0001439222-22-000024 | 10-K | XBRL Viewer | Agios Pharmaceuticals INC

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Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Current assets:
Cash and cash equivalents	$ 203,126	$ 127,436
Marketable securities	816,892	445,493
Other receivable	4,378	0
Prepaid expenses and other current assets	39,835	15,889
Current assets of discontinued operations	0	47,859
Total current assets	1,064,231	636,677
Marketable securities	266,375	97,608
Operating lease assets	75,124	84,661
Property and equipment, net	28,923	30,815
Financing lease assets	183	590
Other non-current assets	2,900	0
Non-current assets of discontinued operations	0	2,601
Total assets	1,437,736	852,952
Current liabilities:
Accounts payable	16,700	17,724
Accrued expenses	31,967	30,801
Operating lease liabilities	10,828	7,093
Financing lease liabilities	331	317
Current liabilities of discontinued operations	0	38,459
Total current liabilities	59,826	94,394
Operating lease liabilities, net of current portion	85,659	97,458
Financing lease liabilities, net of current portion	276	331
Non-current liabilities of discontinued operations	0	261,269
Total liabilities	145,761	453,452
Commitments and contingent liabilities (Note 9)
Stockholders’ equity:
Preferred stock, $0.001 par value; 25,000,000 shares authorized, no shares issued and outstanding at December 31, 2021 and 2020	0	0
Common stock, $0.001 par value; 125,000,000 shares authorized; 70,550,631 shares issued and 54,334,220 outstanding at December 31, 2021 and 69,293,920 shares issued and outstanding at December 31, 2020	71	69
Additional paid-in capital	2,334,348	2,242,801
Accumulated other comprehensive (loss) income	(1,198)	105
Accumulated deficit	(238,760)	(1,843,475)
Treasury stock, at cost (16,216,411 shares at December 31, 2021 and no shares at December 31, 2020)	(802,486)	0
Total stockholders’ equity	1,291,975	399,500
Total liabilities and stockholders’ equity	$ 1,437,736	$ 852,952

Consolidated Balance Sheets (Parenthetical) - $ / shares	Dec. 31, 2021	Dec. 31, 2020
Statement of Financial Position [Abstract]
Preferred stock, par value (in usd per share)	$ 0.001	$ 0.001
Preferred stock, shares authorized (in shares)	25,000,000	25,000,000
Preferred stock, shares issued (in shares)	0	0
Preferred stock, shares outstanding (in shares)	0	0
Common stock, par value (in usd per share)	$ 0.001	$ 0.001
Common stock, shares authorized (in shares)	125,000,000	125,000,000
Common stock, shares issued (in shares)	70,550,631	69,293,920
Common stock, shares outstanding (in shares)	54,334,220	69,293,920
Treasury stock (in shares)	16,216,411	0

Consolidated Statements of Operations - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Cost and expenses:
Research and development	$ 256,973	$ 220,811	$ 214,262
Selling, general and administrative	121,445	115,105	102,007
Total cost and expenses	378,418	335,916	316,269
Net income (loss) from discontinued operations, net of tax	(378,418)	(335,916)	(316,269)
Gain on sale of oncology business	6,639	0	0
Interest income, net	836	6,611	14,861
Other income, net	14,433	0	0
Total	(356,510)	(329,305)	(301,408)
Less: Net income (loss) from discontinued operations	1,961,225	1,935	(110,064)
Net income (loss)	$ 1,604,715	$ (327,370)	$ (411,472)
Net loss from continuing operations per share - basic (in usd per share)	$ (5.90)	$ (4.77)	$ (5.02)
Net loss from continuing operations per share - diluted (in usd per share)	(5.90)	(4.77)	(5.02)
Net (loss) income from discontinued operations per share - basic (in usd per share)	32.45	0.03	(1.84)
Net (loss) income from discontinued operations per share - diluted (in usd per share)	32.45	0.03	(1.84)
Net loss per share – basic (in usd per share)	26.55	(4.74)	(6.86)
Net loss per share – diluted (in usd per share)	$ 26.55	$ (4.74)	$ (6.86)
Weighted-average number of common shares used in computing net loss per share – basic (in shares)	60,447,346	68,997,879	59,994,539
Weighted-average number of common shares used in computing net loss per share – diluted (in shares)	60,447,346	68,997,879	59,994,539

Consolidated Statements of Comprehensive Income (Loss) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Statement of Comprehensive Income [Abstract]
Net income (loss)	$ 1,604,715	$ (327,370)	$ (411,472)
Other comprehensive (loss) income:
Unrealized (loss) gain on available-for-sale securities	(1,303)	(97)	2,373
Comprehensive income (loss)	$ 1,603,412	$ (327,467)	$ (409,099)

- Definition

The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.

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+ Details

Consolidated Statements of Stockholders' Equity - USD ($) $ in Thousands	Total	Common Stock	Additional Paid-In Capital	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit	Treasury Stock
Beginning balance (in shares) at Dec. 31, 2018		58,218,653
Beginning balance at Dec. 31, 2018	$ 687,537	$ 58	$ 1,794,283	$ (2,171)	$ (1,104,633)	$ 0
Ending balance (in shares) at Dec. 31, 2018						0
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Unrealized (loss) gain on available-for-sale securities	2,373			2,373
Net income (loss)	(411,472)				(411,472)
Stock-based compensation expense	58,050		58,050
Issuance of common stock under stock incentive and employee stock purchase plan (in shares)		694,952
Issuance of common stock under stock incentive and employee stock purchase plans	12,516	$ 1	12,515
Issuance of common stock for follow-on offering (in shares)		9,487,500
Issuance of common stock for follow-on offering	277,201	$ 9	277,192
Disposition of oncology business	14,323		14,323
Ending balance (in shares) at Dec. 31, 2019		68,401,105
Ending balance at Dec. 31, 2019	640,528	$ 68	2,156,363	202	(1,516,105)	$ 0
Ending balance (in shares) at Dec. 31, 2019						0
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Unrealized (loss) gain on available-for-sale securities	(97)			(97)
Net income (loss)	(327,370)				(327,370)
Stock-based compensation expense	61,602		61,602
Issuance of common stock under stock incentive and employee stock purchase plan (in shares)		892,815
Issuance of common stock under stock incentive and employee stock purchase plans	11,317	$ 1	11,316
Disposition of oncology business	13,520		13,520
Ending balance (in shares) at Dec. 31, 2020		69,293,920
Ending balance at Dec. 31, 2020	399,500	$ 69	2,242,801	105	(1,843,475)	$ 0
Ending balance (in shares) at Dec. 31, 2020						0
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Unrealized (loss) gain on available-for-sale securities	(1,303)			(1,303)
Net income (loss)	1,604,715				1,604,715
Stock-based compensation expense	$ 53,508		53,508
Issuance of common stock under stock incentive and employee stock purchase plan (in shares)	758,685	1,256,711
Issuance of common stock under stock incentive and employee stock purchase plans	$ 37,296	$ 2	37,294
Disposition of oncology business	745		745
Shares repurchased (in shares)						(16,216,411)
Repurchase of common stock	(802,486)					$ (802,486)
Ending balance (in shares) at Dec. 31, 2021		70,550,631
Ending balance at Dec. 31, 2021	$ 1,291,975	$ 71	$ 2,334,348	$ (1,198)	$ (238,760)	$ (802,486)
Ending balance (in shares) at Dec. 31, 2021						(16,216,411)

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Operating activities
Net income (loss)	$ 1,604,715	$ (327,370)	$ (411,472)
Less: Net income (loss) from discontinued operations	1,961,225	1,935	(110,064)
Net loss from continuing operations	(356,510)	(329,305)	(301,408)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization	9,240	9,790	8,088
Stock-based compensation expense	53,508	61,602	58,050
Net amortization of premium (accretion of discount) on marketable securities	6,949	3,022	(3,195)
Loss on disposal of property and equipment	12	0	1,052
Non-cash operating lease expense	9,537	8,982	8,532
Changes in operating assets and liabilities:
Other receivables	(4,378)	0	0
Prepaid expenses and other current and non-current assets	(26,846)	(3)	(3,751)
Accounts payable	1,863	3,330	4,162
Accrued expenses	66	6,765	(825)
Operating lease liabilities	(7,527)	(8,127)	(6,861)
Net cash used in operating activities	(314,086)	(243,944)	(236,156)
Net cash used in operating activities - discontinued operations	(93,234)	(46,815)	(134,466)
Net cash used in operating activities	(407,320)	(290,759)	(370,622)
Investing activities
Purchases of marketable securities	(1,378,221)	(557,030)	(488,566)
Proceeds from maturities and sales of marketable securities	829,804	647,685	592,177
Purchases of property and equipment	(5,741)	(14,106)	(12,028)
Net cash (used in) provided by investing activities	(554,158)	76,549	91,583
Net cash provided by (used in) investing activities - discontinued operations	1,802,936	(803)	(143)
Net cash provided by investing activities	1,248,778	75,746	91,440
Financing activities
Payments on financing lease obligations	(578)	(336)	(113)
Purchase of treasury stock	(802,486)	0	0
Proceeds from public offering of common stock, net of reimbursements	0		277,201
Net proceeds from stock option exercises and employee stock purchase plan	37,296	11,317	12,523
Net cash (used in) provided by financing activities	(765,768)	10,981	289,611
Net cash provided by financing activities - discontinued operations	0	250,537	0
Net cash (used in) provided by financing activities	(765,768)	261,518	289,611
Net change in cash and cash equivalents	75,690	46,505	10,429
Cash and cash equivalents at beginning of the period	127,436	80,931	70,502
Cash and cash equivalents at end of the period	203,126	127,436	80,931
Supplemental disclosure of non-cash investing and financing transactions:
Additions to property and equipment in accounts payable and accrued expenses	1,678	465	5,168
Cash taxes paid	16,078	0	0
Operating lease liabilities arising from obtaining operating lease assets	0	0	42,322
Financing lease liabilities arising from obtaining financing lease assets	$ 511	$ 0	$ 1,052

Nature of Business	12 Months Ended
Nature of Business	Dec. 31, 2021
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Nature of Business	Nature of Business References to Agios Throughout this Annual Report on Form 10-K, “the Company,” “we,” “us,” and “our,” and similar expressions, except where the context requires otherwise, refer to Agios Pharmaceuticals, Inc. and its consolidated subsidiaries, and “our board of directors” refers to the board of directors of Agios Pharmaceuticals, Inc. Overview We are a biopharmaceutical company committed to transforming patients’ lives through scientific leadership in the field of cellular metabolism and adjacent areas of biology, with the goal of creating differentiated, small molecule medicines for genetically defined diseases. We take a systems biology approach to deeply understand disease states, drive the discovery and validation of novel therapeutic targets, and define patient selection strategies, thereby increasing the probability that our experimental medicines will have the desired therapeutic effect, while cultivating connections with patient communities, healthcare professionals, partners and colleagues to discover, develop and deliver potential therapies for genetically defined diseases, or GDDs. We are located in Cambridge, Massachusetts. The lead product candidate in our GDD portfolio, PYRUKYND® (mitapivat), is an activator of both wild-type and mutant pyruvate kinase, or PK, enzymes for the potential treatment of hemolytic anemias. On February 17, 2022, the FDA approved PYRUKYND® for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States. In addition, we are currently evaluating PYRUKYND® for the treatment of thalassemia and sickle cell disease, or SCD, in clinical trials. We are also developing AG-946, a novel, next-generation PKR activator, for the potential treatment of hemolytic anemias and other indications. In addition to the aforementioned development programs, we foster a productive research engine and are seeking to advance multiple novel, investigational therapies in clinical and preclinical development in our focus area of GDDs, based on our scientific leadership in the field of cellular metabolism and adjacent areas of biology. 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. Sale of our Oncology Business to Servier On March 31, 2021, we completed the sale of our oncology business to Servier Pharmaceuticals LLC, or Servier. The transaction included the sale of our oncology business, including TIBSOVO®, our clinical-stage product candidates vorasidenib, AG-270 and AG-636, and our oncology research programs for a payment of approximately $1.8 billion in cash at the closing, subject to certain adjustments, and a payment of $200 million in cash, if, prior to January 1, 2027, vorasidenib is granted new drug application, or NDA, approval from the U.S. Food and Drug Administration, or FDA, with an approved label that permits vorasidenib’s use as a single agent for the adjuvant treatment of patients with Grade 2 glioma that have an isocitrate dehydrogenase 1 or 2 mutation (and, to the extent required by such approval, the vorasidenib companion diagnostic test is granted an FDA premarket approval), as well as a royalty of 5% of U.S. net sales of TIBSOVO® from the close of the transaction through loss of exclusivity, and a royalty of 15% of U.S. net sales of vorasidenib from the first commercial sale of vorasidenib through loss of exclusivity. Servier also acquired our co-commercialization rights for Bristol Myers Squibb’s IDHIFA® and the right to receive a $25.0 million potential milestone payment under our prior collaboration agreement with Celgene Corporation, or Celgene, and following the sale Servier is responsible for conducting certain clinical development activities within the IDHIFA® development program. We recorded income from royalties of approximately $6.6 million on U.S. net sales of TIBSOVO® by Servier in the gain on sale of oncology business line item within the condensed consolidated statements of operations, for the year ended December 31, 2021. Reclassifications Certain amounts in prior periods have been reclassified to reflect the impact of the discontinued operations treatment of the oncology business in order to conform to the current period presentation. Liquidity On March 31, 2021, we completed the sale of our oncology business to Servier, and received approximately $1.8 billion in cash at closing. In connection with the sale, on March 25, 2021, we announced that our board of directors authorized the repurchase of up to $1.2 billion of our outstanding shares of common stock, or the Repurchase Program, using the proceeds from the sale of our oncology business to Servier. On March 31, 2021, in connection with the Repurchase Program, we entered into a definitive share repurchase agreement with Bristol-Myers Squibb Company, or BMS, to repurchase 7.1 million shares of our common stock held by certain subsidiaries of BMS for an aggregate purchase price of $344.5 million, or $48.38 per share. This repurchase was completed on April 5, 2021. Further, on April 2, 2021, in connection with the Repurchase Program, we entered into a Rule 10b5-1 repurchase plan pursuant to which we may repurchase up to $600 million of shares of our common stock. On October 5, 2021, we terminated our Rule 10b5-1 share repurchase program and on October 13, 2021 entered into a Rule 10b-18 repurchase plan that allows us to conduct open market repurchases over time up to our remaining authorization. As of December 31, 2021, we have repurchased approximately 9.1 million shares of common stock for $458.0 million, or $50.35 per share, under the Rule 10b5-1 repurchase plan. As of December 31, 2021, we have not repurchased any shares under the Rule 10b-18 repurchase plan. In total, as of December 31, 2021, we have repurchased 16.2 million shares of common stock for $802.5 million, or $49.49 per share, under the Repurchase Program. We have paused our share repurchases for the foreseeable future. On April 30, 2020, we entered into an at-the-market sales agreement, or the 2020 sales agreement, with Cowen & Company LLC, or Cowen, pursuant to which we may offer and sell shares of our common stock having an aggregate offering price of up to $250.0 million through Cowen pursuant to a universal shelf registration statement on Form S-3 filed with the SEC on April 30, 2020. As of December 31, 2021, $250.0 million in common stock remained available for future issuance under the 2020 sales agreement. As of December 31, 2021, we had cash, cash equivalents and marketable securities of $1,286.4 million. Although we have incurred recurring losses and expect to continue to incur losses for the foreseeable future, we expect our cash, cash equivalents and marketable securities to be sufficient to fund current operations for at least the next twelve months from the issuance of the financial statements. If we are unable to raise additional funds through equity or debt financings, we may be required to delay, limit, reduce or terminate product development or future commercialization efforts or grant rights to develop and market products or product candidates that we would otherwise prefer to develop and market ourselves.

Summary of Significant Accounting Policies

12 Months Ended

Dec. 31, 2021

Accounting Policies [Abstract]

Summary of Significant Accounting Policies

Principles of consolidation

The consolidated financial statements include our accounts and the accounts of our wholly owned subsidiaries, Agios Securities Corporation, Agios International Sarl (GmbH), Agios Germany GmbH, Agios Netherlands B.V., Agios Italy S.R.L., Agios France SARL, and Agios Limited. All intercompany transactions have been eliminated in consolidation. The consolidated financial statements have been prepared in conformity with U.S. generally accepted accounting principles, or U.S. GAAP.

Use of estimates

The preparation of financial statements in conformity with U.S. GAAP requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of revenue and expenses during the reporting period. On an ongoing basis we evaluate our estimates, judgments and methodologies. We base our estimates on historical experience and on various other assumptions that we believe are reasonable, the results of which form the basis for making judgments about the carrying values of assets, liabilities and equity and the amount of revenues and expenses. The full extent to which the COVID-19 pandemic will directly or indirectly impact our business, results of operations and financial condition, including expenses, reserves and allowances, clinical trials, research and development costs and employee-related amounts, will depend on future developments that are highly uncertain, including as a result of new information that may emerge concerning COVID-19 and any variant strains of the virus and the actions taken to contain the pandemic or treat COVID-19, as well as the economic impact on local, regional, national and international customers and markets. We have made estimates of the impact of COVID-19 within our financial statements and there may be changes to those estimates in future periods. Actual results may differ from these estimates.

Cash and cash equivalents

We consider highly liquid investments with a maturity of three months or less when purchased to be cash equivalents. Cash equivalents are stated at fair value.

Marketable securities

Marketable securities at December 31, 2021 and 2020 consisted of investments in U.S. Treasuries, government securities and corporate debt securities. We determine the appropriate classification of the securities at the time they are acquired and evaluate the appropriateness of such classifications at each balance sheet date. We classify our marketable securities as available-for-sale pursuant to Accounting Standards Codification, or ASC, 320, Investments – Debt and Equity Securities. Marketable securities are recorded at fair value. Unrealized gains are included as a component of accumulated other comprehensive (loss) income in the consolidated balance sheets and statements of stockholders’ equity and a component of total comprehensive income (loss) in the consolidated statements of comprehensive income (loss), until realized. Realized gains and losses are included in investment income on a specific-identification basis.

At December 31, 2021 and 2020, we held both current and non-current investments. Investments classified as current have maturities of less than one year. Investments classified as non-current are those that: (i) have a maturity of one to two years, and (ii) we do not intend to liquidate within the next twelve months, although these funds are available for use and therefore classified as available-for-sale.

We review marketable securities for impairment whenever the fair value of a marketable security is less than the amortized cost and evidence indicates that a marketable security’s carrying amount is not recoverable. Unrealized losses are evaluated for impairment under ASC 326, Financial Instruments - Credit Losses, to determine if the impairment is credit-related or noncredit-related. Credit-related impairment is recognized as an allowance on the balance sheet with a corresponding adjustment to earnings, and noncredit-related impairment is recognized in other comprehensive income (loss), net of taxes. Evidence considered in this assessment includes reasons for the impairment, compliance with our investment policy, the severity of the impairment, collectability of the security, and any adverse conditions specifically related to the security, an industry, or geographic area.

Fair value measurements

We record cash equivalents and marketable securities at fair value. ASC 820, Fair Value Measurements and Disclosures, establishes a fair value hierarchy for those instruments measured at fair value that distinguishes between assumptions based on market data (observable inputs) and our own assumptions (unobservable inputs). The hierarchy consists of three levels:

Level 1 – Unadjusted quoted prices in active markets for identical assets or liabilities.

Level 2 – Quoted prices for similar assets and liabilities in active markets, quoted prices in markets that are not active, or inputs which are observable, either directly or indirectly, for substantially the full term of the asset or liability.

Level 3 – Unobservable inputs that reflect our own assumptions about the assumptions market participants would use in pricing the asset or liability in which there is little, if any, market activity for the asset or liability at the measurement date.

Our financial assets, which include cash equivalents and marketable securities, have been initially valued at the transaction price, and subsequently revalued at the end of each reporting period, utilizing third-party pricing services or other observable market data. The pricing services utilize industry standard valuation models, including both income and market based approaches, and observable market inputs to determine value. After completing our validation procedures, we did not adjust or override any fair value measurements provided by the pricing services as of December 31, 2021 or 2020. Fair value information for these assets, including their classification in the fair value hierarchy is included in Note 4. Fair Value Measurements.

There have been no changes to the valuation methods during the years ended December 31, 2021 and 2020. We evaluate transfers between levels at the end of each reporting period.

The carrying amounts of other receivable, prepaid expenses and other current assets, accounts payable, and accrued expenses approximate their fair values due to their short-term maturities.

Concentrations of credit risk

Financial instruments which potentially subject us to credit risk consist primarily of cash, cash equivalents, and marketable securities. We hold these investments in highly rated financial institutions, and, by policy, limit the amounts of credit exposure to any one financial institution. These amounts at times may exceed federally insured limits. We have not experienced any credit losses in such accounts and do not believe we are exposed to any significant credit risk on these funds. We have no off-balance sheet concentrations of credit risk, such as foreign currency exchange contracts, option contracts, or other hedging arrangements.

Property and equipment

Property and equipment consist of laboratory equipment, computer equipment and software, leasehold improvements, furniture and fixtures, and office equipment. Costs of major additions and betterment are capitalized; maintenance and repairs, which do not improve or extend the life of the respective assets, are charged to expense as incurred. Upon retirement or sale, the cost of the disposed asset and the related accumulated depreciation are removed from the accounts and the resulting gain or loss is recognized.

Property and equipment is stated at cost, and depreciated using the straight-line method over the estimated useful lives of the respective assets:


						Years
Laboratory equipment						5
Computer equipment and software						3
Furniture and fixtures						5
Office equipment						5

Leasehold improvements are amortized over the lesser of the remaining lease term or the estimated useful life of the improvement.

Impairment of long-lived assets

We periodically evaluate our long-lived assets for potential impairment in accordance with ASC 360, Property, Plant and Equipment. Potential impairment is assessed when there is evidence that events or changes in circumstances indicate that the carrying amount of an asset may not be recovered. Recoverability of these assets is assessed based on the undiscounted expected future cash flows from the assets, considering a number of factors, including past operating results, budgets and economic projections, market trends and product development cycles. If impairments are identified, assets are written down to their estimated fair value. We did not recognize any impairment charges through December 31, 2021.

Leases

We determine if an arrangement is a lease at inception. An arrangement is determined to contain a lease if the contract conveys the right to control the use of an identified property or equipment for a period of time in exchange for consideration. If we can benefit from the various underlying assets of a lease on their own or together with other resources that are readily available, or if the various underlying assets are neither highly dependent on nor highly interrelated with other underlying assets in the arrangement, they are considered to be a separate lease component. In the event multiple underlying assets are identified, the lease consideration is allocated to the various components based on each of the component’s relative fair value.

Operating lease assets represent our right to use an underlying asset for the lease term and operating lease liabilities represent our obligation to make lease payments arising from the leasing arrangement. Operating lease assets and operating lease liabilities are recognized at commencement date based on the present value of lease payments over the lease term. As most of our leases do not provide an implicit rate, in determining the operating lease liabilities, we use an estimate of our incremental borrowing rate. The incremental borrowing rate is determined using two alternative credit scoring models to estimate our credit rating, adjusted for collateralization. The calculation of the operating lease assets includes any lease payments made and excludes any lease incentives. Our lease terms may include options to extend or terminate the lease when it is reasonably certain that we will exercise that option.

For operating leases, we record operating lease assets and lease liabilities in our consolidated balance sheets. Lease expense for lease payments is recognized on a straight-line basis over the lease term. Short-term leases, or leases that have a lease term of 12 months or less at commencement date, are excluded from this treatment and are recognized on a straight-line basis over the term of the lease.

We have not entered into any material short-term leases or financing leases as of December 31, 2021.

Research and development costs

Research and development costs, including those accrued as of each balance sheet date, are expensed as incurred. These costs include salaries and personnel-related costs, consulting fees, fees paid for contract research services, fees paid to contract research organizations, or CROs, and other third parties in connection with clinical trials and preclinical development activities, fees paid to investigative sites in connection with clinical studies, the costs associated with the product manufacturing, development, and distribution of clinical supplies, the costs of laboratory equipment and facilities, and other external costs.

Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred and capitalized. Additionally, there may be instances in which payments made to our vendors will exceed the level of services provided, and result in a prepayment of the research and development expense. The capitalized amounts are expensed as the related goods are delivered or the services are performed. We estimate the time period over which services will be performed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we adjust the accrual or prepaid accordingly.

Stock-based compensation

We account for stock-based compensation awards in accordance with ASC 718, Compensation –Stock Compensation, or ASC 718. For stock-based awards granted to employees and to members of the board of directors for their services and for participation in our employee stock purchase plan, we primarily estimate the grant date fair value of each option award using the Black-Scholes option-pricing model. The use of the Black-Scholes option-pricing model requires us to make assumptions with respect to the expected term of the option, the expected volatility of the common stock consistent with the expected life of the option, risk-free interest rates and expected dividend yields of the common stock. For awards subject to service-based vesting conditions, we recognize stock-based compensation expense equal to the grant date fair value of stock options on a straight-line basis over the requisite service period. For awards subject to both performance and service-based vesting conditions, we recognize stock-based compensation expense over the remaining service period if the performance condition is considered probable of achievement using management’s best estimates.

Income taxes

Income taxes are recorded in accordance with ASC 740, Accounting for Income Taxes, or ASC 740, which provides for deferred taxes using an asset and liability approach. We recognize deferred tax assets and liabilities for the expected future tax consequences of events that have been included in our financial statements or tax returns. We determine our deferred tax assets and liabilities based on differences between the financial reporting and tax bases of assets and liabilities, which are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. Valuation allowances are provided, if based upon the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized.

We also account for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, we recognize the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances.

Comprehensive income (loss)

Comprehensive income (loss) is defined as the change in equity of a business enterprise during a period from transactions, and other events and circumstances, and currently consists of net loss and unrealized gains and losses on available-for-sale securities. Accumulated other comprehensive (loss) income consists entirely of unrealized gains and losses from available-for-sale securities as of December 31, 2021 and 2020.

Net income (loss) per share

Basic net income (loss) per share is calculated by dividing net income (loss) by the weighted-average shares outstanding during the period, without consideration for common stock equivalents. Diluted net income (loss) per share is calculated by adjusting weighted-average shares outstanding for the dilutive effect of common stock equivalents outstanding for the period, determined using the treasury-stock method. For purposes of the dilutive net income (loss) per share calculation, stock options, restricted stock units, or RSUs, performance-based stock units, or PSUs, and market-based stock units, or MSUs, for which the performance vesting conditions have been met, and employee stock purchase plan shares are considered to be common stock equivalents but are excluded from the calculation of diluted net income (loss) per share as their effect would be anti-dilutive.

We utilize the control number concept in the computation of diluted earnings per share to determine whether potential common stock equivalents are dilutive. The control number used is loss from continuing operations. The control number concept requires that the same number of potentially dilutive securities applied in computing diluted earnings per share from continuing operations be applied to all other categories of income or loss, regardless of their anti-dilutive effect on such categories. Since we had a net loss for continuing operations for all periods presented, no dilutive effect has been recognized in the calculation of income (loss) from discontinued operations per share or net income (loss) per share.

Segment and geographic information

Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision maker, or decision-making group, in making decisions on how to

allocate resources and assess performance. Our chief operating decision maker is the chief executive officer. Our chief operating decision maker and we view our operations and manage our business as one operating segment.

Discontinued Operations

We accounted for the sale of our oncology business in accordance with Accounting Standards Codification, ASC, 205 Discontinued Operations and Accounting Standards Update, ASU, No. 2014-08, Reporting of Discontinued Operations and Disclosures of Disposals of Components of an Entity. We followed the held-for-sale criteria as defined in ASC 360 and ASC 205. ASC 205 requires that a component of an entity that has been disposed of or is classified as held for sale and has operations and cash flows that can be clearly distinguished from the rest of the entity be reported as assets held for sale and discontinued operations. In the period a component of an entity has been disposed of or classified as held for sale, the results of operations for the periods presented are reclassified into separate line items in the consolidated statements of operations. Assets and liabilities are also reclassified into separate line items on the related consolidated balance sheets for the periods presented. The statements of cash flows for the periods presented are also reclassified to reflect the results of discontinued operations as separate line items. ASU 2014-08 requires that only a disposal of a component of an entity, or a group of components of an entity, that represents a strategic shift that has, or will have, a major effect on the reporting entity’s operations and financial results be reported in the financial statements as discontinued operations. ASU 2014-08 also provides guidance on the financial statement presentations and disclosures of discontinued operations.

Due to the sale of the oncology business during the first quarter of 2021, in accordance with ASC 205, Discontinued Operations, we have classified the results of the oncology business as discontinued operations in our consolidated statements of operations and cash flows for all periods presented, see Note 3, Discontinued Operations. All assets and liabilities associated with our oncology business were therefore classified as assets and liabilities of discontinued operations in our consolidated balance sheets for the periods presented. All amounts included in the notes to the consolidated financial statements relate to continuing operations unless otherwise noted.

Treasury Stock

Treasury stock purchases are accounted for under the cost method whereby the entire cost of the acquired stock is recorded as treasury stock.

Recent accounting pronouncements

Leases

In February 2016, the Financial Accounting Standard Board, or FASB issued Accounting Standards Update, or ASU, No. 2016-02, Leases (Topic 842), which was codified as ASC 842, Leases, and amended through subsequent ASUs. We adopted ASC 842 effective January 1, 2019 using the optional transition method provided for under ASU 2018-11, Leases (Topic 842): Targeted Improvements, whereby we applied the new lease requirements through a cumulative-effect adjustment, which after completing our implementation analysis, resulted in no material adjustment to our January 1, 2019 beginning accumulated deficit balance. We also elected the package of practical expedients provided for under ASU 2018-11, which allows us not to reassess whether contracts are or contain leases, lease classification, and whether initial direct costs qualify for capitalization. Additionally, as an accounting policy, for our building leases, we chose not to separate the non-lease components from the lease components and, instead, accounted for each non-lease component and lease component as a single component.

We completed our assessment over the impact of the standard and determined that the only material leases that we hold are our building leases. Upon adoption of the standard on January 1, 2019, we recorded operating right of use assets of $59.9 million and operating lease liabilities of $77.3 million on our consolidated balance sheets.

Other recent accounting pronouncements

In June 2018, the FASB issued ASU 2018-07 – Compensation-Stock Compensation (Topic 718)-Improvements to Nonemployee Share-Based Payment Accounting. ASU 2018-07 simplifies the accounting for share-based payments to nonemployees by aligning it with the accounting for share-based payments to employees, with certain exceptions. ASU 2018-07 is effective for fiscal years beginning after December 15, 2018. The Company adopted the new standard as of January 1, 2019. There was no material impact to the Company’s consolidated financial position, results of operation, or cash flows.

In December 2019, the FASB issued ASU 2019-12 – Income Taxes (Topic 740) Simplifying the Accounting for Income Taxes, as part of its initiative to reduce complexity in the accounting standards. The amendments in ASU 2019-12 eliminate certain exceptions related to the approach for intraperiod tax allocation, the methodology for calculating income taxes in an interim period and the recognition of deferred tax liabilities for outside basis differences. ASU 2019-12 also clarifies and simplifies other aspects of the accounting for income taxes. The amendments in ASU 2019-12 are effective for the fiscal years beginning after December 15, 2020. Early adoption is permitted, including adoption in any interim period. The Company has early

adopted this amendment as of January 1, 2019. There was no material impact to the Company’s consolidated financial position, results of operation, or cash flows.

In June 2016, the FASB issued ASU 2016-13, Financial Instruments - Credit Losses (Topic 326), which introduces new guidance for the accounting for credit losses on instruments within its scope. The new guidance introduces an approach based on expected losses to estimate credit losses on certain types of financial instruments. Credit losses relating to available-for-sale debt securities will also be recorded through an allowance for credit losses rather than as a reduction in the amortized cost basis of the securities. The guidance is effective for fiscal years beginning after December 31, 2019, including interim periods within those years. The Company adopted this amendment as of January 1, 2020, which eliminated the concept of other-than-temporary impairments and required credit losses on debt securities to be recorded through an allowance for credit losses instead of as a reduction in the amortized cost basis of the securities. Application of the amendments is through a cumulative-effect adjustment to retained earnings as of the effective date. There was no material impact to the Company’s consolidated financial position, results of operation, or cash flows.

Other accounting standards that have been issued by the FASB or other standards-setting bodies that do not require adoption until a future date are not expected to have a material impact on our financial statements upon adoption.

Subsequent events

We considered events or transactions occurring after the balance sheet date, but prior to the issuance of the consolidated financial statements, for potential recognition or disclosure in our consolidated financial statements. All significant subsequent events have been properly disclosed in the consolidated financial statements.

Discontinued Operations

12 Months Ended

Dec. 31, 2021

Discontinued Operations and Disposal Groups [Abstract]

Discontinued Operations

On March 31, 2021, we completed the sale of our oncology business to Servier. We have determined the sale of the oncology business represents a strategic shift that had a major effect on our business and therefore met the criteria for classification as discontinued operations at March 31, 2021. Accordingly, the oncology business is reported as discontinued operations in accordance with ASC 205-20, Discontinued Operations. The related assets and liabilities of the oncology business are classified as assets and liabilities of discontinued operations in the consolidated balance sheets and the results of operations from the oncology business as discontinued operations in the consolidated statements of operations. Applicable amounts in prior years have been recast to conform to this discontinued operations presentation. We recognized a gain on the sale of the oncology business upon closing.

The following table presents the assets and liabilities of the discontinued operations as of December 31, 2020:


(in thousands)	December 31, 2020
Assets
Current assets:
Accounts receivable, net	$	21,328
Collaboration receivable – related party	2,123
Collaboration receivable – other	1,948
Inventory	14,698
Prepaid expenses and other current assets	7,762
Total current assets of discontinued operations	47,859
Other non-current assets	2,601
Total assets of discontinued operations	$	50,460
Liabilities
Current liabilities:
Accounts payable	$	9,120
Accrued expenses	29,339
Total current liabilities of discontinued operations	38,459
Liability related to the sale of future revenue, net of debt issuance costs	261,269
Total liabilities of discontinued operations	$	299,728

The following table presents the net liabilities transferred for the sale of the oncology business at March 31, 2021:


(in thousands)	March 31, 2021
Assets
Current assets:
Accounts receivable, net	$	25,386
Collaboration receivable – related party	2,253
Collaboration receivable – other	2,438
Inventory	16,190
Prepaid expenses and other current assets	7,125
Total current assets of discontinued operations	53,392
Other non-current assets	2,234
Total assets of discontinued operations	$	55,626

Liabilities
Current liabilities:
Accounts payable	$	4,245
Accrued expenses	30,288
Total current liabilities of discontinued operations	34,533
Liability related to the sale of future revenue, net of debt issuance costs	264,281
Total liabilities of discontinued operations	298,814
Net liabilities distributed to Servier	$	(243,188)

The following table presents the gain on the sale for the year ended December 31, 2021:


(in thousands)	December 31, 2021
Cash proceeds	$	1,802,936
Less: transaction and insurance costs	(53,573)
Plus: net liabilities distributed, including working capital adjustment	239,770
Gain on sale, pre-tax	1,989,133
Income tax expense	(12,799)
Gain on sale, net of tax	$	1,976,334

As of December 31, 2021, there were no assets or liabilities classified as discontinued operations.

The following table presents the financial results of the discontinued operations:


(in thousands)	2021		2020		2019
Revenues:
Product revenue, net	$	36,909	$	121,089	$	59,851
Collaboration revenue – related party	1,350		68,274		39,257
Collaboration revenue – other	491		3,571		8,262
Royalty revenue – related party	2,659		10,262		10,542
Total revenue	41,409		203,196		117,912
Cost and expenses:
Cost of sales	706		2,805		1,317
Research and development	41,564		146,659		196,632
Selling, general and administrative	8,551		33,965		30,027
Total cost and expenses	50,821		183,429		227,976
(Loss) income from discontinued operations	(9,412)		19,767		(110,064)
Non-cash interest expense for the sale of future revenue	(5,697)		(17,832)		—
Gain on the sale of the oncology business	1,989,133		—
(Loss) income from discontinued operations, pre-tax	1,974,024		1,935		(110,064)
Income tax expense	(12,799)		—		—
Net (loss) income from discontinued operations	$	1,961,225	$	1,935	$	(110,064)

In accordance with ASC 205-20, only expenses specifically identifiable and related to a business to be disposed may be presented in discontinued operations. As such, the research and development, marketing, selling and general and administrative expenses in discontinued operations include corporate costs incurred directly to solely support our oncology business.

We have also entered into a Transition Services Agreement with Servier, through which we will provide transitional services related to discovery, clinical development, technical operations, commercial and general and administrative related activities for periods ranging from one month to approximately one year through March 31, 2022.

The milestone payment for approval of vorasidenib and royalty payments related to vorasidenib and TIBSOVO® represent contingent consideration. Contingent consideration has been accounted for as a gain contingency in accordance with ASC 450, Contingencies, and will be recognized in earnings in the period when realizable.

Fair Value Measurements

12 Months Ended

Dec. 31, 2021

Fair Value Disclosures [Abstract]

Fair Value Measurements

The following table summarizes our cash equivalents and marketable securities measured at fair value and by level (as described in Note 2. Summary of Significant Accounting Policies) on a recurring basis as of December 31, 2021:


(In thousands)	Level 1		Level 2		Level 3		Total
Cash equivalents	$	156,229	$	21,524	$	—	$	177,753
Total cash equivalents	156,229		21,524		—		177,753

Marketable securities:

U.S. Treasuries	—		309,658		—		309,658
Government securities	—		166,104		—		166,104
Corporate debt securities	—		607,505		—		607,505
Total marketable securities	—		1,083,267		—		1,083,267
Total cash equivalents and marketable securities	$	156,229	$	1,104,791	$	—	$	1,261,020

There were no transfers between Level 1 and Level 2 and we had no financial assets or liabilities that were classified as Level 3 at any point during the year ended December 31, 2021.

- Definition

The entire disclosure for the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired information.

+ References + Details

Marketable Securities

12 Months Ended

Dec. 31, 2021

Investments, Debt and Equity Securities [Abstract]

Marketable Securities

Marketable securities at December 31, 2021 consisted of the following:


(In thousands)	Amortized Cost		Unrealized Gains		Unrealized Losses		Fair Value
Current:

U.S. Treasuries	$	269,109	$	—	$	(36)	$	269,073
Government securities	17,764		1		(10)		17,755
Corporate debt securities	530,490		3		(429)		530,064
Total Current	817,363		4		(475)		816,892

Non-current:
U.S. Treasuries	40,607		—		(23)		40,584
Government securities	148,820		—		(470)		148,350
Corporate debt securities	77,675		—		(234)		77,441
Total Non-current	267,102		—		(727)		266,375
Total marketable securities	$	1,084,465	$	4	$	(1,202)	$	1,083,267

Marketable securities at December 31, 2020 consisted of the following:


(In thousands)	Amortized Cost		Unrealized Gains		Unrealized Losses		Fair Value
Current:

U.S. Treasuries	$	113,559	$	134	$	(21)	$	113,672
Government securities	108,263		37		(8)		108,292
Corporate debt securities	223,461		140		(72)		223,529
Total Current	445,283		311		(101)		445,493

Non-current:
U.S. Treasuries	15,147		—		(10)		15,137
Government securities	26,831		8		—		26,839
Corporate debt securities	55,735		2		(105)		55,632
Total Non-current	97,713		10		(115)		97,608
Total marketable securities	$	542,996	$	321	$	(216)	$	543,101

There were no material realized gains or losses on marketable securities for the years ended December 31, 2021 and 2020.

At December 31, 2021 and 2020, we held 294 and 87 debt securities, respectfully, that were in an unrealized loss position for less than one year. We did not record an allowance for credit losses as of December 31, 2021 and December 31, 2020 related to these securities. The aggregate fair value of debt securities in an unrealized loss position at December 31, 2021 and 2020 was $950.5 million and $299.0 million, respectively. There were no individual securities that were in a significant unrealized loss position as of December 31, 2021 and 2020. We regularly review the securities in an unrealized loss position and evaluate the current expected credit loss by considering factors such as historical experience, market data, issuer-specific factors, and current economic conditions. We do not consider these marketable securities to be impaired as of December 31, 2021 and 2020.

Property and Equipment, net

12 Months Ended

Dec. 31, 2021

Property, Plant and Equipment [Abstract]

Property and Equipment, net

Property and equipment, net consisted of the following at December 31:


(In thousands)	2021		2020
Laboratory equipment	$	22,165	$	23,858
Computer equipment and software	6,913		6,945
Leasehold improvements	32,726		32,568
Furniture and fixtures	3,035		3,035
Office equipment	1,690		1,651
Construction in progress	7,368		4,111
Total property and equipment	73,897		72,168
Less: accumulated depreciation	(44,974)		(41,353)
Total property and equipment, net	$	28,923	$	30,815

Depreciation expense for the years ended December 31, 2021, 2020 and 2019 was $8.8 million, $9.4 million and $8.0 million, respectively.

Leases

12 Months Ended

Dec. 31, 2021

Leases [Abstract]

Leases

Our building leases are comprised of office and laboratory space under non-cancelable operating leases. These lease agreements have remaining lease terms of six years and contain various clauses for renewal at our option. The renewal options were not included in the calculation of the operating lease assets and the operating lease liabilities as the renewal option is not reasonably certain of being exercised. The lease agreements do not contain residual value guarantees.

On April 11, 2019, we entered into an agreement to lease approximately 13,000 square feet of office space located at 38 Sidney Street, Cambridge, Massachusetts, or the 38 Sidney Lease, with Thirty-Eight Sidney Street, LLC. The initial term of the 38 Sidney Lease commenced on May 1, 2019 and expires on February 29, 2028. At the end of the lease term, we have the option to extend the 38 Sidney Lease for two consecutive terms of five years at fair market rent at the time of the extension. The 38 Sidney Lease provides us with the right to lease additional space within the 38 Sidney Street building and also includes rent escalation clauses and a tenant improvement allowance of $1.0 million.

In connection with the 38 Sidney Lease, we also amended our existing building leases at 88 Sidney Street, Cambridge, Massachusetts and at 64 Sidney Street, Cambridge, Massachusetts to extend the initial terms of those leases by approximately three years through February 29, 2028. The amendments also provide us with the right to lease additional space at the 64 Sidney Street building. Our existing extension options for the 88 Sidney Street building and 64 Sidney Street building continue as set forth in the existing leases for those buildings.

The components of lease expense and other information related to leases were as follows:


(In millions)	2021		2020		2019
Operating Lease Costs	$	15.2	$	15.2	$	15.1
Cash paid for amounts included in the measurement of operating lease liabilities	14.4		14.4		12.8

We have not entered into any material short-term leases or financing leases as of December 31, 2021.

In arriving at the operating lease liabilities as of December 31, 2021, we applied the weighted-average incremental borrowing rate of 5.7% from inception over a weighted-average remaining lease term of 6.2 years. In arriving at the operating lease liabilities as of December 31, 2020, we applied the weighted-average incremental borrowing rate of 5.7% over a weighted-average remaining lease term of 7.2 years.

As of December 31, 2021, undiscounted minimum rental commitments under non-cancelable leases, for each of the next five years and total thereafter, were as follows:


(In thousands)
2022	$	15,560
2023	18,126
2024	18,660
2025	19,507
2026	20,151
Thereafter	24,234
Undiscounted minimum rental commitments	116,238
Interest	(19,751)
Total operating lease liabilities	$	96,487

We provided our landlord a standby letter of credit of $2.9 million as security for our leases. We are not required to maintain any cash collateral for the standby letter of credit.

In August 2021, we entered into a long-term sublease agreement for 13,000 square feet of the office space at 38 Sidney Street Cambridge, Massachusetts. The term of the lease runs until December 2024. We recorded operating sublease income of $0.5 million for the year ended December 31, 2021 in other income, net in the consolidated statements of operations.

As of December 31, 2021, the future minimum lease payments to be received under the long-term sublease agreement were as follows:


(In thousands)
2022	1,118
2023	1,152
2024	1,186
Total	$	3,456

Accrued Expenses

12 Months Ended

Dec. 31, 2021

Payables and Accruals [Abstract]

Accrued Expenses

Accrued expenses consisted of the following at December 31:


(In thousands)	2021		2020
Accrued compensation	$	19,818	$	20,345
Accrued research and development costs	5,980		5,444
Accrued professional fees	2,335		2,897
Accrued other	3,834		2,115
Total accrued expenses	$	31,967	$	30,801

Commitments and Contingent Liabilities	12 Months Ended
Commitments and Contingent Liabilities	Dec. 31, 2021
Commitments and Contingencies Disclosure [Abstract]
Commitments and Contingent Liabilities	Commitments and Contingent Liabilities Manufacturing Commitments We are party to various agreements with contract manufacturing organizations that we are not contractually able to terminate for convenience and avoid any and all future obligations to the vendors. Under such agreements, we are obligated to make certain minimum payments, with the exact amounts in the event of termination to be based on the timing of the termination and the exact terms of the agreement. Legal Contingencies From time to time, we may be involved in disputes and legal proceedings in the ordinary course of business. These proceedings may include allegations of infringement of intellectual property, employment or other matters. We do not have any ongoing legal proceedings that, based on our estimates, could have a material effect on our consolidated financial statements.

Common Stock	12 Months Ended
Common Stock	Dec. 31, 2021
Equity [Abstract]
Common Stock	Common StockWe are authorized to issue 125,000,000 shares of our common stock. Holders of common stock are entitled to one vote per share. Additionally, holders of common stock are entitled to receive dividends, if and when declared by our board of directors, and to share ratably in our assets legally available for distribution to our shareholders in the event of liquidation.

- Definition

The entire disclosure for shareholders' equity comprised of portions attributable to the parent entity and noncontrolling interest, including other comprehensive income. Includes, but is not limited to, balances of common stock, preferred stock, additional paid-in capital, other capital and retained earnings, accumulated balance for each classification of other comprehensive income and amount of comprehensive income.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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-Name Accounting Standards Codification
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
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-URI http://asc.fasb.org/extlink&oid=123467817&loc=SL123496171-112644

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
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Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 505
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-Section 50
-Paragraph 18
-Subparagraph (d)
-URI http://asc.fasb.org/extlink&oid=123467817&loc=SL123496189-112644

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
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Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 505
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-URI http://asc.fasb.org/extlink&oid=123467817&loc=SL123496189-112644

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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Reference 11: http://www.xbrl.org/2003/role/disclosureRef
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Reference 12: http://www.xbrl.org/2003/role/disclosureRef
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Reference 13: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
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-URI http://asc.fasb.org/extlink&oid=123467817&loc=SL123496180-112644

Reference 14: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 505
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Reference 15: http://www.xbrl.org/2003/role/disclosureRef
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+ Details

Share-Based Payments

12 Months Ended

Dec. 31, 2021

Share-based Payment Arrangement [Abstract]

Share-Based Payments

Stock incentive plans

In June 2013, our Board of Directors adopted and, in July 2013 our stockholders approved, the 2013 Stock Incentive Plan, or the 2013 Plan. The 2013 Plan became effective upon the closing of our initial public offering and provides for the grant of incentive stock options, non-qualified stock options, stock appreciation rights, restricted stock awards, restricted stock units, or RSUs, performance-based share units, or PSUs, and other stock-based awards to employees, non-employees and non-employee directors. Following the adoption of the 2013 Plan, we granted no further stock options or other awards under the 2007 Stock Incentive Plan, or the 2007 Plan. Any options or awards outstanding under the 2007 Plan at the time of adoption of the 2013 Plan remain outstanding and effective. As of December 31, 2021, the total number of shares reserved under the 2007 Plan and the 2013 Plan was 11,422,409, and we had 5,343,905 shares available for future issuance under the 2013 Plan.

The 2013 Plan provides for an annual increase, to be added on the first day of each fiscal year, beginning with the fiscal year ending December 31, 2014 and continuing until the expiration of the 2013 Plan, equal to the lesser of (i) 2,000,000 shares of common stock, (ii) 4% of the outstanding shares of common stock on such date or (iii) an amount determined by our Board of Directors. On January 1, 2022, the annual increase for the 2013 Plan resulted in an additional 2,000,000 shares authorized for issuance.

Stock options

The following table summarizes the stock option activity of all stock incentive plans for the year ended December 31, 2021:


	Number of Stock Options	Weighted- Average Exercise Price		Weighted- Average Remaining Contractual Term (in years)	Aggregate Intrinsic Value (in thousands)
Outstanding at December 31, 2020	6,143,046	$	58.46	6.68	$	13,714
Granted	1,073,989	55.54
Exercised	(758,685)	44.73
Forfeited/Expired	(1,659,524)	62.70
Outstanding at December 31, 2021	4,798,826	$	58.51	6.24	$	4,697
Exercisable at December 31, 2021	3,367,239	$	60.52	5.25	$	4,697
Vested and expected to vest at December 31, 2021	4,798,826	$	58.51	6.24	$	4,697

The weighted-average grant date fair value of options granted was $31.20, $32.10 and $36.44 during the years ended December 31, 2021, 2020 and 2019, respectively. The total intrinsic value of options exercised was $8.5 million, $10.4 million and $6.4 million during the years ended December 31, 2021, 2020 and 2019, respectively.

At December 31, 2021, the total unrecognized compensation expense related to unvested stock option awards was $39.8 million, which we expect to recognize over a weighted-average period of approximately 2.33 years.

Restricted stock units

Upon vesting, each RSU entitles the holder to receive a specified number of shares of our common stock. The following table presents RSU activity for the year ended December 31, 2021:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2020	1,284,378	$	50.78
Granted	835,698	55.49
Vested	(403,138)	56.90
Forfeited	(714,014)	51.81
Unvested shares at December 31, 2021	1,002,924	$	51.51

As of December 31, 2021, there was approximately $29.5 million of total unrecognized compensation expense related to RSUs, which we expect to be recognized over a weighted-average period of 1.74 years.

Performance-based stock units

At the achievement of the performance-based and service-based vesting criteria, each PSU entitles the holder to receive a specified number of shares of our common stock. The following table presents PSU activity for the year ended December 31, 2021:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2020	142,229	$	54.28
Granted	141,000	54.20
Vested	—	—
Forfeited	(49,170)	54.08
Unvested shares at December 31, 2021	234,059	$	54.28

Stock-based compensation expense associated with these PSUs is recognized if the underlying performance condition is considered probable of achievement using our management’s best estimates. As of December 31, 2021, there was no unrecognized compensation expense related to PSUs with performance-based vesting criteria that are considered probable of achievement that we expect to recognize. There is $12.7 million of total unrecognized compensation expense related to PSUs with performance-based vesting criteria that are considered not probable of achievement.

Market-based stock units

The Company has issued certain equity awards that contain market based vesting conditions, in which shares of stock are earned at vesting based on stock price performance. The fair value of MSUs are estimated using a Monte Carlo simulation model. Assumptions and estimates utilized in the model include the risk-free interest rate, dividend yield, expected stock volatility and the estimated period to achievement of the market condition. The following table presents MSU activity for the year ended December 31, 2021:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2020	42,695	$	41.50
Granted	—	—
Unvested shares at December 31, 2021	42,695	$	41.50

As of December 31, 2021, there was no remaining unrecognized compensation expense related to MSUs.

2013 Employee Stock Purchase Plan

In June 2013, our Board of Directors adopted, and in July 2013 our stockholders approved, the 2013 Employee Stock Purchase Plan, or the 2013 ESPP. On January 1, 2022, the annual increase for the 2013 ESPP resulted in an additional 509,091 shares authorized for issuance. We issued 94,888 shares and 120,293 shares during the years ended December 31, 2021 and 2020, respectively, under the 2013 ESPP. The 2013 ESPP provides participating employees with the opportunity to purchase up to an

aggregate of 1,345,454 shares of our common stock. As of December 31, 2021, we had 885,556 shares available for future issuance under the 2013 ESPP.

Stock-based compensation expense

During the years ended December 31, 2021, 2020 and 2019, we recorded stock-based compensation expense for employee and non-employee stock options, RSUs, PSUs, ESPP shares and other stock-based awards. Stock-based compensation expense by award type included within the consolidated statements of operations is as follows:


(In thousands)	2021		2020		2019
Stock options	$	30,985	$	37,705	$	38,650
Restricted stock units	21,510		19,893		14,733
Performance-based stock units	—		1,760		2,239
Employee Stock Purchase Plan	1,013		1,463		1,437
Other stock awards	—		781		991
Total stock-based compensation expense	$	53,508	$	61,602	$	58,050

Expenses related to equity-based awards were allocated as follows in the consolidated statements of operations:


(In thousands)	2021		2020		2019
Research and development expense	$	24,527	$	27,119	$	27,287
Selling, general and administrative expense	28,981		34,483		30,763
Total stock-based compensation expense	$	53,508	$	61,602	$	58,050

No related tax benefits were recognized for the years ended December 31, 2021, 2020 and 2019.

The fair value of each stock option granted to employees and nonemployees is estimated on the date of grant using the Black-Scholes option-pricing model. The following table summarizes the weighted average assumptions used in calculating the grant date fair value of the awards:


	2021		2020		2019
Risk-free interest rate	.72	%	1.24	%	2.32	%
Expected dividend yield	—		—		—
Expected term (in years)	6.05		6.05		6.06
Expected volatility	61.72	%	73.80	%	76.19	%

Expected term

We use the “simplified method” as prescribed by the Securities and Exchange Commission Staff Accounting Bulletin No. 107, Share Based Payments, to estimate the expected term of stock option grants. Under this approach, the weighted-average expected life is presumed to be the average of the contractual term of ten years and the weighted-average vesting term of the stock options, taking into consideration multiple vesting tranches. We utilize this method due to lack of historical data and the plain-vanilla nature of our share-based awards.

Volatility

The expected volatility has been determined using Agios' historical volatilities for a period equal to the expected term of the option grant.

Risk-free rate

The risk-free rate is based on the yield curve of U.S. Treasury securities with periods commensurate with the expected term of the options being valued.

Dividends

We have never paid, and do not anticipate paying, any cash dividends in the foreseeable future, and, therefore, use an expected dividend yield of zero in the option-pricing model.

Forfeitures

We account for forfeitures as they occur and, therefore, do not estimate forfeitures.

Income Taxes

12 Months Ended

Dec. 31, 2021

Income Tax Disclosure [Abstract]

Income Taxes

The domestic and foreign components of loss from continuing operations before income taxes are as follows:


(In thousands)	2021		2020		2019
Domestic	$	(356,665)	$	(330,669)	$	(322,471)
Foreign	155		1,364		21,063
Total	$	(356,510)	$	(329,305)	$	(301,408)

We did not have any material provision for income taxes for the years ended December 31, 2021, 2020 and 2019.

A reconciliation of the expected income tax benefit (expense) computed using the federal statutory income tax rate to our effective income tax rate is as follows for the years ended December 31, 2021, 2020 and 2019:


	2021		2020		2019
Income tax benefit computed at federal statutory tax rate	21.0	%	21.0	%	21.0	%
State taxes, net of federal benefit	2.6	%	2.5	%	3.9	%
Change in valuation allowance	(24.5)	%	(28.2)	%	(29.5)	%
General business credits and other credits	5.3	%	7.0	%	6.9	%
Permanent differences and other adjustments	(3.9)	%	(1.6)	%	(1.9)	%
Stock based compensation	(0.5)	%	(0.7)	%	(0.9)	%
Foreign rate differential	—	%	—	%	0.5	%

Total	—	%	—	%	—	%

Deferred income taxes reflect the net tax effects of temporary differences between the carrying amount of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. Significant components of our deferred tax assets and liabilities for the years ended December 31, 2021 and 2020 are as follows:


(In thousands)	2021		2020
Deferred tax assets:
Net operating loss carryforwards	$	39,186	$	310,841

Tax credit carryforwards	152,128		163,589
Purchased intangible assets	12,150		13,543
Stock-based compensation	27,217		34,284
Operating lease liability	22,963		25,085
Non-deductible accruals and reserves, including inventory	4,033		12,730
RPI Royalty Sale	—		58,048
Other	—		1,230
Total deferred tax assets	257,677		619,350
Depreciation and amortization	(3,168)		(4,002)
Operating lease right of use asset	(18,031)		(20,596)
Less: valuation allowance	(236,478)		(594,752)
Net deferred taxes	$	—	$	—

On March 27, 2020, the Coronavirus Aid, Relief, and Economic Security (CARES) Act was signed into law making several changes to the Internal Revenue Code. The changes include, but are not limited to: increasing the limitation on the amount of deductible interest expense, allowing companies to carryback certain net operating losses, and increasing the amount of net operating loss carryforwards that corporations can use to offset taxable income. The tax law changes in the Act did not have a material impact on the Company’s income tax provision.

As of December 31, 2021, we had net operating loss carryforwards, or NOLs, available to reduce federal, state and foreign income taxes of approximately $22.1 million, $420.0 million and $65.2 million, respectively. The federal NOLs have an indefinite life, however, if not utilized, the state and foreign NOLs begin to expire in 2035 and 2024, respectively. At December 31, 2021, we also had available research and development tax credits for federal and state income tax purposes of

approximately $13.5 million and $24.0 million, respectively. If not utilized, the credits begin to expire in 2029 and 2027 for federal and state income tax purposes. We engaged in clinical testing activities and incurred expenses that qualify for the federal orphan drug tax credit. At December 31, 2021, we had available orphan drug tax credits for federal purposes only of approximately $119.6 million. If not utilized, the orphan drug credits begin to expire in 2035.

As provided by Section 382 of the Internal Revenue Code of 1986, or Section 382, and similar state provisions, utilization of NOLs and tax credit carryforwards may be subject to substantial annual limitations due to ownership change limitations that have previously occurred or that could occur in the future. Ownership changes may limit the amount of NOLs and tax credit carryforwards that can be utilized annually to offset future taxable income and tax, respectively. In general, an ownership change, as defined by Section 382, results from transactions that increase the ownership of five percent stockholders in the stock of a corporation by more than 50 percent in the aggregate over a three year period. We completed a review of our changes in ownership through December 31, 2021 and determined that transactions have resulted in no ownership changes during the year ended December 31, 2021, as defined by Section 382. The impact of the historical ownership changes has been reflected in our deferred tax assets in the table above.

As required by ASC 740, we have evaluated the positive and negative evidence bearing upon the realizability of our deferred tax assets. Based on the weight of available evidence, both positive and negative, we recorded a valuation allowance of $236.5 million and $594.8 million as of December 31, 2021 and December 31, 2020, respectively, because we have determined that it is more likely than not that these assets will not be fully realized. The valuation allowance decreased by $358.3 million for the year ended December 31, 2021 primarily due to the utilization of net operating losses and tax credits and increased by $92.5 million for the year ended December 31, 2020 primarily due to the generation of net operating losses.

The following table presents our change in valuation allowance for the years ended December 31, 2021 and, 2020:


(in thousands)	2021		2020
Valuation allowance at the beginning of the year	$	594,752	$	502,209
(Decrease) Increase for the current period	(358,274)		92,543
Valuation allowance at the end of the year	$	236,478	$	594,752

In December 2019, the FASB issued Accounting Standards Update No. 2019-12 – Income Taxes (Topic 740) Simplifying the Accounting for Income Taxes, as part of its initiative to reduce complexity in the accounting standards. The amendments in ASU 2019-12 eliminate certain exceptions related to the approach for intraperiod tax allocation, the methodology for calculating income taxes in an interim period and the recognition of deferred tax liabilities for outside basis differences. ASU 2019-12 also clarifies and simplifies other aspects of the accounting for income taxes. The amendments in ASU 2019-12 are effective for the fiscal years beginning after December 15, 2020. Early adoption is permitted, including adoption in any interim period. The Company has early adopted this amendment as of January 1, 2019. There was no material impact to the Company’s consolidated financial position, results of operation, or cash flows.

As of December 31, 2021, the unremitted earnings of our foreign subsidiaries are not material. We have not provided for U.S. income taxes or foreign withholding taxes on these earnings as it is our current intention to permanently reinvest these earnings outside the U.S. The tax liability on these earnings is also not material. Events that could trigger a tax liability include, but are not limited to, distributions, reorganizations or restructurings and/or tax law changes.

We apply the accounting guidance in ASC 740 related to accounting for uncertainty in income taxes. Our reserves related to taxes are based on a determination of whether, and how much of, a tax benefit taken by us in our tax filings or positions is more likely than not to be realized following resolution of any potential contingencies present related to the tax benefit.

The following table presents our unrecognized tax benefits activity for the years ended December 31, 2021 and 2020:


(In thousands)	2021		2020
Unrecognized tax benefits at the beginning of the year	$	21,131	$	17,460
Gross increases - current period tax positions	3,089		3,671
Unrecognized tax benefits at the end of the year	$	24,220	$	21,131

We will recognize interest and penalties related to uncertain tax positions above the line as an expense to continuing operations. As of December 31, 2021 and 2020, we had no accrued interest or penalties related to uncertain tax positions and no such amounts have been recognized. If all of the Company’s unrecognized tax benefits as of December 31, 2021 were to become recognizable in the future, we would record $24.2 million of unrecognized tax benefits. The uncertain tax position does not impact our effective income tax rate due to the full valuation allowance.

We are subject to taxation in the United States, Switzerland, Netherlands, Germany, Italy and France. The statute of limitations for assessment by the IRS and state tax authorities is open for tax years ending December 31, 2021, 2020, 2019, and 2018, although carryforward attributes that were generated for tax years prior to 2018 may still be adjusted upon examination by the IRS or state tax authorities if they either have been, or will be, used in a future period. The statute of limitations for assessment in Switzerland remains open for tax years ending December 31, 2021, 2020, 2019, and 2018. The Company’s subsidiaries in the Netherlands and Germany were incorporated in 2019 and therefore the statute of limitations for assessment that remain open in these jurisdictions are for the tax years ending December 31, 2021, 2020 and 2019. The Company’s subsidiaries in Italy and France were incorporated in 2020 and therefore the statute of limitations for assessment that remain open in these jurisdictions are for the tax years ending December 31, 2021 and 2020. There are currently no federal, state or foreign audits in progress.

As of December 31, 2021, we have an income tax receivable of $2.9 million recorded within prepaid expenses and other assets. There was no income tax receivable at December 31, 2020.

- Definition

The entire disclosure for income taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
-Topic 740
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-Topic 740
-SubTopic 10
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-Paragraph 2
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-URI http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

+ Details

Defined Contribution Benefit Plan	12 Months Ended
Defined Contribution Benefit Plan	Dec. 31, 2021
Retirement Benefits [Abstract]
Defined Contribution Benefit Plan	Defined Contribution Benefit PlanWe sponsor a 401(k) retirement plan, in which substantially all of our full-time employees are eligible to participate. Participants may contribute a percentage of their annual compensation to this plan, subject to statutory limitations. We will make matching contributions equal to 100% of the employee’s contributions, subject to a maximum of 4% of eligible compensation.

- Definition

The entire disclosure for retirement benefits.

+ References

Reference 1: http://www.xbrl.org/2003/role/exampleRef
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+ Details

Net Income (Loss) per Share

12 Months Ended

Dec. 31, 2021

Earnings Per Share [Abstract]

Net Income (Loss) per Share

Basic net loss per share is calculated by dividing net loss by the weighted-average shares outstanding during the period, without consideration for common stock equivalents. Diluted net loss per share is calculated by adjusting the weighted average shares outstanding for the dilutive effect of common stock equivalents outstanding for the period, determined using the treasury stock method. For purposes of the dilutive net loss per share calculation, stock options, RSUs, PSUs and MSUs for which the performance and market vesting conditions, respectively, have been deemed probable, and 2013 ESPP shares are considered to be common stock equivalents, while PSUs and MSUs with performance and market vesting conditions, respectively, that were not deemed probable as of December 31, 2021 are not considered to be common stock equivalents.

We utilize the control number concept in the computation of diluted earnings per share to determine whether potential common stock equivalents are dilutive. The control number used is loss from continuing operations. The control number concept requires that the same number of potentially dilutive securities applied in computing diluted earnings per share from continuing operations be applied to all other categories of income or loss, regardless of their anti-dilutive effect on such categories. Since we had a net loss for continuing operations for all periods presented, no dilutive effect has been recognized in the calculation of income from discontinued operations per share. Basic and diluted net loss per share was the same for all periods presented.

The following common stock equivalents were excluded from the calculation of diluted net loss per share applicable to common stockholders for the periods indicated because including them would have had an anti-dilutive effect:


	Years ended December 31,
	2021	2020	2019
Stock options	4,798,826	6,143,046	6,201,485
Restricted stock units	1,002,924	1,284,378	766,953
Performance-based stock units	—	—	72,046
Employee Stock Purchase Plan shares	39,864	46,439	49,418
Total	5,841,614	7,473,863	7,089,902

Share Repurchase Program	12 Months Ended
Share Repurchase Program	Dec. 31, 2021
Equity [Abstract]
Share Repurchase Program	Share Repurchase Program On March 25, 2021, we announced that our board of directors authorized the Repurchase Program for the repurchase of up to $1.2 billion of our outstanding shares of common stock. On March 31, 2021, in connection with the Repurchase Program, we entered into a definitive share repurchase agreement with BMS to repurchase 7.1 million shares of our common stock held by certain subsidiaries of BMS for an aggregate purchase price of $344.5 million, or $48.38 per share. This repurchase was completed on April 5, 2021. Further, on April 2, 2021, in connection with the Repurchase Program, we entered into a Rule 10b5-1 repurchase plan to which we may repurchase up to $600 million of shares of our common stock. As of December 31, 2021, we have repurchased approximately 9.1 million shares of common stock for $458.0 million, or $50.35 per share, under the Rule 10b5-1 repurchase plan. In total, as of December 31, 2021, we have repurchased 16.2 million shares of common stock for $802.5 million, or $49.49 per share, under the Repurchase Program. On October 5, 2021, we terminated our Rule 10b5-1 share repurchase plan and on October 13, 2021 we entered into a Rule 10b-18 repurchase plan that allows us to conduct open market repurchases over time up to our remaining authorization under the Repurchase Program. Repurchased shares are held as treasury stock until they are retired or re-issued. Treasury stock purchases are accounted for under the cost method whereby the entire cost of the acquired stock is recorded as treasury stock. Repurchases of our common stock are accounted for as of the settlement date. There were no retirements or re-issuances of treasury stock during the year ended December 31, 2021.

Selected Quarterly Financial Data (Unaudited)

12 Months Ended

Dec. 31, 2021

Quarterly Financial Information Disclosure [Abstract]

Selected Quarterly Financial Data (Unaudited)

The following table contains quarterly financial information for 2021 and 2020:


2021 (in thousands, except per share data)	First Quarter		Second Quarter		Third Quarter		Fourth Quarter
Loss from continuing operations	$	(90,877)	$	(82,790)	$	(84,259)	$	(98,584)
Net income (loss) from discontinued operations, net of tax	1,965,202		(3,427)		(4,507)		3,957
Net income (loss)	1,874,325		(86,217)		(88,766)		(94,627)
Net loss from continuing operations per share - basic and diluted	(1.31)		(1.36)		(1.48)		(1.81)
Net income (loss) from discontinued operations per share - basic and diluted	28.26		(0.06)		(0.08)		0.07
Net income (loss) per share - basic and diluted	26.95		(1.41)		(1.56)		(1.74)

2020 (in thousands, except per share data)	First Quarter		Second Quarter		Third Quarter		Fourth Quarter
Loss from continuing operations	$	(84,094)	$	(81,495)	$	(79,175)	$	(84,541)
Net income (loss) from discontinued operations, net of tax	43,838		(8,983)		(19,804)		(13,116)
Net income (loss)	(40,256)		(90,478)		(98,979)		(97,657)
Net loss from continuing operations per share - basic and diluted	(1.23)		(1.18)		(1.15)		(1.22)
Net income (loss) from discontinued operations per share - basic and diluted	0.64		(0.13)		(0.29)		(0.19)
Net income (loss) per share - basic and diluted	(0.59)		(1.31)		(1.43)		(1.41)

Subsequent Events	12 Months Ended
Subsequent Events	Dec. 31, 2021
Subsequent Events [Abstract]
Subsequent Events	Subsequent EventsOn February 17, 2022, the FDA approved PYRUKYND® for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States.

Summary of Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2021

Accounting Policies [Abstract]

Principles of consolidation

Use of estimates

Cash and cash equivalents

We consider highly liquid investments with a maturity of three months or less when purchased to be cash equivalents. Cash equivalents are stated at fair value.

Marketable securities

Fair value measurements

Level 1 – Unadjusted quoted prices in active markets for identical assets or liabilities.

There have been no changes to the valuation methods during the years ended December 31, 2021 and 2020. We evaluate transfers between levels at the end of each reporting period.

The carrying amounts of other receivable, prepaid expenses and other current assets, accounts payable, and accrued expenses approximate their fair values due to their short-term maturities.

Concentrations of credit risk

Property and equipment

Property and equipment is stated at cost, and depreciated using the straight-line method over the estimated useful lives of the respective assets:


						Years
Laboratory equipment						5
Computer equipment and software						3
Furniture and fixtures						5
Office equipment						5

Leasehold improvements are amortized over the lesser of the remaining lease term or the estimated useful life of the improvement.

Impairment of long-lived assets

Leases

We have not entered into any material short-term leases or financing leases as of December 31, 2021.

Research and development costs

Stock-based compensation

Income taxes

Comprehensive income (loss)

Net loss per share

Net income (loss) per share

Segment and geographic information

Discontinued Operations

Treasury Stock

Treasury StockTreasury stock purchases are accounted for under the cost method whereby the entire cost of the acquired stock is recorded as treasury stock.

Recent accounting pronouncements

Leases

Other recent accounting pronouncements

adopted this amendment as of January 1, 2019. There was no material impact to the Company’s consolidated financial position, results of operation, or cash flows.

Subsequent events

Summary of Significant Accounting Policies (Tables)

12 Months Ended

Dec. 31, 2021

Accounting Policies [Abstract]

Estimated Useful Lives of Property and Equipment

Property and equipment is stated at cost, and depreciated using the straight-line method over the estimated useful lives of the respective assets:


						Years
Laboratory equipment						5
Computer equipment and software						3
Furniture and fixtures						5
Office equipment						5

Discontinued Operations and Disposal Groups (Tables)

12 Months Ended

Dec. 31, 2021

Discontinued Operations and Disposal Groups [Abstract]

Disposal Groups, Including Discontinued Operations

The following table presents the assets and liabilities of the discontinued operations as of December 31, 2020:


(in thousands)	December 31, 2020
Assets
Current assets:
Accounts receivable, net	$	21,328
Collaboration receivable – related party	2,123
Collaboration receivable – other	1,948
Inventory	14,698
Prepaid expenses and other current assets	7,762
Total current assets of discontinued operations	47,859
Other non-current assets	2,601
Total assets of discontinued operations	$	50,460
Liabilities
Current liabilities:
Accounts payable	$	9,120
Accrued expenses	29,339
Total current liabilities of discontinued operations	38,459
Liability related to the sale of future revenue, net of debt issuance costs	261,269
Total liabilities of discontinued operations	$	299,728

The following table presents the net liabilities transferred for the sale of the oncology business at March 31, 2021:


(in thousands)	March 31, 2021
Assets
Current assets:
Accounts receivable, net	$	25,386
Collaboration receivable – related party	2,253
Collaboration receivable – other	2,438
Inventory	16,190
Prepaid expenses and other current assets	7,125
Total current assets of discontinued operations	53,392
Other non-current assets	2,234
Total assets of discontinued operations	$	55,626

Liabilities
Current liabilities:
Accounts payable	$	4,245
Accrued expenses	30,288
Total current liabilities of discontinued operations	34,533
Liability related to the sale of future revenue, net of debt issuance costs	264,281
Total liabilities of discontinued operations	298,814
Net liabilities distributed to Servier	$	(243,188)

The following table presents the gain on the sale for the year ended December 31, 2021:


(in thousands)	December 31, 2021
Cash proceeds	$	1,802,936
Less: transaction and insurance costs	(53,573)
Plus: net liabilities distributed, including working capital adjustment	239,770
Gain on sale, pre-tax	1,989,133
Income tax expense	(12,799)
Gain on sale, net of tax	$	1,976,334

The following table presents the financial results of the discontinued operations:


(in thousands)	2021		2020		2019
Revenues:
Product revenue, net	$	36,909	$	121,089	$	59,851
Collaboration revenue – related party	1,350		68,274		39,257
Collaboration revenue – other	491		3,571		8,262
Royalty revenue – related party	2,659		10,262		10,542
Total revenue	41,409		203,196		117,912
Cost and expenses:
Cost of sales	706		2,805		1,317
Research and development	41,564		146,659		196,632
Selling, general and administrative	8,551		33,965		30,027
Total cost and expenses	50,821		183,429		227,976
(Loss) income from discontinued operations	(9,412)		19,767		(110,064)
Non-cash interest expense for the sale of future revenue	(5,697)		(17,832)		—
Gain on the sale of the oncology business	1,989,133		—
(Loss) income from discontinued operations, pre-tax	1,974,024		1,935		(110,064)
Income tax expense	(12,799)		—		—
Net (loss) income from discontinued operations	$	1,961,225	$	1,935	$	(110,064)

- Definition

Tabular disclosure of information related to a disposal group. Includes, but is not limited to, a discontinued operation, disposal classified as held-for-sale or disposed of by means other than sale or disposal of an individually significant component.

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+ Details

Fair Value Measurements (Tables)

12 Months Ended

Dec. 31, 2021

Fair Value Disclosures [Abstract]

Cash Equivalents and Marketable Securities Measured at Fair Value on a Recurring Basis


(In thousands)	Level 1		Level 2		Level 3		Total
Cash equivalents	$	156,229	$	21,524	$	—	$	177,753
Total cash equivalents	156,229		21,524		—		177,753

Marketable securities:

U.S. Treasuries	—		309,658		—		309,658
Government securities	—		166,104		—		166,104
Corporate debt securities	—		607,505		—		607,505
Total marketable securities	—		1,083,267		—		1,083,267
Total cash equivalents and marketable securities	$	156,229	$	1,104,791	$	—	$	1,261,020

Marketable Securities (Tables)

12 Months Ended

Dec. 31, 2021

Investments, Debt and Equity Securities [Abstract]

Summary of Marketable Securities

Marketable securities at December 31, 2021 consisted of the following:


(In thousands)	Amortized Cost		Unrealized Gains		Unrealized Losses		Fair Value
Current:

U.S. Treasuries	$	269,109	$	—	$	(36)	$	269,073
Government securities	17,764		1		(10)		17,755
Corporate debt securities	530,490		3		(429)		530,064
Total Current	817,363		4		(475)		816,892

Non-current:
U.S. Treasuries	40,607		—		(23)		40,584
Government securities	148,820		—		(470)		148,350
Corporate debt securities	77,675		—		(234)		77,441
Total Non-current	267,102		—		(727)		266,375
Total marketable securities	$	1,084,465	$	4	$	(1,202)	$	1,083,267

Marketable securities at December 31, 2020 consisted of the following:


(In thousands)	Amortized Cost		Unrealized Gains		Unrealized Losses		Fair Value
Current:

U.S. Treasuries	$	113,559	$	134	$	(21)	$	113,672
Government securities	108,263		37		(8)		108,292
Corporate debt securities	223,461		140		(72)		223,529
Total Current	445,283		311		(101)		445,493

Non-current:
U.S. Treasuries	15,147		—		(10)		15,137
Government securities	26,831		8		—		26,839
Corporate debt securities	55,735		2		(105)		55,632
Total Non-current	97,713		10		(115)		97,608
Total marketable securities	$	542,996	$	321	$	(216)	$	543,101

Property and Equipment, net (Tables)

12 Months Ended

Dec. 31, 2021

Property, Plant and Equipment [Abstract]

Summary of Property and Equipment

Property and equipment, net consisted of the following at December 31:


(In thousands)	2021		2020
Laboratory equipment	$	22,165	$	23,858
Computer equipment and software	6,913		6,945
Leasehold improvements	32,726		32,568
Furniture and fixtures	3,035		3,035
Office equipment	1,690		1,651
Construction in progress	7,368		4,111
Total property and equipment	73,897		72,168
Less: accumulated depreciation	(44,974)		(41,353)
Total property and equipment, net	$	28,923	$	30,815

Leases (Tables)

12 Months Ended

Dec. 31, 2021

Leases [Abstract]

Schedule of Lease Cost and Other Information

The components of lease expense and other information related to leases were as follows:


(In millions)	2021		2020		2019
Operating Lease Costs	$	15.2	$	15.2	$	15.1
Cash paid for amounts included in the measurement of operating lease liabilities	14.4		14.4		12.8

Schedule of Undiscounted Minimum Rental Commitments

As of December 31, 2021, undiscounted minimum rental commitments under non-cancelable leases, for each of the next five years and total thereafter, were as follows:


(In thousands)
2022	$	15,560
2023	18,126
2024	18,660
2025	19,507
2026	20,151
Thereafter	24,234
Undiscounted minimum rental commitments	116,238
Interest	(19,751)
Total operating lease liabilities	$	96,487

Schedule of Future Minimum Lease Payments to be Received

As of December 31, 2021, the future minimum lease payments to be received under the long-term sublease agreement were as follows:


(In thousands)
2022	1,118
2023	1,152
2024	1,186
Total	$	3,456

Accrued Expenses (Tables)

12 Months Ended

Dec. 31, 2021

Payables and Accruals [Abstract]

Summary of Accrued Expenses

Accrued expenses consisted of the following at December 31:


(In thousands)	2021		2020
Accrued compensation	$	19,818	$	20,345
Accrued research and development costs	5,980		5,444
Accrued professional fees	2,335		2,897
Accrued other	3,834		2,115
Total accrued expenses	$	31,967	$	30,801

Share-Based Payments (Tables)

12 Months Ended

Dec. 31, 2021

Share-based Payment Arrangement [Abstract]

Summary of Company's Stock Option Activity of all Stock Incentive Plans

The following table summarizes the stock option activity of all stock incentive plans for the year ended December 31, 2021:


	Number of Stock Options	Weighted- Average Exercise Price		Weighted- Average Remaining Contractual Term (in years)	Aggregate Intrinsic Value (in thousands)
Outstanding at December 31, 2020	6,143,046	$	58.46	6.68	$	13,714
Granted	1,073,989	55.54
Exercised	(758,685)	44.73
Forfeited/Expired	(1,659,524)	62.70
Outstanding at December 31, 2021	4,798,826	$	58.51	6.24	$	4,697
Exercisable at December 31, 2021	3,367,239	$	60.52	5.25	$	4,697
Vested and expected to vest at December 31, 2021	4,798,826	$	58.51	6.24	$	4,697

Schedule of Restricted Stock Unit Activity

The following table presents RSU activity for the year ended December 31, 2021:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2020	1,284,378	$	50.78
Granted	835,698	55.49
Vested	(403,138)	56.90
Forfeited	(714,014)	51.81
Unvested shares at December 31, 2021	1,002,924	$	51.51

Schedule of Performance-Based Unit Activity

The following table presents PSU activity for the year ended December 31, 2021:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2020	142,229	$	54.28
Granted	141,000	54.20
Vested	—	—
Forfeited	(49,170)	54.08
Unvested shares at December 31, 2021	234,059	$	54.28

Schedule of Market-Based Unit Activity

The following table presents MSU activity for the year ended December 31, 2021:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2020	42,695	$	41.50
Granted	—	—
Unvested shares at December 31, 2021	42,695	$	41.50

Schedule of Stock-Based Compensation Expense by Award Type Included Within the Condensed Consolidated Statements of Operations

Stock-based compensation expense by award type included within the consolidated statements of operations is as follows:


(In thousands)	2021		2020		2019
Stock options	$	30,985	$	37,705	$	38,650
Restricted stock units	21,510		19,893		14,733
Performance-based stock units	—		1,760		2,239
Employee Stock Purchase Plan	1,013		1,463		1,437
Other stock awards	—		781		991
Total stock-based compensation expense	$	53,508	$	61,602	$	58,050

Stock-Based Compensation Expense for Employee and Non-Employee Stock Options, Restricted Stock Units, Performance-Based Stock Options, Performance-Based Stock Units and Employee Stock Purchase Plan Shares

Expenses related to equity-based awards were allocated as follows in the consolidated statements of operations:


(In thousands)	2021		2020		2019
Research and development expense	$	24,527	$	27,119	$	27,287
Selling, general and administrative expense	28,981		34,483		30,763
Total stock-based compensation expense	$	53,508	$	61,602	$	58,050

Schedule of Grant Date Fair Value Option Award Weighted Average Assumptions Used

The following table summarizes the weighted average assumptions used in calculating the grant date fair value of the awards:


	2021		2020		2019
Risk-free interest rate	.72	%	1.24	%	2.32	%
Expected dividend yield	—		—		—
Expected term (in years)	6.05		6.05		6.06
Expected volatility	61.72	%	73.80	%	76.19	%

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2021

Income Tax Disclosure [Abstract]

Schedule of Domestic and Foreign Components of Loss Before Income Taxes

The domestic and foreign components of loss from continuing operations before income taxes are as follows:


(In thousands)	2021		2020		2019
Domestic	$	(356,665)	$	(330,669)	$	(322,471)
Foreign	155		1,364		21,063
Total	$	(356,510)	$	(329,305)	$	(301,408)

Reconciliation of Expected Income Tax Benefit (Expense) Computed Using Federal Statutory Income Tax Rate


	2021		2020		2019
Income tax benefit computed at federal statutory tax rate	21.0	%	21.0	%	21.0	%
State taxes, net of federal benefit	2.6	%	2.5	%	3.9	%
Change in valuation allowance	(24.5)	%	(28.2)	%	(29.5)	%
General business credits and other credits	5.3	%	7.0	%	6.9	%
Permanent differences and other adjustments	(3.9)	%	(1.6)	%	(1.9)	%
Stock based compensation	(0.5)	%	(0.7)	%	(0.9)	%
Foreign rate differential	—	%	—	%	0.5	%

Total	—	%	—	%	—	%

Company's Deferred Tax Assets and Liabilities

Significant components of our deferred tax assets and liabilities for the years ended December 31, 2021 and 2020 are as follows:


(In thousands)	2021		2020
Deferred tax assets:
Net operating loss carryforwards	$	39,186	$	310,841

Tax credit carryforwards	152,128		163,589
Purchased intangible assets	12,150		13,543
Stock-based compensation	27,217		34,284
Operating lease liability	22,963		25,085
Non-deductible accruals and reserves, including inventory	4,033		12,730
RPI Royalty Sale	—		58,048
Other	—		1,230
Total deferred tax assets	257,677		619,350
Depreciation and amortization	(3,168)		(4,002)
Operating lease right of use asset	(18,031)		(20,596)
Less: valuation allowance	(236,478)		(594,752)
Net deferred taxes	$	—	$	—

Changes in Valuation Allowance

The following table presents our change in valuation allowance for the years ended December 31, 2021 and, 2020:


(in thousands)	2021		2020
Valuation allowance at the beginning of the year	$	594,752	$	502,209
(Decrease) Increase for the current period	(358,274)		92,543
Valuation allowance at the end of the year	$	236,478	$	594,752

Schedule of Unrecognized Tax Benefits Rollforward

The following table presents our unrecognized tax benefits activity for the years ended December 31, 2021 and 2020:


(In thousands)	2021		2020
Unrecognized tax benefits at the beginning of the year	$	21,131	$	17,460
Gross increases - current period tax positions	3,089		3,671
Unrecognized tax benefits at the end of the year	$	24,220	$	21,131

Net Income (Loss) per Share (Tables)

12 Months Ended

Dec. 31, 2021

Earnings Per Share [Abstract]

Common Stock Excluded from Calculation of Diluted Earnings Per Share


	Years ended December 31,
	2021	2020	2019
Stock options	4,798,826	6,143,046	6,201,485
Restricted stock units	1,002,924	1,284,378	766,953
Performance-based stock units	—	—	72,046
Employee Stock Purchase Plan shares	39,864	46,439	49,418
Total	5,841,614	7,473,863	7,089,902

Selected Quarterly Financial Data (Unaudited) (Tables)

12 Months Ended

Dec. 31, 2021

Quarterly Financial Information Disclosure [Abstract]

Summary of Quarterly Financial Data

The following table contains quarterly financial information for 2021 and 2020:


2021 (in thousands, except per share data)	First Quarter		Second Quarter		Third Quarter		Fourth Quarter
Loss from continuing operations	$	(90,877)	$	(82,790)	$	(84,259)	$	(98,584)
Net income (loss) from discontinued operations, net of tax	1,965,202		(3,427)		(4,507)		3,957
Net income (loss)	1,874,325		(86,217)		(88,766)		(94,627)
Net loss from continuing operations per share - basic and diluted	(1.31)		(1.36)		(1.48)		(1.81)
Net income (loss) from discontinued operations per share - basic and diluted	28.26		(0.06)		(0.08)		0.07
Net income (loss) per share - basic and diluted	26.95		(1.41)		(1.56)		(1.74)

2020 (in thousands, except per share data)	First Quarter		Second Quarter		Third Quarter		Fourth Quarter
Loss from continuing operations	$	(84,094)	$	(81,495)	$	(79,175)	$	(84,541)
Net income (loss) from discontinued operations, net of tax	43,838		(8,983)		(19,804)		(13,116)
Net income (loss)	(40,256)		(90,478)		(98,979)		(97,657)
Net loss from continuing operations per share - basic and diluted	(1.23)		(1.18)		(1.15)		(1.22)
Net income (loss) from discontinued operations per share - basic and diluted	0.64		(0.13)		(0.29)		(0.19)
Net income (loss) per share - basic and diluted	(0.59)		(1.31)		(1.43)		(1.41)

Nature of Business - Additional Information (Details) - USD ($) $ / shares in Units, $ in Thousands			9 Months Ended		12 Months Ended
	Apr. 05, 2021	Mar. 31, 2021	Dec. 31, 2021	Dec. 31, 2021	Dec. 31, 2021	Apr. 02, 2021	Mar. 25, 2021	Apr. 30, 2020
Subsidiary, Sale of Stock [Line Items]
Repurchase of common stock					$ 802,486
Cash, cash equivalents and marketable securities			$ 1,286,400	$ 1,286,400	1,286,400
Repurchase Program
Subsidiary, Sale of Stock [Line Items]
Stock repurchase program, authorized amount							$ 1,200,000
Shares repurchased (in shares)			16,200,000
Repurchase of common stock			$ 802,500
Shares repurchased (in usd per share)			$ 49.49
BMS Repurchase
Subsidiary, Sale of Stock [Line Items]
Shares repurchased (in shares)	7,100,000
Repurchase of common stock	$ 344,500
Shares repurchased (in usd per share)	$ 48.38
Rule 10b5-1 Repurchase
Subsidiary, Sale of Stock [Line Items]
Stock repurchase program, authorized amount						$ 600,000
Shares repurchased (in shares)				9,100,000
Repurchase of common stock				$ 458,000
Shares repurchased (in usd per share)				$ 50.35
U.S. \| TIBSOVO
Subsidiary, Sale of Stock [Line Items]
Earn-out revenue for royalties					6,600
Discontinued Operations, Disposed of by Sale \| Agios Oncology Business
Subsidiary, Sale of Stock [Line Items]
Cash proceeds		$ 1,800,000			1,802,936
Contingent milestone payment		$ 200,000
Discontinued Operations, Disposed of by Sale \| Agios Oncology Business \| U.S. \| TIBSOVO
Subsidiary, Sale of Stock [Line Items]
Contingent royalty payment		5.00%
Discontinued Operations, Disposed of by Sale \| Agios Oncology Business \| U.S. \| vorasidenib
Subsidiary, Sale of Stock [Line Items]
Contingent royalty payment		15.00%
At-the-market Offering
Subsidiary, Sale of Stock [Line Items]
Maximum value of shares issued								$ 250,000
Value of common stock reserved for future issuance			$ 250,000	$ 250,000	$ 250,000
2010 Agreement
Subsidiary, Sale of Stock [Line Items]
Milestone payment for achievement of specified ex-U.S. commercial milestone event		$ 25,000

Summary of Significant Accounting Policies - Additional Information (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2021 USD ($) segment	Dec. 31, 2020 USD ($)	Jan. 01, 2019 USD ($)
Schedule of Significant Accounting Policies [Line Items]
Minimum period to liquidate	12 months
Number of operating segments \| segment	1
Operating right of use assets	$ 75,124	$ 84,661
Total operating lease liabilities	$ 96,487
ASU 2016-02
Schedule of Significant Accounting Policies [Line Items]
Operating right of use assets			$ 59,900
Total operating lease liabilities			$ 77,300
Minimum
Schedule of Significant Accounting Policies [Line Items]
Investment maturity period, non-current	1 year
Maximum
Schedule of Significant Accounting Policies [Line Items]
Investment maturity period, current	1 year
Investment maturity period, non-current	2 years

Summary of Significant Accounting Policies - Estimated Useful Lives of Property and Equipment (Details)	12 Months Ended
	Dec. 31, 2021
Laboratory equipment
Property, Plant and Equipment [Line Items]
Estimated useful lives of property and equipment (in years)	5 years
Computer equipment and software
Property, Plant and Equipment [Line Items]
Estimated useful lives of property and equipment (in years)	3 years
Furniture and fixtures
Property, Plant and Equipment [Line Items]
Estimated useful lives of property and equipment (in years)	5 years
Office equipment
Property, Plant and Equipment [Line Items]
Estimated useful lives of property and equipment (in years)	5 years

Discontinued Operations - Assets and Liabilities of Discontinued Operations (Details) - USD ($)	Dec. 31, 2021	Mar. 31, 2021	Dec. 31, 2020
Income Statement, Balance Sheet and Additional Disclosures by Disposal Groups, Including Discontinued Operations [Line Items]
Current assets of discontinued operations	$ 0		$ 47,859,000
Non-current assets of discontinued operations	0		2,601,000
Current liabilities of discontinued operations	0		38,459,000
Agios Oncology Business \| Discontinued Operations, Disposed of by Sale
Income Statement, Balance Sheet and Additional Disclosures by Disposal Groups, Including Discontinued Operations [Line Items]
Accounts receivable, net		$ 25,386,000	21,328,000
Collaboration receivable – related party		2,253,000	2,123,000
Collaboration receivable – other		2,438,000	1,948,000
Inventory		16,190,000	14,698,000
Prepaid expenses and other current assets		7,125,000	7,762,000
Current assets of discontinued operations		53,392,000	47,859,000
Non-current assets of discontinued operations		2,234,000	2,601,000
Total assets of discontinued operations	0	55,626,000	50,460,000
Accounts payable		4,245,000	9,120,000
Accrued expenses		30,288,000	29,339,000
Current liabilities of discontinued operations		34,533,000	38,459,000
Liability related to the sale of future revenue, net of debt issuance costs		264,281,000	261,269,000
Total liabilities of discontinued operations	$ 0	$ 298,814,000	$ 299,728,000

Discontinued Operations - Summary of Gain on Sale of Discontinued Operations (Details) - Agios Oncology Business - Discontinued Operations, Disposed of by Sale - USD ($) $ in Thousands		12 Months Ended
	Mar. 31, 2021	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Income Statement, Balance Sheet and Additional Disclosures by Disposal Groups, Including Discontinued Operations [Line Items]
Cash proceeds	$ 1,800,000	$ 1,802,936
Less: transaction and insurance costs		(53,573)
Plus: net liabilities distributed, including working capital adjustment	$ 243,188	239,770
Gain on the sale of the oncology business		1,989,133	$ 0
Income tax expense		(12,799)	$ 0	$ 0
Gain on sale, net of tax		$ 1,976,334

- Definition

Amount of tax expense (benefit) related to a discontinued operation. Includes, but is not limited to, tax expense (benefit) related to income (loss) from operations during the phase-out period, tax expense (benefit) related to gain (loss) on disposal, tax expense (benefit) related to gain (loss) for reversal of write-down (write-down) to fair value, less cost to sell, and tax expense (benefit) related to adjustments of a prior period gain (loss) on disposal.

+ References

Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 205
-SubTopic 20
-Section 45
-Paragraph 3B
-URI http://asc.fasb.org/extlink&oid=109222160&loc=SL51721525-107759

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 20
-Section 45
-Paragraph 2
-Subparagraph (b)
-URI http://asc.fasb.org/extlink&oid=123586238&loc=d3e38679-109324

Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 205
-SubTopic 20
-Section 45
-Paragraph 4
-URI http://asc.fasb.org/extlink&oid=109222160&loc=d3e1012-107759

Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 205
-SubTopic 20
-Section 50
-Paragraph 1
-Subparagraph (b)
-URI http://asc.fasb.org/extlink&oid=109222650&loc=d3e1361-107760

Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 205
-SubTopic 20
-Section 45
-Paragraph 3A
-URI http://asc.fasb.org/extlink&oid=109222160&loc=SL51721523-107759

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SAB TOPIC 6.I.7)
-URI http://asc.fasb.org/extlink&oid=122134291&loc=d3e330036-122817

Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 205
-SubTopic 20
-Section 50
-Paragraph 5C
-Subparagraph (b)(2)
-URI http://asc.fasb.org/extlink&oid=109222650&loc=SL51721675-107760

Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 205
-SubTopic 20
-Section 50
-Paragraph 5B
-Subparagraph (a)
-URI http://asc.fasb.org/extlink&oid=109222650&loc=SL51721673-107760

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section 50
-Paragraph 10
-URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32672-109319

+ Details

Discontinued Operations - Financial Results of Discontinued Operations (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2021	Sep. 30, 2021	Jun. 30, 2021	Mar. 31, 2021	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Cost and expenses:
Net (loss) income from discontinued operations	$ 3,957	$ (4,507)	$ (3,427)	$ 1,965,202	$ (13,116)	$ (19,804)	$ (8,983)	$ 43,838	$ 1,961,225	$ 1,935	$ (110,064)
Agios Oncology Business \| Discontinued Operations, Disposed of by Sale
Revenues:
Total revenue									41,409	203,196	117,912
Cost and expenses:
Cost of sales									706	2,805	1,317
Research and development									41,564	146,659	196,632
Selling, general and administrative									8,551	33,965	30,027
Total cost and expenses									50,821	183,429	227,976
(Loss) income from discontinued operations									(9,412)	19,767	(110,064)
Net income (loss) from discontinued operations, net of tax									(5,697)	(17,832)	0
Gain on the sale of the oncology business									1,989,133	0
(Loss) income from discontinued operations, pre-tax									1,974,024	1,935	(110,064)
Income tax expense									(12,799)	0	0
Net (loss) income from discontinued operations									1,961,225	1,935	(110,064)
Agios Oncology Business \| Product revenue, net \| Discontinued Operations, Disposed of by Sale
Revenues:
Total revenue									36,909	121,089	59,851
Agios Oncology Business \| Collaboration revenue – related party \| Discontinued Operations, Disposed of by Sale
Revenues:
Total revenue									1,350	68,274	39,257
Agios Oncology Business \| Collaboration revenue – other \| Discontinued Operations, Disposed of by Sale
Revenues:
Total revenue									491	3,571	8,262
Agios Oncology Business \| Royalty revenue – related party \| Discontinued Operations, Disposed of by Sale
Revenues:
Total revenue									$ 2,659	$ 10,262	$ 10,542

Discontinued Operations - Additional Information (Details) - Agios Oncology Business - Discontinued Operations, Disposed of by Sale - USD ($)	12 Months Ended
	Dec. 31, 2021	Mar. 31, 2021	Dec. 31, 2020
Income Statement, Balance Sheet and Additional Disclosures by Disposal Groups, Including Discontinued Operations [Line Items]
Total assets of discontinued operations	$ 0	$ 55,626,000	$ 50,460,000
Total liabilities of discontinued operations	$ 0	$ 298,814,000	$ 299,728,000
Minimum
Income Statement, Balance Sheet and Additional Disclosures by Disposal Groups, Including Discontinued Operations [Line Items]
Transitional services period	1 month
Maximum
Income Statement, Balance Sheet and Additional Disclosures by Disposal Groups, Including Discontinued Operations [Line Items]
Transitional services period	1 year

Fair Value Measurements - Cash Equivalents and Marketable Securities Measured at Fair Value on a Recurring Basis (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	$ 1,083,267	$ 543,101
Fair Value, Measurements, Recurring
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total cash equivalents	177,753
Total marketable securities	1,083,267
Total cash equivalents and marketable securities	1,261,020
Fair Value, Measurements, Recurring \| Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total cash equivalents	177,753
Fair Value, Measurements, Recurring \| U.S. Treasuries
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	309,658
Fair Value, Measurements, Recurring \| Government securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	166,104
Fair Value, Measurements, Recurring \| Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	607,505
Fair Value, Measurements, Recurring \| Level 1
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total cash equivalents	156,229
Total marketable securities	0
Total cash equivalents and marketable securities	156,229
Fair Value, Measurements, Recurring \| Level 1 \| Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total cash equivalents	156,229
Fair Value, Measurements, Recurring \| Level 1 \| U.S. Treasuries
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	0
Fair Value, Measurements, Recurring \| Level 1 \| Government securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	0
Fair Value, Measurements, Recurring \| Level 1 \| Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	0
Fair Value, Measurements, Recurring \| Level 2
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total cash equivalents	21,524
Total marketable securities	1,083,267
Total cash equivalents and marketable securities	1,104,791
Fair Value, Measurements, Recurring \| Level 2 \| Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total cash equivalents	21,524
Fair Value, Measurements, Recurring \| Level 2 \| U.S. Treasuries
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	309,658
Fair Value, Measurements, Recurring \| Level 2 \| Government securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	166,104
Fair Value, Measurements, Recurring \| Level 2 \| Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	607,505
Fair Value, Measurements, Recurring \| Level 3
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total cash equivalents	0
Total marketable securities	0
Total cash equivalents and marketable securities	0
Fair Value, Measurements, Recurring \| Level 3 \| Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total cash equivalents	0
Fair Value, Measurements, Recurring \| Level 3 \| U.S. Treasuries
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	0
Fair Value, Measurements, Recurring \| Level 3 \| Government securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	0
Fair Value, Measurements, Recurring \| Level 3 \| Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Total marketable securities	$ 0

Fair Value Measurements - Additional Information (Details)	Dec. 31, 2021 USD ($)
Fair Value, Measurements, Recurring \| Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Fair value of assets (liabilities)	$ 0

Marketable Securities - Summary of Marketable Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	$ 1,084,465	$ 542,996
Unrealized Gains	4	321
Unrealized Losses	(1,202)	(216)
Fair Value	1,083,267	543,101
Current
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	817,363	445,283
Unrealized Gains	4	311
Unrealized Losses	(475)	(101)
Fair Value	816,892	445,493
Current \| U.S. Treasuries
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	269,109	113,559
Unrealized Gains	0	134
Unrealized Losses	(36)	(21)
Fair Value	269,073	113,672
Current \| Government securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	17,764	108,263
Unrealized Gains	1	37
Unrealized Losses	(10)	(8)
Fair Value	17,755	108,292
Current \| Corporate debt securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	530,490	223,461
Unrealized Gains	3	140
Unrealized Losses	(429)	(72)
Fair Value	530,064	223,529
Non Current
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	267,102	97,713
Unrealized Gains	0	10
Unrealized Losses	(727)	(115)
Fair Value	266,375	97,608
Non Current \| U.S. Treasuries
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	40,607	15,147
Unrealized Gains	0	0
Unrealized Losses	(23)	(10)
Fair Value	40,584	15,137
Non Current \| Government securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	148,820	26,831
Unrealized Gains	0	8
Unrealized Losses	(470)	0
Fair Value	148,350	26,839
Non Current \| Corporate debt securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	77,675	55,735
Unrealized Gains	0	2
Unrealized Losses	(234)	(105)
Fair Value	$ 77,441	$ 55,632

Marketable Securities - Additional Information (Details)	12 Months Ended
	Dec. 31, 2021 USD ($) security	Dec. 31, 2020 USD ($) security
Investments, Debt and Equity Securities [Abstract]
Realized gain (loss) on marketable securities	$ 0	$ 0
Number of debt securities in an unrealized loss position for less than one year \| security	294	87
Allowance for credit losses	$ 0	$ 0
Aggregate fair value of debt securities in an unrealized loss position	$ 950,500,000	$ 299,000,000
Number of unrealized loss position \| security	0	0

Property and Equipment, net - Summary of Property and Equipment (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 73,897	$ 72,168
Less: accumulated depreciation	(44,974)	(41,353)
Property and equipment, net	28,923	30,815
Laboratory equipment
Property, Plant and Equipment [Line Items]
Total property and equipment	22,165	23,858
Computer equipment and software
Property, Plant and Equipment [Line Items]
Total property and equipment	6,913	6,945
Leasehold improvements
Property, Plant and Equipment [Line Items]
Total property and equipment	32,726	32,568
Furniture and fixtures
Property, Plant and Equipment [Line Items]
Total property and equipment	3,035	3,035
Office equipment
Property, Plant and Equipment [Line Items]
Total property and equipment	1,690	1,651
Construction in progress
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 7,368	$ 4,111

Property and Equipment, net - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Property, Plant and Equipment [Abstract]
Depreciation expense	$ 8.8	$ 9.4	$ 8.0

Leases - Additional Information (Details) ft² in Thousands, $ in Millions		12 Months Ended
	Apr. 11, 2019 USD ($) ft² lease_term	Dec. 31, 2021 USD ($)	Aug. 31, 2021 ft²	Dec. 31, 2020
Lessee, Lease, Description [Line Items]
Remaining lease terms		6 years
Weighted-average incremental borrowing rate		5.70%		5.70%
Weighted-average remaining lease term		6 years 2 months 12 days		7 years 2 months 12 days
Standby letter of credit		$ 2.9
Area of premises subleased (in square feet) \| ft²			13
Sublease income		$ 0.5
38 Sidney Street Lease
Lessee, Lease, Description [Line Items]
Number of square feet of office space (in square feet) \| ft²	13
Number of optional terms available at end of current lease term (in lease terms) \| lease_term	2
Term for extension of operating lease (in years)	5 years
Tenant improvement allowance	$ 1.0
64 Sidney Street Lease
Lessee, Lease, Description [Line Items]
Term for extension of operating lease (in years)	3 years
88 Sidney Street Lease
Lessee, Lease, Description [Line Items]
Term for extension of operating lease (in years)	3 years

Leases - Schedule of Lease Cost and Other Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Leases [Abstract]
Operating Lease Costs	$ 15.2	$ 15.2	$ 15.1
Cash paid for amounts included in the measurement of operating lease liabilities	$ 14.4	$ 14.4	$ 12.8

Leases - Schedule of Undiscounted Minimum Rental Commitments (Details) $ in Thousands	Dec. 31, 2021 USD ($)
Leases [Abstract]
2022	$ 15,560
2023	18,126
2024	18,660
2025	19,507
2026	20,151
Thereafter	24,234
Undiscounted minimum rental commitments	116,238
Interest	(19,751)
Total operating lease liabilities	$ 96,487

Leases - Schedule of Future Minimum Lease Payments to be Received (Details) $ in Thousands	Dec. 31, 2021 USD ($)
Leases [Abstract]
2022	$ 1,118
2023	1,152
2024	1,186
Total	$ 3,456

Accrued Expenses - Summary of Accrued Expenses and Other Current Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Payables and Accruals [Abstract]
Accrued compensation	$ 19,818	$ 20,345
Accrued research and development costs	5,980	5,444
Accrued professional fees	2,335	2,897
Accrued other	3,834	2,115
Accrued expenses	$ 31,967	$ 30,801

Commitments and Contingent Liabilities - Additional Information (Details)	Dec. 31, 2021 lawsuit
Commitments and Contingencies Disclosure [Abstract]
Number of ongoing legal proceedings	0

Common Stock - Additional Information (Details) - shares	Dec. 31, 2021	Dec. 31, 2020
Equity [Abstract]
Common stock, shares authorized (in shares)	125,000,000	125,000,000

Share-Based Payments - Additional Information (Details) - USD ($)		12 Months Ended
	Jan. 01, 2022	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Tax benefits related to stock based compensation		$ 0	$ 0	$ 0
Expected contractual term		10 years
Expected dividend yield		0.00%	0.00%	0.00%
Restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Weighted-average period to recognize compensation expense		1 year 8 months 26 days
Unrecognized compensation expense excluding options		$ 29,500,000
Performance-based stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized compensation expense excluding options		0
Unrecognized compensation cost not expected to be recognized		12,700,000
Market-based stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized compensation expense excluding options		$ 0
2007 Plan and 2013 Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share based awards reserved for issuance (in shares)		11,422,409
2013 Stock Incentive Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares available for future issuance (in shares)		5,343,905
Annual increase in common stock (in shares)		2,000,000
Percentage of outstanding shares of common stock		4.00%
Weighted-average grant date fair value of options (in usd per share)		$ 31.2	$ 32.1	$ 36.44
Intrinsic value of options exercised		$ 8,500,000	$ 10,400,000	$ 6,400,000
Unrecognized compensation expense related to options		$ 39,800,000
Weighted-average period to recognize compensation expense		2 years 3 months 29 days
2013 Stock Incentive Plan \| Subsequent Event
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Additional shares authorized for issuance (in shares)	2,000,000
2013 Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares available for future issuance (in shares)		885,556
Shares issued under 2013 ESPP (in shares)		94,888	120,293
Opportunity to purchase common stock (in shares)		1,345,454
2013 Employee Stock Purchase Plan \| Subsequent Event
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Additional shares authorized for issuance (in shares)	509,091

Share-Based Payments - Summary of Company's Stock Option Activity of all Stock Incentive Plans (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Share-based Compensation Arrangement by Share-based Payment Award, Options, Outstanding [Roll Forward]
Number of stock options, outstanding, beginning balance (in shares)	6,143,046
Number of stock options, granted (in shares)	1,073,989
Number of stock options, exercised (in shares)	(758,685)
Number of stock options, forfeited/expired (in shares)	(1,659,524)
Number of stock options, outstanding, ending balance (in shares)	4,798,826	6,143,046
Share-based Compensation Arrangement by Share-based Payment Award, Options, Outstanding, Weighted Average Exercise Price [Abstract]
Weighted-average exercise price, outstanding, beginning balance (in usd per share)	$ 58.46
Weighted-average exercise price, granted (in usd per share)	55.54
Weighted-average exercise price, exercised (in usd per share)	44.73
Weighted-average exercise price, forfeited/expired (in usd per share)	62.70
Weighted-average exercise price, outstanding, ending balance (in usd per share)	$ 58.51	$ 58.46
Share-based Compensation Arrangement by Share-based Payment Award, Options, Additional Disclosures [Abstract]
Weighted-average remaining contractual term, outstanding (in years)	6 years 2 months 26 days	6 years 8 months 4 days
Aggregate intrinsic value, outstanding	$ 4,697	$ 13,714
Number of stock options, exercisable (in shares)	3,367,239
Weighted-average exercise price, exercisable (in usd per share)	$ 60.52
Weighted-average remaining contractual term, exercisable (in years)	5 years 3 months
Aggregate intrinsic value, exercisable	$ 4,697
Number of stock options, vested and expected to vest (in shares)	4,798,826
Weighted-average exercise price, vested and expected to vest (in usd per share)	$ 58.51
Weighted-average remaining contractual term, vested and expected to vest (in years)	6 years 2 months 26 days
Aggregate intrinsic value, vested and expected to vest	$ 4,697

Share-Based Payments - Summary of Unvested RSUs, Performance-Based Stock and Market-Based Stock Unit Activity (Details)	12 Months Ended
	Dec. 31, 2021 $ / shares shares
Restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Number of Shares [Roll Forward]
Unvested shares beginning of period (in shares) \| shares	1,284,378
Granted (in shares) \| shares	835,698
Vested (in shares) \| shares	(403,138)
Forfeited (in shares) \| shares	(714,014)
Unvested shares end of period (in shares) \| shares	1,002,924
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Weighted Average Grant Date Fair Value [Abstract]
Weighted-average grant date fair value, unvested shares beginning of period (in usd per share) \| $ / shares	$ 50.78
Weighted-average grant date fair value, granted (in usd per share) \| $ / shares	55.49
Weighted-average grant date fair value, vested (in usd per share) \| $ / shares	56.90
Weighted-average grant date fair value, forfeited/expired (in usd per share) \| $ / shares	51.81
Weighted-average grant date fair value, unvested shares end of period (in usd per share) \| $ / shares	$ 51.51
Performance-based stock units
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Number of Shares [Roll Forward]
Unvested shares beginning of period (in shares) \| shares	142,229
Granted (in shares) \| shares	141,000
Vested (in shares) \| shares	0
Forfeited (in shares) \| shares	(49,170)
Unvested shares end of period (in shares) \| shares	234,059
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Weighted Average Grant Date Fair Value [Abstract]
Weighted-average grant date fair value, unvested shares beginning of period (in usd per share) \| $ / shares	$ 54.28
Weighted-average grant date fair value, granted (in usd per share) \| $ / shares	54.20
Weighted-average grant date fair value, vested (in usd per share) \| $ / shares	0
Weighted-average grant date fair value, forfeited/expired (in usd per share) \| $ / shares	54.08
Weighted-average grant date fair value, unvested shares end of period (in usd per share) \| $ / shares	$ 54.28
Market-based stock units
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Number of Shares [Roll Forward]
Unvested shares beginning of period (in shares) \| shares	42,695
Granted (in shares) \| shares	0
Unvested shares end of period (in shares) \| shares	42,695
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Weighted Average Grant Date Fair Value [Abstract]
Weighted-average grant date fair value, unvested shares beginning of period (in usd per share) \| $ / shares	$ 41.50
Weighted-average grant date fair value, granted (in usd per share) \| $ / shares	0
Weighted-average grant date fair value, unvested shares end of period (in usd per share) \| $ / shares	$ 41.50

Share-Based Payments - Schedule of Stock-Based Compensation by Award Type Included Within the Consolidated Statements of Operations (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	$ 53,508	$ 61,602	$ 58,050
Stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	30,985	37,705	38,650
Restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	21,510	19,893	14,733
Performance-based stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	0	1,760	2,239
Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	1,013	1,463	1,437
Other stock awards
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	$ 0	$ 781	$ 991

Share-Based Payments - Stock-Based Compensation Expense for Equity-Based Awards (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Allocated share based compensation expense	$ 53,508	$ 61,602	$ 58,050
Research and development expense
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Allocated share based compensation expense	24,527	27,119	27,287
Selling, general and administrative expense
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Allocated share based compensation expense	$ 28,981	$ 34,483	$ 30,763

Share-Based Payments - Schedule of Grant Date Fair Value Option Award Weighted Average Assumptions Used (Details)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share-based Payment Arrangement [Abstract]
Risk-free interest rate	0.72%	1.24%	2.32%
Expected dividend yield	0.00%	0.00%	0.00%
Expected term (in years)	6 years 18 days	6 years 18 days	6 years 21 days
Expected volatility	61.72%	73.80%	76.19%

Income Taxes - Schedule of Domestic and Foreign Components of Loss Before Income Taxes (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2021	Sep. 30, 2021	Jun. 30, 2021	Mar. 31, 2021	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Income Tax Disclosure [Abstract]
Domestic									$ (356,665)	$ (330,669)	$ (322,471)
Foreign									155	1,364	21,063
Total	$ (98,584)	$ (84,259)	$ (82,790)	$ (90,877)	$ (84,541)	$ (79,175)	$ (81,495)	$ (84,094)	$ (356,510)	$ (329,305)	$ (301,408)

- Definition

Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (c)
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8933-108599

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 30
-Subparagraph (b)
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8906-108599

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (f)
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8933-108599

Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 940
-SubTopic 20
-Section 25
-Paragraph 1
-URI http://asc.fasb.org/extlink&oid=123384075&loc=d3e41242-110953

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 22
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8736-108599

Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 220
-SubTopic 10
-Section S99
-Paragraph 2
-Subparagraph (SX 210.5-03(10))
-URI http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227

Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 944
-SubTopic 220
-Section S99
-Paragraph 1
-Subparagraph (SX 210.7-04(8))
-URI http://asc.fasb.org/extlink&oid=120400993&loc=SL114874131-224263

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 942
-SubTopic 235
-Section S99
-Paragraph 1
-Subparagraph (SX 210.9-05(b)(2))
-URI http://asc.fasb.org/extlink&oid=120399901&loc=d3e537907-122884

Reference 9: http://www.xbrl.org/2003/role/exampleRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 31
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8924-108599

Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 942
-SubTopic 220
-Section S99
-Paragraph 1
-Subparagraph (SX 210.9-04(15))
-URI http://asc.fasb.org/extlink&oid=120399700&loc=SL114874048-224260

+ Details

Income Taxes - Reconciliation of Expected Income Tax Benefit (Expense) Computed Using Federal Statutory Income Tax Rate (Details)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Income Tax Disclosure [Abstract]
Income tax benefit computed at federal statutory tax rate	21.00%	21.00%	21.00%
State taxes, net of federal benefit	2.60%	2.50%	3.90%
Change in valuation allowance	(24.50%)	(28.20%)	(29.50%)
General business credits and other credits	5.30%	7.00%	6.90%
Permanent differences and other adjustments	(3.90%)	(1.60%)	(1.90%)
Stock based compensation	(0.50%)	(0.70%)	(0.90%)
Foreign rate differential	0.00%	0.00%	0.50%
Total	0.00%	0.00%	0.00%

Income Taxes - Components of Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Deferred tax assets:
Net operating loss carryforwards	$ 39,186	$ 310,841
Tax credit carryforwards	152,128	163,589
Purchased intangible assets	12,150	13,543
Stock-based compensation	27,217	34,284
Operating lease liability	22,963	25,085
Non-deductible accruals and reserves, including inventory	4,033	12,730
RPI Royalty Sale	0	58,048
Other	0	1,230
Total deferred tax assets	257,677	619,350
Depreciation and amortization	(3,168)	(4,002)
Operating lease right of use asset	(18,031)	(20,596)
Less: valuation allowance	(236,478)	(594,752)	$ (502,209)
Net deferred taxes	$ 0	$ 0

Income Taxes - Additional Information (Details)	12 Months Ended
Income Taxes - Additional Information (Details)	Dec. 31, 2021 USD ($) Ownership Audit	Dec. 31, 2020 USD ($)	Dec. 31, 2019 USD ($)
Income Taxes Disclosure [Line Items]
Percentage of stock owned resulting in an ownership change	50.00%
Aggregate period	3 years
Number of ownership changes \| Ownership	0
Valuation allowance	$ 236,478,000	$ 594,752,000	$ 502,209,000
(Decrease) Increase for the current period	(358,274,000)	92,543,000
Accrued interest and penalties related to uncertain tax positions	0	0
Unrecognized tax benefits	$ 24,220,000	21,131,000	$ 17,460,000
Number of federal, state or foreign audits in process \| Audit	0
Prepaid Expenses and Other Current Assets
Income Taxes Disclosure [Line Items]
Income tax receivable	$ 2,900,000	$ 0
Federal Orphan Drug Tax Credit
Income Taxes Disclosure [Line Items]
Research and development tax credit	119,600,000
Federal
Income Taxes Disclosure [Line Items]
Net operating loss carryforwards	22,100,000
Federal \| Research Tax Credit Carryforward
Income Taxes Disclosure [Line Items]
Research and development tax credit	13,500,000
State and Local Jurisdiction
Income Taxes Disclosure [Line Items]
Net operating loss carryforwards	420,000,000
State and Local Jurisdiction \| Research Tax Credit Carryforward
Income Taxes Disclosure [Line Items]
Research and development tax credit	24,000,000
Foreign Income Tax
Income Taxes Disclosure [Line Items]
Net operating loss carryforwards	$ 65,200,000

Income Taxes - Changes in Valuation Allowance (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Deferred Tax Assets, Valuation Allowance [Roll Forward]
Valuation allowance, beginning balance	$ 594,752	$ 502,209
(Decrease) Increase for the current period	(358,274)	92,543
Valuation allowance, ending balance	$ 236,478	$ 594,752

Income Taxes - Unrecognized Tax Benefits Rollforward (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Reconciliation of Unrecognized Tax Benefits, Excluding Amounts Pertaining to Examined Tax Returns [Roll Forward]
Unrecognized tax benefits, beginning balance	$ 21,131	$ 17,460
Gross increases - current period tax positions	3,089	3,671
Unrecognized tax benefits, ending balance	$ 24,220	$ 21,131

Defined Contribution Benefit Plan - Additional Information (Details)	12 Months Ended
	Dec. 31, 2021
Retirement Benefits [Abstract]
Employer's matching contribution percentage	100.00%
Employer's contribution percentage of eligible compensation	4.00%

Net Income (Loss) per Share - Common Stock Excluded from Calculation of Diluted Net Loss Per Share (Detail) - shares	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	5,841,614	7,473,863	7,089,902
Stock options
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	4,798,826	6,143,046	6,201,485
Restricted stock units
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	1,002,924	1,284,378	766,953
Performance-based stock units
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	0	0	72,046
Employee Stock Purchase Plan shares
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	39,864	46,439	49,418

Share Repurchase Program (Details) - USD ($) $ / shares in Units, $ in Thousands		9 Months Ended		12 Months Ended
	Apr. 05, 2021	Dec. 31, 2021	Dec. 31, 2021	Dec. 31, 2021	Apr. 02, 2021	Mar. 25, 2021
Equity, Class of Treasury Stock [Line Items]
Repurchase of common stock				$ 802,486
Repurchase Program
Equity, Class of Treasury Stock [Line Items]
Stock repurchase program, authorized amount						$ 1,200,000
Shares repurchased (in shares)		16,200,000
Repurchase of common stock		$ 802,500
Shares repurchased (in usd per share)		$ 49.49
BMS Repurchase
Equity, Class of Treasury Stock [Line Items]
Shares repurchased (in shares)	7,100,000
Repurchase of common stock	$ 344,500
Shares repurchased (in usd per share)	$ 48.38
Rule 10b5-1 Repurchase
Equity, Class of Treasury Stock [Line Items]
Stock repurchase program, authorized amount					$ 600,000
Shares repurchased (in shares)			9,100,000
Repurchase of common stock			$ 458,000
Shares repurchased (in usd per share)			$ 50.35

Selected Quarterly Financial Data (Unaudited) - Summary of Quarterly Financial Data (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2021	Sep. 30, 2021	Jun. 30, 2021	Mar. 31, 2021	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Quarterly Financial Information Disclosure [Abstract]
Loss from continuing operations	$ (98,584)	$ (84,259)	$ (82,790)	$ (90,877)	$ (84,541)	$ (79,175)	$ (81,495)	$ (84,094)	$ (356,510)	$ (329,305)	$ (301,408)
Net income (loss) from discontinued operations, net of tax	3,957	(4,507)	(3,427)	1,965,202	(13,116)	(19,804)	(8,983)	43,838	$ 1,961,225	$ 1,935	$ (110,064)
Net income (loss)	$ (94,627)	$ (88,766)	$ (86,217)	$ 1,874,325	$ (97,657)	$ (98,979)	$ (90,478)	$ (40,256)
Net loss from continuing operations per share - basic (in usd per share)	$ (1.81)	$ (1.48)	$ (1.36)	$ (1.31)	$ (1.22)	$ (1.15)	$ (1.18)	$ (1.23)	$ (5.90)	$ (4.77)	$ (5.02)
Net loss from continuing operations per share - diluted (in usd per share)	0.07	(0.08)	(0.06)	28.26	(0.19)	(0.29)	(0.13)	0.64	(5.90)	(4.77)	(5.02)
Net loss per share – basic (in usd per share)	(1.74)	(1.56)	(1.41)	26.95	(1.41)	(1.43)	(1.31)	(0.59)	26.55	(4.74)	(6.86)
Net loss per share – diluted (in usd per share)	$ (1.74)	$ (1.56)	$ (1.41)	$ 26.95	$ (1.41)	$ (1.43)	$ (1.31)	$ (0.59)	$ 26.55	$ (4.74)	$ (6.86)

- Definition

The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.

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