits — 3,196 Capitalized research and development and start-up costs 13,163 18,138 Deferred revenue 13,576 20,853 Deferred compensation 42,990 51,355 Intangible assets 9,018 14,725 Partnership interest — 1,623 Other 11,608 7,845 Total deferred tax assets 689,021 576,882 Deferred tax liabilities: Unrealized gain on available-for-sale securities (765 ) (1,524 ) Deferred tax asset valuation allowance (688,256 ) (575,358 ) Net deferred tax liability $ — $ —
Schedule of Effective Income Tax Rate Differs from Statutory Federal Income Tax Rate	Our effective income tax rate differs from the statutory federal income tax rate as follows for the years ended December 31, 2017, 2016 and 2015: 2017 2016 2015 At U.S. federal statutory rate 35.0 % 35.0 % 35.0 % State taxes, net of federal effect 3.8 3.7 4.0 Stock-based compensation 3.3 (1.4 ) (1.1 ) Tax credits 9.9 11.8 8.0 Orphan drug credit (3.4 ) (3.5 ) (2.0 ) Other permanent items (1.0 ) (0.4 ) (0.1 ) Foreign rate differential (8.1 ) (5.1 ) (5.4 ) Tax reform change (46.5 ) — — Other (0.9 ) — — Valuation allowance 7.9 (40.1 ) (38.4 ) Effective income tax rate — % — % — %

ACCRUED EXPENSES (Tables)

ACCRUED EXPENSES (Tables)	12 Months Ended
	Dec. 31, 2017
Accrued Liabilities Current [Abstract]
Accrued Expenses	Accrued expenses consist of the following at December 31, 2017 and 2016, in thousands: At December 31, 2017 2016 Compensation and related $ 33,826 $ 13,689 Clinical trial and manufacturing 20,004 11,756 Consulting and professional services 7,276 2,788 Pre-clinical 239 1,257 Other 10,858 12,628 $ 72,203 $ 42,118

QUARTERLY FINANCIAL DATA (UNA30

QUARTERLY FINANCIAL DATA (UNAUDITED) (Tables)	12 Months Ended
	Dec. 31, 2017
Quarterly Financial Information Disclosure [Abstract]
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, 2017 June 30, 2017 September 30, 2017 December 31, 2017 (In thousands, except per share data) Revenues $ 18,960 $ 15,932 $ 17,096 $ 37,924 Operating expenses 125,471 136,406 142,896 $ 185,227 Net loss $ (107,290 ) $ (118,420 ) $ (122,937 ) $ (142,227 ) Net loss per common share — basic and diluted $ (1.25 ) $ (1.34 ) $ (1.34 ) $ (1.48 ) Weighted-average common shares — basic and diluted 86,027 88,098 91,828 96,139 Three Months Ended March 31, 2016 June 30, 2016 September 30, 2016 December 31, 2016 (In thousands, except per share data) Revenues $ 7,345 $ 8,709 $ 13,651 $ 17,454 Operating expenses 117,373 101,159 120,327 132,887 Net loss $ (102,974 ) $ (90,129 ) $ (104,071 ) $ (112,934 ) Net loss per common share — basic and diluted $ (1.21 ) $ (1.05 ) $ (1.21 ) $ (1.32 ) Weighted-average common shares — basic and diluted 85,277 85,545 85,716 85,843

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, 2017	Dec. 31, 2016	Dec. 31, 2015
Sanofi Genzyme
Concentration Risk [Line Items]
Concentration risk percentage	61.00%	68.00%	27.00%
MDCO
Concentration Risk [Line Items]
Concentration risk percentage	34.00%	24.00%	25.00%
Takeda
Concentration Risk [Line Items]
Concentration risk percentage			22.00%
Monsanto
Concentration Risk [Line Items]
Concentration risk percentage			14.00%

Customers that Represent Grea32

Customers that Represent Greater than Ten Percent of Billed and Unbilled Collaboration Receivables (Detail) - Accounts Receivable - Credit Concentration Risk	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016
MDCO
Concentration Risk [Line Items]
Concentration risk percentage	59.00%
Sanofi Genzyme
Concentration Risk [Line Items]
Concentration risk percentage	39.00%	97.00%

Summary of Significant Accoun33

Summary of Significant Accounting Policies - Additional Information (Detail)	12 Months Ended
	Dec. 31, 2017USD ($)Segment	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)	Mar. 31, 2018USD ($)
Significant Accounting Policies [Line Items]
Realized gain (loss) on sale of marketable securities	$ (1,894,000)	$ 6,977,000
Marketable securities classified as cash equivalents, maximum original maturity	90 days
Policy for marketable securities	90 days
Deferred revenue, current	$ 41,705,000	33,540,000
Deferred revenue, net of current portion	43,075,000	49,392,000
Significant interest and penalty expense related to uncertain tax positions	$ 0
Number of reporting segment | Segment	1
Scenario, Forecast | Reduction In Deferred Revenue
Significant Accounting Policies [Line Items]
Offsetting adjustments to accumulated deficit				$ (68,300,000)
Scenario, Forecast | Reduction In Deferred Tax Asset
Significant Accounting Policies [Line Items]
Offsetting adjustments to accumulated deficit				$ (13,600,000)
Research and Development
Significant Accounting Policies [Line Items]
License fee	$ 7,700,000	$ 2,400,000	$ 3,500,000

Estimated Useful Lives of Prope

Estimated Useful Lives of Property, Plant and Equipment (Detail)	12 Months Ended
	Dec. 31, 2017
Laboratory equipment
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	5 years
Computer equipment and software | Minimum
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	3 years
Computer equipment and software | Maximum
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	10 years
Furniture and Fixtures
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	5 years
Leasehold improvements
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	Shorter of asset life or lease term

Potential Common Shares Exclude

Potential Common Shares Excluded from Calculation of Net Loss Per Common Share (Detail) - shares shares in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities excluded from computation of earnings per share	11,388	12,441	9,979
Options to purchase common stock
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities excluded from computation of earnings per share	11,239	12,270	9,960
Unvested restricted common stock
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities excluded from computation of earnings per share	149	171	19

Revenue from Collaborators (Det

Revenue from Collaborators (Detail) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators	$ 37,924	$ 17,096	$ 15,932	$ 18,960	$ 17,454	$ 13,651	$ 8,709	$ 7,345	$ 89,912	$ 47,159	$ 41,097
Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators									54,625	32,015	11,005
MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators									30,217	11,220	10,301
Takeda
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators											8,867
Monsanto
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators									2,500		5,621
Other
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total net revenues from collaborators									$ 2,570	$ 3,924	$ 5,303

Schedule of Research and Develo

Schedule of Research and Development Expenses Incurred by Type that are Directly Attributable to Each Significant Agreement (Detail) - USD ($) $ in Thousands		12 Months Ended
		Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses	[1]	$ 390,635	$ 382,392	$ 276,495
Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		184,703	160,580	115,768
MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		5,527	1,275	4,575
Ionis
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		3,250	525	3,300
Clinical trial and manufacturing | Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		174,901	150,179	108,903
Clinical trial and manufacturing | MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		5,421	1,211	3,308
External services | Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		4,475	7,366	3,151
External services | MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses				770
External services | Ionis
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		3,250
Other | Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		5,327	3,035	3,714
Other | MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		$ 106	64	497
Other | Ionis
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses			$ 525	$ 3,300
[1]	Stock-based compensation expenses included in operating expenses are as follows: Research and development $51,872 $42,946 $27,086 General and administrative 40,947 32,582 18,697

Significant Agreements - Additi

Significant Agreements - Additional Information (Detail)

Feb. 01, 2016USD ($)shares

Jan. 22, 2015USD ($)shares

Jan. 14, 2014USD ($)

Oct. 31, 2012USD ($)

Jan. 31, 2018USD ($)MilestonePayment

Nov. 30, 2017USD ($)$ / sharesshares

May 31, 2017USD ($)$ / sharesshares

Jan. 31, 2017USD ($)

Oct. 31, 2016

Sep. 28, 2015

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

Sep. 30, 2014USD ($)

Mar. 31, 2014USD ($)shares

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

Feb. 28, 2013USD ($)

Aug. 31, 2012USD ($)

May 31, 2008USD ($)

Mar. 31, 2004USD ($)License

Dec. 31, 2017USD ($)

Dec. 31, 2014USD ($)

Dec. 31, 2013USD ($)

Sep. 30, 2016

Dec. 31, 2017USD ($)Program

Dec. 31, 2016USD ($)

Dec. 31, 2015USD ($)

Dec. 31, 2014USD ($)

Sep. 30, 2014USD ($)

Dec. 31, 2017USD ($)

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

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

6,440,000

5,000,000

5,447,368

Proceeds from issuance of common stock to Sanofi Genzyme

$ 21,381,000

$ 14,301,000

$ 89,018,000

Common stock price | $ / shares

$ 125

$ 71.87

$ 95

Provision for (Benefit from) income taxes

0

0

0

Research and Development

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

License fee

$ 7,700,000

2,400,000

3,500,000

Ionis

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

Collaborative agreement termination notice period

90 days

Maximum | Monsanto Alliance

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

Estimated range of expiration for fundamental patents

2,025

Minimum | Monsanto Alliance

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

Estimated range of expiration for fundamental patents

2,016

Product Alliances | MDCO

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

Upfront fee received

$ 25,000,000

Amount earned upon achievement of milestone

$ 20,000,000

$ 20,000,000

$ 10,000,000

Deferred revenue

5,700,000

$ 5,700,000

$ 5,700,000

Maximum number of potential future milestones

180,000,000

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

Next potential milestone payment

25,000,000

Revenue from reimbursement of costs incurred

12,200,000

Revenue recognizing period

5 years

Product Alliances | MDCO | Licensing Agreements

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

Revenue from reimbursement of costs incurred

$ 5,400,000

3,000,000

3,800,000

Product Alliances | MDCO | Phase 1 Clinical Trial

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

Amount earned upon achievement of milestone

$ 10,000,000

Product Alliances | Maximum | MDCO

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

Estimated range of expiration for fundamental patents

2,028

Product Alliances | Minimum | MDCO

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

Estimated range of expiration for fundamental patents

2,016

Platform Alliances | Monsanto Alliance

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

Upfront fee received

$ 29,200,000

Amount earned upon achievement of milestone

$ 4,000,000

Deferred revenue

2,500,000

$ 2,500,000

2,500,000

Maximum number of potential future milestones

$ 5,000,000

Next potential milestone payment

0

Revenue recognizing period

5 years

Period of exclusivity in the collaboration

10 years

Final required milestone payment cancelled

$ 1,000,000

Deferred revenue, potential refundable amount

$ 5,000,000

2,500,000

2,500,000

2,500,000

Period for services under contract

5 years

Contractual agreement obligation period

30 months

Additional revenue, recognized

2,500,000

Deferred revenue potential refundable payment additional

2,500,000

2,500,000

2,500,000

Platform Alliances | Monsanto Alliance | Amended Agreement

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

Deferred revenue

$ 16,800,000

$ 16,800,000

Platform Alliances | Takeda

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

Upfront fee received

$ 100,000,000

Deferred revenue

0

0

0

Maximum number of potential future milestones

171,000,000

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

Next potential milestone payment

$ 2,000,000

Granted period of royalty bearing license

5 years

Milestone fees to company upon achievement of specified technology transfer milestones

$ 50,000,000

License and collaborations agreements, prior written notice period before termination

180 days

Platform Alliances | Takeda | Joint Technology Transfer Committee

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

Maximum life of collaboration committee

7 years

Platform Alliances | Takeda | Joint Delivery Collaboration Committee

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

Maximum life of collaboration committee

7 years

Platform Alliances | Maximum | Takeda

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

Estimated range of expiration for fundamental patents

2,025

Platform Alliances | Minimum | Takeda

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

Estimated range of expiration for fundamental patents

2,016

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 | License

10

Additional number of licensed products | License

1

Discovery and Development Alliances | Ionis | Research and Development

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

License fee

$ 200,000

200,000

1,900,000

License fees incurred but not yet paid

1,000,000

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]

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

3,400,000

Discovery and Development Alliances | Ionis | Therapeutic target

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

License fee

$ 500,000

Sanofi Genzyme

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

Amount earned upon achievement of milestone

$ 25,000,000

Deferred revenue

$ 49,168,000

$ 49,168,000

$ 49,168,000

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

344,448

8,766,338

Proceeds from issuance of common stock to Sanofi Genzyme

$ 23,000,000

$ 700,000,000

Voting percentage

20.00%

Minimum percentage of ownership interest terminate

7.50%

Agreement lock-up period, extension term

2 years

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

Fair value of shares issued

$ 751,500,000

Excess of fair value over cash received for stock issuance

51,450,000

Provision for (Benefit from) income taxes

$ (15,200,000)

Percentage ownership interest owned by noncontrolling owners

11.00%

11.00%

11.00%

Revenue from reimbursement of costs incurred

$ 51,846,000

$ 54,337,000

$ 33,949,000

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

297,501

744,566

Proceeds from issuance of common stock to Sanofi Genzyme

$ 21,400,000

$ 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

205,030

196,251

Proceeds from issuance of common stock to Sanofi Genzyme

$ 14,300,000

$ 18,300,000

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 | Maximum

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

Agreement to acquire outstanding shares of common stock percentage

30.00%

Sanofi Genzyme | Maximum | Following the two-year anniversary

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

Percentage of sale of initial shares

25.00%

Sanofi Genzyme | Minimum

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

Agreement to acquire outstanding shares of common stock percentage

5.00%

Percentage of ownership interest

30.00%

Sanofi Genzyme | Minimum | Following the two-year anniversary

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 | Product Alliances

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

Upfront fee received

$ 22,500,000

Amount earned upon achievement of milestone

$ 11,000,000

Deferred revenue

$ 33,500,000

Sanofi Genzyme | Product Alliances | Patisiran and Revusiran

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

Performance period

5 years

6 years

Sanofi Genzyme | Product Alliances | Fitusiran

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

Performance period

5 years

6 years

Sanofi Genzyme | Regional Collaboration Product

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

Percentage of sharing in development cost

20.00%

Maximum number of potential future milestones

$ 75,000,000

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 | Co-developed/ Co-commercialized Collaboration Product

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

Percentage of sharing in development cost

50.00%

Royalty rate

20.00%

Received incremental share of co-development costs for exercise of right, fitusiran

$ 6,000,000

Expected first milestone payment to be received fitusiran

$ 25,000,000

$ 25,000,000

$ 25,000,000

Sanofi Genzyme | Co-developed/ Co-commercialized Collaboration Product | Revusiran

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

Amount earned upon achievement of milestone

$ 25,000,000

Sanofi Genzyme | Global Collaboration Product

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

Percentage of sharing in development cost

100.00%

Maximum number of potential future milestones

$ 200,000,000

Potential future payment for the achievement of certain development milestones

100,000,000

Potential future payment for the achievement of specified commercialization milestones

$ 100,000,000

Royalty rate

20.00%

Sanofi Genzyme | AT3 License Terms and the Exclusive TTR License | Subsequent Event

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

Maximum funding for development and commercialization costs for fitusiran, during transition period

$ 50,000,000

Sanofi Genzyme | TTR License | Subsequent Event | Maximum

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

Royalty rate

15.00%

Sanofi Genzyme | TTR License | Patisiran | Subsequent Event | Japan

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

Royalty rate

25.00%

Sanofi Genzyme | TTR License | Patisiran | Subsequent Event | Maximum

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

Royalty rate

25.00%

Sanofi Genzyme | TTR License | TTRsc02 | Subsequent Event | Maximum

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

Royalty rate

30.00%

Sanofi Genzyme | TTR License | TTRsc02 | Subsequent Event | Minimum

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

Royalty rate

15.00%

Sanofi Genzyme | AT3 License Terms | Subsequent Event

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

Royalty rate

15.00%

Number of milestone payments required | MilestonePayment

1

Expected milestone payment to be received fitusiran

$ 50,000,000

Sanofi Genzyme | AT3 License Terms | Subsequent Event | Maximum

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

Royalty rate

30.00%

Sanofi Genzyme | AT3 License Terms | Subsequent Event | Minimum

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

Royalty rate

15.00%

Sanofi Genzyme | Investors

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

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

3

Information Related to 2014 San

Information Related to 2014 Sanofi Genzyme Collaboration (Detail) - Sanofi Genzyme - USD ($) $ in Thousands	1 Months Ended	3 Months Ended	12 Months Ended
	Feb. 28, 2014	Dec. 31, 2013	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015	Dec. 31, 2014
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Excess of fair value of our common stock issued to Sanofi Genzyme in February 2014	$ (51,450)
Deferred revenue			$ 49,168
Milestone payment received:
Milestone payment						$ 25,000
Development expense reimbursement from Sanofi Genzyme:
Development expense reimbursement			51,846	$ 54,337	$ 33,949
Total consideration at December 31, 2017			147,182
Cumulative revenue recognized at December 31, 2017			$ 98,014
Product Alliances
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Deferred revenue		$ 33,500
Milestone payment received:
Milestone payment		$ 11,000

Fair Value of Assets Measured o

Fair Value of Assets Measured on a Recurring Basis (Detail) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	$ 1,059,176	$ 748,984
Recurring
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale equity securities, Fair value disclosure		8,997
Total	1,577,988	928,130
Recurring | Commercial paper
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	82,262	17,199
Available for sale debt securities, Fair value disclosure	56,951	59,340
Recurring | Corporate notes
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	18,116
Available for sale debt securities, Fair value disclosure	373,252	333,872
Recurring | U.S. government-sponsored enterprise securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	231,122
Available for sale debt securities, Fair value disclosure	398,298	297,773
Recurring | U.S. treasury securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	62,855
Available for sale debt securities, Fair value disclosure	200,475	40,000
Recurring | Money Market Funds
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	122,986	151,479
Restricted cash	1,471	1,471
Recurring | Certificate of deposit
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	30,200	17,999
Recurring | Quoted Prices in Active Markets (Level 1)
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale equity securities, Fair value disclosure		8,997
Total	124,457	161,947
Recurring | Quoted Prices in Active Markets (Level 1) | Money Market Funds
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	122,986	151,479
Restricted cash	1,471	1,471
Recurring | Significant Observable Inputs (Level 2)
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total	1,453,531	766,183
Recurring | Significant Observable Inputs (Level 2) | Commercial paper
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	82,262	17,199
Available for sale debt securities, Fair value disclosure	56,951	59,340
Recurring | Significant Observable Inputs (Level 2) | Corporate notes
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	18,116
Available for sale debt securities, Fair value disclosure	373,252	333,872
Recurring | Significant Observable Inputs (Level 2) | U.S. government-sponsored enterprise securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	231,122
Available for sale debt securities, Fair value disclosure	398,298	297,773
Recurring | Significant Observable Inputs (Level 2) | U.S. treasury securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	62,855
Available for sale debt securities, Fair value disclosure	200,475	40,000
Recurring | Significant Observable Inputs (Level 2) | Certificate of deposit
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	$ 30,200	$ 17,999

Fair Value Measurements - Addit

Fair Value Measurements - Additional Information (Detail) $ in Millions	Dec. 31, 2017USD ($)
Significant Unobservable Inputs (Level 3)
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Fair value of long-term debt	$ 30.1

Summary of Fair Value, Accumula

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, 2017	Dec. 31, 2016	Dec. 31, 2015
Schedule of Available-for-sale Securities [Line Items]
Intraperiod tax allocation recorded as a benefit from income taxes	$ (765)	$ (1,524)
Accumulated other comprehensive income (loss), net of tax	(2,886)	(30,833)	$ (44,394)
Regulus Therapeutics Inc
Schedule of Available-for-sale Securities [Line Items]
Carrying value		8,093	11,935
Accumulated other comprehensive income (loss), before tax		904	39,484
Investment in equity securities of Regulus Therapeutics Inc., as reported		8,997	51,419
Intraperiod tax allocation recorded as a benefit from income taxes	(32,792)	(32,792)	(32,792)
Accumulated other comprehensive income (loss), net of tax	(32,792)	(31,888)	$ 6,692
Regulus Therapeutics Inc | Sales of Regulus Shares
Schedule of Available-for-sale Securities [Line Items]
Carrying value	(7,485)	(3,842)
Accumulated other comprehensive income (loss), before tax	1,894	(6,977)
Investment in equity securities of Regulus Therapeutics Inc., as reported	(5,591)	(10,819)
Accumulated other comprehensive income (loss), net of tax	1,894	(6,977)
Regulus Therapeutics Inc | All Other Activity
Schedule of Available-for-sale Securities [Line Items]
Carrying value	(608)
Accumulated other comprehensive income (loss), before tax	(2,798)	(31,603)
Investment in equity securities of Regulus Therapeutics Inc., as reported	(3,406)	(31,603)
Accumulated other comprehensive income (loss), net of tax	$ (2,798)	$ (31,603)

Summary of Company's Marketable

Summary of Company's Marketable Securities Excluding Regulus (Detail) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	$ 1,060,817	$ 750,537
Gross Unrealized Gains	12	57
Gross Unrealized Losses	(1,653)	(1,610)
Fair Value	1,059,176	748,984
Certificate of deposit
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	30,200	17,999
Fair Value	30,200	17,999
Commercial paper
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	56,951	59,340
Fair Value	56,951	59,340
Corporate notes
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	373,736	334,266
Gross Unrealized Gains	11	47
Gross Unrealized Losses	(495)	(441)
Fair Value	373,252	333,872
U.S. government-sponsored enterprise securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	399,281	298,910
Gross Unrealized Gains		9
Gross Unrealized Losses	(983)	(1,146)
Fair Value	398,298	297,773
U.S. treasury securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	200,649	40,022
Gross Unrealized Gains	1	1
Gross Unrealized Losses	(175)	(23)
Fair Value	$ 200,475	$ 40,000

Summary of Available-For-Sale D

Summary of Available-For-Sale Debt Securities by Contractual Maturity (Detail) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Amortized Cost
Less than one year	$ 1,046,834
Greater than one year but less than two years	13,983
Amortized Cost	1,060,817	$ 750,537
Fair Value
Less than one year	1,045,257
Greater than one year but less than two years	13,919
Total	$ 1,059,176	$ 748,984

Property Plant and Equipment Ne

Property Plant and Equipment Net (Detail) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Property Plant And Equipment [Abstract]
Laboratory equipment	$ 40,462	$ 37,303
Computer equipment and software	9,608	9,650
Furniture and fixtures	5,844	6,002
Leasehold improvements	50,612	45,362
Land	9,080	9,080
Construction in progress	133,645	68,182
Property, Plant and Equipment Gross	249,251	175,579
Less: accumulated depreciation	(67,351)	(61,007)
Property, Plant and Equipment, Net	$ 181,900	$ 114,572

Property Plant and Equipment 46

Property Plant and Equipment Net - Additional Information (Detail) $ in Thousands	12 Months Ended
	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)	Apr. 30, 2016a
Property, Plant and Equipment [Line Items]
Depreciation expense	$ 11,900	$ 9,600	$ 6,700
Property, plant and equipment, net	181,900	114,572
Norton, Massachusetts
Property, Plant and Equipment [Line Items]
Undeveloped land acquired | a				12
Norton, Massachusetts | Land and costs related to the construction of manufacturing facility
Property, Plant and Equipment [Line Items]
Property, plant and equipment, net	$ 140,500	$ 73,200

Fixed, Estimated and Cancelable

Fixed, Estimated and Cancelable Payments under Existing License and Other Technology Agreements (Detail) $ in Thousands	Dec. 31, 2017USD ($)
Commitments And Contingencies Disclosure [Abstract]
2,018	$ 21,012
2,019	12,277
2,020	795
2,021	795
2,022	595
Thereafter	1,500
Total	$ 36,974

Commitments and Contingencies -

Commitments and Contingencies - Additional Information (Detail)

Dec. 27, 2017USD ($)

Apr. 29, 2016USD ($)

Feb. 28, 2014ft²

Feb. 10, 2012ft²

Aug. 31, 2016RenewalOption

May 31, 2015USD ($)ft²RenewalOption$ / ft²

Apr. 30, 2015USD ($)ft²RenewalOption

Mar. 31, 2015USD ($)RenewalOption

Mar. 31, 2014RenewalOption

Dec. 31, 2017USD ($)

Dec. 31, 2016USD ($)

Dec. 31, 2015USD ($)

Oct. 14, 2015USD ($)

Commitments And Contingencies [Line Items]

Fixed, non-cancelable payment due in 2018

$ 5,000,000

Fixed, non-cancelable payment due in 2019

5,000,000

Rent expense

18,700,000

$ 15,900,000

$ 10,500,000

Repayment of outstanding principal amount in full

120,000,000

Restricted investments

30,000,000

150,000,000

Litigation, motion filed for reimbursement of costs and fees

$ 8,000,000

Term Loan Facility | Other Income (Expense)

Commitments And Contingencies [Line Items]

Interest expense

800,000

1,200,000

Bank of America N.A

Commitments And Contingencies [Line Items]

Cash collateral required for principal amount outstanding, percentage

100.00%

Bank of America N.A | Term Loan Facility

Commitments And Contingencies [Line Items]

Line of credit facility, maximum borrowing capacity

$ 120,000,000

Repayment of outstanding principal amount in full

$ 120,000,000

Line of credit facility, expiration date

Apr. 29, 2021

Bank of America N.A | Term Loan Facility | LIBOR

Commitments And Contingencies [Line Items]

Debt instrument, basis spread on variable rate

0.45%

Wells Fargo Bank, National Association

Commitments And Contingencies [Line Items]

Cash collateral required for principal amount outstanding, percentage

100.00%

Wells Fargo Bank, National Association | Term Loan Facility

Commitments And Contingencies [Line Items]

Line of credit facility, maximum borrowing capacity

$ 30,000,000

Line of credit facility, expiration date

Apr. 29, 2021

Wells Fargo Bank, National Association | Term Loan Facility | LIBOR

Commitments And Contingencies [Line Items]

Debt instrument, basis spread on variable rate

0.45%

Other Assets

Commitments And Contingencies [Line Items]

Restricted cash

$ 1,500,000

$ 1,500,000

Third Street Lease

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 lease | ft²

129,000

Amended lease extension period

5 years

Number of lease extension options | RenewalOption

1

Lease expiration date

2016-09

BMR-665 Concord Avenue Lease

Commitments And Contingencies [Line Items]

Lease extension period

5 years

Lease extended expiration date

Aug. 31, 2022

Area of office and laboratory space held under lease | ft²

15,000

Amended lease extension period

5 years

Number of lease extension options | RenewalOption

1

Lease expiration date

2017-08

BMR-675 West Kendall Lease

Commitments And Contingencies [Line Items]

Area of office and laboratory space held under lease | ft²

295,000

Number of lease extension options | RenewalOption

2

Lease term

15 years

Lease renewal options period

5 years

Facility lease annual rent for the first year

$ 19,800,000

Facility lease percentage of annual rent increase after first year

3.00%

Cost of base building and tenant improvement

$ 56,100,000

101 Main Street Leases

Commitments And Contingencies [Line Items]

Area of office and laboratory space held under lease | ft²

72,000

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

1

101 Main Street Initial Leases

Commitments And Contingencies [Line Items]

Number of lease extension options | RenewalOption

1

Operating lease term

4 years

Operating lease renewal options period

5 years

Operating lease annual rent for the first year

$ 1,700,000

101 Main Street Additional Leases

Commitments And Contingencies [Line Items]

Number of lease extension options | RenewalOption

1

Operating lease term

5 years 6 months

Operating lease renewal options period

5 years

Operating lease annual rent for the first year

$ 3,500,000

Future Minimum Lease Payments u

Future Minimum Lease Payments under Non-Cancelable Lease (Detail) $ in Thousands	Dec. 31, 2017USD ($)
Commitments And Contingencies Disclosure [Abstract]
2,018	$ 14,464
2,019	32,446
2,020	34,570
2,021	30,928
2,022	23,050
Thereafter	297,726
Total	$ 433,184

Stockholders Equity - Additiona

Stockholders Equity - Additional Information (Detail) - USD ($) $ / shares in Units, $ in Thousands	1 Months Ended			12 Months Ended
	Nov. 30, 2017	May 31, 2017	Jan. 31, 2015	Dec. 31, 2017	Dec. 31, 2015	Dec. 31, 2016
Stockholders Equity Note [Abstract]
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)	6,440,000	5,000,000	5,447,368
Underwritten public offering amount per share	$ 125	$ 71.87	$ 95
Issuance of common stock, net of offering costs	$ 784,500	$ 355,200	$ 496,400	$ 1,139,625	$ 496,400
Underwriting discounts and commissions and other offering expenses	$ 20,500	$ 4,200	$ 21,100

Stock-Based Compensation - Addi

Stock-Based Compensation - Additional Information (Detail) - USD ($)	Dec. 31, 2017	May 08, 2017	Feb. 06, 2017	Sep. 19, 2016	Dec. 17, 2014	Jan. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015	May 31, 2017	May 31, 2015	Apr. 30, 2015	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	15,556,526						15,556,526
Option vesting percentage on the first anniversary of grant date	25.00%						25.00%
Option vesting percentage at the end of each successive three-month period	6.25%						6.25%
Change in control agreement period to avail benefits for an employee							12 months
Stock-based compensation							$ 92,819,000	$ 75,528,000	$ 45,783,000
Employee stock purchase plan, offering period							6 months
Stock Options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares available for future grant	11,239,128						11,239,128
Equity awards, term							10 years
Restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares available for future grant	148,670						148,670
Additional Equity Awards
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares available for future grant	3,641,501						3,641,501
Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares authorized										1,215,789			715,789	315,789
Stock incentive plan, shares available for future grant	527,227						527,227
Stock-based compensation							$ 2,155,000	$ 1,360,000	$ 694,000
Employee stock purchase plan, purchase price as a percentage of common stock closing price							85.00%
Employee stock purchase plan, shares issued							103,666	53,499	22,639
Weighted average fair value awards granted							$ 17.10	$ 24.90	$ 29.96
Expected volatility							91.00%	55.00%	55.00%
Expected option life							6 months	6 months	6 months
Risk-free interest rate, approximate							0.70%	0.10%	0.10%
Performance-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock options granted							25,000	25,000
Aggregate intrinsic value of stock option exercised							$ 1,800,000	$ 35,000	$ 1,400,000
Stock options vested							614,796	159,122	0
Weighted average fair value of stock options vested							$ 37.86	$ 52.29
Stock options granted, exercise price							$ 52.61
Stock-based compensation							$ 23,260,000	$ 8,337,000
Inducement Equity Grants
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Equity awards, term		10 years	10 years	10 years
Stock options granted		150,000		150,000
Time-vested options under Inducement Equity Grants
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Option vesting percentage on the first anniversary of grant date		25.00%	25.00%	25.00%
Option vesting percentage at the end of each successive three-month period		6.25%	6.25%	6.25%
Stock options granted		125,000	50,000	125,000
Performance-based stock options under Inducement Equity Grants
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock options granted		25,000		25,000
Time-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Weighted average fair value of stock options granted							$ 44.76	$ 31.66	$ 51.28
Aggregate intrinsic value of stock option exercised							$ 111,300,000	$ 22,000,000	$ 130,000,000
Stock options granted, exercise price							$ 75.66
Stock-based compensation							$ 61,802,000	$ 62,800,000	$ 43,078,000
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
Performance-based restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted Stock Awards Granted						172,718
Fair value of equity awards granted						$ 16,100,000
Stock-based compensation	$ 0
Minimum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected option life							5 years 8 months 12 days	3 years 6 months	3 years 6 months
Minimum | Performance-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Vesting period							1 year
Minimum | Performance-based stock options under Inducement Equity Grants
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Vesting period		1 year		1 year
Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected option life							7 years 2 months 12 days	7 years 6 months	7 years 6 months
Stock Incentive Plan 2004
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares authorized	12,366,485						12,366,485
Stock Incentive Plan 2009
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock incentive plan, shares authorized										15,480,000	11,700,000	5,900,000

Summary of Stock-Based Compensa

Summary of Stock-Based Compensation Expense by Type of Award (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	$ 92,819	$ 75,528	$ 45,783
Time-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	61,802	62,800	43,078
Performance-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	23,260	8,337
Restricted stock awards
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	541	497	555
ESPP share issuances
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	2,155	1,360	694
Other Equity Programs
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	1,946	1,846
Non-employee stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	$ 3,115	$ 688	$ 1,456

Summary of Unrecognized Stock-B

Summary of Unrecognized Stock-Based Compensation Expense, Net of Estimated Forfeitures (Detail) $ in Thousands	12 Months Ended
	Dec. 31, 2017USD ($)
Time-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 124,295
Weighted-average Recognition Period	2 years 7 months 6 days
Performance-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 59,416
Performance-based restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	14,649
ESPP share issuances
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 970
Weighted-average Recognition Period	3 months 29 days

Valuation Assumptions for Stock

Valuation Assumptions for Stock Options (Detail)	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Risk-free interest rate, minimum	1.90%	0.90%	1.00%
Risk-free interest rate, maximum	2.30%	2.20%	2.00%
Expected volatility, minimum	61.00%	55.00%	53.00%
Expected volatility, maximum	67.00%	65.00%	60.00%
Minimum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected option life	5 years 8 months 12 days	3 years 6 months	3 years 6 months
Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected option life	7 years 2 months 12 days	7 years 6 months	7 years 6 months

Stock Option and Inducement Gra

Stock Option and Inducement Grant Activity (Detail) $ / shares in Units, shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2017USD ($)$ / sharesshares
Time-based stock options
Number of Options
Outstanding, December 31, 2016 | shares	9,913
Granted | shares	1,664
Exercised | shares	(1,796)
Cancelled | shares	(680)
Outstanding, December 31, 2017 | shares	9,101
Exercisable at December 31, 2017 | shares	5,294
Vested or expected to vest at December 31, 2017 | shares	8,670
Weighted-average Exercise Price
Outstanding, December 31, 2016 | $ / shares	$ 56.05
Granted | $ / shares	75.66
Exercised | $ / shares	42.81
Cancelled | $ / shares	83.70
Outstanding, December 31, 2017 | $ / shares	60.18
Exercisable at December 31, 2017 | $ / shares	51.54
Vested or expected to vest at December 31, 2017 | $ / shares	$ 59.64
Weighted-average Remaining Contractual Term (in years)
Outstanding, December 31, 2017	6 years 11 months 1 day
Exercisable at December 31, 2017	5 years 7 months 2 days
Vested or expected to vest at December 31, 2017	6 years 9 months 25 days
Aggregate Intrinsic Value
Outstanding, December 31, 2017 | $	$ 609,620
Exercisable at December 31, 2017 | $	400,390
Vested or expected to vest at December 31, 2017 | $	$ 587,480
Performance-based stock options
Number of Options
Outstanding, December 31, 2016 | shares	2,357
Granted | shares	25
Exercised | shares	(54)
Cancelled | shares	(190)
Outstanding, December 31, 2017 | shares	2,138
Exercisable at December 31, 2017 | shares	813
Weighted-average Exercise Price
Outstanding, December 31, 2016 | $ / shares	$ 69.61
Granted | $ / shares	52.61
Exercised | $ / shares	80.46
Cancelled | $ / shares	69.59
Outstanding, December 31, 2017 | $ / shares	69.14
Exercisable at December 31, 2017 | $ / shares	$ 73.66
Weighted-average Remaining Contractual Term (in years)
Outstanding, December 31, 2017	7 years 9 months 14 days
Exercisable at December 31, 2017	7 years 2 months 23 days
Aggregate Intrinsic Value
Outstanding, December 31, 2017 | $	$ 123,795
Exercisable at December 31, 2017 | $	$ 43,416

Schedule of Domestic and Foreig

Schedule of Domestic and Foreign Components of Loss before Income Taxes (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Income (Loss) Before Income Tax
Domestic	$ (378,293)	$ (350,704)	$ (245,681)
Foreign	(112,581)	(59,404)	(44,392)
Loss before income taxes	$ (490,874)	$ (410,108)	$ (290,073)

Schedule of Components of Net D

Schedule of Components of Net Deferred Tax (Liability) Asset (Detail) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Deferred tax assets:
Net operating loss carryforwards	$ 405,784	$ 346,965
Research and development credits	192,094	111,394
AMT credits	788	788
Foreign tax credits		3,196
Capitalized research and development and start-up costs	13,163	18,138
Deferred revenue	13,576	20,853
Deferred compensation	42,990	51,355
Intangible assets	9,018	14,725
Partnership interest		1,623
Other	11,608	7,845
Total deferred tax assets	689,021	576,882
Deferred tax liabilities:
Unrealized gain on available-for-sale securities	(765)	(1,524)
Deferred tax asset valuation allowance	$ (688,256)	$ (575,358)

Schedule of Effective Income Ta

Schedule of Effective Income Tax Rate Differs from Statutory Federal Income Tax Rate (Detail)	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Effective Income Tax Rate Reconciliation, Percent
At U.S. federal statutory rate	35.00%	35.00%	35.00%
State taxes, net of federal effect	3.80%	3.70%	4.00%
Stock-based compensation	3.30%	(1.40%)	(1.10%)
Tax credits	9.90%	11.80%	8.00%
Orphan drug credit	(3.40%)	(3.50%)	(2.00%)
Other permanent items	(1.00%)	(0.40%)	(0.10%)
Foreign rate differential	(8.10%)	(5.10%)	(5.40%)
Tax reform change	(46.50%)
Other	(0.90%)
Valuation allowance	7.90%	(40.10%)	(38.40%)

Income Taxes - Additional Infor

Income Taxes - Additional Information (Detail) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015	Jan. 01, 2017
Income Taxes [Line Items]
Increase (decrease) in valuation allowance		$ 112,900,000	$ 177,900,000	$ 129,100,000
Corporate tax rate		35.00%	35.00%	35.00%
Tax cuts and jobs act of 2017, provision to income tax expense in continuing operations and corresponding reduction in the valuation allowance		$ 227,900,000
Provision for (Benefit from) income taxes		0	$ 0	$ 0
Increased in deferred tax assets, associated with net operating losses		405,784,000	346,965,000
Increased in deferred tax assets, associated with research credit		$ 192,094,000	111,394,000
Net operating loss carryforwards expiration year		2,037
Unrecognized tax benefits that, if recognized, would favorably impact our effective income tax rate		$ 0	$ 0	$ 0
Interest and penalties on unrecognized tax benefits		$ 0
Earliest tax year
Income Taxes [Line Items]
Open tax year		2,014
Latest tax year
Income Taxes [Line Items]
Open tax year		2,017
Federal
Income Taxes [Line Items]
Net operating loss carryforward		$ 1,470,000,000
State and local jurisdiction
Income Taxes [Line Items]
Net operating loss carryforward		$ 1,550,000,000
Research and development and investment tax credit
Income Taxes [Line Items]
Tax credit carryforwards expiration year		2,037
Research and development and investment tax credit | Federal
Income Taxes [Line Items]
Tax credit carryforwards		$ 180,000,000
Research and development and investment tax credit | State and local jurisdiction
Income Taxes [Line Items]
Tax credit carryforwards		15,300,000
Alternative minimum tax
Income Taxes [Line Items]
Tax credit carryforwards		$ 800,000
Tax credits refundable year		2,021
Accounting Guidance Issued by FASB in March 2016
Income Taxes [Line Items]
Increased in deferred tax assets, associated with net operating losses					$ 122,200,000
Increased in deferred tax assets, associated with research credit					$ 30,800,000
Scenario, Forecast
Income Taxes [Line Items]
Corporate tax rate	21.00%

Accrued Expenses (Detail)

Accrued Expenses (Detail) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Accrued Liabilities Current [Abstract]
Compensation and related	$ 33,826	$ 13,689
Clinical trial and manufacturing	20,004	11,756
Consulting and professional services	7,276	2,788
Pre-clinical	239	1,257
Other	10,858	12,628
Accrued expenses	$ 72,203	$ 42,118

Schedule of Quarterly Financial

Schedule of Quarterly Financial Information (Detail) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Selected Quarterly Financial Information [Abstract]
Revenues	$ 37,924	$ 17,096	$ 15,932	$ 18,960	$ 17,454	$ 13,651	$ 8,709	$ 7,345	$ 89,912	$ 47,159	$ 41,097
Operating expenses	185,227	142,896	136,406	125,471	132,887	120,327	101,159	117,373	590,000	471,746	337,105
Net loss	$ (142,227)	$ (122,937)	$ (118,420)	$ (107,290)	$ (112,934)	$ (104,071)	$ (90,129)	$ (102,974)	$ (490,874)	$ (410,108)	$ (290,073)
Net loss per common share — basic and diluted	$ (1.48)	$ (1.34)	$ (1.34)	$ (1.25)	$ (1.32)	$ (1.21)	$ (1.05)	$ (1.21)	$ (5.42)	$ (4.79)	$ (3.45)
Weighted-average common shares — basic and diluted	96,139	91,828	88,098	86,027	85,843	85,716	85,545	85,277	90,554	85,596	83,992