Sage Therapeutics (SAGE) 10-Q 8 Nov 22 2022 Q3 Quarterly report Financial data

Document and Entity Information

Document and Entity Information - shares	9 Months Ended
	Sep. 30, 2022	Nov. 01, 2022
Cover [Abstract]
Document Type	10-Q
Amendment Flag	false
Document Period End Date	Sep. 30, 2022
Document Fiscal Year Focus	2022
Document Fiscal Period Focus	Q3
Trading Symbol	SAGE
Entity Registrant Name	Sage Therapeutics, Inc.
Entity Central Index Key	0001597553
Current Fiscal Year End Date	--12-31
Entity Filer Category	Large Accelerated Filer
Entity Small Business	false
Entity Emerging Growth Company	false
Title of 12(b) Security	Common Stock, par value $0.0001 per share
Security Exchange Name	NASDAQ
Entity Current Reporting Status	Yes
Entity Common Stock, Shares Outstanding		59,493,704
Entity Shell Company	false
Entity File Number	001-36544
Entity Tax Identification Number	27-4486580
Entity Address, Address Line One	215 First Street
Entity Address, City or Town	Cambridge
Entity Address, State or Province	MA
Entity Address, Postal Zip Code	02142
City Area Code	617
Local Phone Number	299-8380
Entity Interactive Data Current	Yes
Entity Incorporation, State or Country Code	DE
Document Quarterly Report	true
Document Transition Report	false

Condensed Consolidated Balance

Condensed Consolidated Balance Sheets - USD ($) $ in Thousands	Sep. 30, 2022	Dec. 31, 2021
Current assets:
Cash and cash equivalents	$ 199,826	$ 294,233
Marketable securities	1,193,813	1,448,063
Prepaid expenses and other current assets	53,017	39,841
Collaboration receivable - related party	18,448	18,506
Total current assets	1,465,104	1,800,643
Property and equipment, net	2,821	3,016
Restricted cash	1,269	1,269
Right-of-use operating asset	11,970	16,109
Other long-term assets	4,909	4,251
Total assets	1,486,073	1,825,288
Current liabilities:
Accounts payable	7,077	10,450
Accrued expenses	85,007	67,275
Operating lease liability, current portion	7,603	7,468
Total current liabilities	99,687	85,193
Operating lease liability, net of current portion	6,164	10,964
Other liabilities	100	100
Total liabilities	105,951	96,257
Commitments and contingencies (Note 5)
Stockholders’ equity:
Preferred stock, $0.0001 par value per share; 5,000,000 shares authorized at September 30, 2022 and December 31, 2021; no shares issued or outstanding at September 30, 2022 and December 31, 2021
Common stock, $0.0001 par value per share; 120,000,000 shares authorized at September 30, 2022 and December 31, 2021; 59,496,737 and 58,940,083 shares issued at September 30, 2022 and December 31, 2021; 59,493,704 and 58,937,050 shares outstanding at September 30, 2022 and December 31, 2021	6	6
Treasury stock, at cost, 3,033 shares at September 30, 2022 and December 31, 2021	(400)	(400)
Additional paid-in capital	3,276,423	3,227,471
Accumulated deficit	(1,881,024)	(1,495,386)
Accumulated other comprehensive loss	(14,883)	(2,660)
Total stockholders’ equity	1,380,122	1,729,031
Total liabilities and stockholders’ equity	$ 1,486,073	$ 1,825,288

Condensed Consolidated Balanc_2

Condensed Consolidated Balance Sheets (Parenthetical) - $ / shares	Sep. 30, 2022	Dec. 31, 2021
Statement Of Financial Position [Abstract]
Preferred stock, par value	$ 0.0001	$ 0.0001
Preferred stock, shares authorized	5,000,000	5,000,000
Preferred stock, shares issued	0	0
Preferred stock, shares outstanding	0	0
Common stock, par value	$ 0.0001	$ 0.0001
Common stock, shares authorized	120,000,000	120,000,000
Common stock, shares issued	59,496,737	58,940,083
Common stock, shares outstanding	59,493,704	58,937,050
Treasury stock, shares	3,033	3,033

Condensed Consolidated Statemen

Condensed Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2022	Sep. 30, 2021	Sep. 30, 2022	Sep. 30, 2021
Income Statement [Abstract]
Total revenue	$ 1,739	$ 1,440	$ 4,821	$ 4,666
Operating costs and expenses:
Cost of goods sold	184	131	670	466
Research and development	81,553	83,497	236,868	207,723
Selling, general and administrative	61,482	48,706	160,370	131,899
Total operating costs and expenses	143,219	132,334	397,908	340,088
Loss from operations	(141,480)	(130,894)	(393,087)	(335,422)
Interest income, net	4,127	692	7,397	2,132
Other income, net	30	31	52	110
Net loss	$ (137,323)	$ (130,171)	$ (385,638)	$ (333,180)
Net loss per share—basic	$ (2.31)	$ (2.21)	$ (6.51)	$ (5.69)
Net loss per share—diluted	$ (2.31)	$ (2.21)	$ (6.51)	$ (5.69)
Weighted average number of common shares outstanding— basic	59,428,123	58,819,548	59,242,563	58,593,743
Weighted average number of common shares outstanding— diluted	59,428,123	58,819,548	59,242,563	58,593,743
Comprehensive loss:
Net loss	$ (137,323)	$ (130,171)	$ (385,638)	$ (333,180)
Other comprehensive items:
Unrealized loss on marketable securities	(1,011)	(21)	(12,223)	(721)
Total other comprehensive loss	(1,011)	(21)	(12,223)	(721)
Total comprehensive loss	$ (138,334)	$ (130,192)	$ (397,861)	$ (333,901)

Condensed Consolidated Statem_2

Condensed Consolidated Statements of Cash Flows - USD ($) $ in Thousands	9 Months Ended
	Sep. 30, 2022	Sep. 30, 2021
Cash flows from operating activities
Net loss	$ (385,638)	$ (333,180)
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation expense	46,358	83,981
Premium on marketable securities	(1,464)	(19,792)
Amortization of premium on marketable securities	7,182	8,722
Depreciation expense	832	3,849
Changes in operating assets and liabilities:
Prepaid expenses and other current assets	(13,176)	(11,522)
Collaboration receivable - related party	58	(24,185)
Other long-term assets	(658)	(534)
Right-of-use operating asset	4,139	3,898
Operating lease liabilities, current	135	152
Operating lease liabilities, non-current	(4,800)	(4,427)
Accounts payable	(3,357)	1,042
Accrued expenses and other liabilities	17,285	11,315
Net cash used in operating activities	(333,104)	(280,681)
Cash flows from investing activities
Proceeds from sales and maturities of marketable securities	918,816	699,212
Purchases of marketable securities	(682,505)	(1,671,399)
Purchases of property and equipment	(655)
Net cash provided by (used in) investing activities	235,656	(972,187)
Cash flows from financing activities
Proceeds from stock option exercises and employee stock purchase plan issuances	3,080	14,300
Payment of employee tax obligations related to vesting of restricted stock units	(39)	(796)
Net cash provided by financing activities	3,041	13,504
Net decrease in cash, cash equivalents and restricted cash	(94,407)	(1,239,364)
Cash, cash equivalents and restricted cash at beginning of period	295,502	1,662,798
Cash, cash equivalents and restricted cash at end of period	201,095	423,434
Supplemental disclosure of non-cash operating and investing activities
Purchases of property and equipment included in accounts payable	$ 54
Lease asset de-recognized upon lease cancellation		$ 3,733

Condensed Consolidated Statem_3

Condensed Consolidated Statements of Changes in Stockholders' Equity (Unaudited) - USD ($) $ in Thousands	Total	Common Stock [Member]	Treasury Stock [Member]	Additional Paid-in Capital [Member]	Accumulated Other Comprehensive Loss [Member]	Accumulated Deficit [Member]
Balances at Dec. 31, 2020	$ 2,072,334	$ 6	$ (400)	$ 3,109,807	$ 415	$ (1,037,494)
Balances, Shares at Dec. 31, 2020		58,308,411	3,033
Issuance of common stock from exercises of stock options, Amount	4,687			4,687
Issuance of common stock from exercises of stock options, Shares		80,338
Issuance of common stock under the employee stock purchase plan	936			936
Issuance of common stock under the employee stock purchase plan, Shares		18,072
Stock-based compensation expense	21,734			21,734
Change in unrealized loss on available-for-sale securities	(651)				(651)
Net loss	(95,764)					(95,764)
Balances at Mar. 31, 2021	2,003,276	$ 6	$ (400)	3,137,164	(236)	(1,133,258)
Balance, Shares at Mar. 31, 2021		58,406,821	3,033
Balances at Dec. 31, 2020	2,072,334	$ 6	$ (400)	3,109,807	415	(1,037,494)
Balances, Shares at Dec. 31, 2020		58,308,411	3,033
Net loss	(333,180)
Balances at Sep. 30, 2021	1,835,654	$ 6	$ (400)	3,207,028	(306)	(1,370,674)
Balance, Shares at Sep. 30, 2021		58,832,373	3,033
Balances at Mar. 31, 2021	2,003,276	$ 6	$ (400)	3,137,164	(236)	(1,133,258)
Balances, Shares at Mar. 31, 2021		58,406,821	3,033
Issuance of common stock from exercises of stock options, Amount	6,861			6,861
Issuance of common stock from exercises of stock options, Shares		159,070
Stock-based compensation expense	27,465			27,465
Change in unrealized loss on available-for-sale securities	(49)				(49)
Vesting of restricted stock units, net of employee tax obligations	(796)			(796)
Vesting of restricted stock units, net of employee tax obligations, Shares		204,473
Net loss	(107,245)					(107,245)
Balances at Jun. 30, 2021	1,929,512	$ 6	$ (400)	3,170,694	(285)	(1,240,503)
Balance, Shares at Jun. 30, 2021		58,770,364	3,033
Issuance of common stock from exercises of stock options, Amount	430			430
Issuance of common stock from exercises of stock options, Shares		33,322
Issuance of common stock under the employee stock purchase plan	1,825			1,825
Issuance of common stock under the employee stock purchase plan, Shares		28,687
Stock-based compensation expense	34,079			34,079
Change in unrealized loss on available-for-sale securities	(21)				(21)
Net loss	(130,171)					(130,171)
Balances at Sep. 30, 2021	1,835,654	$ 6	$ (400)	3,207,028	(306)	(1,370,674)
Balance, Shares at Sep. 30, 2021		58,832,373	3,033
Balances at Dec. 31, 2021	1,729,031	$ 6	$ (400)	3,227,471	(2,660)	(1,495,386)
Balances, Shares at Dec. 31, 2021		58,937,050	3,033
Issuance of common stock from exercises of stock options, Amount	646			646
Issuance of common stock from exercises of stock options, Shares		105,474
Issuance of common stock under the employee stock purchase plan	1,153			1,153
Issuance of common stock under the employee stock purchase plan, Shares		23,625
Stock-based compensation expense	18,268			18,268
Change in unrealized loss on available-for-sale securities	(8,541)				(8,541)
Net loss	(122,055)					(122,055)
Balances at Mar. 31, 2022	1,618,502	$ 6	$ (400)	3,247,538	(11,201)	(1,617,441)
Balance, Shares at Mar. 31, 2022		59,066,149	3,033
Balances at Dec. 31, 2021	1,729,031	$ 6	$ (400)	3,227,471	(2,660)	(1,495,386)
Balances, Shares at Dec. 31, 2021		58,937,050	3,033
Net loss	(385,638)
Balances at Sep. 30, 2022	1,380,122	$ 6	$ (400)	3,276,423	(14,883)	(1,881,024)
Balance, Shares at Sep. 30, 2022		59,493,704	3,033
Balances at Mar. 31, 2022	1,618,502	$ 6	$ (400)	3,247,538	(11,201)	(1,617,441)
Balances, Shares at Mar. 31, 2022		59,066,149	3,033
Issuance of common stock from exercises of stock options, Amount	37			37
Issuance of common stock from exercises of stock options, Shares		31,801
Stock-based compensation expense	14,652			14,652
Change in unrealized loss on available-for-sale securities	(2,671)				(2,671)
Vesting of restricted stock units, net of employee tax obligations	(24)			(24)
Vesting of restricted stock units, net of employee tax obligations, Shares		290,779
Net loss	(126,260)					(126,260)
Balances at Jun. 30, 2022	1,504,236	$ 6	$ (400)	3,262,203	(13,872)	(1,743,701)
Balance, Shares at Jun. 30, 2022		59,388,729	3,033
Issuance of common stock from exercises of stock options, Amount	320			320
Issuance of common stock from exercises of stock options, Shares		11,808
Issuance of common stock under the employee stock purchase plan	1,193			1,193
Issuance of common stock under the employee stock purchase plan, Shares		33,614
Stock-based compensation expense	12,722			12,722
Change in unrealized loss on available-for-sale securities	(1,011)				(1,011)
Vesting of restricted stock units, net of employee tax obligations	(15)			(15)
Vesting of restricted stock units, net of employee tax obligations, Shares		59,553
Net loss	(137,323)					(137,323)
Balances at Sep. 30, 2022	$ 1,380,122	$ 6	$ (400)	$ 3,276,423	$ (14,883)	$ (1,881,024)
Balance, Shares at Sep. 30, 2022		59,493,704	3,033

Nature of the Business

Nature of the Business	9 Months Ended
	Sep. 30, 2022
Organization Consolidation And Presentation Of Financial Statements [Abstract]
Nature of the Business	1. Nature of the Business Sage Therapeutics, Inc. (“Sage” or the “Company”) is a biopharmaceutical company with a mission to pioneer solutions to deliver life-changing brain health medicines, so every person can thrive. The Company’s first product, ZULRESSO® (brexanolone) CIV injection, is approved in the U.S. as a treatment for postpartum depression (“PPD”) in adults. The Company launched ZULRESSO commercially in the U.S. in June 2019. The Company plans to complete submission of a new drug application for its lead investigational product candidate, zuranolone, for the treatment of major depressive disorder (“MDD”) and PPD in December 2022. The Company has a portfolio of other product candidates with a current focus on modulating two critical central nervous system (“CNS”) receptor systems, GABA and NMDA. The GABA receptor family, which is recognized as the major inhibitory neurotransmitter in the CNS, mediates downstream neurologic and bodily function via activation of GABA A receptors. The NMDA-type receptors of the glutamate receptor system are a major excitatory receptor system in the CNS. Dysfunction in these systems is implicated in a broad range of CNS disorders. The Company is currently targeting diseases and disorders of the brain with three key focus areas: depression, neurology and neuropsychiatry. The Company was incorporated under the laws of the State of Delaware on April 16, 2010, and commenced operations on January 19, 2011 as Sterogen Biopharma, Inc. On September 13, 2011, the Company changed its name to Sage Therapeutics, Inc. Risks and Uncertainties The Company is subject to risks and uncertainties common to companies in the biotechnology and pharmaceutical industries, including, but not limited to, the risks associated with developing product candidates at each stage of non-clinical and clinical development; the challenges associated with gaining regulatory approval of such product candidates; the risks associated with the marketing and sale of pharmaceutical products; the potential for development by third parties of new technological innovations that may compete with the Company’s products and product candidates; the dependence on key personnel; the challenges of protecting proprietary technology; the need to comply with government regulations; the high costs of drug development; the uncertainty of being able to secure additional capital when needed to fund operations; and the impact of the COVID-19 pandemic and related downstream effects on its development activities, operations and financial condition. The product candidates developed by the Company require approvals from the U.S. Food and Drug Administration (“FDA”) or foreign regulatory agencies prior to commercial sales. There can be no assurance that the current and future product candidates of the Company will receive, or that the Company’s current product, ZULRESSO, will maintain, the necessary approvals. If the Company fails to successfully complete clinical development and generate results sufficient to file for regulatory approval or is denied approval or approval is delayed for any of its product candidates, such occurrences may have a material adverse impact on the Company’s business and its financial condition. The Company is also subject to additional risks and uncertainties related to the ongoing COVID-19 pandemic and other macroeconomic and geopolitical events, which collectively have caused and may continue to cause major disruptions to businesses and economies worldwide. The rapid spread of COVID-19 in the U.S. resulted in a significant reduction in patient demand for ZULRESSO and in the number of sites available to administer ZULRESSO. There have been and continue to be healthcare staffing shortages and other changes to the macroeconomic environment as downstream effects of the pandemic have continued. These factors have had a significant and sustained negative impact on the Company’s revenue from sales of ZULRESSO. While the Company has not experienced any other material disruptions to date as a result of the COVID-19 pandemic, any prolonged material disruptions to the work of the Company’s employees, suppliers, contract manufacturers, or vendors could negatively impact the Company’s activities, availability of supplies, or operating results. In addition, while the Company has seen slower patient recruitment in certain clinical trials due to the COVID-19 pandemic and its downstream effects, and has experienced some challenges in qualifying and activating clinical trial sites, including due to capacity and resource constraints and employee attrition at our vendors and at sites, the Company has not experienced other significant impacts to the Company’s development activities as a result of the COVID-19 pandemic. Any material disruption to the Company’s development activities may cause delays, increase the Company’s costs and impact the Company’s operating results. In addition, the COVID-19 pandemic initially caused major volatility in capital markets and a significant global economic downturn, and the Company’s ability to access the capital markets in the future could be negatively impacted if there are long-term negative effects of the COVID-19 pandemic on the macroeconomic environment or capital markets, even after the pandemic has subsided. Moreover, U.S. and global financial markets have experienced volatility and disruption due to other macroeconomic and geopolitical events such as rising inflation, the risk of a recession and the ongoing conflict between Russia and Ukraine. The Company cannot predict at this time to what extent it and its collaborators, employees, suppliers, contract manufacturers and/or vendors could potentially be negatively impacted by these events. Going Concern Under Accounting Standards Update (“ASU”) No. 2014-15, Presentation of Financial Statements—Going Concern (Subtopic 205-40), the Company has the responsibility to evaluate whether conditions and/or events raise substantial doubt about its ability to meet its future financial obligations as they become due within one year after the date that the financial statements are issued. The Company has incurred losses and negative cash flows from operations in each year since its inception, except for net income of $ 606.1 million for the year ended December 31, 2020, reflecting revenue recognized under a collaboration and license agreement with Biogen MA Inc. (“BIMA”) and Biogen International GmbH (collectively with BIMA, “Biogen”) (the “Biogen Collaboration Agreement”). As of September 30, 2022, the Company had an accumulated deficit of $ 1.9 billion. From its inception through September 30, 2022, the Company has received aggregate net proceeds of $ 2.8 billion from the sales of redeemable convertible preferred stock prior to its initial public offering (“IPO”), the issuance of convertible notes, and the sales of common stock in its IPO in July 2014, in follow-on public offerings, and to BIMA under a stock purchase agreement executed in connection with the Biogen Collaboration Agreement. The Company has also received $ 1.0 billion in upfront payments under its collaborations with Biogen and Shionogi & Co., Ltd. (“Shionogi”). Until such time, if ever, as the Company can generate substantial product revenue and achieve profitability, the Company expects to finance its cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances, licensing arrangements and other sources of funding. If the Company is unable to raise additional funds through equity or debt financings or other sources of funding when needed, the Company 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 the Company would otherwise prefer to develop and market itself. The Company expects that, based on its current operating plans, the Company’s existing cash, cash equivalents and marketable securities will be sufficient to fund its currently planned operations for at least the next 12 months from the filing date of these unaudited interim condensed consolidated financial statements (“condensed consolidated financial statements”). At some point after that time, the Company anticipates it will require additional financing to fund its future operations. Even if the Company believes it has sufficient funds for its current or future operating plans, the Company may seek to raise additional capital if market conditions are favorable or in light of other strategic considerations.

Summary of Significant Accounti

Summary of Significant Accounting Policies	9 Months Ended
	Sep. 30, 2022
Accounting Policies [Abstract]
Summary of Significant Accounting Policies	2. Summary of Significant Accounting Policies The following is a summary of significant accounting policies followed in the preparation of these condensed consolidated financial statements. Basis of Presentation The condensed consolidated financial statements of the Company included herein have been prepared pursuant to the rules and regulations of the Securities and Exchange Commission. Certain information and footnote disclosures normally included in financial statements prepared in accordance with accounting principles generally accepted in the United States of America (“GAAP”) have been condensed or omitted from this report, as is permitted by such rules and regulations. Accordingly, these condensed consolidated financial statements should be read in conjunction with the audited consolidated financial statements as of and for the year ended December 31, 2021, included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2021. The condensed consolidated financial statements have been prepared on the same basis as the audited consolidated financial statements. In the opinion of the Company’s management, the accompanying condensed consolidated financial statements contain all adjustments, consisting of only normal recurring adjustments, necessary for a fair statement of its financial position as of September 30, 2022, its results of operations and comprehensive loss for the three and nine months ended September 30, 2022 and 2021, its cash flows for the nine months ended September 30, 2022 and 2021, and its statements of changes in stockholders’ equity for the three and nine months ended September 30, 2022 and 2021. The consolidated balance sheet at December 31, 2021 was derived from audited financial statements, but does not include all disclosures required by GAAP. The results for the three and nine months ended September 30, 2022 are not necessarily indicative of the results for the year ending December 31, 2022, or for any future period. Principles of Consolidation The condensed consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries as disclosed in Note 2, Summary of Significant Accounting Policies , within the “Notes to Consolidated Financial Statements” accompanying its Annual Report on Form 10-K for the fiscal year ended December 31, 2021 . Intercompany accounts and transactions have been eliminated. Use of Estimates The preparation of condensed consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the condensed consolidated financial statements and the reported amounts of revenues and expenses during the reporting period. The full extent to which the COVID-19 pandemic and its downstream effects may directly or indirectly impact the Company’s business, results of operations and financial condition, including sales, expenses, reserves and allowances, manufacturing, clinical trials, research and development costs and employee-related amounts, will depend in large part on future developments, which cannot be predicted with confidence at this time, including: the scope, duration and severity of ongoing and future waves of the pandemic, including the impact of any variant strains of the COVID-19 virus; the extent of healthcare staffing shortages that have continued even as COVID-19-related restrictions have eased; the impact of the pandemic on the Company’s customers and vendors, including capacity and resource constraints; the impact of the pandemic on the willingness of women with PPD to seek treatment with ZULRESSO and the number of physicians willing to prescribe it; the impact of the downstream effects of the pandemic on business operations across the U.S.; and the scope and extent of any future actions or restrictive measures taken to contain or mitigate the impact of the pandemic . The Company has made estimates of the impact of the COVID-19 pandemic within its condensed consolidated financial statements. Due to the evolving nature of the COVID-19 pandemic, its downstream effects, and their impacts, there may be changes to those estimates in future periods, and a ctual results could differ from those estimates. Research and Development Costs and Accruals Research and development expenses are comprised of costs incurred in performing research and development activities, including salaries and benefits, overhead costs, depreciation, contract services and other related costs. Research and development costs are expensed to operations as the related obligation is incurred. The Company has entered into various research and development contracts with research institutions and other companies both inside and outside of the U.S. These agreements are generally cancelable, and related costs are recorded as research and development expenses as incurred. The Company records accruals for estimated ongoing research and development costs. When billing terms under these contracts do not coincide with the timing of when the work is performed, the Company is required to make estimates of outstanding obligations to those third parties as of the end of the reporting period. Any accrual estimates are based on a number of factors, including the Company’s knowledge of the progress towards completion of the research and development activities, invoicing to date under the contracts, communication from the research institution or other companies of any actual costs incurred during the period that have not yet been invoiced, and the costs included in the contracts. Significant judgments and estimates are made in determining the accrued balances at the end of any reporting period. Actual results could differ from the estimates made by the Company. The historical accrual estimates made by the Company have not been materially different from the actual costs. Revenue Recognition The Company generates revenue from the sale of ZULRESSO, which was approved by the FDA in March 2019 and the Company subsequently began selling in June 2019, and from collaboration and supply agreements with the Company’s collaborators. To date, revenue from collaboration agreements has come from initial, upfront payments allocated to licenses of intellectual property delivered to the Company’s collaborators and from the supply of material for clinical trials under a supply agreement. Under Accounting Standards Codification (“ASC”) Topic 606, Revenue from Contracts with Customers (“Topic 606”), an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration that the entity expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that an entity determines are within the scope of Topic 606, the entity performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price, including variable consideration, if any; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the entity satisfies a performance obligation. Arrangements that include rights to additional goods or services that are exercisable at a customer’s discretion are generally considered options. The Company assesses if these options provide a material right to the customer and if so, they are considered performance obligations. The exercise of a material right may be accounted for as a contract modification or as a continuation of the contract for accounting purposes. For contracts determined to be within the scope of Topic 606, the Company assesses whether the goods or services promised within each contract are distinct to identify those that are performance obligations. This assessment involves subjective determinations and requires management to make judgments about the individual promised goods or services and whether such are separable from the other aspects of the contractual relationship. Promised goods and services are considered distinct provided that: (i) the customer can benefit from the good or service either on its own or together with other resources that are readily available to the customer and (ii) the entity’s promise to transfer the good or service to the customer is separately identifiable from other promises in the contract. The Company allocates the transaction price (the amount of consideration it expects to be entitled to from a customer in exchange for the promised goods or services) to each performance obligation and recognizes the associated revenue when (or as) each performance obligation is satisfied. The Company’s estimate of the transaction price for each contract includes all variable consideration to which the Company expects to be entitled. Collaboration and License Revenue In assessing whether a promised good or service is distinct in the evaluation of a collaboration or license arrangement subject to Topic 606, the Company considers factors such as the research, manufacturing and commercialization capabilities of the collaboration partner and the availability of the associated expertise in the general marketplace. The Company also considers the intended benefit of the contract in assessing whether a promised good or service is separately identifiable from other promises in the contract. If a promised good or service is not distinct, the Company is required to combine that good or service with other promised goods or services until it identifies a bundle of goods or services that is distinct. The transaction price is then determined and allocated to the identified performance obligations in proportion to their standalone selling prices (“SSP”) on a relative SSP basis. SSP is determined at contract inception and is not updated to reflect changes between contract inception and when the performance obligations are satisfied. Determining the SSP for performance obligations requires significant judgment. In developing the SSP for a performance obligation, the Company considers applicable market conditions and relevant entity-specific factors, including factors that were contemplated in negotiating the agreement with the customer and estimated costs. In certain circumstances, the Company may apply the residual method to determine the SSP of a good or service if the standalone selling price is considered highly variable or uncertain. The Company validates the SSP for performance obligations by evaluating whether changes in the key assumptions used to determine the SSP will have a significant effect on the allocation of arrangement consideration between multiple performance obligations. If the consideration promised in a contract includes a variable amount, the Company estimates the amount of consideration to which it will be entitled in exchange for transferring the promised goods or services to a customer. The Company determines the amount of variable consideration by using the expected value method or the most likely amount method. The Company includes the unconstrained amount of estimated variable consideration in the transaction price. The amount included in the transaction price is constrained to the amount for which it is probable that a significant reversal of cumulative revenue recognized will not occur. At the end of each subsequent reporting period, the Company re-evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis in the period of adjustment. If an arrangement includes development and regulatory milestone payments, the Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the Company’s control or the licensee’s control, such as regulatory approvals, are generally not considered probable of being achieved until those approvals are received. In determining the transaction price, the Company adjusts consideration for the effects of the time value of money if the timing of payments provides the Company with a significant benefit of financing. The Company does not assess whether a contract has a significant financing component if the expectation at contract inception is such that the period between payment by the licensees and the transfer of the promised goods or services to the licensees will be one year or less. The Company assessed its arrangements with Shionogi and Biogen and concluded that a significant financing component does not exist for either arrangement. For arrangements with licenses of intellectual property that include sales-based royalties or milestone payments based on the level of sales, and the license is deemed to be the predominant item to which the royalties or milestone payments relate, the Company recognizes royalty revenue and sales-based milestones at the later of (i) when the related sales occur, or (ii) when the performance obligation to which the royalty or milestone payment has been allocated has been satisfied. The Company then recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) each performance obligation is satisfied at a point in time or over time, and if over time this is based on the use of an output or input method. Revenue from the Company’s collaboration agreement with Shionogi has come from initial, upfront consideration upon execution of the agreement and for the supply of drug product for Shionogi’s clinical trials. Revenue from the Company’s collaboration agreement with Biogen has come from initial, upfront consideration related to the execution of the Biogen Collaboration Agreement. For additional information, refer to Note 6, Collaboration Agreements . Product Revenue, Net The Company recognizes product revenues, net of variable consideration related to certain allowances and accruals that are determined using the expected value method, in its condensed consolidated financial statements at the point in time when control transfers to the customer, which is typically when the product has been delivered to the customer’s location. The amount included in the transaction price is constrained to the amount for which it is probable that a significant reversal of cumulative revenue recognized will not occur. The Company’s only performance obligation identified for ZULRESSO is to deliver the product to the location specified by the customer’s order. The Company records shipping and handling costs associated with delivery of product to its customers within selling, general and administrative expenses on its condensed consolidated statements of operations and comprehensive loss. The Company expenses incremental costs of obtaining a contract as incurred if the expected amortization period of the asset would be less than one year . If the Company were to incur incremental costs with an amortization period greater than a year, such costs would be capitalized as contract assets, as they are expected to be recovered, and would be expensed by amortizing on a systematic basis that is consistent with the transfer to the customer of the goods or services to which the asset relates. The Company did not have any contract assets (unbilled receivables) at September 30, 2022, as customer invoicing generally occurs before or at the time of revenue recognition. The Company did not have any contract liabilities at September 30, 2022, as the Company did not receive any payments in advance of satisfying its performance obligations to its customers. Amounts billed or invoiced that are considered trade accounts receivable are included in prepaid expenses and other current assets on the condensed consolidated balance sheets. As of September 30, 2022 and December 31, 2021, the Company had not provided any allowance for bad debts against the trade accounts receivable, and the amount of trade accounts receivable was not significant. The Company records reserves, based on contractual terms, for the following components of variable consideration related to product sold during the reporting period, as well as its estimate of product that remains in the distribution channel inventory of its customers at the end of the reporting period. On a quarterly basis, the Company updates its estimates, if necessary, and records any material adjustments in the period they are identified. Chargebacks : The Company estimates chargebacks from its customers who directly purchase the product from the Company for discounts resulting from contractual commitments to sell products to eligible healthcare settings at prices lower than the list prices charged to its customers. Customers charge the Company for the difference between what they pay to the Company for the product and the selling price to the eligible healthcare settings. Reserves for chargebacks consist of credits that the Company expects to issue for units that remain in the distribution channel inventories at the end of each reporting period that the Company expects will be sold to eligible healthcare settings, and chargebacks that customers have claimed, but for which the Company has not yet issued a credit. Government Rebates : The Company is subject to discount obligations under government programs, including Medicaid. The Company records reserves for rebates in the same period the related product revenue is recognized, resulting in a reduction of ZULRESSO product revenues and a current liability that is included in accrued expenses on its condensed consolidated balance sheets. The Company’s liability for these rebates consists of invoices received for claims from prior quarters that have not been paid or for which an invoice has not yet been received, estimates of claims for the current quarter, and estimates of future claims that will be made for product that has been recognized as revenue, but which remains in the distribution channel at the end of each reporting period. Trade Discounts and Allowances : The Company generally provides customary invoice discounts on ZULRESSO sales to its customers for prompt payment and the Company pays fees for sales order management, data, and distribution services. The Company estimates its customers will earn these discounts and fees and deducts these discounts and fees in full from gross ZULRESSO revenues and accounts receivable at the time the Company recognizes the related revenues. Financial Assistance : The Company provides voluntary financial assistance programs to patients with commercial insurance that have coverage and reside in states that allow financial assistance. The Company estimates the financial assistance amounts for ZULRESSO and records any such amounts within accrued expenses on its condensed consolidated balance sheets. The calculation of the accrual for financial assistance is based on an estimate of claims and the cost per claim that the Company expects to receive using demographics for patients who have registered and been approved for assistance. Any adjustments are recorded in the same period the related revenue is recognized, resulting in a reduction of product revenue and the establishment of a current liability, which is included as a component of accrued expenses on the condensed consolidated balance sheets. Product Returns : Consistent with industry practice, the Company offers product return rights to customers for damaged, defective or expiring product, provided it is within a specified period around the product expiration date as set forth in the Company’s return goods policy. The Company estimates the amount of its product sales that may be returned by its customers and records this estimate as a reduction of revenue in the period the related product revenue is recognized, as well as a reserve within accrued expenses on the condensed consolidated balance sheets. Product returns have been immaterial to date and are expected to remain immaterial in the future. Collaborative Arrangements The Company analyzes its collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, Collaborative Arrangements (“Topic 808”). This assessment is performed throughout the life of the arrangement based on changes in the responsibilities of all parties in the arrangement. For collaboration arrangements within the scope of Topic 808 that contain multiple elements, the Company first determines which elements of the collaboration are deemed to be within the scope of Topic 808 and which elements of the collaboration are more reflective of a vendor-customer relationship and therefore within the scope of Topic 606. For elements of collaboration arrangements that are accounted for pursuant to Topic 808, an appropriate recognition method is determined and applied consistently, either by analogy to authoritative accounting literature or by applying a reasonable and rational policy election. For those elements of the arrangement that are accounted for pursuant to Topic 606, the Company applies the five-step model described above, and presents the arrangement as collaboration revenue in the condensed consolidated statements of operations and comprehensive loss. For collaboration arrangements that are within the scope of Topic 808, the Company evaluates the income statement classification for presentation of amounts due from or owed to other participants associated with multiple activities in a collaboration arrangement based on the nature of each separate activity. Payments or reimbursements that are the result of a collaborative relationship instead of a customer relationship, such as co-development and co-commercialization activities, are recorded as research and development expense or selling, general and administrative expense, in the event of a payment to the collaborative partner in a period, or a reduction to these expense line items in the event of a reimbursement from the collaboration partner in a period, as appropriate. Fair Value Measurements Fair value is the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. Financial assets and liabilities carried at fair value are classified and disclosed in one of the following three categories: Level 1 — Quoted market prices in active markets for identical assets or liabilities. Level 2 — Observable inputs other than Level 1 prices, such as quoted prices for similar assets or liabilities; quoted prices in markets that are not active; or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities. Level 3 — Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the assets or liabilities. The Company’s cash equivalents and marketable securities at September 30, 2022 and December 31, 2021 were carried at fair value, determined according to the fair value hierarchy; see Note 3, Fair Value Measurements . The carrying amounts reflected in the condensed consolidated balance sheets for the collaboration receivable – related party, accounts payable and accrued expenses approximate their fair values due to their short-term maturities at September 30, 2022 and December 31, 2021, respectively. Recently Issued Accounting Pronouncements Accounting standards that have been issued or proposed 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 the Company’s condensed consolidated financial statements upon adoption.

Fair Value Measurements

Fair Value Measurements	9 Months Ended
	Sep. 30, 2022
Fair Value Disclosures [Abstract]
Fair Value Measurements	3. Fair Value Measurements The Company’s cash equivalents are classified within Level 1 and Level 2 of the fair value hierarchy. The Company’s investments in marketable securities are classified within Level 2 of the fair value hierarchy. The fair values of the Company’s marketable securities are based on prices obtained from independent pricing sources. Consistent with the fair value hierarchy described in Note 2, Summary of Significant Accounting Policies , marketable securities with validated quotes from pricing services are reflected within Level 2, as they are primarily based on observable pricing for similar assets or other market observable inputs. Typical inputs used by these pricing services include, but are not limited to, reported trades, benchmark yields, issuer spreads, bids, offers or estimates of cash flow, prepayment spreads and default rates. The Company performs validation procedures to ensure the reasonableness of this data. The Company performs its own review of prices received from the independent pricing services by comparing these prices to other sources. After completing the validation procedures, the Company did not adjust or override any fair value measurements provided by the pricing services as of September 30, 2022 and December 31, 2021. The following tables summarize the Company’s cash equivalents and marketable securities as of September 30, 2022 and December 31, 2021: September 30, 2022 Total Quoted Significant Significant (in thousands) Cash equivalents: Money market funds $ 168,766 $ 168,766 $ — $ — U.S. corporate bonds 4,443 — 4,443 — U.S. commercial paper 7,883 — 7,883 — International commercial paper 10,979 — 10,979 — U.S. municipal securities 6,672 — 6,672 — Total cash equivalents 198,743 168,766 29,977 — Marketable securities: U.S. government securities 393,969 — 393,969 — U.S. corporate bonds 398,792 — 398,792 — International corporate bonds 151,048 — 151,048 — U.S. commercial paper 52,671 — 52,671 — International commercial paper 130,216 — 130,216 — U.S. certificates of deposit 13,727 — 13,727 — U.S. municipal securities 53,390 — 53,390 — Total marketable securities 1,193,813 — 1,193,813 — $ 1,392,556 $ 168,766 $ 1,223,790 $ — December 31, 2021 Total Quoted Significant Significant (in thousands) Cash equivalents: Money market funds $ 289,440 $ 289,440 $ — $ — U.S. commercial paper 2,000 — 2,000 — International commercial paper 1,999 — 1,999 — Total cash equivalents 293,439 289,440 3,999 — Marketable securities: U.S. government securities 324,532 — 324,532 — U.S. corporate bonds 627,780 — 627,780 — International corporate bonds 236,812 — 236,812 — U.S. commercial paper 80,176 — 80,176 — International commercial paper 142,335 — 142,335 — U.S. municipal securities 36,428 — 36,428 — Total marketable securities 1,448,063 — 1,448,063 — $ 1,741,502 $ 289,440 $ 1,452,062 $ — During the nine months ended September 30, 2022 and 2021 , there were no transfers among the Level 1, Level 2 and Level 3 categories. The following tables summarize the gross unrealized gains and losses of the Company’s marketable securities as of September 30, 2022 and December 31, 2021: September 30, 2022 Amortized Gross Unrealized Gross Unrealized Credit Losses Fair Value (in thousands) Assets: U.S. government securities $ 400,180 $ 3 $ ( 6,214 ) $ — $ 393,969 U.S. corporate bonds 404,074 — ( 5,282 ) — 398,792 International corporate bonds 153,088 3 ( 2,043 ) — 151,048 U.S. commercial paper 52,778 — ( 107 ) — 52,671 International commercial paper 130,461 — ( 245 ) — 130,216 U.S. certificates of deposit 13,727 — — — 13,727 U.S. municipal securities 54,388 9 ( 1,007 ) — 53,390 $ 1,208,696 $ 15 $ ( 14,898 ) $ — $ 1,193,813 December 31, 2021 Amortized Gross Unrealized Gross Unrealized Credit Losses Fair Value (in thousands) Assets: U.S. government securities $ 325,514 $ — $ ( 982 ) $ — $ 324,532 U.S. corporate bonds 628,836 27 ( 1,083 ) — 627,780 International corporate bonds 237,303 — ( 491 ) — 236,812 U.S. commercial paper 80,194 — ( 18 ) — 80,176 International commercial paper 142,358 — ( 23 ) — 142,335 U.S. municipal securities 36,518 — ( 90 ) — 36,428 $ 1,450,723 $ 27 $ ( 2,687 ) $ — $ 1,448,063 The following tables summarize the fair value and the unrealized losses of the Company’s marketable securities that are in a loss position as of September 30, 2022 and December 31, 2021: September 30, 2022 Less than 12 months Greater than 12 months Total Fair Unrealized Fair Unrealized Fair Unrealized (in thousands) U.S. government securities $ 268,949 $ ( 3,872 ) $ 120,107 $ ( 2,342 ) $ 389,056 $ ( 6,214 ) U.S. corporate bonds 337,682 ( 4,485 ) 61,969 ( 797 ) 399,651 ( 5,282 ) International corporate bonds 120,338 ( 1,676 ) 30,151 ( 367 ) 150,489 ( 2,043 ) U.S. commercial paper 21,996 ( 106 ) 2,999 ( 1 ) 24,995 ( 107 ) International commercial paper 41,813 ( 245 ) — — 41,813 ( 245 ) U.S. municipal securities 47,652 ( 1,007 ) — — 47,652 ( 1,007 ) $ 838,430 $ ( 11,391 ) $ 215,226 $ ( 3,507 ) $ 1,053,656 $ ( 14,898 ) December 31, 2021 Less than 12 months Greater than 12 months Total Fair Unrealized Fair Unrealized Fair Unrealized (in thousands) U.S. government securities $ 309,588 $ ( 982 ) $ — $ — $ 309,588 $ ( 982 ) U.S. corporate bonds 601,475 ( 1,083 ) — — 601,475 ( 1,083 ) International corporate bonds 231,672 ( 491 ) — — 231,672 ( 491 ) U.S. commercial paper 21,968 ( 18 ) — — 21,968 ( 18 ) International commercial paper 35,059 ( 23 ) — — 35,059 ( 23 ) U.S. municipal securities 24,953 ( 90 ) — — 24,953 ( 90 ) $ 1,224,715 $ ( 2,687 ) $ — $ — $ 1,224,715 $ ( 2,687 ) As of September 30, 2022 and December 31, 2021, the unrealized losses on the Company’s investments in U.S. government securities, U.S. corporate bonds, and international corporate bonds were caused by interest rate increases. The Company purchased those investments at a premium relative to their face amount. The current credit ratings are all within the guidelines of the investment policy of the Company and the Company does not expect the issuers to settle any security at a price less than the amortized cost basis of the investment. The Company does not intend to sell the investments and it is not probable that the Company will be required to sell the investments before recovery of their amortized cost basis. As of September 30, 2022 , all marketable securities held by the Company had remaining contractual maturities of one year or less, except for U.S. government securities, U.S. corporate bonds, international corporate bonds and municipal securities with a fair value of $ 178.3 million and maturities of one to two years . As of December 31, 2021 , all marketable securities held by the Company had remaining contractual maturities of one year or less, except for U.S. government securities, U.S. corporate bonds, international corporate bonds and municipal securities with a fair value of $ 436.1 million and maturities of one to two years . All marketable securities, including those with remaining contractual maturities of more than one year, are classified as current assets on the balance sheet because they are considered to be “available for sale” and the Company can convert them into cash to fund current operations . There have been no impairments of the Company’s assets measured and carried at fair value during the nine months ended September 30, 2022 and the year ended December 31, 2021 .

Accrued Expenses

Accrued Expenses	9 Months Ended
	Sep. 30, 2022
Payables And Accruals [Abstract]
Accrued Expenses	4. Accrued Expenses Accrued expenses consist of the following: September 30, December 31, 2022 2021 (in thousands) Accrued research and development costs $ 47,182 $ 39,147 Employee-related 20,176 18,618 Professional services 17,129 8,893 Other 520 617 $ 85,007 $ 67,275

Leases, Commitments and Conting

Leases, Commitments and Contingencies	9 Months Ended
	Sep. 30, 2022
Commitments And Contingencies Disclosure [Abstract]
Leases, Commitments and Contingencies	5. Leases, Commitments and Contingencies Operating Leases The Company leases office space and certain equipment. All of the leases recorded on the condensed consolidated balance sheets are operating leases. The Company’s leases have remaining lease terms ranging from less than one year to approximately 2.25 years. Some of the leases include options to extend the leases for up to five years . These options were not included for the purpose of determining the right-of-use assets and associated lease liabilities as the Company determined that the renewal of these leases is not reasonably certain so only the original lease term was taken into consideration. The leases do not include any restrictions or covenants that had to be accounted for under the lease guidance. As of January 1, 2021, the Company leased office space in three multi-tenant buildings in Cambridge, Massachusetts, consisting of 63,017 square feet in the first building, under an operating lease that will expire on August 31, 2024 ; 40,419 square feet in the second building, under an operating lease that will expire on August 31, 2024 ; and 15,975 square feet in the third building, under an operating lease that began on March 1, 2019 and was initially scheduled to expire on February 29, 2024 ; and in a multi-tenant building in Raleigh, North Carolina, consisting of 15,525 square feet under an operating lease that will expire on November 30, 2024 . During the three months ended March 31, 2021, the Company terminated the operating lease for office space in the third multi-tenant building in Cambridge, Massachusetts and the remaining right-of-use asset of $ 3.7 million and the associated liabilities related to this lease were de-recognized upon termination of the lease. Additionally, during the three months ended June 30, 2021, the Company entered into a sublease for a portion of the leased office space in the second multi-tenant building in Cambridge, Massachusetts. License Agreements CyDex License Agreement In September 2015, the Company amended and restated its existing commercial license agreement with CyDex Pharmaceuticals, Inc. (“CyDex”), a wholly owned subsidiary of Ligand Pharmaceuticals Incorporated. Under the terms of the commercial license agreement as amended and restated, CyDex has granted to the Company an exclusive license to CyDex’s Captisol drug formulation technology and related intellectual property for the manufacture of pharmaceutical products incorporating brexanolone and the Company’s compound known as SAGE-689, and the development and commercialization of the resulting products for the treatment, prevention or diagnosis of any disease or symptom in humans or animals other than (i) the ocular treatment of any disease or condition with a formulation, including a hormone; (ii) topical ocular treatment of inflammatory conditions; (iii) treatment and prophylaxis of fungal infections in humans; and (iv) any ocular treatment for retinal degeneration. The Company is required to pay a royalty to CyDex on sales of brexanolone and will be required to pay a royalty on any sales of SAGE-689, if such product candidate is successfully developed in the future. Royalty rates are in the low single digits based on levels of net sales. From the effective date of the agreement to September 30, 2022 , the Company has paid to CyDex $ 1.0 million for licensing fees, which was recorded as research and development expense. Under the amended and restated license agreement with CyDex, the Company agreed to make milestone payments on the achievement of clinical development and regulatory milestones in the amount of up to $ 0.8 million in clinical milestones and up to $ 3.8 million in regulatory milestones for each of the first two fields with respect to brexanolone; up to $ 1.3 million in clinical milestones and up to $ 8.5 million in regulatory milestones for each of the third and fourth fields with respect to brexanolone; and up to $ 0.8 million in clinical milestones and up to $ 1.8 million in regulatory milestones for one field with respect to SAGE-689. From the effective date of the agreement to September 30, 2022 , the Company has recorded research and development expense and made cash payments of $ 3.6 million related to these clinical development and regulatory milestones and has recorded an intangible asset and made a cash payment of $ 3.0 million related to these regulatory milestones. For the three and nine months ended September 30, 2021, an additional clinical development milestone was met under the license agreement with CyDex related to SAGE-689, and accordingly, the Company recorded research and development expense and made a cash payment of $ 0.1 million . For the nine months ended September 30, 2021 , the Company made a milestone payment of $ 1.3 million in cash for clinical development milestones for the brexanolone program under the license agreement with CyDex that was recorded as research and development expense during the year ended December 31, 2020. For the nine months ended September 30, 2022 , the Company did no t record any expense or intangible asset, or make any milestone payments related to clinical development or regulatory milestones for the brexanolone program or SAGE-689 under the license agreement with CyDex. University of California License Agreements In October 2013, the Company entered into a non-exclusive license agreement with The Regents of the University of California (the “Regents”) under which the Company was granted a non-exclusive license to certain clinical data and clinical material related to brexanolone for use in the development and commercialization of biopharmaceutical products in the licensed field, including status epilepticus and postpartum depression. In May 2014, the license agreement was amended to add the treatment of essential tremor to the licensed field of use, materials and milestone fee provisions of the agreement. The Company paid to the Regents clinical development milestones of $ 0.1 million, prior to December 31, 2015; no other milestones are outstanding under this non-exclusive license agreement. The Company is required to pay royalties of less than 1 % on net sales for a period of fifteen years following the sale of the first product developed using the data and materials, and the Company began to pay these royalties in 2019. The license will terminate on the earlier to occur of (i) 27 years after the effective date or (ii) 15 years after the last-derived product is first commercially sold. In June 2015, the Company entered into an exclusive license agreement with the Regents whereby the Company was granted an exclusive license to certain patent rights related to the use of allopregnanolone to treat various diseases. In exchange for such license, the Company paid an upfront payment of $ 50,000 and was required to make payments of $ 15,000 for annual maintenance fees until the calendar year following the first sale of ZULRESSO. The Company is obligated to make milestone payments following the achievement of specified regulatory and sales milestones of up to $ 0.7 million and $ 2.0 million in the aggregate, respectively. The Company pays royalties at a low single digit percentage of net sales of ZULRESSO, subject to specified minimum annual royalty amounts. Unless terminated by operation of law or by acts of the parties under the terms of the agreement, the license agreement will terminate when the last-to-expire patents or last-to-be abandoned patent applications expire, whichever is later. From the effective date of the agreement to September 30, 2022 , the Company has recorded research and development expense and made cash payments of $ 0.3 million related to these regulatory and sales milestones; and has recorded an intangible asset and made a cash payment of $ 0.5 million related to these regulatory and sales milestones. For the nine months ended September 30, 2022 and 2021 , the Company did no t record any expense or make any milestone payments under the license agreements with the Regents.

Collaboration Agreements

Collaboration Agreements	9 Months Ended
	Sep. 30, 2022
Shionogi Collaboration Agreement [Member]
Collaboration Agreements	6. Collaboration Agreements Shionogi In June 2018 , the Company entered into a strategic collaboration with Shionogi for the clinical development and commercialization of zuranolone for the treatment of MDD and other potential indications in Japan, Taiwan and South Korea (the “Shionogi Territory”). In October 2018, the Company entered into a supply agreement with Shionogi for the Company to supply zuranolone clinical material to Shionogi. Under the terms of the collaboration agreement, Shionogi is responsible for all clinical development and regulatory filings for zuranolone in MDD and other indications in the Shionogi Territory and would be responsible for commercialization of zuranolone in the Shionogi Territory, if zuranolone is successfully developed and obtains marketing approval in any of the countries within the Shionogi Territory. Shionogi was required to make an upfront payment to the Company of $ 90.0 million, and the Company will be eligible to receive additional payments of up to $ 485.0 million if certain regulatory and commercial milestones are achieved by Shionogi. The potential future milestone payments include up to $ 70.0 million for the achievement of specified regulatory milestones, up to $ 30.0 million for the achievement of specified commercialization milestones, and up to $ 385.0 million for the achievement of specified net sales milestones. The Company is eligible to receive tiered royalties on sales of zuranolone in the Shionogi Territory, if development efforts are successful, with tiers averaging in the low to mid- twenty percent range, subject to other terms of the agreement. Shionogi has also granted to the Company certain rights to co-promote zuranolone in Japan. As between the Company and Shionogi, the Company maintains exclusive rights to develop and commercialize zuranolone outside of the Shionogi Territory. The upfront cash payment and any payments for milestones and royalties are non-refundable and non-creditable. Due to the uncertainty of pharmaceutical development and the high historical failure rates generally associated with drug development, the Company may not receive any milestone payments or any royalty payments from Shionogi. The Company concluded that Shionogi meets the definition to be accounted for as a customer because the Company is delivering intellectual property and know-how rights for the zuranolone program in support of territories in which the parties are not jointly sharing the risks and rewards. In addition, the Company determined that the Shionogi collaboration met the requirements to be accounted for as a contract, including that it was probable that the Company will collect the consideration to which the Company was entitled in exchange for the goods or services that will be delivered to Shionogi. In determining the appropriate amount of revenue to be recognized under Topic 606, the Company performed the following steps: (i) identified the promised goods or services in the contract; (ii) determined whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measured the transaction price, including the constraint on variable consideration; (iv) allocated the transaction price to the performance obligations; and (v) recognized revenue when (or as) the Company satisfied each performance obligation. The Company determined that the performance obligations in the Shionogi collaboration agreement included the license to zuranolone and the supply of certain materials during the clinical development phase, which includes the supply of active pharmaceutical ingredient (“API”). The performance obligation related to the license to zuranolone was determined to be distinct from other performance obligations and therefore was a separate performance obligation for which control was transferred upon signing. The obligation to provide certain clinical materials, including API for use during the development period, was determined to be a separate performance obligation. Given that Shionogi is not obligated to purchase any minimum amount or quantities of commercial API, the supply of API to Shionogi for commercial use was determined to be an option for Shionogi, rather than a performance obligation of the Company, at contract inception and will be accounted for if and when exercised. The Company also determined that there was no separate material right in connection with the supply of API for commercial use as the expected pricing was not at a discount. Given this fact pattern, the Company has concluded the agreement has two performance obligations. Under the clinical supply agreement, the Company is obligated to manufacture and supply to Shionogi (i) clinical quantities of API reasonably required by Shionogi for the development of licensed products in the Shionogi territory under the collaboration and license agreement and (ii) quantities of drug product reasonably required for use by Shionogi in Phase 1 clinical trials of zuranolone in the Shionogi territory under the collaboration and license agreement, in the quantities agreed to by the parties. Collaboration revenue from the clinical supply agreement, which excludes the $ 90.0 million upfront payment, pertains to the clinical material sold under the terms of the clinical supply agreement. The Company records the costs related to the clinical supply agreement in research and development expense on its condensed consolidated statements of operations and comprehensive loss. For the nine months ended September 30, 2022 and 2021 , the Company recognized no collaboration revenue from the Company’s agreement with Shionogi. The Company completed the evaluation of the standalone selling prices of each of the performance obligations and determined that the standalone selling price of the license performance obligation was $ 90.0 million. The Company recognized the transaction price allocated to the license performance obligation of $ 90.0 million as revenue during the quarter upon delivery of the license to Shionogi and resulting ability of Shionogi to use and benefit from the license, which was in the three months ended June 30, 2018. The remaining transaction price related to the performance obligation for the supply of certain clinical material is not significant. The potential milestone payments that the Company is eligible to receive were excluded from the transaction price, as all milestone amounts were fully constrained based on the probability of achievement. The Company will re-evaluate the transaction price at the end of each reporting period and as uncertain events are resolved or other changes in circumstances occur, and, if necessary, adjust its estimate of the transaction price. Biogen In November 2020, the Company entered into the Biogen Collaboration Agreement to jointly develop and commercialize SAGE-217 products for MDD, PPD and other disorders and SAGE-324 products for essential tremor and other disorders. Concurrently, the Company also entered into a stock purchase agreement with BIMA (the “Biogen Stock Purchase Agreement”) under which BIMA purchased shares of the Company’s common stock. The Biogen Collaboration Agreement became effective on December 28, 2020 (the “Effective Date”). Under the terms of the Biogen Collaboration Agreement, the Company granted Biogen co-exclusive licenses to develop and commercialize SAGE-217 products and SAGE-324 products (each, a “Product Class” and together, the “Licensed Products”) in the U.S., an exclusive license to develop and commercialize SAGE-217 products in all countries of the world other than the U.S. and the Shionogi Territory, and an exclusive license to develop and commercialize SAGE-324 products in all countries of the world other than the U.S. The Company refers to the territories outside the U.S. to which Biogen has rights under the Biogen Collaboration Agreement with respect to the applicable Licensed Product as the “Biogen Territory”. In connection with the effectiveness of the Biogen Collaboration Agreement and the closing of the sale of shares to BIMA in December 2020, the Company received $ 1.5 billion in consideration, comprised of an upfront payment of $ 875.0 million and the $ 650.0 million purchase price for 6,241,473 newly issued shares of the Company’s common stock (the “Biogen Shares”). As a result of the purchase of the Biogen Shares, Biogen has become a related party of the Company. The Company is eligible to receive additional payments of up to $ 1.6 billion if certain regulatory and commercial milestones are achieved. The potential future milestone payments for SAGE-217 products include up to $ 475.0 million for the achievement of specified regulatory and commercial milestones and up to $ 300.0 million for the achievement of specified net sales milestones. The potential future milestone payments for SAGE-324 products include up to $ 520.0 million for the achievement of specified regulatory and commercial milestones and up to $ 300.0 million for the achievement of specified net sales milestones. The Company is also eligible to receive tiered royalties on net sales of SAGE-217 products and SAGE-324 products in the Biogen Territory at percentage rates ranging from the high teens to low twenties. Due to the uncertainty of pharmaceutical development and the high historical failure rates generally associated with drug development, the Company may never receive any milestone payments or any royalty payments under the Biogen Collaboration Agreement. Development and commercialization activities in the U.S. are conducted pursuant to plans agreed to by the Company and Biogen and overseen by a joint steering committee that will consist at all times of an equal number of representatives of each party. The Company and Biogen will share equally in the costs for development and commercialization, as well as the profits and losses upon FDA approval and commencement of product sales, in the U.S., subject to the Company’s opt-out right described below. Biogen will be solely responsible for all development activities and costs related to any development and commercialization of SAGE-217 products and SAGE-324 products for the Biogen Territory, and the Company will receive royalties on any sales in the Biogen Territory, as mentioned above. The Company will supply API and bulk drug product for the Biogen Territory and API and final drug product for the U.S. to support development and commercialization activities. Biogen has the right to assume manufacturing responsibilities for API for the Biogen Territory at any time during the term of the agreement and will, within a reasonable period of time after the Effective Date, assume manufacturing responsibility for bulk drug product for the Biogen Territory. Unless terminated earlier, the Biogen Collaboration Agreement will continue on a Licensed Product-by-Licensed Product and country-by-country basis until the date on which (a) in any country in the Biogen Territory, the royalty term has expired for all Licensed Products in a Product Class in such country, and (b) for the U.S., the parties agree to permanently cease to commercialize all Licensed Products in a Product Class. Biogen also has the right to terminate the Biogen Collaboration Agreement for convenience in its entirety, on a Product Class-by-Product Class basis or as to a particular region, upon advance written notice. The Company has an opt-out right to convert the co-exclusive licenses in the U.S. to an exclusive license to Biogen on a Product Class-by-Product Class basis. Following the exercise of the opt-out right, the Company would no longer share equally in the profits and losses in the U.S. and would be entitled to receive certain royalty payments at percentage rates ranging from the high teens to low twenties and additional sales milestones. The Company concluded that the Biogen Collaboration Agreement and the Biogen Stock Purchase Agreement should be combined and treated as a single arrangement for accounting purposes as the agreements were entered into contemporaneously and in contemplation of one another. The Company determined that the combined agreements had elements that were within the scope of Topic 606 and Topic 808. As of the Effective Date, the Company identified the following promises in the Biogen Collaboration Agreement that were evaluated under the scope of Topic 606: delivery of (i) a co-exclusive license for SAGE-217 products in the U.S.; (ii) an exclusive license for SAGE-217 products in the Biogen Territory; (iii) a co-exclusive license for SAGE-324 products in the U.S.; (iv) an exclusive license for SAGE-324 products in the Biogen Territory; (v) the clinical manufacturing supply of API and bulk drug product for SAGE-217 products in the Biogen Territory; and (vi) the clinical manufacturing supply of API and bulk drug product for SAGE-324 products in the Biogen Territory. The Company also evaluated whether certain options outlined within the Biogen Collaboration Agreement represented material rights that would give rise to a performance obligation and concluded that none of the options convey a material right to Biogen and therefore are not considered separate performance obligations within the Biogen Collaboration Agreement. The Company assessed the above promises and determined that the co-exclusive licenses for SAGE-217 products and SAGE-324 products in the U.S. are reflective of a vendor-customer relationship and therefore represent performance obligations within the scope of Topic 606. The co-exclusive license for SAGE-217 products and SAGE-324 products in the U.S. are considered functional intellectual property and distinct from other promises under the contract. The exclusive licenses for SAGE-217 products and SAGE-324 products in the Biogen Territory are considered functional licenses that are distinct in the context of the Biogen Collaboration Agreement as Biogen can benefit from the licenses on its own or together with other readily available resources. As the co-exclusive licenses in the U.S. and the exclusive licenses in the Biogen Territory are delivered at the same time, they are considered one performance obligation at contract inception. The clinical manufacturing supply of API and bulk drug product for SAGE-217 products and SAGE-324 products for the Biogen Territory are considered distinct in the context of the Biogen Collaboration Agreement as Biogen can benefit from the manufacturing services together with the licenses transferred by the Company at the inception of the agreement. Therefore, each represents a separate performance obligation within a contract with a customer under the scope of Topic 606 at contract inception. The Company considers the collaborative activities associated with the co-development, co-commercialization, and co-manufacturing of SAGE-217 products and SAGE-324 products in the U.S. to be separate units of account within the scope of Topic 808 as the Company and Biogen are both active participants in the development and commercialization activities and are exposed to significant risks and rewards that are dependent on the development and commercial success of the activities in the arrangement. The Company has determined that the supply of API and bulk drug product for the Biogen Territory and API and final drug product for the U.S. to Biogen will be classified as collaboration revenue – related party in the condensed consolidated statements of operations and comprehensive loss. During the nine months ended September 30, 2022 and 2021 , no collaboration revenue – related party was recognized related to the Biogen Collaboration Agreement. Payments to or reimbursements from Biogen related to the co-development, co-commercialization, and co-manufacturing activities and the agreement of the parties to share equally the cost of these activities will be accounted for as an increase to or reduction of research and development expenses or selling, general and administrative expenses, depending on the nature of the activity. During the three and nine months ended September 30, 2022, the Company recorded a net reimbursement of $ 18.3 million and $ 62.2 million, respectively, for the amounts due from Biogen as a reduction of the related operating expense categories in the condensed consolidated statement of operations and comprehensive loss. During the three and nine months ended September 30, 2021, the Company recorded a net reimbursement of $ 24.2 million and $ 72.6 million, respectively, for the amounts due from Biogen as a reduction of the related operating expense categories in the condensed consolidated statement of operations and comprehensive loss. As of September 30, 2022, the Company recorded a collaboration receivable – related party of $ 18.4 million in the condensed consolidated balance sheet for the amounts due for the three months ended September 30, 2022. During the nine months ended September 30, 2022 and the year ended December 31, 2021, no payments were made to Biogen. During the nine months ended September 30, 2022, the Company received $ 62.2 million from Biogen for the amounts due for the three months ended December 31, 2021 and the six months ended June 30, 2022. During the nine months ended September 30, 2021, the Company received $ 48.4 million from Biogen for the amounts due for the six months ended June 30, 2021. The following table summarizes expenses related to the Biogen Collaboration Agreement that were incurred by the Company and the related reimbursement from Biogen, reflected by category of operating expenses: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 (in thousands) (in thousands) Expenses related to the Biogen Collaboration Agreement $ 53,139 $ 50,950 $ 161,111 $ 149,653 Net reimbursement from Biogen reflected in the condensed Research and development expenses ( 17,867 ) ( 21,634 ) ( 57,364 ) ( 63,843 ) Selling, general and administrative expenses ( 480 ) ( 2,551 ) ( 4,788 ) ( 8,780 ) ( 18,347 ) ( 24,185 ) ( 62,152 ) ( 72,623 ) Total net expenses related to the Biogen Collaboration $ 34,792 $ 26,765 $ 98,959 $ 77,030 The Company determined the transaction price under Topic 606 at the inception of the Biogen Collaboration Agreement to be $ 1.1 billion, consisting of the upfront payment of $ 875.0 million plus $ 232.5 million in excess proceeds from the equity investment under the Biogen Stock Purchase Agreement, when measured at fair value, plus future variable consideration for manufacturing supply of clinical API and bulk drug product for the Biogen Territory. The amount of variable consideration related to the future manufacturing services was not material. The Company determined that any variable consideration related to clinical development and regulatory milestones is deemed to be fully constrained and therefore excluded from the transaction price due to the high degree of uncertainty and risk associated with these potential payments, as the Company determined that it could not assert that it was probable that a significant reversal in the amount of cumulative revenue recognized will not occur. The Company also determined that royalties and sales milestones relate solely to the licenses of intellectual property and are therefore excluded from the transaction price under the sales- or usage-based royalty exception of Topic 606. Revenue related to these royalties and sales milestones will only be recognized when the associated sales occur and relevant thresholds are met. As noted above, the Company identified three performance obligations in the Biogen Collaboration Agreement: (i) the delivery of the co-exclusive licenses for SAGE-217 products and SAGE-324 products in the U.S. and the exclusive licenses for SAGE-217 products and SAGE-324 products in the Biogen Territory; (ii) the clinical manufacturing supply of API and bulk drug product for SAGE-217 products in the Biogen Territory; and (iii) the clinical manufacturing supply of the API and bulk drug product for SAGE-324 products in the Biogen Territory. The selling price of each performance obligation in the Biogen Collaboration Agreement was determined based on the Company’s SSP with the objective of determining the price at which it would sell such an item if it were to be sold regularly on a standalone basis. The Company allocated the variable consideration related to the manufacturing obligations to the future clinical supply of SAGE-217 products and SAGE 324 products in the Biogen Territory and the remaining fixed consideration to the license obligation. The variable consideration related to the manufacturing obligations was not material. As such, the entirety of the $ 1.1 billion fixed consideration of the transaction price has been allocated to the transfer of the co-exclusive licenses for SAGE-217 products and SAGE-324 products in the U.S. and the exclusive licenses for SAGE-217 products and SAGE-324 products in the Biogen Territory. The Company recognizes revenue for the license performance obligations at a point in time, that is upon transfer of the licenses to Biogen. As control of these licenses was transferred on the Effective Date and Biogen could begin to use and benefit from the licenses, the Company recognized $ 1.1 billion of license revenue during the year ended December 31, 2020 under the Biogen Collaboration Agreement. The Company will recognize revenue for the clinical manufacturing supply obligations at a point in time, that is upon the delivery of the supply to Biogen. Accounting for the Biogen Stock Purchase Agreement In connection with the execution of the Biogen Collaboration Agreement, the Company and BIMA entered into the Biogen Stock Purchase Agreement. Pursuant to the Biogen Stock Purchase Agreement, the Company sold the Biogen Shares to BIMA at a price of approximately $ 104.14 per share, which represented a 40 percent premium over the 30-day volume-weighted average share price as of the last trading day prior to the date the Biogen Collaboration Agreement and Biogen Stock Purchase Agreement were executed in November 2020, for aggregate consideration of $ 650.0 million. The sale of the shares to BIMA closed on December 31, 2020. The Biogen Stock Purchase Agreement includes certain standstill provisions, lock-up restrictions, and a voting agreement with respect to the Biogen Shares. Pursuant to the terms of the Biogen Stock Purchase Agreement, BIMA has agreed not to, and to cause its affiliates not to, directly or indirectly acquire the Company’s securities, seek or propose a tender or exchange offer or merger between the Company and Biogen, solicit proxies or consents with respect to any matter, or undertake other specified actions, in each case subject to specified conditions. The standstill restrictions terminate on the earliest of (i) a specified regulatory milestone under the Biogen Collaboration Agreement, (ii) the date one year following the termination of the Biogen Collaboration Agreement and (iii) the seventh anniversary of the Effective Date. BIMA also agreed not to, and to cause its affiliates not to, sell or transfer any of the Biogen Shares for a period of eighteen months from the closing of the sale of the Biogen Shares, which period expired on June 30, 2022, and to limit sales and transfers of the Biogen Shares for an additional eighteen-month period, in each case subject to specified conditions and exceptions. The Company determined the fair value of the common shares issued using an option pricing valuation model to take into consideration the holding period restrictions. The fair value of the Company’s common stock was considered a Level 2 fair value measurement within the fair value hierarchy. The most significant assumptions within the model are the Company’s stock price, the term of the restrictions and the stock price volatility, which is based upon a blend of historical and implied volatility of the Company’s stock. Based on the fair value adjustments made by management, the fair value of the shares issued was determined to be $ 417.5 million, which was $ 232.5 million less than the proceeds received from BIMA for the issuance of the Company’s common stock under the Biogen Stock Purchase Agreement. As such, the $232.5 million in excess proceeds has been included in the $ 1.1 billion transaction price of the Biogen Collaboration Agreement determined above.

Stock-Based Compensation

Stock-Based Compensation	9 Months Ended
	Sep. 30, 2022
Disclosure Of Compensation Related Costs Sharebased Payments [Abstract]
Stock-Based Compensation	7. Stock-Based Compensation Equity Plans On July 2, 2014, the stockholders of the Company approved the 2014 Stock Option and Incentive Plan (the “2014 Plan”), which became effective immediately prior to the completion of the Company’s IPO. The 2014 Plan provides for the grant of restricted stock awards, restricted stock units, incentive stock options and non-statutory stock options. The 2014 Plan replaced the Company’s 2011 Stock Option and Grant Plan (the “2011 Plan”). The Company no longer grants stock options or other awards under its 2011 Plan, but any stock options outstanding under the 2011 Plan remain outstanding and effective in accordance with their terms. The 2014 Plan provides for an annual increase, to be added on the first day of each fiscal year, by up to 4% of the Company’s outstanding shares of common stock as of the last day of the prior year. On January 1, 2022, 2,357,482 shares of common stock, representing 4 % of the Company’s outstanding shares of common stock as of December 31, 2021, were added to the 2014 Plan. On December 15, 2016, the Board of Directors of the Company (the “Board”) approved the 2016 Inducement Equity Plan (as amended and restated, the “2016 Plan”). The 2016 Plan provides for the grant of equity awards to individuals who have not previously been an employee or a non-employee director of the Company to induce them to accept employment and to provide them with a proprietary interest in the Company. On September 20, 2018, the Board amended the 2016 Plan to increase the total number of shares reserved for issuance by 1,200,000 shares. Terms of equity grants, including vesting requirements, are determined by the Board or the Compensation Committee of the Board, subject to the provisions of the applicable plan. Stock options granted by the Company that are not performance-based are considered time-based because they vest based on the continued service of the grantee with the Company during a specified period following grant. These awards, when granted to employees, generally vest ratably over four years , with 25 % vesting at the one-year anniversary. All stock option awards expire 10 years after the date of grant. As of September 30, 2022, the total number of shares underlying outstanding awards under all equity plans was 9,088,581 and the total number of shares available for future issuance under all equity plans was 7,223,536 shares. On June 16, 2022, the Company’s stockholders approved an amendment to the amended 2014 Employee Stock Purchase Plan (the “ESPP”), which had been previously approved by the Board, to add 300,000 shares of common stock to the ESPP. Restricted Stock Units The following table summarizes activity relating to time-based restricted stock units and performance restricted stock units: Shares Outstanding as of December 31, 2021 1,256,098 Granted 569,410 Vested ( 351,455 ) Forfeited ( 84,796 ) Outstanding as of September 30, 2022 1,389,257 During the three months ended June 30, 2020, the Company granted 550,890 time-based restricted stock units to certain employees of the Company. These time-based restricted stock units vested over two years , with 25 % vesting at the one-year anniversary of the grant date and 75 % vesting at the two-year anniversary of the grant date, which was in April 2021 and April 2022 , respectively. During the three months ended June 30, 2021, 113,941 of these time-based restricted stock units vested, with a fair value equal to $ 8.8 million. During the three months ended June 30, 2022, 291,505 of these time-based restricted stock units vested, with a fair value equal to $ 9.5 million. During the three months ended December 31, 2021, the Company granted 268,119 time-based restricted stock units to certain employees of the Company. These time-based restricted stock units vest over four years , with 25 % vesting at the one-year anniversary of the vesting start date, which was in September 2022 ; and the remaining 75 % will vest ratably in quarterly increments over the remaining three years . During the three months ended September 30, 2022, 59,950 of these time-based restricted stock units vested, with a fair value equal to $ 2.3 million. During the three months ended March 31, 2022 and 2021, and the three months ended September 30, 2021, no time-based restricted stock units vested. During the nine months ended September 30, 2022 and 2021 , the Company granted no time-based restricted stock units. During the three months ended September 30, 2022 and 2021, the Company granted 57,480 and 47,040 performance restricted stock units, respectively, to its employees and consultants. During the nine months ended September 30, 2022 and 2021, the Company granted 569,410 and 420,161 performance restricted stock units, respectively, to its employees and consultants. The performance restricted stock units granted during the nine months ended September 30, 2022 are related to the achievement of certain clinical and regulatory development milestones related to product candidates and commercial milestones. Recognition of stock-based compensation expense associated with performance restricted stock units commences when the performance condition is considered probable of achievement, using management’s best estimates, which consider the inherent risk and uncertainty regarding the future outcomes of the milestones. During the three months ended June 30, 2021, one milestone for outstanding performance restricted stock units was achieved, and the fair value of the performance restricted stock units that vested upon achievement was $ 6.1 million. 39 % of the performance restricted stock units that were granted during the year ended December 31, 2020 included this milestone as a vesting condition. No performance restricted stock units vested during the nine months ended September 30, 2022 and the three months ended March 31, 2021 and September 30, 2021. During the three months ended September 30, 2021, the Company considered probable the achievement of a specific clinical milestone which was the criteria for vesting of certain performance restricted stock units but which had not been met as of September 30, 2021. Therefore, $ 12.6 million of stock-based compensation expense was recognized related to these awards for the three months ended September 30, 2021. Performance restricted stock units with this milestone were granted during the years ended December 31, 2020 and 2019. As of September 30, 2022 , for performance-based restricted stock units that were outstanding, the achievement of the milestones that had not been met was considered not probable, and therefore no expense has been recognized related to these awards during the nine months ended September 30, 2022. At September 30, 2022, 179,676 time-based restricted stock units were both outstanding and unvested, and the total unrecognized stock-based compensation expense related to these awards was $ 5.5 million. At September 30, 2022, 1,209,581 performance restricted stock units were both outstanding and unvested, and the total unrecognized stock-based compensation expense related to these awards was $ 69.5 million. Stock Option Rollforward The following table summarizes activity related to time-based and performance-based stock options: Shares Weighted Weighted Average Aggregate Outstanding as of December 31, 2021 7,283,439 $ 84.17 6.74 $ 16,590 Granted 1,008,027 $ 39.59 Exercised ( 149,083 ) $ 6.73 Forfeited ( 443,059 ) $ 94.18 Outstanding as of September 30, 2022 7,699,324 $ 79.26 6.53 $ 8,606 Exercisable as of September 30, 2022 4,953,687 $ 85.77 5.39 $ 6,584 At September 30, 2022, the Company had unrecognized stock-based compensation expense related to its unvested time-based stock option awards of $ 70.5 million, which is expected to be recognized over the remaining weighted average vesting period of 2.73 years. The intrinsic value of stock options exercised during the nine months ended September 30, 2022 and 2021 was $ 4.4 million and $ 8.0 million, respectively. Performance-Based Stock Options Recognition of stock-based compensation expense associated with performance-based stock options commences when the performance condition is considered probable of achievement, using management’s best estimates, which consider the inherent risk and uncertainty regarding the future outcomes of the milestones. As of September 30, 2022 and 2021 , for performance-based stock option grants that were outstanding, the achievement of the milestones that had not been met was considered not probable, and therefore no expense has been recognized related to these awards during the nine months ended September 30, 2022 and 2021, respectively. During the three months ended March 31, 2021, in connection with the hiring of its chief executive officer, the Company granted to its chief executive officer 650,000 stock options to purchase shares of common stock that contain performance-based vesting criteria, such that the shares underlying such stock options which will vest upon the achievement of certain regulatory and commercial milestones. During the nine months ended September 30, 2022 , and the three months ended June 30, 2021 and September 30, 2021, the Company granted no stock options to employees to purchase shares of common stock that contain performance-based vesting criteria. During the nine months ended September 30, 2022 and 2021 , no milestones were achieved under performance-based stock options granted to employees. As of September 30, 2022, 681,451 performance-based stock options were both outstanding and unvested, the total unrecognized stock-based compensation expense related to these awards was $ 11.8 million and the timing of recognition of this stock-based compensation expense is subject to judgment of the Company as to when the performance conditions are considered probable of being achieved. Stock-Based Compensation Expense The following table summarizes stock-based compensation expense recognized during the three and nine months ended September 30, 2022 and 2021: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 (in thousands) Research and development $ 5,964 $ 17,864 $ 21,037 $ 40,598 Selling, general and administrative 7,205 16,478 25,321 43,383 $ 13,169 $ 34,342 $ 46,358 $ 83,981 The following table summarizes stock-based compensation expense by award type recognized during the three and nine months ended September 30, 2022 and 2021: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 (in thousands) Stock options $ 11,992 $ 19,516 $ 40,659 $ 60,740 Restricted stock units 730 14,563 4,982 22,538 Employee stock purchase plan 447 263 717 703 $ 13,169 $ 34,342 $ 46,358 $ 83,981 The weighted average grant date fair value per share of stock options granted under the Company’s stock option plans during the nine months ended September 30, 2022 and 2021 was $ 25.96 and $ 53.42 , respectively.

Net Loss Per Share

Net Loss Per Share	9 Months Ended
	Sep. 30, 2022
Earnings Per Share [Abstract]
Net Loss Per Share	8. Net Loss Per Share The following table shows the calculation of basic and diluted net loss per share for the three and nine months ended September 30, 2022 and 2021: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 Basic net loss per share: Numerator: Net loss (in thousands) $ ( 137,323 ) $ ( 130,171 ) $ ( 385,638 ) $ ( 333,180 ) Denominator: Weighted average common stock 59,428,123 58,819,548 59,242,563 58,593,743 Dilutive effect of shares of common — — — — Weighted average common stock 59,428,123 58,819,548 59,242,563 58,593,743 Net loss per share—basic and diluted $ ( 2.31 ) $ ( 2.21 ) $ ( 6.51 ) $ ( 5.69 ) The following table summarizes common stock equivalents outstanding that were excluded from the calculation of diluted net loss per share because including them would have been anti-dilutive as of September 30, 2022 and 2021: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 Stock options 7,017,873 6,728,998 7,017,873 6,728,998 Restricted stock units 179,676 310,418 179,676 310,418 Employee stock purchase plan 43,877 15,437 43,877 15,437 7,241,426 7,054,853 7,241,426 7,054,853 Stock options and restricted stock units that are outstanding and contain performance-based vesting criteria for which the performance conditions have not been met are excluded from the calculation of common stock equivalents outstanding.

Summary of Significant Accoun_2

Summary of Significant Accounting Policies (Policies)	9 Months Ended
	Sep. 30, 2022
Accounting Policies [Abstract]
Risks and Uncertainties	Risks and Uncertainties The Company is subject to risks and uncertainties common to companies in the biotechnology and pharmaceutical industries, including, but not limited to, the risks associated with developing product candidates at each stage of non-clinical and clinical development; the challenges associated with gaining regulatory approval of such product candidates; the risks associated with the marketing and sale of pharmaceutical products; the potential for development by third parties of new technological innovations that may compete with the Company’s products and product candidates; the dependence on key personnel; the challenges of protecting proprietary technology; the need to comply with government regulations; the high costs of drug development; the uncertainty of being able to secure additional capital when needed to fund operations; and the impact of the COVID-19 pandemic and related downstream effects on its development activities, operations and financial condition. The product candidates developed by the Company require approvals from the U.S. Food and Drug Administration (“FDA”) or foreign regulatory agencies prior to commercial sales. There can be no assurance that the current and future product candidates of the Company will receive, or that the Company’s current product, ZULRESSO, will maintain, the necessary approvals. If the Company fails to successfully complete clinical development and generate results sufficient to file for regulatory approval or is denied approval or approval is delayed for any of its product candidates, such occurrences may have a material adverse impact on the Company’s business and its financial condition. The Company is also subject to additional risks and uncertainties related to the ongoing COVID-19 pandemic and other macroeconomic and geopolitical events, which collectively have caused and may continue to cause major disruptions to businesses and economies worldwide. The rapid spread of COVID-19 in the U.S. resulted in a significant reduction in patient demand for ZULRESSO and in the number of sites available to administer ZULRESSO. There have been and continue to be healthcare staffing shortages and other changes to the macroeconomic environment as downstream effects of the pandemic have continued. These factors have had a significant and sustained negative impact on the Company’s revenue from sales of ZULRESSO. While the Company has not experienced any other material disruptions to date as a result of the COVID-19 pandemic, any prolonged material disruptions to the work of the Company’s employees, suppliers, contract manufacturers, or vendors could negatively impact the Company’s activities, availability of supplies, or operating results. In addition, while the Company has seen slower patient recruitment in certain clinical trials due to the COVID-19 pandemic and its downstream effects, and has experienced some challenges in qualifying and activating clinical trial sites, including due to capacity and resource constraints and employee attrition at our vendors and at sites, the Company has not experienced other significant impacts to the Company’s development activities as a result of the COVID-19 pandemic. Any material disruption to the Company’s development activities may cause delays, increase the Company’s costs and impact the Company’s operating results. In addition, the COVID-19 pandemic initially caused major volatility in capital markets and a significant global economic downturn, and the Company’s ability to access the capital markets in the future could be negatively impacted if there are long-term negative effects of the COVID-19 pandemic on the macroeconomic environment or capital markets, even after the pandemic has subsided. Moreover, U.S. and global financial markets have experienced volatility and disruption due to other macroeconomic and geopolitical events such as rising inflation, the risk of a recession and the ongoing conflict between Russia and Ukraine. The Company cannot predict at this time to what extent it and its collaborators, employees, suppliers, contract manufacturers and/or vendors could potentially be negatively impacted by these events.
Going Concern	Going Concern Under Accounting Standards Update (“ASU”) No. 2014-15, Presentation of Financial Statements—Going Concern (Subtopic 205-40), the Company has the responsibility to evaluate whether conditions and/or events raise substantial doubt about its ability to meet its future financial obligations as they become due within one year after the date that the financial statements are issued. The Company has incurred losses and negative cash flows from operations in each year since its inception, except for net income of $ 606.1 million for the year ended December 31, 2020, reflecting revenue recognized under a collaboration and license agreement with Biogen MA Inc. (“BIMA”) and Biogen International GmbH (collectively with BIMA, “Biogen”) (the “Biogen Collaboration Agreement”). As of September 30, 2022, the Company had an accumulated deficit of $ 1.9 billion. From its inception through September 30, 2022, the Company has received aggregate net proceeds of $ 2.8 billion from the sales of redeemable convertible preferred stock prior to its initial public offering (“IPO”), the issuance of convertible notes, and the sales of common stock in its IPO in July 2014, in follow-on public offerings, and to BIMA under a stock purchase agreement executed in connection with the Biogen Collaboration Agreement. The Company has also received $ 1.0 billion in upfront payments under its collaborations with Biogen and Shionogi & Co., Ltd. (“Shionogi”). Until such time, if ever, as the Company can generate substantial product revenue and achieve profitability, the Company expects to finance its cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances, licensing arrangements and other sources of funding. If the Company is unable to raise additional funds through equity or debt financings or other sources of funding when needed, the Company 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 the Company would otherwise prefer to develop and market itself. The Company expects that, based on its current operating plans, the Company’s existing cash, cash equivalents and marketable securities will be sufficient to fund its currently planned operations for at least the next 12 months from the filing date of these unaudited interim condensed consolidated financial statements (“condensed consolidated financial statements”). At some point after that time, the Company anticipates it will require additional financing to fund its future operations. Even if the Company believes it has sufficient funds for its current or future operating plans, the Company may seek to raise additional capital if market conditions are favorable or in light of other strategic considerations.
Basis of Presentation	Basis of Presentation The condensed consolidated financial statements of the Company included herein have been prepared pursuant to the rules and regulations of the Securities and Exchange Commission. Certain information and footnote disclosures normally included in financial statements prepared in accordance with accounting principles generally accepted in the United States of America (“GAAP”) have been condensed or omitted from this report, as is permitted by such rules and regulations. Accordingly, these condensed consolidated financial statements should be read in conjunction with the audited consolidated financial statements as of and for the year ended December 31, 2021, included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2021. The condensed consolidated financial statements have been prepared on the same basis as the audited consolidated financial statements. In the opinion of the Company’s management, the accompanying condensed consolidated financial statements contain all adjustments, consisting of only normal recurring adjustments, necessary for a fair statement of its financial position as of September 30, 2022, its results of operations and comprehensive loss for the three and nine months ended September 30, 2022 and 2021, its cash flows for the nine months ended September 30, 2022 and 2021, and its statements of changes in stockholders’ equity for the three and nine months ended September 30, 2022 and 2021. The consolidated balance sheet at December 31, 2021 was derived from audited financial statements, but does not include all disclosures required by GAAP. The results for the three and nine months ended September 30, 2022 are not necessarily indicative of the results for the year ending December 31, 2022, or for any future period.
Principles of Consolidation	Principles of Consolidation The condensed consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries as disclosed in Note 2, Summary of Significant Accounting Policies , within the “Notes to Consolidated Financial Statements” accompanying its Annual Report on Form 10-K for the fiscal year ended December 31, 2021 . Intercompany accounts and transactions have been eliminated.
Use of Estimates	Use of Estimates The preparation of condensed consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the condensed consolidated financial statements and the reported amounts of revenues and expenses during the reporting period. The full extent to which the COVID-19 pandemic and its downstream effects may directly or indirectly impact the Company’s business, results of operations and financial condition, including sales, expenses, reserves and allowances, manufacturing, clinical trials, research and development costs and employee-related amounts, will depend in large part on future developments, which cannot be predicted with confidence at this time, including: the scope, duration and severity of ongoing and future waves of the pandemic, including the impact of any variant strains of the COVID-19 virus; the extent of healthcare staffing shortages that have continued even as COVID-19-related restrictions have eased; the impact of the pandemic on the Company’s customers and vendors, including capacity and resource constraints; the impact of the pandemic on the willingness of women with PPD to seek treatment with ZULRESSO and the number of physicians willing to prescribe it; the impact of the downstream effects of the pandemic on business operations across the U.S.; and the scope and extent of any future actions or restrictive measures taken to contain or mitigate the impact of the pandemic . The Company has made estimates of the impact of the COVID-19 pandemic within its condensed consolidated financial statements. Due to the evolving nature of the COVID-19 pandemic, its downstream effects, and their impacts, there may be changes to those estimates in future periods, and a ctual results could differ from those estimates.
Research and Development Costs and Accruals	Research and Development Costs and Accruals Research and development expenses are comprised of costs incurred in performing research and development activities, including salaries and benefits, overhead costs, depreciation, contract services and other related costs. Research and development costs are expensed to operations as the related obligation is incurred. The Company has entered into various research and development contracts with research institutions and other companies both inside and outside of the U.S. These agreements are generally cancelable, and related costs are recorded as research and development expenses as incurred. The Company records accruals for estimated ongoing research and development costs. When billing terms under these contracts do not coincide with the timing of when the work is performed, the Company is required to make estimates of outstanding obligations to those third parties as of the end of the reporting period. Any accrual estimates are based on a number of factors, including the Company’s knowledge of the progress towards completion of the research and development activities, invoicing to date under the contracts, communication from the research institution or other companies of any actual costs incurred during the period that have not yet been invoiced, and the costs included in the contracts. Significant judgments and estimates are made in determining the accrued balances at the end of any reporting period. Actual results could differ from the estimates made by the Company. The historical accrual estimates made by the Company have not been materially different from the actual costs.
Revenue Recognition	Revenue Recognition The Company generates revenue from the sale of ZULRESSO, which was approved by the FDA in March 2019 and the Company subsequently began selling in June 2019, and from collaboration and supply agreements with the Company’s collaborators. To date, revenue from collaboration agreements has come from initial, upfront payments allocated to licenses of intellectual property delivered to the Company’s collaborators and from the supply of material for clinical trials under a supply agreement. Under Accounting Standards Codification (“ASC”) Topic 606, Revenue from Contracts with Customers (“Topic 606”), an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration that the entity expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that an entity determines are within the scope of Topic 606, the entity performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price, including variable consideration, if any; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the entity satisfies a performance obligation. Arrangements that include rights to additional goods or services that are exercisable at a customer’s discretion are generally considered options. The Company assesses if these options provide a material right to the customer and if so, they are considered performance obligations. The exercise of a material right may be accounted for as a contract modification or as a continuation of the contract for accounting purposes. For contracts determined to be within the scope of Topic 606, the Company assesses whether the goods or services promised within each contract are distinct to identify those that are performance obligations. This assessment involves subjective determinations and requires management to make judgments about the individual promised goods or services and whether such are separable from the other aspects of the contractual relationship. Promised goods and services are considered distinct provided that: (i) the customer can benefit from the good or service either on its own or together with other resources that are readily available to the customer and (ii) the entity’s promise to transfer the good or service to the customer is separately identifiable from other promises in the contract. The Company allocates the transaction price (the amount of consideration it expects to be entitled to from a customer in exchange for the promised goods or services) to each performance obligation and recognizes the associated revenue when (or as) each performance obligation is satisfied. The Company’s estimate of the transaction price for each contract includes all variable consideration to which the Company expects to be entitled. Collaboration and License Revenue In assessing whether a promised good or service is distinct in the evaluation of a collaboration or license arrangement subject to Topic 606, the Company considers factors such as the research, manufacturing and commercialization capabilities of the collaboration partner and the availability of the associated expertise in the general marketplace. The Company also considers the intended benefit of the contract in assessing whether a promised good or service is separately identifiable from other promises in the contract. If a promised good or service is not distinct, the Company is required to combine that good or service with other promised goods or services until it identifies a bundle of goods or services that is distinct. The transaction price is then determined and allocated to the identified performance obligations in proportion to their standalone selling prices (“SSP”) on a relative SSP basis. SSP is determined at contract inception and is not updated to reflect changes between contract inception and when the performance obligations are satisfied. Determining the SSP for performance obligations requires significant judgment. In developing the SSP for a performance obligation, the Company considers applicable market conditions and relevant entity-specific factors, including factors that were contemplated in negotiating the agreement with the customer and estimated costs. In certain circumstances, the Company may apply the residual method to determine the SSP of a good or service if the standalone selling price is considered highly variable or uncertain. The Company validates the SSP for performance obligations by evaluating whether changes in the key assumptions used to determine the SSP will have a significant effect on the allocation of arrangement consideration between multiple performance obligations. If the consideration promised in a contract includes a variable amount, the Company estimates the amount of consideration to which it will be entitled in exchange for transferring the promised goods or services to a customer. The Company determines the amount of variable consideration by using the expected value method or the most likely amount method. The Company includes the unconstrained amount of estimated variable consideration in the transaction price. The amount included in the transaction price is constrained to the amount for which it is probable that a significant reversal of cumulative revenue recognized will not occur. At the end of each subsequent reporting period, the Company re-evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis in the period of adjustment. If an arrangement includes development and regulatory milestone payments, the Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the Company’s control or the licensee’s control, such as regulatory approvals, are generally not considered probable of being achieved until those approvals are received. In determining the transaction price, the Company adjusts consideration for the effects of the time value of money if the timing of payments provides the Company with a significant benefit of financing. The Company does not assess whether a contract has a significant financing component if the expectation at contract inception is such that the period between payment by the licensees and the transfer of the promised goods or services to the licensees will be one year or less. The Company assessed its arrangements with Shionogi and Biogen and concluded that a significant financing component does not exist for either arrangement. For arrangements with licenses of intellectual property that include sales-based royalties or milestone payments based on the level of sales, and the license is deemed to be the predominant item to which the royalties or milestone payments relate, the Company recognizes royalty revenue and sales-based milestones at the later of (i) when the related sales occur, or (ii) when the performance obligation to which the royalty or milestone payment has been allocated has been satisfied. The Company then recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) each performance obligation is satisfied at a point in time or over time, and if over time this is based on the use of an output or input method. Revenue from the Company’s collaboration agreement with Shionogi has come from initial, upfront consideration upon execution of the agreement and for the supply of drug product for Shionogi’s clinical trials. Revenue from the Company’s collaboration agreement with Biogen has come from initial, upfront consideration related to the execution of the Biogen Collaboration Agreement. For additional information, refer to Note 6, Collaboration Agreements . Product Revenue, Net The Company recognizes product revenues, net of variable consideration related to certain allowances and accruals that are determined using the expected value method, in its condensed consolidated financial statements at the point in time when control transfers to the customer, which is typically when the product has been delivered to the customer’s location. The amount included in the transaction price is constrained to the amount for which it is probable that a significant reversal of cumulative revenue recognized will not occur. The Company’s only performance obligation identified for ZULRESSO is to deliver the product to the location specified by the customer’s order. The Company records shipping and handling costs associated with delivery of product to its customers within selling, general and administrative expenses on its condensed consolidated statements of operations and comprehensive loss. The Company expenses incremental costs of obtaining a contract as incurred if the expected amortization period of the asset would be less than one year . If the Company were to incur incremental costs with an amortization period greater than a year, such costs would be capitalized as contract assets, as they are expected to be recovered, and would be expensed by amortizing on a systematic basis that is consistent with the transfer to the customer of the goods or services to which the asset relates. The Company did not have any contract assets (unbilled receivables) at September 30, 2022, as customer invoicing generally occurs before or at the time of revenue recognition. The Company did not have any contract liabilities at September 30, 2022, as the Company did not receive any payments in advance of satisfying its performance obligations to its customers. Amounts billed or invoiced that are considered trade accounts receivable are included in prepaid expenses and other current assets on the condensed consolidated balance sheets. As of September 30, 2022 and December 31, 2021, the Company had not provided any allowance for bad debts against the trade accounts receivable, and the amount of trade accounts receivable was not significant. The Company records reserves, based on contractual terms, for the following components of variable consideration related to product sold during the reporting period, as well as its estimate of product that remains in the distribution channel inventory of its customers at the end of the reporting period. On a quarterly basis, the Company updates its estimates, if necessary, and records any material adjustments in the period they are identified. Chargebacks : The Company estimates chargebacks from its customers who directly purchase the product from the Company for discounts resulting from contractual commitments to sell products to eligible healthcare settings at prices lower than the list prices charged to its customers. Customers charge the Company for the difference between what they pay to the Company for the product and the selling price to the eligible healthcare settings. Reserves for chargebacks consist of credits that the Company expects to issue for units that remain in the distribution channel inventories at the end of each reporting period that the Company expects will be sold to eligible healthcare settings, and chargebacks that customers have claimed, but for which the Company has not yet issued a credit. Government Rebates : The Company is subject to discount obligations under government programs, including Medicaid. The Company records reserves for rebates in the same period the related product revenue is recognized, resulting in a reduction of ZULRESSO product revenues and a current liability that is included in accrued expenses on its condensed consolidated balance sheets. The Company’s liability for these rebates consists of invoices received for claims from prior quarters that have not been paid or for which an invoice has not yet been received, estimates of claims for the current quarter, and estimates of future claims that will be made for product that has been recognized as revenue, but which remains in the distribution channel at the end of each reporting period. Trade Discounts and Allowances : The Company generally provides customary invoice discounts on ZULRESSO sales to its customers for prompt payment and the Company pays fees for sales order management, data, and distribution services. The Company estimates its customers will earn these discounts and fees and deducts these discounts and fees in full from gross ZULRESSO revenues and accounts receivable at the time the Company recognizes the related revenues. Financial Assistance : The Company provides voluntary financial assistance programs to patients with commercial insurance that have coverage and reside in states that allow financial assistance. The Company estimates the financial assistance amounts for ZULRESSO and records any such amounts within accrued expenses on its condensed consolidated balance sheets. The calculation of the accrual for financial assistance is based on an estimate of claims and the cost per claim that the Company expects to receive using demographics for patients who have registered and been approved for assistance. Any adjustments are recorded in the same period the related revenue is recognized, resulting in a reduction of product revenue and the establishment of a current liability, which is included as a component of accrued expenses on the condensed consolidated balance sheets. Product Returns : Consistent with industry practice, the Company offers product return rights to customers for damaged, defective or expiring product, provided it is within a specified period around the product expiration date as set forth in the Company’s return goods policy. The Company estimates the amount of its product sales that may be returned by its customers and records this estimate as a reduction of revenue in the period the related product revenue is recognized, as well as a reserve within accrued expenses on the condensed consolidated balance sheets. Product returns have been immaterial to date and are expected to remain immaterial in the future.
Collaborative Arrangements	Collaborative Arrangements The Company analyzes its collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, Collaborative Arrangements (“Topic 808”). This assessment is performed throughout the life of the arrangement based on changes in the responsibilities of all parties in the arrangement. For collaboration arrangements within the scope of Topic 808 that contain multiple elements, the Company first determines which elements of the collaboration are deemed to be within the scope of Topic 808 and which elements of the collaboration are more reflective of a vendor-customer relationship and therefore within the scope of Topic 606. For elements of collaboration arrangements that are accounted for pursuant to Topic 808, an appropriate recognition method is determined and applied consistently, either by analogy to authoritative accounting literature or by applying a reasonable and rational policy election. For those elements of the arrangement that are accounted for pursuant to Topic 606, the Company applies the five-step model described above, and presents the arrangement as collaboration revenue in the condensed consolidated statements of operations and comprehensive loss. For collaboration arrangements that are within the scope of Topic 808, the Company evaluates the income statement classification for presentation of amounts due from or owed to other participants associated with multiple activities in a collaboration arrangement based on the nature of each separate activity. Payments or reimbursements that are the result of a collaborative relationship instead of a customer relationship, such as co-development and co-commercialization activities, are recorded as research and development expense or selling, general and administrative expense, in the event of a payment to the collaborative partner in a period, or a reduction to these expense line items in the event of a reimbursement from the collaboration partner in a period, as appropriate.
Fair Value Measurements	Fair Value Measurements Fair value is the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. Financial assets and liabilities carried at fair value are classified and disclosed in one of the following three categories: Level 1 — Quoted market prices in active markets for identical assets or liabilities. Level 2 — Observable inputs other than Level 1 prices, such as quoted prices for similar assets or liabilities; quoted prices in markets that are not active; or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities. Level 3 — Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the assets or liabilities. The Company’s cash equivalents and marketable securities at September 30, 2022 and December 31, 2021 were carried at fair value, determined according to the fair value hierarchy; see Note 3, Fair Value Measurements . The carrying amounts reflected in the condensed consolidated balance sheets for the collaboration receivable – related party, accounts payable and accrued expenses approximate their fair values due to their short-term maturities at September 30, 2022 and December 31, 2021, respectively.
Recently Issued Accounting Pronouncements	Recently Issued Accounting Pronouncements Accounting standards that have been issued or proposed 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 the Company’s condensed consolidated financial statements upon adoption.

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	9 Months Ended
	Sep. 30, 2022
Fair Value Disclosures [Abstract]
Summary of Company's Cash Equivalents and Marketable Securities	The following tables summarize the Company’s cash equivalents and marketable securities as of September 30, 2022 and December 31, 2021: September 30, 2022 Total Quoted Significant Significant (in thousands) Cash equivalents: Money market funds $ 168,766 $ 168,766 $ — $ — U.S. corporate bonds 4,443 — 4,443 — U.S. commercial paper 7,883 — 7,883 — International commercial paper 10,979 — 10,979 — U.S. municipal securities 6,672 — 6,672 — Total cash equivalents 198,743 168,766 29,977 — Marketable securities: U.S. government securities 393,969 — 393,969 — U.S. corporate bonds 398,792 — 398,792 — International corporate bonds 151,048 — 151,048 — U.S. commercial paper 52,671 — 52,671 — International commercial paper 130,216 — 130,216 — U.S. certificates of deposit 13,727 — 13,727 — U.S. municipal securities 53,390 — 53,390 — Total marketable securities 1,193,813 — 1,193,813 — $ 1,392,556 $ 168,766 $ 1,223,790 $ — December 31, 2021 Total Quoted Significant Significant (in thousands) Cash equivalents: Money market funds $ 289,440 $ 289,440 $ — $ — U.S. commercial paper 2,000 — 2,000 — International commercial paper 1,999 — 1,999 — Total cash equivalents 293,439 289,440 3,999 — Marketable securities: U.S. government securities 324,532 — 324,532 — U.S. corporate bonds 627,780 — 627,780 — International corporate bonds 236,812 — 236,812 — U.S. commercial paper 80,176 — 80,176 — International commercial paper 142,335 — 142,335 — U.S. municipal securities 36,428 — 36,428 — Total marketable securities 1,448,063 — 1,448,063 — $ 1,741,502 $ 289,440 $ 1,452,062 $ —
Summary of Gross Unrealized Gains and Losses of Marketable Securities	The following tables summarize the gross unrealized gains and losses of the Company’s marketable securities as of September 30, 2022 and December 31, 2021: September 30, 2022 Amortized Gross Unrealized Gross Unrealized Credit Losses Fair Value (in thousands) Assets: U.S. government securities $ 400,180 $ 3 $ ( 6,214 ) $ — $ 393,969 U.S. corporate bonds 404,074 — ( 5,282 ) — 398,792 International corporate bonds 153,088 3 ( 2,043 ) — 151,048 U.S. commercial paper 52,778 — ( 107 ) — 52,671 International commercial paper 130,461 — ( 245 ) — 130,216 U.S. certificates of deposit 13,727 — — — 13,727 U.S. municipal securities 54,388 9 ( 1,007 ) — 53,390 $ 1,208,696 $ 15 $ ( 14,898 ) $ — $ 1,193,813 December 31, 2021 Amortized Gross Unrealized Gross Unrealized Credit Losses Fair Value (in thousands) Assets: U.S. government securities $ 325,514 $ — $ ( 982 ) $ — $ 324,532 U.S. corporate bonds 628,836 27 ( 1,083 ) — 627,780 International corporate bonds 237,303 — ( 491 ) — 236,812 U.S. commercial paper 80,194 — ( 18 ) — 80,176 International commercial paper 142,358 — ( 23 ) — 142,335 U.S. municipal securities 36,518 — ( 90 ) — 36,428 $ 1,450,723 $ 27 $ ( 2,687 ) $ — $ 1,448,063
Summary of Fair Value And Unrealized Losses of Marketable Securities In Loss Position	The following tables summarize the fair value and the unrealized losses of the Company’s marketable securities that are in a loss position as of September 30, 2022 and December 31, 2021: September 30, 2022 Less than 12 months Greater than 12 months Total Fair Unrealized Fair Unrealized Fair Unrealized (in thousands) U.S. government securities $ 268,949 $ ( 3,872 ) $ 120,107 $ ( 2,342 ) $ 389,056 $ ( 6,214 ) U.S. corporate bonds 337,682 ( 4,485 ) 61,969 ( 797 ) 399,651 ( 5,282 ) International corporate bonds 120,338 ( 1,676 ) 30,151 ( 367 ) 150,489 ( 2,043 ) U.S. commercial paper 21,996 ( 106 ) 2,999 ( 1 ) 24,995 ( 107 ) International commercial paper 41,813 ( 245 ) — — 41,813 ( 245 ) U.S. municipal securities 47,652 ( 1,007 ) — — 47,652 ( 1,007 ) $ 838,430 $ ( 11,391 ) $ 215,226 $ ( 3,507 ) $ 1,053,656 $ ( 14,898 ) December 31, 2021 Less than 12 months Greater than 12 months Total Fair Unrealized Fair Unrealized Fair Unrealized (in thousands) U.S. government securities $ 309,588 $ ( 982 ) $ — $ — $ 309,588 $ ( 982 ) U.S. corporate bonds 601,475 ( 1,083 ) — — 601,475 ( 1,083 ) International corporate bonds 231,672 ( 491 ) — — 231,672 ( 491 ) U.S. commercial paper 21,968 ( 18 ) — — 21,968 ( 18 ) International commercial paper 35,059 ( 23 ) — — 35,059 ( 23 ) U.S. municipal securities 24,953 ( 90 ) — — 24,953 ( 90 ) $ 1,224,715 $ ( 2,687 ) $ — $ — $ 1,224,715 $ ( 2,687 )

Accrued Expenses (Tables)

Accrued Expenses (Tables)	9 Months Ended
	Sep. 30, 2022
Payables And Accruals [Abstract]
Summary of Accrued Expenses	Accrued expenses consist of the following: September 30, December 31, 2022 2021 (in thousands) Accrued research and development costs $ 47,182 $ 39,147 Employee-related 20,176 18,618 Professional services 17,129 8,893 Other 520 617 $ 85,007 $ 67,275

Collaboration Agreements (Table

Collaboration Agreements (Tables)	9 Months Ended
	Sep. 30, 2022
Collaboration Agreement [Abstract]
Summary of Operating Expenses Category Related to Collaboration Agreement	The following table summarizes expenses related to the Biogen Collaboration Agreement that were incurred by the Company and the related reimbursement from Biogen, reflected by category of operating expenses: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 (in thousands) (in thousands) Expenses related to the Biogen Collaboration Agreement $ 53,139 $ 50,950 $ 161,111 $ 149,653 Net reimbursement from Biogen reflected in the condensed Research and development expenses ( 17,867 ) ( 21,634 ) ( 57,364 ) ( 63,843 ) Selling, general and administrative expenses ( 480 ) ( 2,551 ) ( 4,788 ) ( 8,780 ) ( 18,347 ) ( 24,185 ) ( 62,152 ) ( 72,623 ) Total net expenses related to the Biogen Collaboration $ 34,792 $ 26,765 $ 98,959 $ 77,030

Stock-Based Compensation (Table

Stock-Based Compensation (Tables)	9 Months Ended
	Sep. 30, 2022
Disclosure Of Compensation Related Costs Sharebased Payments [Abstract]
Summary of Activity Relating to Restricted Stock Units	The following table summarizes activity relating to time-based restricted stock units and performance restricted stock units: Shares Outstanding as of December 31, 2021 1,256,098 Granted 569,410 Vested ( 351,455 ) Forfeited ( 84,796 ) Outstanding as of September 30, 2022 1,389,257
Summary of Activity Relating to Time Based and Performance Based Stock Options	The following table summarizes activity related to time-based and performance-based stock options: Shares Weighted Weighted Average Aggregate Outstanding as of December 31, 2021 7,283,439 $ 84.17 6.74 $ 16,590 Granted 1,008,027 $ 39.59 Exercised ( 149,083 ) $ 6.73 Forfeited ( 443,059 ) $ 94.18 Outstanding as of September 30, 2022 7,699,324 $ 79.26 6.53 $ 8,606 Exercisable as of September 30, 2022 4,953,687 $ 85.77 5.39 $ 6,584
Summary of Stock-Based Compensation Expense Recognized	The following table summarizes stock-based compensation expense recognized during the three and nine months ended September 30, 2022 and 2021: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 (in thousands) Research and development $ 5,964 $ 17,864 $ 21,037 $ 40,598 Selling, general and administrative 7,205 16,478 25,321 43,383 $ 13,169 $ 34,342 $ 46,358 $ 83,981
Summary of Stock-Based Compensation Expense by Award Type	The following table summarizes stock-based compensation expense by award type recognized during the three and nine months ended September 30, 2022 and 2021: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 (in thousands) Stock options $ 11,992 $ 19,516 $ 40,659 $ 60,740 Restricted stock units 730 14,563 4,982 22,538 Employee stock purchase plan 447 263 717 703 $ 13,169 $ 34,342 $ 46,358 $ 83,981

Net Loss Per Share (Tables)

Net Loss Per Share (Tables)	9 Months Ended
	Sep. 30, 2022
Earnings Per Share [Abstract]
Summary of Basic and Diluted Net Loss Per Share	The following table shows the calculation of basic and diluted net loss per share for the three and nine months ended September 30, 2022 and 2021: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 Basic net loss per share: Numerator: Net loss (in thousands) $ ( 137,323 ) $ ( 130,171 ) $ ( 385,638 ) $ ( 333,180 ) Denominator: Weighted average common stock 59,428,123 58,819,548 59,242,563 58,593,743 Dilutive effect of shares of common — — — — Weighted average common stock 59,428,123 58,819,548 59,242,563 58,593,743 Net loss per share—basic and diluted $ ( 2.31 ) $ ( 2.21 ) $ ( 6.51 ) $ ( 5.69 )
Summary of Anti-Dilutive Common Stock Equivalents Outstanding	The following table summarizes common stock equivalents outstanding that were excluded from the calculation of diluted net loss per share because including them would have been anti-dilutive as of September 30, 2022 and 2021: Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 Stock options 7,017,873 6,728,998 7,017,873 6,728,998 Restricted stock units 179,676 310,418 179,676 310,418 Employee stock purchase plan 43,877 15,437 43,877 15,437 7,241,426 7,054,853 7,241,426 7,054,853

Nature of the Business - Additi

Nature of the Business - Additional Information (Detail) - USD ($) $ in Thousands	9 Months Ended	12 Months Ended	150 Months Ended
	Sep. 30, 2022	Dec. 31, 2020	Sep. 30, 2022	Dec. 31, 2021
Nature Of Business [Line Items]
Accumulated deficit	$ 1,881,024		$ 1,881,024	$ 1,495,386
Net income from up-front		$ 606,100
Up-front payments receive	$ 1,000,000
Redeemable Convertible Preferred Stock [Member] | Convertible Notes [Member] | Initial Public Offering [Member]
Nature Of Business [Line Items]
Net proceeds from sale of equity and notes			$ 2,800,000

Summary of Significant Accoun_3

Summary of Significant Accounting Policies - Additional Information (Detail)	9 Months Ended
	Sep. 30, 2022
Product Revenue [Member]
Summary Of Significant Accounting Policies [Line Items]
Incremental costs incurred expected amortization period of asset	true

Fair Value Measurements - Summa

Fair Value Measurements - Summary of Company's Cash Equivalents and Marketable Securities (Detail) - USD ($) $ in Thousands	Sep. 30, 2022	Dec. 31, 2021
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	$ 198,743	$ 293,439
Total marketable securities	1,193,813	1,448,063
Total cash equivalents and marketable securities	1,392,556	1,741,502
Fair Value, Inputs, Level 1 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	168,766	289,440
Total cash equivalents and marketable securities	168,766	289,440
Fair Value, Inputs, Level 2 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	29,977	3,999
Total marketable securities	1,193,813	1,448,063
Total cash equivalents and marketable securities	1,223,790	1,452,062
Money Market Funds [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	168,766	289,440
Money Market Funds [Member] | Fair Value, Inputs, Level 1 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	168,766	289,440
International Corporate Bonds [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total marketable securities	151,048	236,812
International Corporate Bonds [Member] | Fair Value, Inputs, Level 2 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total marketable securities	151,048	236,812
U.S. Government Securities [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total marketable securities	393,969	324,532
U.S. Government Securities [Member] | Fair Value, Inputs, Level 2 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total marketable securities	393,969	324,532
U.S. Corporate Bonds [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	4,443
Total marketable securities	398,792	627,780
U.S. Corporate Bonds [Member] | Fair Value, Inputs, Level 2 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	4,443
Total marketable securities	398,792	627,780
U.S. Commercial Paper [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	7,883	2,000
Total marketable securities	52,671	80,176
U.S. Commercial Paper [Member] | Fair Value, Inputs, Level 2 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	7,883	2,000
Total marketable securities	52,671	80,176
International Commercial Paper [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	10,979	1,999
Total marketable securities	130,216	142,335
International Commercial Paper [Member] | Fair Value, Inputs, Level 2 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	10,979	1,999
Total marketable securities	130,216	142,335
U.S. Municipal Securities [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	6,672
Total marketable securities	53,390	36,428
U.S. Municipal Securities [Member] | Fair Value, Inputs, Level 2 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total cash equivalents	6,672
Total marketable securities	53,390	$ 36,428
U.S. Certificates of Deposit [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total marketable securities	13,727
U.S. Certificates of Deposit [Member] | Fair Value, Inputs, Level 2 [Member]
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total marketable securities	$ 13,727

Fair Value Measurements - Addit

Fair Value Measurements - Additional Information (Detail) - USD ($)	9 Months Ended	12 Months Ended
	Sep. 30, 2022	Dec. 31, 2021	Sep. 30, 2021
Debt Instrument Fair Value Carrying Value [Line Items]
Transfers among the Level 1, Level 2 and Level 3 categories	$ 0		$ 0
Impairment of assets	0	$ 0
US Treasury Bond Securities | Corporate Bonds and Municipal Securities [Member]
Debt Instrument Fair Value Carrying Value [Line Items]
Marketable securities fair value held to maturity	$ 178,300,000	$ 436,100,000
Maximum [Member] | US Treasury Bond Securities | U.S. Corporate Bonds [Member]
Debt Instrument Fair Value Carrying Value [Line Items]
Marketable securities, remaining contractual maturities	1 year	1 year
Maximum [Member] | US Treasury Bond Securities | Corporate Bonds and Municipal Securities [Member]
Debt Instrument Fair Value Carrying Value [Line Items]
Marketable securities held, maturity period	2 years	2 years
Minimum [Member] | US Treasury Bond Securities | Corporate Bonds and Municipal Securities [Member]
Debt Instrument Fair Value Carrying Value [Line Items]
Marketable securities held, maturity period	1 year	1 year

Fair Value Measurements - Sum_2

Fair Value Measurements - Summary of Gross Unrealized Gains and Losses of Marketable Securities (Detail) - USD ($) $ in Thousands	Sep. 30, 2022	Dec. 31, 2021
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	$ 1,208,696	$ 1,450,723
Gross Unrealized Gains	15	27
Gross Unrealized Losses	(14,898)	(2,687)
Fair Value	1,193,813	1,448,063
U.S. Government Securities [Member]
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	400,180	325,514
Gross Unrealized Gains	3
Gross Unrealized Losses	(6,214)	(982)
Fair Value	393,969	324,532
U.S. Corporate Bonds [Member]
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	404,074	628,836
Gross Unrealized Gains		27
Gross Unrealized Losses	(5,282)	(1,083)
Fair Value	398,792	627,780
International Corporate Bonds [Member]
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	153,088	237,303
Gross Unrealized Gains	3
Gross Unrealized Losses	(2,043)	(491)
Fair Value	151,048	236,812
U.S. Commercial Paper [Member]
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	52,778	80,194
Gross Unrealized Losses	(107)	(18)
Fair Value	52,671	80,176
International Commercial Paper [Member]
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	130,461	142,358
Gross Unrealized Losses	(245)	(23)
Fair Value	130,216	142,335
U.S. Certificates of Deposit [Member]
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	13,727
Fair Value	13,727
U.S. Municipal Securities [Member]
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	54,388	36,518
Gross Unrealized Gains	9
Gross Unrealized Losses	(1,007)	(90)
Fair Value	$ 53,390	$ 36,428

Fair Value Measurements - Sum_3

Fair Value Measurements - Summary of Fair Value And Unrealized Losses of Marketable Securities In Loss Position (Detail) - USD ($) $ in Thousands	Sep. 30, 2022	Dec. 31, 2021
Schedule of Available-for-sale Securities [Line Items]
Less than 12 months, Fair Value	$ 838,430	$ 1,224,715
Less than 12 months, Unrealized Losses	(11,391)	(2,687)
Greater than 12 months, Fair Value	215,226
Greater than 12 months, Unrealized Losses	(3,507)
Fair Value	1,053,656	1,224,715
Unrealized Losses	(14,898)	(2,687)
U.S. Government Securities [Member]
Schedule of Available-for-sale Securities [Line Items]
Less than 12 months, Fair Value	268,949	309,588
Less than 12 months, Unrealized Losses	(3,872)	(982)
Greater than 12 months, Fair Value	120,107
Greater than 12 months, Unrealized Losses	(2,342)
Fair Value	389,056	309,588
Unrealized Losses	(6,214)	(982)
U.S. Corporate Bonds [Member]
Schedule of Available-for-sale Securities [Line Items]
Less than 12 months, Fair Value	337,682	601,475
Less than 12 months, Unrealized Losses	(4,485)	(1,083)
Greater than 12 months, Fair Value	61,969
Greater than 12 months, Unrealized Losses	(797)
Fair Value	399,651	601,475
Unrealized Losses	(5,282)	(1,083)
International Corporate Bonds [Member]
Schedule of Available-for-sale Securities [Line Items]
Less than 12 months, Fair Value	120,338	231,672
Less than 12 months, Unrealized Losses	(1,676)	(491)
Greater than 12 months, Fair Value	30,151
Greater than 12 months, Unrealized Losses	(367)
Fair Value	150,489	231,672
Unrealized Losses	(2,043)	(491)
U.S. Commercial Paper [Member]
Schedule of Available-for-sale Securities [Line Items]
Less than 12 months, Fair Value	21,996	21,968
Less than 12 months, Unrealized Losses	(106)	(18)
Greater than 12 months, Fair Value	2,999
Greater than 12 months, Unrealized Losses	(1)
Fair Value	24,995	21,968
Unrealized Losses	(107)	(18)
International Commercial Paper [Member]
Schedule of Available-for-sale Securities [Line Items]
Less than 12 months, Fair Value	41,813	35,059
Less than 12 months, Unrealized Losses	(245)	(23)
Fair Value	41,813	35,059
Unrealized Losses	(245)	(23)
U.S. Municipal Securities [Member]
Schedule of Available-for-sale Securities [Line Items]
Less than 12 months, Fair Value	47,652	24,953
Less than 12 months, Unrealized Losses	(1,007)	(90)
Fair Value	47,652	24,953
Unrealized Losses	$ (1,007)	$ (90)

Accrued Expenses - Summary of A

Accrued Expenses - Summary of Accrued Expenses (Detail) - USD ($) $ in Thousands	Sep. 30, 2022	Dec. 31, 2021
Payables And Accruals [Abstract]
Accrued research and development costs	$ 47,182	$ 39,147
Employee-related	20,176	18,618
Professional services	17,129	8,893
Other	520	617
Total accrued expenses	$ 85,007	$ 67,275

Leases, Commitments and Conti_2

Leases, Commitments and Contingencies - Operating Leases - Additional Information (Detail) $ in Thousands		9 Months Ended
	Jan. 01, 2021 ft²	Sep. 30, 2022 USD ($)	Dec. 31, 2021 USD ($)	Mar. 31, 2021 USD ($)
Commitments And Contingencies [Line Items]
Operating lease option to extend		true
Operating lease renewal term		5 years
Right-of-use operating asset | $		$ 11,970	$ 16,109	$ 3,700
Operating Lease One [Member]
Commitments And Contingencies [Line Items]
Office space rent under operating lease	63,017
Lease expire date	Aug. 31, 2024
Operating Lease Two [Member]
Commitments And Contingencies [Line Items]
Office space rent under operating lease	40,419
Lease expire date	Aug. 31, 2024
Operating Lease Three [Member]
Commitments And Contingencies [Line Items]
Office space rent under operating lease	15,525
Lease expire date	Nov. 30, 2024
Operating Lease Five [Member]
Commitments And Contingencies [Line Items]
Office space rent under operating lease	15,975
Lease expire date	Feb. 29, 2024
Minimum [Member]
Commitments And Contingencies [Line Items]
Operating lease remaining lease terms		1 year
Maximum [Member]
Commitments And Contingencies [Line Items]
Operating lease remaining lease terms		2 years 3 months

Leases, Commitments and Conti_3

Leases, Commitments and Contingencies - CyDex License Agreement - Additional Information (Detail) - USD ($)	3 Months Ended		9 Months Ended
	Sep. 30, 2022	Sep. 30, 2021	Sep. 30, 2022	Sep. 30, 2021
Commitments And Contingencies [Line Items]
Research and development expense	$ 81,553,000	$ 83,497,000	$ 236,868,000	$ 207,723,000
CyDex License Agreement [Member]
Commitments And Contingencies [Line Items]
Research and development expense			1,000,000
CyDex License Agreement [Member] | Brexanolone [Member]
Commitments And Contingencies [Line Items]
Research and development expense related to milestone expense			0	0
Milestone payments			0	0
CyDex License Agreement [Member] | First and Second Clinical Development Milestones [Member] | Brexanolone [Member] | Maximum [Member]
Commitments And Contingencies [Line Items]
Expected milestone payments	800,000		800,000
CyDex License Agreement [Member] | First and Second Regulatory Milestones [Member] | Brexanolone [Member] | Maximum [Member]
Commitments And Contingencies [Line Items]
Expected milestone payments	3,800,000		3,800,000
CyDex License Agreement [Member] | Additional Clinical Development Milestone [Member] | SAGE-689 [Member]
Commitments And Contingencies [Line Items]
Research and development expense		100,000		100,000
CyDex License Agreement [Member] | Third and Fourth Clinical Development Milestones [Member] | Brexanolone [Member]
Commitments And Contingencies [Line Items]
Expected milestone payments		1,300,000		1,300,000
CyDex License Agreement [Member] | Third and Fourth Clinical Development Milestones [Member] | Brexanolone [Member] | Maximum [Member]
Commitments And Contingencies [Line Items]
Expected milestone payments	1,300,000		1,300,000
CyDex License Agreement [Member] | Third and Fourth Regulatory Milestones [Member] | Brexanolone [Member] | Maximum [Member]
Commitments And Contingencies [Line Items]
Expected milestone payments	8,500,000		8,500,000
CyDex License Agreement [Member] | Clinical Development [Member] | Brexanolone [Member]
Commitments And Contingencies [Line Items]
Milestone payments related to intangible assets			0	0
CyDex License Agreement [Member] | Clinical Development [Member] | SAGE-689 [Member] | Maximum [Member]
Commitments And Contingencies [Line Items]
Expected milestone payments	800,000		800,000
CyDex License Agreement [Member] | Regulatory Milestones [Member] | Brexanolone [Member]
Commitments And Contingencies [Line Items]
Research and development expense related to milestone expense			0	0
Milestone payments			0	0
Intangible asset related to milestone	0	$ 0	0	0
Milestone payments related to intangible assets			0	$ 0
CyDex License Agreement [Member] | Regulatory Milestones [Member] | SAGE-689 [Member] | Maximum [Member]
Commitments And Contingencies [Line Items]
Expected milestone payments	1,800,000		1,800,000
CyDex License Agreement [Member] | Clinical Development and Regulatory Milestones [Member]
Commitments And Contingencies [Line Items]
Research and development expense related to milestone expense			3,600,000
Milestone payments			3,600,000
Intangible asset related to milestone	$ 3,000,000		$ 3,000,000

Leases, Commitments and Conti_4

Leases, Commitments and Contingencies - University of California License Agreements - Additional Information (Detail) - University of California License Agreements [Member] - USD ($)		1 Months Ended	9 Months Ended		12 Months Ended
	Dec. 31, 2015	Jun. 30, 2015	Sep. 30, 2022	Sep. 30, 2021	Dec. 31, 2015
Commitments And Contingencies [Line Items]
Upfront payment		$ 50,000
Annual license maintenance fee					$ 15,000
Milestone payments			$ 0	$ 0
After The Effective Date [Member]
Commitments And Contingencies [Line Items]
Licenses Expiration period, maximum	27 years
After The First Sale [Member]
Commitments And Contingencies [Line Items]
Licenses Expiration period, maximum	15 years
Clinical Development [Member]
Commitments And Contingencies [Line Items]
Milestone payments	$ 100,000
Milestone outstanding	$ 0
Clinical Development [Member] | Maximum [Member]
Commitments And Contingencies [Line Items]
Percentage of net sales paid as royalties	1%
Regulatory Milestones [Member] | Maximum [Member]
Commitments And Contingencies [Line Items]
Expected milestone payments		700,000
Sales Milestones [Member] | Maximum [Member]
Commitments And Contingencies [Line Items]
Expected milestone payments		$ 2,000,000
Regulatory and Sales Milestones [Member]
Commitments And Contingencies [Line Items]
Research and development expense related to milestone expense			300,000
Milestone payments			300,000
Intangible asset related to milestone			500,000
Milestone payments related to intangible assets			$ 500,000

Collaboration Agreements - Addi

Collaboration Agreements - Additional Information (Detail) - USD ($)			3 Months Ended			9 Months Ended		12 Months Ended
	Nov. 30, 2020	Jun. 30, 2018	Sep. 30, 2022	Sep. 30, 2021	Jun. 30, 2018	Sep. 30, 2022	Sep. 30, 2021	Dec. 31, 2021	Dec. 31, 2020	Jun. 12, 2018
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Revenue			$ 1,739,000	$ 1,440,000		$ 4,821,000	$ 4,666,000
Collaboration receivable - related party			18,448,000			18,448,000		$ 18,506,000
Shionogi Collaboration Agreement [Member] | Collaboration Revenue [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Revenue						0	0
Shionogi Collaboration Agreement [Member] | SAGE-217 [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration agreement effective date		Jun. 30, 2018
Upfront payment		$ 90,000,000
Average percentage on tiered royalties		20%
Revenue					$ 90,000,000
Standalone selling price of license performance obligation		$ 90,000,000			90,000,000
Shionogi Collaboration Agreement [Member] | SAGE-217 [Member] | Maximum [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Additional milestone payment receivable		485,000,000			$ 485,000,000
Shionogi Collaboration Agreement [Member] | SAGE-217 [Member] | Maximum [Member] | Regulatory Milestones [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments		70,000,000
Shionogi Collaboration Agreement [Member] | SAGE-217 [Member] | Maximum [Member] | Commercial Milestones [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments		30,000,000
Shionogi Collaboration Agreement [Member] | SAGE-217 [Member] | Maximum [Member] | Sales Milestones [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments		$ 385,000,000
Biogen Collaboration Agreement [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration agreement effective date	Dec. 28, 2020
Upfront payment									$ 875,000,000
Revenue						0	0		1,100,000,000
Standalone selling price of license performance obligation									1,100,000,000
Sale of stock, consideration received									$ 1,500,000,000
Number of shares issued									6,241,473
Purchase price									$ 650,000,000
Operating expenses			18,347,000	$ 24,185,000		62,152,000	72,623,000
Collaboration receivable - related party			$ 18,400,000			18,400,000
Payments to related parties						0		$ 0
Proceeds from related parties						$ 62,200,000	$ 48,400,000
Biogen Collaboration Agreement [Member] | SAGE-217 [Member] | Maximum [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Additional milestone payment receivable										$ 1,600,000,000
Biogen Collaboration Agreement [Member] | SAGE-217 [Member] | Maximum [Member] | Sales Milestones [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments	$ 300,000,000
Biogen Collaboration Agreement [Member] | SAGE-217 [Member] | Maximum [Member] | Regulatory and Commercial Milestones [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments	475,000,000
Biogen Collaboration Agreement [Member] | SAGE-324 [Member] | Maximum [Member] | Sales Milestones [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments	300,000,000
Biogen Collaboration Agreement [Member] | SAGE-324 [Member] | Maximum [Member] | Regulatory and Commercial Milestones [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments	$ 520,000,000
Biogen Stock Purchase Agreement [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront payment									875,000,000
Purchase price									650,000,000
Transaction price, total									1,100,000,000
Premium amount on equity investment									$ 232,500,000
Price per share									$ 104.14
Premium on per share price									40%
Biogen stock purchase agreement, description						The standstill restrictions terminate on the earliest of (i) a specified regulatory milestone under the Biogen Collaboration Agreement, (ii) the date one year following the termination of the Biogen Collaboration Agreement and (iii) the seventh anniversary of the Effective Date. BIMA also agreed not to, and to cause its affiliates not to, sell or transfer any of the Biogen Shares for a period of eighteen months from the closing of the sale of the Biogen Shares, which period expired on June 30, 2022, and to limit sales and transfers of the Biogen Shares for an additional eighteen-month period, in each case subject to specified conditions and exceptions.
Stock issued									$ 417,500,000

Collaboration Agreements - Summ

Collaboration Agreements - Summary of Operating Expenses Category Related to Collaboration Agreement (Detail) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2022	Sep. 30, 2021	Sep. 30, 2022	Sep. 30, 2021
Net reimbursement from Biogen reflected in the condensed consolidated statement of operations and comprehensive loss:
Total operating costs and expenses	$ 143,219	$ 132,334	$ 397,908	$ 340,088
Biogen Collaboration Agreement [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Expenses related to the Biogen Collaboration Agreement incurred by Sage	53,139	50,950	161,111	149,653
Net reimbursement from Biogen reflected in the condensed consolidated statement of operations and comprehensive loss:
Selling, general and administrative expenses	(480)	(2,551)	(4,788)	(8,780)
Operating expenses	(18,347)	(24,185)	(62,152)	(72,623)
Total operating costs and expenses	34,792	26,765	98,959	77,030
Research and Development [Member] | Biogen Collaboration Agreement [Member]
Net reimbursement from Biogen reflected in the condensed consolidated statement of operations and comprehensive loss:
Research and development expenses	$ (17,867)	$ (21,634)	$ (57,364)	$ (63,843)

Stock-Based Compensation - Addi

Stock-Based Compensation - Additional Information (Detail)			3 Months Ended								9 Months Ended		12 Months Ended
	Jun. 16, 2022 shares	Jan. 01, 2022 shares	Sep. 30, 2022 USD ($) shares	Jun. 30, 2022 USD ($) shares	Mar. 31, 2022 shares	Dec. 31, 2021 shares	Sep. 30, 2021 USD ($) shares	Jun. 30, 2021 USD ($) shares	Mar. 31, 2021 USD ($) shares	Jun. 30, 2020 shares	Sep. 30, 2022 USD ($) Milestone $ / shares shares	Sep. 30, 2021 USD ($) Milestone $ / shares shares	Dec. 31, 2021 shares	Dec. 31, 2020	Sep. 20, 2018 shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share based compensation granted under plan vested period											4 years
Share based compensation, vest period											1 year
Share based compensation, term of plan											10 years
Total number of shares outstanding			9,088,581								9,088,581
Common stock available for issuance under stock option plan			7,223,536								7,223,536
Issuance of common stock under the employee stock purchase plan, Shares	300,000
Stock-based compensation expense | $			$ 13,169,000				$ 34,342,000				$ 46,358,000	$ 83,981,000
Weighted average grant date fair value per share | $ / shares											$ 25.96	$ 53.42
Time Based Restricted Stock Units [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share based compensation granted under plan vested period						4 years				2 years
Share based compensation remaining vesting period						3 years
Share based compensation vesting frequency						quarterly
Restricted stock units granted						268,119				550,890	0	0
Restricted stock units vested			59,950	291,505	0		0	113,941	0
Fair value of restricted stock units vested | $			$ 2,300,000	$ 9,500,000				$ 8,800,000
Outstanding and unvested restricted stock units			179,676								179,676
Total unrecognized stock-based compensation expense | $			$ 5,500,000								$ 5,500,000
Performance Restricted Stock Units [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Outstanding and unvested restricted stock units			1,209,581								1,209,581
Total unrecognized stock-based compensation expense | $			$ 69,500,000								$ 69,500,000
Stock Options [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Options granted											1,008,027
Total number of shares outstanding			7,699,324			7,283,439					7,699,324		7,283,439
Stock-based compensation expense | $			$ 11,992,000				$ 19,516,000				$ 40,659,000	$ 60,740,000
Total unrecognized stock-based compensation expense | $			70,500,000								$ 70,500,000
Weighted average period of unrecognized compensation costs											2 years 8 months 23 days
Intrinsic value of options exercised | $											$ 4,400,000	8,000,000
Performance-Based Stock Options [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation expense | $											$ 0	$ 0
Milestones achieved | Milestone											0	0
Performance Shares [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Options granted							0	0			0
Total unrecognized stock-based compensation expense | $			$ 11,800,000								$ 11,800,000
Number of shares outstanding and unvested stock options			681,451								681,451
Performance Shares [Member] | Chief Executive Officer [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Options granted									650,000
Restricted Stock Units [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted stock units granted											569,410
Stock-based compensation expense | $			$ 730,000				$ 14,563,000				$ 4,982,000	$ 22,538,000
Outstanding and unvested restricted stock units			1,389,257			1,256,098					1,389,257		1,256,098
Restricted Stock Units Vest One Year Anniversary [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted stock units vesting percentage											25%
Restricted Stock Units Vest One Year Anniversary [Member] | Time Based Restricted Stock Units [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted stock units vesting percentage						25%				25%
Restricted stock units vesting period month and year						2022-09				2021-04
Share-Based Payment Arrangement, Tranche Two | Time Based Restricted Stock Units [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted stock units vesting percentage						75%				75%
Restricted stock units vesting period month and year										2022-04
2011 Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Options granted											0
2014 Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Common stock shares annual increase added to plan		2,357,482
2014 Plan [Member] | Performance Restricted Stock Units [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted stock units granted			57,480				47,040				569,410	420,161
Fair value of restricted stock units vested | $							$ 0	$ 6,100,000	$ 0		$ 0
Milestone performance restricted stock percentage														39
Stock-based compensation expense | $							$ 12,600,000				$ 0
2014 Plan [Member] | Maximum [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Percentage of increase on outstanding shares of Common stock													4%
2016 Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total number of shares reserved for issuance															1,200,000

Stock-Based Compensation - Summ

Stock-Based Compensation - Summary of Activity Relating to Restricted Stock Units (Detail) - Restricted Stock Units [Member]	9 Months Ended
	Sep. 30, 2022 shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Outstanding, Shares at beginning balance	1,256,098
Granted, Shares	569,410
Vested, Shares	(351,455)
Forfeited, Shares	(84,796)
Outstanding, Shares at ending balance	1,389,257

Stock-Based Compensation - Su_2

Stock-Based Compensation - Summary of Activity Relating to Time Based and Performance Based Stock Options (Detail) $ / shares in Units, $ in Thousands	9 Months Ended	12 Months Ended
	Sep. 30, 2022 USD ($) $ / shares shares	Dec. 31, 2021 USD ($) $ / shares shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Ending balance, Outstanding Shares	9,088,581
Stock Options [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Beginning balance, Outstanding Shares	7,283,439
Granted, Shares	1,008,027
Exercised, Shares	(149,083)
Forfeited, Shares	(443,059)
Ending balance, Outstanding Shares	7,699,324	7,283,439
Exercisable, Shares	4,953,687
Beginning balance, Outstanding Weighted Average Exercise Price | $ / shares	$ 84.17
Granted, Weighted Average Exercise Price | $ / shares	39.59
Exercised, Weighted Average Exercise Price | $ / shares	6.73
Forfeited, Weighted Average Exercise Price | $ / shares	94.18
Ending balance, Outstanding Weighted Average Exercise Price | $ / shares	79.26	$ 84.17
Exercisable, Weighted Average Exercise Price | $ / shares	$ 85.77
Outstanding, Weighted Average Remaining Life	6 years 6 months 10 days	6 years 8 months 26 days
Exercisable, Weighted Average Remaining Life	5 years 4 months 20 days
Outstanding, Aggregate Intrinsic Value | $	$ 8,606	$ 16,590
Exercisable, Aggregate Intrinsic Value | $	$ 6,584

Stock-Based Compensation - Su_3

Stock-Based Compensation - Summary of Stock-Based Compensation Expense Recognized (Detail) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2022	Sep. 30, 2021	Sep. 30, 2022	Sep. 30, 2021
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total Stock-based compensation expense	$ 13,169	$ 34,342	$ 46,358	$ 83,981
Research and Development [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total Stock-based compensation expense	5,964	17,864	21,037	40,598
Selling, General and Administrative [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total Stock-based compensation expense	$ 7,205	$ 16,478	$ 25,321	$ 43,383

Stock-Based Compensation - Su_4

Stock-Based Compensation - Summary of Stock-Based Compensation Expense by Award Type Recognized (Detail) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2022	Sep. 30, 2021	Sep. 30, 2022	Sep. 30, 2021
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total Stock-based compensation expense	$ 13,169	$ 34,342	$ 46,358	$ 83,981
Stock Options [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total Stock-based compensation expense	11,992	19,516	40,659	60,740
Restricted Stock Units [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total Stock-based compensation expense	730	14,563	4,982	22,538
Employee Stock Purchase Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total Stock-based compensation expense	$ 447	$ 263	$ 717	$ 703

Net Loss Per Share - Summary of

Net Loss Per Share - Summary of Basic and Diluted Net Loss Per Share (Detail) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended						9 Months Ended
	Sep. 30, 2022	Jun. 30, 2022	Mar. 31, 2022	Sep. 30, 2021	Jun. 30, 2021	Mar. 31, 2021	Sep. 30, 2022	Sep. 30, 2021
Numerator:
Net loss	$ (137,323)	$ (126,260)	$ (122,055)	$ (130,171)	$ (107,245)	$ (95,764)	$ (385,638)	$ (333,180)
Denominator:
Weighted average number of common shares outstanding— basic	59,428,123			58,819,548			59,242,563	58,593,743
Dilutive effect of shares of common stock equivalents resulting from common stock options and restricted stock units	0			0			0	0
Weighted average common stock outstanding —diluted	59,428,123			58,819,548			59,242,563	58,593,743
Net loss per share—basic	$ (2.31)			$ (2.21)			$ (6.51)	$ (5.69)
Net loss per share—diluted	$ (2.31)			$ (2.21)			$ (6.51)	$ (5.69)

Net Loss Per Share - Summary _2

Net Loss Per Share - Summary of Anti-Dilutive Common Stock Equivalents Outstanding (Detail) - shares	3 Months Ended		9 Months Ended
	Sep. 30, 2022	Sep. 30, 2021	Sep. 30, 2022	Sep. 30, 2021
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive common stock equivalents	7,241,426	7,054,853	7,241,426	7,054,853
Stock Options [Member]
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive common stock equivalents	7,017,873	6,728,998	7,017,873	6,728,998
Restricted Stock Units [Member]
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive common stock equivalents	179,676	310,418	179,676	310,418
Employee Stock Purchase Plan [Member]
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive common stock equivalents	43,877	15,437	43,877	15,437