0000950170-23-003441 | 10-K | XBRL Viewer

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Document and Entity Information - USD ($) $ in Billions	12 Months Ended
Document and Entity Information - USD ($) $ in Billions	Dec. 31, 2022	Feb. 16, 2023	Jun. 30, 2022
Cover [Abstract]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2022
Document Fiscal Year Focus	2022
Document Fiscal Period Focus	FY
Title of 12(b) Security	Common Shares, nominal value CHF 0.03
Trading Symbol	CRSP
Security Exchange Name	NASDAQ
Entity Registrant Name	CRISPR THERAPEUTICS AG
Entity Central Index Key	0001674416
Entity Tax Identification Number	00-0000000
Current Fiscal Year End Date	--12-31
Entity Well-known Seasoned Issuer	Yes
Entity Current Reporting Status	Yes
Entity Voluntary Filers	No
Entity Filer Category	Large Accelerated Filer
Entity Small Business	false
Entity Emerging Growth Company	false
Entity Shell Company	false
Entity File Number	001-37923
Entity Address, Address Line One	Baarerstrasse 14
Entity Address, City or Town	Zug
Entity Address, Country	CH
Entity Address, Postal Zip Code	6300
City Area Code	41 (0)41
Local Phone Number	561 32 77
Entity Interactive Data Current	Yes
Entity Incorporation, State or Country Code	V8
Document Annual Report	true
Document Transition Report	false
Entity Common Stock, Shares Outstanding		78,646,679
Entity Public Float			$ 4.3
ICFR Auditor Attestation Flag	true
Documents Incorporated by Reference	Portions of the Registrant’s Definitive Proxy Statement relating to the 2023 Annual General Meeting of Shareholders, which the Registrant intends to file with the Securities and Exchange Commission pursuant to Regulation 14A within 120 days after the end of the Registrant’s fiscal year ended December 31, 2022, are incorporated by reference into Part III of this Report.
Auditor Name	Ernst & Young LLP
Auditor Firm ID	42
Auditor Location	Boston, Massachusetts

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Current assets:
Cash and cash equivalents	$ 211,885	$ 923,031
Marketable securities	1,603,433	1,456,098
Accounts receivable	0	305
Prepaid expenses and other current assets	37,708	38,079
Total current assets	1,853,026	2,417,513
Property and equipment, net	163,634	137,575
Marketable securities, non-current	53,130	0
Intangible assets, net	71	125
Restricted cash	11,635	16,913
Operating lease assets	156,921	174,460
Other non-current assets	4,640	5,291
Total assets	2,243,057	2,751,877
Current liabilities:
Accounts payable	27,428	14,816
Accrued expenses	77,682	91,003
Deferred revenue, current	0	1,011
Accrued tax liabilities	135	724
Operating lease liabilities	15,842	12,158
Other current liabilities	20	171
Total current liabilities	121,107	119,883
Deferred revenue, non-current	12,323	12,323
Operating lease liabilities, net of current portion	228,179	212,872
Other non-current liabilities	5,969	7,339
Total liabilities	367,578	352,417
Commitments and contingencies (Note 9)
Shareholders’ equity:
Common shares, CHF 0.03 par value, 150,347,467 and 145,364,335 shares authorized at December 31, 2022 and 2021, respectively, 78,692,766 and 77,170,382 shares issued at December 31, 2022 and 2021, respectively, 78,512,450 and 76,990,066 shares outstanding at December 31, 2022 and 2021, respectively.	2,441	2,391
Treasury shares, at cost, 180,316 shares at December 31, 2022 and 2021, respectively	(63)	(63)
Additional paid-in capital	2,734,838	2,598,114
Accumulated deficit	(846,090)	(195,915)
Accumulated other comprehensive loss	(15,647)	(5,067)
Total shareholders’ equity	1,875,479	2,399,460
Total liabilities and shareholders’ equity	$ 2,243,057	$ 2,751,877

Consolidated Balance Sheets (Parenthetical) - SFr / shares	Dec. 31, 2022	Dec. 31, 2021
Statement of Financial Position [Abstract]
Common stock, par value	SFr 0.03	SFr 0.03
Common stock, shares authorized	150,347,467	145,364,335
Common stock, shares issued	78,692,766	77,170,382
Common stock, shares outstanding	78,512,450	76,990,066
Treasury stock, shares	180,316	180,316

Consolidated Statements of Operations and Comprehensive (Loss) Income - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Revenue:
Total revenue	$ 1,198	$ 914,963	$ 719
Operating expenses:
Research and development	461,645	340,567	221,382
General and administrative	102,464	99,690	85,747
Collaboration expense, net	110,250	101,178	48,025
Total operating expenses	674,359	541,435	355,154
(Loss) income from operations	(673,161)	373,528	(354,435)
Other income
Other income, net	22,661	6,003	6,379
Total other income, net	22,661	6,003	6,379
Net income (loss) before income taxes	(650,500)	379,531	(348,056)
Benefit (provision) for income taxes	325	(1,870)	(809)
Net (loss) income	(650,175)	377,661	(348,865)
Foreign currency translation adjustment	(80)	(11)	40
Unrealized loss on marketable securities	(10,500)	(4,973)	(130)
Comprehensive (loss) income	$ (660,755)	$ 372,677	$ (348,955)
Net (loss) income per common share - basic	$ (8.36)	$ 4.97	$ (5.29)
Basic weighted-average common shares outstanding	77,746,575	75,948,686	65,949,672
Net (loss) income per common share - diluted	$ (8.36)	$ 4.70	$ (5.29)
Diluted weighted-average common shares outstanding	77,746,575	80,393,496	65,949,672
Collaboration Revenue [Member]
Revenue:
Total revenue	$ 436	$ 913,081	$ 543
Grant Revenue [Member]
Revenue:
Total revenue	$ 762	$ 1,882	$ 176

Consolidated Statements of Shareholders' Equity - USD ($) $ in Thousands	Total	Common Shares [Member]	Treasury Shares [Member]	Additional Paid-in Capital [Member]	Accumulated Deficit [Member]	Accumulated Other Comprehensive (Loss) Income [Member]
Beginning balance at Dec. 31, 2019	$ 939,425	$ 1,847	$ (63)	$ 1,162,345	$ (224,711)	$ 7
Beginning balance (in shares) at Dec. 31, 2019		60,783,799	250,226
Issuance of common shares, net of issuance costs	973,381	$ 366		973,015
Issuance of common shares, net of issuance costs (in shares)		11,412,519
Vesting of restricted shares	7	$ 7
Vesting of restricted shares (in shares)		204,650
Exercise of vested options, net of issuance costs	32,775	$ 57		32,718
Exercise of vested options, net of issuance costs (in shares)		1,482,636	(37,080)
Purchase of common stock under ESPP	694			694
Purchase of common stock under ESPP (in shares)		13,410
Stock-based compensation expense	66,018			66,018
Issuance of common stock for license agreements	889			889
Issuance of common stock for license agreements (in shares)		17,830	(17,830)
Other comprehensive income (loss)	(90)					(90)
Net (loss) income	(348,865)				(348,865)
Ending balance at Dec. 31, 2020	1,664,234	$ 2,277	$ (63)	2,235,679	(573,576)	(83)
Ending balance (in shares) at Dec. 31, 2020		73,914,844	195,316
Issuance of common shares, net of issuance costs	222,175	$ 45		222,130
Issuance of common shares, net of issuance costs (in shares)		1,353,121
Vesting of restricted shares	15	$ 15
Vesting of restricted shares (in shares)		455,440
Exercise of vested options, net of issuance costs	35,874	$ 54		35,820
Exercise of vested options, net of issuance costs (in shares)		1,245,071	(15,000)
Purchase of common stock under ESPP	2,095			2,095
Purchase of common stock under ESPP (in shares)		21,590
Stock-based compensation expense	102,390			102,390
Other comprehensive income (loss)	(4,984)					(4,984)
Net (loss) income	377,661				377,661
Ending balance at Dec. 31, 2021	2,399,460	$ 2,391	$ (63)	2,598,114	(195,915)	(5,067)
Ending balance (in shares) at Dec. 31, 2021		76,990,066	180,316
Issuance of common shares, net of issuance costs	970			970
Issuance of common shares, net of issuance costs (in shares)		12,365
Vesting of restricted shares	8	$ 8
Vesting of restricted shares (in shares)		237,932
Exercise of vested options, net of issuance costs	$ 35,813	$ 42		35,771
Exercise of vested options, net of issuance costs (in shares)	1,235,528	1,235,528
Purchase of common stock under ESPP	$ 2,036			2,036
Purchase of common stock under ESPP (in shares)		36,559
Stock-based compensation expense	97,947			97,947
Other comprehensive income (loss)	(10,580)					(10,580)
Net (loss) income	(650,175)				(650,175)
Ending balance at Dec. 31, 2022	$ 1,875,479	$ 2,441	$ (63)	$ 2,734,838	$ (846,090)	$ (15,647)
Ending balance (in shares) at Dec. 31, 2022		78,512,450	180,316

Consolidated Statements of Shareholders' Equity (Parenthetical) $ in Millions	12 Months Ended
	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2020 USD ($)
Stock Options [Member]
Issuance costs	$ 0.9	$ 2.6	$ 1.2
Common Shares [Member]
Issuance costs		$ 5.4	$ 46.4

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Operating activities
Net (loss) income	$ (650,175)	$ 377,661	$ (348,865)
Reconciliation of net (loss) income to net cash used in operating activities:
Depreciation and amortization	24,172	17,953	9,184
Equity-based compensation	97,947	102,390	66,018
Other non-cash items, net	12,470	14,109	1,857
Changes in:
Accounts receivable	305	(161)	(45)
Prepaid expenses and other assets	1,598	(13,912)	17,338
Accounts payable and accrued expenses	5,164	37,514	25,747
Deferred revenue	(1,011)	(783)	1,381
Operating lease assets and liabilities	15,310	9,506	(473)
Other liabilities, net	(1,521)	(5,305)	(10,508)
Net cash (used in) provided by operating activities	(495,741)	538,972	(238,366)
Investing activities
Purchase of property, plant and equipment	(37,188)	(81,705)	(18,358)
Purchases of marketable securities	(1,417,800)	(1,509,327)	(593,998)
Maturities of marketable securities	1,196,333	555,602	71,186
Net cash used in investing activities	(258,655)	(1,035,430)	(541,170)
Financing activities
Proceeds from issuance of common shares, net of issuance costs	970	213,267	982,289
Proceeds from exercise of options and ESPP contributions, net of issuance costs	37,622	37,678	33,863
Net cash provided by financing activities	38,592	250,945	1,016,152
Effect of exchange rate changes on cash	(80)	(11)	40
(Decrease) increase in cash	(715,884)	(245,524)	236,656
Cash, cash equivalents and restricted cash, beginning of period	939,944	1,185,468	948,812
Cash, cash equivalents and restricted cash, end of period	224,060	939,944	1,185,468
Supplemental disclosure of non-cash investing and financing activities
Property and equipment purchases in accounts payable and accrued expenses	2,121	8,348	3,412
Equity issuance costs in accounts payable and accrued expenses	$ 99	$ 334	$ 9,590

Consolidated Statements of Cash Flows (Parenthetical) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Cash and cash equivalents	$ 211,885	$ 923,031	$ 1,168,620
Restricted cash	11,635	16,913	16,848
Total	224,060	939,944	1,185,468	$ 948,812
Prepaid Expenses and Other Current Assets [Member]
Prepaid expenses and other current assets	$ 540	$ 0	$ 0

Organization and Operations

12 Months Ended

Dec. 31, 2022

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Organization and Operations

1. Organization and Operations

CRISPR Therapeutics AG (“CRISPR” or the “Company”) was incorporated on October 31, 2013 in Basel, Switzerland. The Company was established to translate CRISPR/Cas9, a genome editing technology, into transformative gene-based medicines for the treatment of serious human diseases. The foundational intellectual property underlying the Company’s operations was licensed to the Company in April 2014. The Company devotes substantially all of its efforts to product research and development activities, initial market development and raising capital. The Company’s principal offices are in Zug, Switzerland, with the U.S. headquarters for research and development in Boston, Massachusetts, additional research and development based in San Francisco, CA, and a cell therapy manufacturing facility in Framingham, Massachusetts.

The Company is subject to risks common to companies in the biotechnology industry, including but not limited to, risks of failure of preclinical studies and clinical trials, the need to obtain marketing approval for any drug product candidate that it may identify and develop, the need to successfully commercialize and gain market acceptance of its product candidates, dependence on key personnel, protection of proprietary technology, compliance with government regulations, development by competitors of technological innovations and ability to transition from pilot-scale manufacturing to large-scale production of products.

The Company had an accumulated deficit of $846.1 million as of December 31, 2022 and has financed its operations to date from a series of preferred shares and convertible loan issuances, proceeds obtained from its initial public offering, subsequent public offerings of its common shares, as well as upfront fees and milestones received under its collaboration and joint venture arrangements. The Company will require additional capital to fund its research and development and ongoing operating expenses.

As of December 31, 2022, the Company had cash, cash equivalents and marketable securities of $1,868.4 million. While the Company was in a net income position in certain previous years due to upfronts associated with the Company's collaborations with Vertex Pharmaceuticals Incorporated and certain of its subsidiaries, or Vertex, the Company has a history of recurring losses and expects to continue to incur losses for the foreseeable future. The Company expects its cash and cash equivalents will be sufficient to fund current planned operations for at least the next twenty-four months.

The full extent of the impact of the coronavirus pandemic on the Company’s business, operations and financial results will depend on numerous evolving factors that we may not be able to accurately predict. See Item 1A: "Risk Factors" section set forth in this Annual Report on Form 10-K for additional details. At this stage, the impact on the Company’s results has not been significant.

Summary of Significant Accounting Policies and Basis of Presentation

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Summary of Significant Accounting Policies and Basis of Presentation

2. Summary of Significant Accounting Policies and Basis of Presentation

Basis of Presentation and Use of Estimates

The accompanying consolidated financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America, or GAAP, and include the accounts of the Company and its wholly-owned subsidiaries as of December 31, 2022. All intercompany accounts and transactions have been eliminated. Any reference in these notes to applicable guidance is meant to refer to the authoritative United States generally accepted accounting principles as found in the Accounting Standards Codification, or ASC, and Accounting Standards Updates, or ASUs, of the Financial Accounting Standards Board.

Beginning in 2022, collaboration costs under the Vertex Agreements accounted for under ASC 808, Collaborative Agreements, or ASC 808, are presented within “collaboration expense, net” in the consolidated statements of operations and comprehensive (loss) income. As a result, collaboration costs under the Vertex Agreements accounted for under ASC 808 for years ended December 31, 2021 and 2020 have been reclassified to conform to the current presentation. No subtotals in the prior period’s consolidated financial statements were impacted. Refer to Note 8 to these consolidated financial statements for further discussion on the Vertex Agreements.

The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the amounts reported in the financial statements and accompanying notes. On an ongoing basis, the Company’s management evaluates its estimates, which include, but are not limited to, revenue recognition, equity-based compensation expense and reported amounts of research and development expenses during the period. Significant estimates in these consolidated financial statements have been made in connection with revenue recognition and equity-based compensation expense. The Company bases its estimates on historical experience and other market-specific or other relevant assumptions that it believes to be reasonable under the circumstances. Actual results may differ from those estimates or assumptions.

Segment Information

The Company and the Company’s chief operating decision maker, namely, the chief executive officer, view the Company’s operations and manage its business as one operating segment, which is the business of discovering, developing and commercializing therapies derived from or incorporating genome-editing technology.

Foreign Currency Translation and Transactions

The majority of the Company’s operations occur in entities that have the U.S. dollar as their functional currency. Non-U.S. dollar denominated functional currency subsidiaries have assets and liabilities translated into U.S. dollars at rates of exchange in effect at the end of the year. Revenue and expense amounts are translated using the average exchange rates for the period. Net unrealized gains and losses resulting from foreign currency translation are included in “Accumulated other comprehensive (loss) income.” Net foreign currency exchange transaction gains or losses are included in “Other income, net” on the Company’s consolidated statement of operations, the impact of which is not significant.

Cash and Cash Equivalents

The Company considers all highly liquid investments with maturities of three months or less from the purchase date to be cash equivalents. As of December 31, 2022 and 2021, the Company had $211.9 million and $923.0 million in cash and cash equivalents, respectively.

Restricted Cash

As of December 31, 2022 and 2021, the Company had $12.2 million and $16.9 million, respectively, in restricted cash representing letters of credit securing the Company’s obligations under certain leased facilities, as well as certain credit card arrangements. The letters of credit are secured by cash held in a restricted depository account, with $0.5 million and $0.0 million, respectively, included in prepaid expenses and other current assets in the accompanying consolidated balance sheets as of December 31, 2022 and 2021, and $11.6 million and $16.9 million, respectively, included in restricted cash in the accompanying consolidated balance sheets as of December 31, 2022 and 2021.

Marketable Securities

As of December 31, 2022 and 2021, the Company had $1,656.6 million and $1,456.1 million, respectively in marketable securities. The Company’s investment strategy is focused on capital preservation. The Company invests in instruments that meet the credit quality standards outlined in the Company’s investment policy. The Company classifies marketable securities with a remaining maturity, when purchased, of greater than three months as available-for-sale. Marketable securities are classified as current assets on the consolidated balance sheets if the marketable securities are available to be converted into cash to fund current operations. Marketable securities in an unrealized loss position for greater than one year with a remaining maturity date greater than one year are classified as non-current assets.

Marketable securities classified as Level 2 within the valuation hierarchy generally consist of U.S. treasury securities and government agency securities, corporate bonds, and commercial paper. Debt securities are carried at fair value with the unrealized gains and losses included in other comprehensive (loss) income as a component of stockholders’ equity until realized. Any premium arising at purchase is amortized to interest expense over the period of the earliest call date, and any discount arising at purchase is accreted to interest income over the life of the instrument. Realized gains and losses on debt securities are determined using the specific identification method and are included in other income, net.

The Company assesses its available-for-sale debt securities under the available-for-sale debt security impairment model in ASU 2016-13, Financial Instruments – Credit Losses (Topic 326): Measurement of Credit Losses on Financial Statements, or ASC 326, as of each reporting date in order to determine if a portion of any decline in fair value below carrying value recognized on its available-for-sale debt securities is the result of a credit loss. The Company records credit losses in the consolidated statements of operations and comprehensive loss as credit loss expense within other expense, net, which is limited to the difference between the fair value and the amortized cost of the security. To date, the Company has not recorded any credit losses on its available-for-sale debt securities.

Other Receivables

Amounts due from collaboration partners where an arrangement is accounted for under ASC 808 are considered other receivables and are included within prepaid and other current assets in the consolidated balance sheets. Other receivables consisted of $11.2 million and $8.4 million as of December 31, 2022 and 2021, respectively and are due from Vertex. Other receivables are recorded at invoiced amounts due under the Vertex collaboration agreement, as described further in Note 8. Vertex is a creditworthy entity that maintains an ongoing relationship with the Company and as such, the Company does not have an allowance for estimated credit losses recorded related to these other receivables.

Concentrations of Credit Risk and Off-balance Sheet Risk

Financial instruments that potentially subject the Company to concentrations of credit risk are primarily cash, cash equivalents and marketable securities. The Company’s cash is held in accounts with financial institutions that management believes are creditworthy. The Company has not experienced any credit losses in such accounts and does not believe it is exposed to any significant credit risk on these funds. The Company has no financial instruments with off-balance sheet risk of loss.

Fair Value of Financial Instruments

The Company has certain financial assets and liabilities recorded at fair value which have been classified as Level 1, 2 or 3 within the fair value hierarchy as described in the accounting standards for fair value measurements:

Level 1 — Quoted prices in active markets that are accessible at the market date for identical unrestricted assets or liabilities.

Level 2 — Inputs other than Level 1 that are observable, either directly or indirectly, such as quoted prices for similar assets or liabilities; quoted prices in markets that are not active; or other inputs for which all significant inputs 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.

To the extent that valuation is based on models or inputs that are less observable or unobservable in the market, the determination of fair value requires more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is greatest for instruments categorized in Level 3. A financial instrument’s level within the fair value hierarchy is based on the lowest level of any input that is significant to the fair value measurement.

Items measured at fair value on a recurring basis include marketable securities (see Note 3, Marketable Securities, and Note 4, Fair Value Measurement). The carrying amount of accounts receivable, other receivables, accounts payable and accrued expenses as reported on the consolidated balance sheets as of December 31, 2022 and 2021, approximate fair value, due to the short-term duration of these instruments.

Property and Equipment

Property and equipment are recorded at cost, less accumulated depreciation. Maintenance and repairs that do not improve or extend the lives of the respective assets are expensed to operations as incurred. Upon disposal, the related cost and accumulated depreciation is removed from the accounts and any resulting gain or loss is included in the results of operations. Depreciation is recorded using the straight-line method over the estimated useful lives of the respective assets, which are as follows:


Asset		Estimated useful life
Computer equipment		3 years
Furniture, fixtures and other		5 years
Laboratory equipment		5 years
Leasehold improvements		Shorter of useful life or remaining lease term

Impairment of Long-lived Assets

The Company reviews long-lived assets when events or changes in circumstances indicate the carrying value of the assets may not be recoverable. Recoverability is measured by comparison of the book values of the assets to future net undiscounted cash flows that the assets are expected to generate. If such assets are considered to be impaired, the impairment to be recognized is measured by the amount by which the book value of the assets exceed their fair value, which is measured based on the projected discounted future net cash flows arising from the assets.

Revenue Recognition

The Company records revenue in accordance with ASC Topic 606, Revenue from Contracts with Customers, or ASC 606. ASC 606 applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases and collaboration arrangements. To determine revenue recognition for arrangements that an entity determines are within the scope of ASC 606, the entity performs the following five steps:

1) Identify the contract with the customer

A contract with a customer exists when (i) the Company enters into an enforceable contract with a customer that defines each party’s rights regarding the goods or services to be transferred and identifies the related payment terms, (ii) the contract has commercial substance and (iii) the Company determines that collection of substantially all consideration for goods and services that are transferred is probable based on the customer’s intent and ability to pay the promised consideration.

2) Identify the performance obligations in the contract

Performance obligations promised in a contract are identified based on the goods and services that will be transferred to the customer that are both capable of being distinct, whereby the customer can benefit from the good or service either on its own or together with other available resources, and are distinct in the context of the contract, whereby the transfer of the good or service is separately identifiable from other promises in the contract. To the extent a contract includes multiple promised goods and services, the Company must apply judgment to determine whether promised goods and services are capable of being distinct and distinct in the context of the contract. If these criteria are not met, the promised goods and services are accounted for as a combined performance obligation.

3) Determine the transaction price

The transaction price is determined based on the consideration to which the Company will be entitled in exchange for transferring goods and services to the customer. To the extent the transaction price includes variable consideration such as research, development, regulatory and commercial milestones, the Company determines if it is probable that it will receive such amounts and there is no risk of a significant revenue reversal. When the Company cannot conclude that receipt of such amounts is probable, the Company constrains the related variable consideration resulting in its exclusion from transaction consideration. In determining the portion of the transaction consideration to be constrained, the Company considers the probability and uncertainty that the related research, developmental, regulatory and commercial milestones will be achieved given the nature of research and clinical development and the stage of the underlying programs. This assessment is performed at each reporting period. In making this evaluation, the Company considers both internal and external information available, including information from industry publications and other relevant factors. Changes to the constraint of variable consideration can have a material effect on the amount of revenue recognized in the period.

4) Allocate the transaction consideration to performance obligations in the contract

If the contract contains a single performance obligation, the entire transaction consideration is allocated to the single performance obligation. Contracts that contain multiple performance obligations require an allocation of the transaction consideration to each performance obligation on a relative standalone selling price basis unless the transaction consideration is variable and meets the criteria to be allocated entirely to a performance obligation or to a distinct service that forms part of a single performance obligation. The consideration to be received is allocated among the separate performance obligations based on relative standalone selling prices. In determining these estimated standalone selling prices, the Company makes a number of significant judgements including, for licenses, management’s assumptions regarding probability weighted projected discounted cash flows for each of the collaboration development programs. The estimated standalone selling prices are sensitive to changes in assumptions, such as probabilities of scientific success, discount rate and certain assumptions that form the basis of forecasted cash flows. In developing these assumptions, management considers both internal and external information available, including information from other guideline companies within the same industry and other relevant factors. Changes to these assumptions can have a material effect on the allocation of the transaction consideration to performance obligations, as well as the amount and timing of revenue recognized.

5) Recognize revenue when or as the Company satisfies a performance obligation

The Company satisfies performance obligations over time or at a point in time, depending on the nature of the performance obligation. Revenue is recognized over time if the customer simultaneously receives and consumes the benefits provided by the entity’s performance, the entity’s performance creates or enhances an asset that the customer controls as the asset is created or enhanced, or the entity’s performance does not create an asset with an alternative use to the entity and the entity has an enforceable right to payment for performance completed to date. If the entity does not satisfy a performance obligation over time, the related performance obligation is satisfied at a point in time by transferring the control of a promised good or service to a customer.

Contract Balances

The Company recognizes a contract asset when the Company transfers goods or services to a customer before the customer pays consideration or before payment is due, excluding any amounts presented as an account or other receivable. A contract asset is an entity’s right to consideration in exchange for goods or services that the entity has transferred to a customer. The contract liabilities, or deferred revenue, primarily relate to contracts where we have received payment, but we have not yet satisfied the related performance obligations. Contract assets are not significant as of December 31, 2022 and 2021. Contract liabilities recorded as deferred revenue as of December 31, 2022 are $12.3 million, which was unchanged from December 31, 2021. The contract liability recorded as deferred revenue is related to the collaboration agreement with Vertex described in Note 8.

Collaboration Arrangements

The Company records the elements of its collaboration agreements that represent joint operating activities in accordance with ASC 808. Accordingly, the elements of the collaboration agreements that represent activities in which both parties are active participants and to which both parties are exposed to the significant risks and rewards that are dependent on the commercial success of the activities, are recorded as collaborative arrangements.

The Company evaluates the proper presentation of the commercial activities and the proﬁt and loss sharing associated with the collaboration agreements. ASC 808 states that when payments between parties in a collaborative arrangement are not within the scope of other authoritative accounting literature, the income statement classification should be based on the nature of the arrangement, the nature of its business operations and the contractual terms of the arrangement. To the extent that these payments are not within the scope of other authoritative accounting literature, the income statement classification for the payments shall be based on an analogy to authoritative accounting literature or if there is no appropriate analogy, a reasonable, rational and consistently applied accounting policy election.

Collaboration costs under the Vertex Agreements accounted for under ASC 808 are presented within “collaboration expense, net” in the consolidated statements of operations and comprehensive (loss) income. Refer to Note 8 to these consolidated financial statements for further discussion on the Vertex Agreements.

Research and Development Expenses

Research and development costs are charged to expense as costs are incurred in performing research and development activities, including salaries and benefits, facilities costs, overhead costs, clinical study and related clinical manufacturing costs, license and milestone fees, contract services and other related costs. Research and development costs, including up-front fees and milestones paid to collaborators, are also expensed as incurred. In circumstances where amounts have been paid in excess of costs incurred, the Company records a prepaid expense. The Company accrues costs for clinical trial activities based upon estimates of the services received and related expenses incurred that have yet to be invoiced by the contract research organizations, clinical study sites, laboratories, consultants or other clinical trial vendors that perform the activities. The Company recognizes the reimbursement associated with collaborative activities to its collaborative partners, excluding collaboration costs under the Vertex Agreements accounted for under ASC 808, as a reduction to research and development expense in the period the services are provided. Costs associated with collaborative activities to collaborative partners accounted for under ASC 808 and included in research and development expense was not significant for the years ended December 31, 2022, 2021 and 2020

Leases

The Company accounts for its leases in accordance with ASC 842, Leases, or ASC 842. At the inception of an arrangement, the Company determines whether the arrangement is or contains a lease based on the unique facts and circumstances present in the arrangement. Leases with a term greater than one year are recognized on the balance sheet as right-of-use assets and short-term and long-term lease liabilities, as applicable. The Company does not have financing leases.

Operating lease liabilities and their corresponding right-of-use assets are initially recorded based on the present value of lease payments over the expected remaining lease term. Certain adjustments to the right-of-use asset may be required for items such as incentives received. The interest rate implicit in lease contracts is typically not readily determinable. As a result, the Company utilizes its incremental borrowing rate to discount lease payments, which reflects the fixed rate at which the Company could borrow on a collateralized basis the amount of the lease payments in the same currency, for a similar term, in a similar economic environment. Prospectively, the Company will adjust the right-of-use assets for straight-line rent expense or any incentives received and remeasure the lease liability at the net present value using the same incremental borrowing rate that was in effect as of the lease commencement or transition date.

The Company has elected not to recognize leases with an original term of one year or less on the balance sheet. The Company typically only includes an initial lease term in its assessment of a lease arrangement. Options to renew a lease are not included in the Company’s assessment unless there is reasonable certainty of renewal.

Assumptions made by the Company at the commencement date are re-evaluated upon occurrence of certain events, including a lease modification. A lease modification results in a separate contract when the modification grants the lessee an additional right of use not included in the original lease and when lease payments increase commensurate with the standalone price for the additional right of use. When a lease modification results in a separate contract, it is accounted for in the same manner as a new lease.

Equity Based Compensation Expense

The Company’s share-based compensation programs grant awards that have included stock options, restricted stock units and restricted stock awards. Grants are awarded to employees and non-employees, including directors.

The Company accounts for its stock-based compensation awards in accordance with ASC Topic 718, Compensation—Stock Compensation, or ASC 718. ASC 718 requires all stock-based payments to employees and non-employee directors, including grants of employee stock options and restricted stock units and modifications to existing stock options, to be recognized in the consolidated statements of operations and comprehensive (loss) income based on their fair values. The Company uses the Black-Scholes option pricing model to determine the fair value of options granted.

The Company accounts for forfeitures as they occur instead of estimating forfeitures at the time of grant and revising those estimates in subsequent periods if actual forfeitures differ from its estimates. Stock-based compensation expense recognized in the financial statements is based on awards for which performance or service conditions are expected to be satisfied.

The Company’s stock-based awards are subject to service or performance-based vesting conditions. Compensation expense related to awards to employees, directors and non-employees with service-based vesting conditions is recognized on a straight-line basis based on the grant date fair value over the associated service period of the award, which is generally the vesting term. Compensation expense related to awards to employees with performance-based vesting conditions is recognized based on the grant date fair value over the requisite service period using the accelerated attribution method to the extent achievement of the performance condition is probable.

The Company expenses restricted stock unit awards to employees based on the fair value of the award on a straight-line basis over the associated service period of the award.

The Company estimates the fair value of its option awards to employees, directors and non-employees using the Black-Scholes option pricing model, which requires the input of subjective assumptions, including (i) the expected stock price volatility, (ii) the calculation of expected term of the award, (iii) the risk-free interest rate and (iv) expected dividends. Due to the lack of complete company-specific historical and implied volatility data for the full expected term of the stock-based awards, the Company bases its estimate of expected volatility on a representative group of publicly traded companies in addition to its own volatility data. For these analyses, the Company selected companies with comparable characteristics to its own, including enterprise value, risk profiles, position within the industry, and with historical share price information sufficient to meet the expected life of the stock-based awards. The Company computes historical volatility data using the daily closing prices for the selected companies’ shares during the equivalent period of the calculated expected term of the stock-based awards. The Company will continue to apply this process until a sufficient amount of historical information regarding the volatility of its own stock price becomes available. The Company has estimated the expected term of its employee stock options using the “simplified” method, whereby the expected term equals the arithmetic average of the vesting term and the original contractual term of the option, due to its lack of sufficient historical data. The risk-free interest rates for periods within the expected term of the option are based on the U.S. Treasury securities with a maturity date commensurate with the expected term of the associated award. The Company has never paid, and does not expect to pay, dividends in the foreseeable future.

Patent Costs

Costs to secure and prosecute patent applications and other legal costs related to the protection of the Company’s intellectual property are expensed as incurred and are classified as general and administrative expenses in the Company’s consolidated statements of operations.

Income Taxes

Income taxes are recorded in accordance with ASC Topic 740, Income Taxes, or ASC 740, which provides for deferred taxes using an asset and liability approach. Under this method, deferred tax assets and liabilities are determined based on the difference between the financial reporting and tax reporting basis of assets and liabilities and are measured using enacted tax rates and laws that are expected to be in effect when the differences are expected to reverse. Valuation allowances are provided if, based upon the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized. The Company has evaluated available evidence and concluded that the Company may not realize all the benefit of its deferred tax assets; therefore, a valuation allowance has been established for the amount of the deferred tax assets that the Company does not believe is more likely than not to be realized.

The Company accounts for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, the Company recognizes the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances. As of December 31, 2022 and 2021, the Company does not have any significant uncertain tax positions. The Company’s practice is to recognize interest and/or penalties related to income tax matters in income tax expense. See Note 14 for further details.

Comprehensive (Loss) Income

Comprehensive (loss) income consists of net income or loss and other comprehensive (loss) income. Other comprehensive (loss) income consists of foreign currency translation adjustments and unrealized losses on marketable securities.

Net (Loss) Income Per Share Attributable to Common Shareholders

Basic net (loss) income per share is calculated by dividing net (loss) income attributable to common shareholders by the weighted-average number of common shares outstanding during the period. Diluted net (loss) income per share is calculated by dividing the net (loss) income attributable to common shareholders by the weighted-average number of common equivalent shares outstanding for the period, including any dilutive effect from outstanding stock options and restricted stock units using the treasury stock method. See Note 12 for further details.

New Accounting Pronouncements

From time to time, new accounting pronouncements are issued by the FASB or other standard setting bodies that the Company adopts as of the specified effective date. The Company does not believe that the adoption of recently issued standards have or may have a material impact on its consolidated financial statements and disclosures.

Marketable Securities

12 Months Ended

Dec. 31, 2022

Investments, Debt and Equity Securities [Abstract]

Marketable Securities

3. Marketable Securities

A summary of the Company’s cash equivalents and marketable securities as of December 31, 2022 and 2021, which are recorded at fair value (and excludes $159.3 million and $405.6 million of cash at December 31, 2022 and 2021, respectively) is shown below (in thousands):


December 31, 2022	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Fair Value
Cash equivalents:
Money market funds	$	17,766	$	—	$	—		$	17,766
Corporate debt securities		2,151		—		(2	)		2,149
Certificates of deposit		—		—		—			—
Commercial paper		32,675		—		—			32,675
Total cash equivalents		52,592		—		(2	)		52,590
Marketable securities:
U.S. Treasury securities		—		—		—			—
Corporate debt securities		1,236,770		615		(15,006	)		1,222,379
Certificates of deposit		92,417		—		—			92,417
Government-sponsored enterprise securities		79,746		11		(712	)		79,045
Commercial paper		263,231		—		(509	)		262,722
Total marketable securities		1,672,164		626		(16,227	)		1,656,563
Total cash equivalents and marketable securities	$	1,724,756	$	626	$	(16,229	)	$	1,709,153


December 31, 2021	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Fair Value

Cash equivalents:
Money market funds	$	507,386	$	—	$	—		$	507,386
Corporate debt securities		—							—
Certificates of deposit		—		—		—			—
Commercial paper		9,997		—		(1	)		9,996
Total cash equivalents		517,383		—		(1	)		517,382
Marketable securities:
U.S. Treasury securities		16,238		6		(52	)		16,192
Corporate debt securities		1,173,659		10		(4,903	)		1,168,766
Certificates of deposit		45,164		—		—			45,164
Government-sponsored enterprise securities		13,334		—		(77	)		13,257
Commercial paper		212,805		—		(86	)		212,719
Total marketable securities		1,461,200		16		(5,118	)		1,456,098
Total cash equivalents and marketable securities	$	1,978,583	$	16	$	(5,119	)	$	1,973,480

As of December 31, 2022 and 2021, the aggregate fair value of marketable securities that were in an unrealized loss position for less than twelve months was $628.4 million and $1,311.6 million, respectively. As of December 31, 2022 and 2021, the aggregate fair value of marketable securities that were in an unrealized loss position for more than twelve months was $619.2 million and $4.6 million, respectively. Of this amount, securities totaling $53.1 million as of December 31, 2022 will mature beyond one year. No securities in an unrealized loss position for more than twelve months as of December 31, 2021 will mature beyond one year. The Company has recorded a net unrealized loss of $10.5 million and $5.0 million, respectively, during the years ended December 31, 2022 and 2021 related to its marketable securities, which is included in comprehensive (loss) income on the consolidated statements of operations and comprehensive (loss) income.

The Company determined that there was no material credit risk of the above investments as of December 31, 2022 and 2021. The Company has the intent and ability to hold such securities until recovery. As a result, the Company did not record any charges for credit-related impairments for its marketable securities for the years ended December 31, 2022 and 2021. No available-for-sale debt securities held as of December 31, 2022 had remaining maturities greater than thirty months.

Fair Value Measurement

12 Months Ended

Dec. 31, 2022

Fair Value Disclosures [Abstract]

Fair Value Measurement

4. Fair Value Measurement

The following tables present information about the Company’s financial assets measured at fair value on a recurring basis and indicate the fair value hierarchy classification of such fair values as of December 31, 2022 and 2021 (in thousands):


	Fair Value Measurements at
	December 31, 2022
	Total		Level 1		Level 2		Level 3
Cash and cash equivalents:
Cash	$	159,295	$	159,295	$	—	$	—
Money market funds		17,766		17,766		—		—
Corporate debt securities		2,149		—		2,149		—
Certificates of deposit		—		—		—		—
Commercial paper		32,675		—		32,675		—
Marketable securities:
U.S. Treasury securities		—		—		—		—
Corporate debt securities		1,222,379		—		1,222,379		—
Certificates of deposit		92,417		—		92,417		—
Government-sponsored enterprise securities		79,045		—		79,045		—
Commercial paper		262,722		—		262,722		—
Other non-current assets		2,212		—		—		2,212
Total	$	1,870,660	$	177,061	$	1,691,387	$	2,212


	Fair Value Measurements at
	December 31, 2021
	Total		Level 1		Level 2		Level 3
Cash and cash equivalents:
Cash	$	405,648	$	405,648	$	—	$	—
Money market funds		507,386		507,386		—		—
Corporate debt securities		—		—		—		—
Certificates of deposit		—		—		—		—
Commercial paper		9,997		—		9,997		—
Marketable securities:
U.S. Treasury securities		16,192		—		16,192		—
Corporate debt securities		1,168,766		—		1,168,766		—
Certificates of deposit		45,164		—		45,164		—
Government-sponsored enterprise securities		13,257		—		13,257		—
Commercial paper		212,719		—		212,719		—
Other non-current assets		2,212		—		—		2,212
Total	$	2,381,341	$	913,034	$	1,466,095	$	2,212

Marketable securities classified as Level 2 within the valuation hierarchy generally consist of U.S. treasury securities and government agency securities, corporate bonds, and commercial paper. The Company estimates the fair values of these marketable securities by taking into consideration valuations obtained from third-party pricing sources.

The Company holds equity securities classified as Level 3 which are not material to the Company’s financial position.

- Definition

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

+ References + Details

Property and Equipment, net

12 Months Ended

Dec. 31, 2022

Property, Plant and Equipment [Abstract]

Property and Equipment, net

5. Property and Equipment, net

Property and equipment, net, consists of the following (in thousands):


	As of December 31,
	2022			2021
Computer equipment	$	3,618		$	1,757
Furniture, fixtures, and other		8,109			4,371
Laboratory equipment		37,897			30,123
Leasehold improvements		141,680			86,735
Construction work in process		6,162			52,396
Total property and equipment, gross		197,466			175,382
Accumulated Depreciation		(33,832	)		(37,807	)
Total property and equipment, net	$	163,634		$	137,575

Depreciation expense for the year ended December 31, 2022, 2021 and 2020 was $24.1 million, $17.9 million, and $9.1 million, respectively.

Accrued Expenses

12 Months Ended

Dec. 31, 2022

Payables and Accruals [Abstract]

Accrued Expenses

6. Accrued Expenses

Accrued expenses consist of the following (in thousands):


	As of December 31,
	2022		2021
Payroll and employee-related costs	$	19,241	$	23,661
Research costs		46,187		47,986
Licensing fees		983		138
Professional fees		4,927		4,720
Intellectual property costs		3,936		6,120
Accrued property and equipment		1,244		7,113
Other		1,164		1,265
Total	$	77,682	$	91,003

Leases

12 Months Ended

Dec. 31, 2022

Leases [Abstract]

Leases

7. Leases

In June 2015, the Company entered into a lease agreement for the lease of research facility space in Cambridge, Massachusetts, with a commencement date of November 15, 2015. The lease was subsequently amended in both 2017 and 2020 and expired in 2022.

In May 2016, the Company entered into a sublease agreement for its primary office and research facility in Cambridge, Massachusetts, with a commencement date of December 23, 2016. The sublease was subsequently amended in 2021 and expired in 2022.

In May 2019, the Company entered into a lease agreement for office facility space in Cambridge, Massachusetts, with a commencement date of June 1, 2019, or the 2019 Lease. The lease expires in November 2026, and the Company has an option to extend the term of the lease for an additional five-year period based on certain conditions within the Company’s control. The 2019 Lease contains escalating rent clauses which require higher rent payments in future years. The right-of-use asset and corresponding lease liability does not include the additional five-year period under the renewal option as the Company is not reasonably certain to exercise that option.

In December 2019, Casebia Therapeutics, Limited Liability Partnership, or Casebia, became a wholly-owned subsidiary of the Company. In connection therewith, Casebia assigned its sublease for an office and research facility in Cambridge, Massachusetts to the Company. The sublease was subsequently amended in 2021 and expired in 2022.

In May 2020, the Company entered into a lease agreement for a cell therapy manufacturing facility in Framingham, Massachusetts, or the Framingham Lease, for clinical and commercial production of the Company’s investigational cell therapy product candidates. The Framingham Lease expires in March 2036 and the Company has an option to extend the term of the lease for two additional seven-year periods. The right-of-use asset and corresponding lease liability does not include the additional seven-year periods under the renewal option as the Company is not reasonably certain to exercise that option.

In July 2020, the Company entered into a lease agreement for an office and laboratory facility in Boston, Massachusetts, with a commencement date of June 1, 2021, or the 2020 Lease. At lease commencement, the Company recorded a right-of-use asset of $149.8 million and a corresponding operating lease liability of $147.9 million. Tenant incentives of $49.2 million were recorded as a reduction to the operating lease asset and liability at lease commencement. The lease expires in March 2034 and the Company has an option to extend the term of the lease for two additional five-year periods. The right-of-use asset and corresponding lease liability does not include the additional five-year periods under the renewal option as the Company is not reasonably certain to exercise that option.

The Company also rents certain office space in Zug, Switzerland, on a short-term basis for which a right-of-use asset and liability are not recorded, in accordance with the practical expedient elected.

The Company has embedded leases in certain research and license agreements for which the Company has recorded a right of use asset and liability. These arrangements are not significant in comparison to the Company’s total operating lease assets and liabilities. In addition, the Company has identified certain short-term leases embedded within its manufacturing contracts which are not recorded on the Company’s balance sheet in accordance with the practical expedient elected.

The Company identified and assessed the following estimates in recognizing the right-of-use asset and corresponding liability:

•

Expected lease term: The expected lease term includes noncancelable lease periods and, when applicable, periods covered by an option to extend the lease if the Company is reasonably certain to exercise that option, as well as periods covered by an option to terminate the lease if the Company is reasonably certain not to exercise that option.

•

Incremental borrowing rate: As the discount rates in the Company’s leases are not implicit, the Company estimated the incremental borrowing rate based on the rate of interest the Company would have to pay to borrow a similar amount on a collateralized basis over a similar term.

The following table summarizes the lease assets and liabilities as of December 31, 2022 and 2021 (in thousands):


	As of December 31,
	2022		2021
Assets
Operating lease assets	$	156,921	$	174,460
Total lease assets		156,921		174,460
Liabilities
Current
Operating lease liabilities		15,842		12,158
Non-current
Operating lease liabilities, net of current portion		228,179		212,872
Total lease liabilities	$	244,021	$	225,030

The following table summarizes operating lease costs included in research and development and general and administrative expense, as well as sublease income for the twelve months ended December 31, 2022, 2021 and 2020 (in thousands):


	Years Ended December 31,
	2022		2021			2020
Operating lease costs	$	34,896	$	22,520		$	14,342
Short-term lease costs		824		11,087			7,339
Variable lease costs		11,882		8,402			6,368
Sublease income		—		(5,253	)		(587	)
Net lease cost	$	47,602	$	36,756		$	27,462

The following table summarizes the maturity of undiscounted payments due under lease liabilities and the present value of those liabilities as of December 31, 2022 (in thousands):


	Total
2023		29,270
2024		26,526
2025		26,251
2026		26,745
2027		25,927
Thereafter		205,495
Total	$	340,214
Present value adjustment		(96,193	)
Present value of lease liabilities	$	244,021

The following table summarizes the lease term (in years) and discount rate for operating leases as of December 31, 2022 and 2021:


	As of December 31,
	2022			2021
Weighted-average remaining lease term		11.8			12.4
Weighted-average discount rate		5.9	%		5.9	%

The following table summarizes the cash paid for amounts included in the measurement of lease liabilities for the years ended December 31, 2022, 2021 and 2020 (in thousands):


	Years Ended December 31,
	2022			2021			2020
Cash paid for amounts included in measurement of lease liabilities:
Operating cash flows used in operating leases	$	(17,004	)	$	(19,753	)	$	(13,161	)
Operating lease non-cash items:
Right-of-use assets (decreased) increased through lease modifications and reassessments		1,208			(14,230	)		3,169
Right-of-use assets obtained in exchange for operating lease liabilities		—			152,486			13,956
Leasehold improvements paid directly by landlord		19,252			30,500			—

Commitments and Contingencies

12 Months Ended

Dec. 31, 2022

Commitments and Contingencies Disclosure [Abstract]

Commitments and Contingencies

9. Commitments and Contingencies

Intellectual Property Agreements

Charpentier License Agreements

In April 2014, the Company entered into certain technology license agreements with Dr. Emmanuelle Charpentier pursuant to which the Company licensed certain intellectual property rights under joint ownership from Dr. Charpentier to develop and commercialize products for the treatment or prevention of human diseases. In connection therewith, Dr. Charpentier is entitled to receive nominal clinical milestone payments, low single digit percentage of sublicensing payments received under any sublicense agreement with a third party, and low single-digit percentage royalties based on annual net sales of licensed products and services by the Company and its affiliates and sublicensees.

Patent Assignment Agreement

In November 2014, the Company entered into a patent assignment agreement with Dr. Charpentier, Dr. Ines Fonfara, and Vienna (collectively, the “Assignors”), pursuant to which the Company was assigned all rights, title and interest in and to certain patent rights claimed in the U.S. Patent Application No.61/905,835. As a result, the Assignors are entitled to receive certain low single digit clinical milestone payments and low single digit royalties based on annual net sales of licensed products and licensed services by the Company, its affiliates and sublicensees.

During the years ended December 31, 2022, 2021 and 2020, the Company paid an immaterial amount of fees to Dr. Charpentier under the Charpentier License Agreements and the Assignors under the Patent Assignment Agreement, which were recorded as research and development expense.

Research, Manufacturing and License Agreements

The Company has engaged several research institutions and companies to identify new delivery strategies and applications of the Company’s gene editing technology. The Company is also a party to a number of license agreements which require significant upfront payments and may be required to make future royalty payments and potential milestone payments from time to time. In addition, the Company is also a party to intellectual property agreements, which require maintenance and milestone payments from time to time. Further, the Company is a party to a number of manufacturing agreements that require upfront payments for the future performance of services.

In association with these agreements, on a product-by-product basis, the counterparties are eligible to receive up to low eight-digit potential payments upon specified research, development and regulatory milestones. In addition, on a product-by-product basis, the counterparties are eligible to receive potential commercial milestone payments based on specified annual sales thresholds. The potential payments are low-single digit percentages of the specified annual sales thresholds. The counterparties are also eligible to receive low single-digit royalties on future net sales.

Under certain circumstances and if certain contingent future events occur, Vertex is eligible to receive up to $395.0 million in potential specified research, development, regulatory and commercial milestones and tiered single-digit percentage royalties on future net sales related to a specified target under an amendment to the 2015 Collaboration Agreement. Vertex also has the option to conduct research at their own cost in certain defined areas that, if beneficial to the exa-cel program and ultimately achieves regulatory approval, then the Company could owe Vertex certain milestone payments aggregating to high eight digits, subject to certain limitations on the profitability of the exa-cel program.

Under the A&R Vertex JDCA, the Company deferred $36.1 million of its share of costs incurred under the arrangement for the year ended December 31, 2022, as spending on the exa-cel program exceeded a specified amount. Any deferred amounts are only payable to Vertex as an offset against future profitability of the exa-cel program and the amounts payable are capped at a specified maximum amount per year. These deferred costs on the exa-cel program will be accrued for when it is probable that a liability has been incurred and the amount can be reasonably estimated. As of December 31, 2022, no contingent payments have been accrued. Refer to Note 8 for further discussion on the Company’s arrangements with Vertex.

Other Matters

On December 15, 2016, the Company entered into a Consent to Assignments, Licensing and Common Ownership and Invention Management Agreement (the “Invention Management Agreement”) with UC, Vienna, Dr. Charpentier, Intellia Therapeutics, Inc., Caribou Biosciences, Inc., ERS Genomics Ltd. and one of the Company’s subsidiaries. Under the Invention Management Agreement, the Company is obligated to share costs related to patent maintenance, defense and prosecution. For the years ended December 31, 2022, 2021 and 2020, the Company incurred $2.2 million, $5.8 million, and $4.5 million, respectively, in shared costs. The Company recorded accrued legal costs from the cost sharing of $1.4 million and 4.0 million as of December 31, 2022 and 2021, respectively. The Company is unable to predict the outcome of these matters and is unable to make a meaningful estimate of the amount or range of loss, if any, that could result from an unfavorable outcome.

Litigation

In the ordinary course of business, the Company is from time to time involved in lawsuits, investigations, proceedings and threats of litigation related to, among other things, the Company’s intellectual property estate (including certain in-licensed intellectual property), commercial arrangements and other matters. Such proceedings may include quasi-litigation, inter partes administrative proceedings in the U.S. Patent and Trademark Office and the European Patent Office involving the Company’s intellectual property estate including certain in-licensed intellectual property. The outcome of any of the foregoing, regardless of the merits, is inherently uncertain. In addition, litigation and related matters are costly and may divert the attention of Company’s management and other resources that would otherwise be engaged in other activities. If the Company is unable to prevail in any such proceedings, the Company’s business, results of operations, liquidity and financial condition could be adversely affected.

Significant Contracts

12 Months Ended

Dec. 31, 2022

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Significant Contracts

8. Significant Contracts

Agreements with Vertex Pharmaceuticals Incorporated and certain of its subsidiaries

Summary

On October 26, 2015, the Company entered into a strategic collaboration, option and license agreement, or the 2015 Collaboration Agreement, with Vertex. The 2015 Collaboration Agreement is focused on the use of the Company’s CRISPR/Cas9 gene editing technology to discover and develop potential new treatments aimed at the underlying genetic causes of human disease.

On December 12, 2017, the Company and Vertex entered into Amendment No. 1 to the 2015 Collaboration Agreement, or Amendment No. 1, and the Joint Development Agreement, or the JDA. Amendment No. 1, among other things, modified certain definitions and provisions of the 2015 Collaboration Agreement to make them consistent with the JDA and clarified how many options are exercised (or deemed exercised) in connection with certain targets specified under the 2015 Collaboration Agreement. Amendment No. 1 also amended other provisions of the 2015 Collaboration Agreement, including the expiration terms.

In connection with the 2015 Collaboration Agreement, Vertex made a nonrefundable upfront payment of $75.0 million. Under the 2015 Collaboration Agreement, Vertex agreed to fund the discovery activities conducted pursuant to the agreement while retaining options to co-exclusive and exclusive licenses. In December 2017, upon execution of the JDA and Amendment No. 1, Vertex exercised its option to obtain a co-exclusive license to develop and commercialize hemoglobinopathy and beta-globin targets. As such, for potential hemoglobinopathy treatments, including treatments for sickle cell disease, the Company and Vertex agreed to share equally all research and development costs and worldwide revenues. In connection with the JDA, the Company received a $7.0 million up-front payment from Vertex and subsequently received a one-time low seven-digit milestone payment upon the dosing of the second patient in a clinical trial with the initial product candidate. In addition, upon execution of the JDA and Amendment No. 1, it was clarified that Vertex may elect to license up to four remaining targets, for which it will lead global development and commercialization activities, and the Company received the right to receive up to $420.0 million in development, regulatory and commercial milestones and royalties on net product sales for each of the targets (inclusive of $10 million due upon exercise of each exclusive option).

In June 2019, the Company and Vertex entered into a series of agreements, which closed in the second quarter of 2019, including a strategic collaboration and license agreement, or the 2019 Collaboration Agreement, for the development and commercialization of products for the treatment of Duchenne muscular dystrophy, or DMD, and Myotonic Dystrophy Type 1, or DM1. Under the terms of the 2019 Collaboration Agreement, the Company received an upfront, nonrefundable payment of $175.0 million. In addition, the Company was initially eligible to receive potential aggregate payments of up to $825.0 million based upon the successful achievement of specified research, development, regulatory and commercial milestones for the DMD and DM1 programs.

The Company is also eligible to receive tiered royalties on future net sales on any products that may result from the 2019 Collaboration Agreement. For the DMD program, Vertex is responsible for all research, development, manufacturing and commercialization activities and all related costs. For the DM1 program, the Company performed specified guide RNA research and Vertex is responsible for all other research, development, manufacturing and commercialization costs. Upon Investigational New Drug, or IND, application filing, the Company has the option to forego the DM1 milestones and royalties, and instead, co-develop and

co-commercialize all DM1 products globally in exchange for payment of 50% of research and development costs incurred by Vertex from the effective date of the agreement through IND filing.

In connection with the execution of the 2019 Collaboration Agreement, the Company and Vertex entered into a second amendment to the 2015 Collaboration Agreement, or Amendment No. 2. Among other things, Amendment No. 2 modified certain definitions and provisions of the 2015 Collaboration Agreement to make them consistent with the 2019 Collaboration Agreement and set forth the number and identity of the collaboration targets under the 2015 Collaboration Agreement. The Company and Vertex agreed that one of the four remaining options under the 2015 Collaboration Agreement, as amended, would not be exercised; instead, the Company reacquired the exclusive rights and agreed to conduct research and development activities for the specified target. Vertex will have the option to co-develop and co-commercialize the specified target upon IND filing in exchange for payment of 50% of research and development costs incurred by the Company from the effective date of the agreement through IND filing. If Vertex does not exercise its option to co-develop and co-commercialize the specified target, Vertex is eligible to receive up to $395.0 million in potential specified research, development, regulatory and commercial milestones and tiered single-digit royalties on future net sales.

In October 2019, Vertex exercised the remaining three options granted to it under the 2015 Collaboration Agreement to exclusively license the collaboration targets developed under the 2015 Collaboration Agreement, resulting in a payment of $30.0 million to the Company in the fourth quarter of 2019. In addition, the Company achieved the first milestone under the 2019 Collaboration Agreement in the first quarter of 2020 and, in connection therewith, received a payment of $25.0 million in April 2020. The Company achieved the second milestone under the 2019 Collaboration Agreement in the fourth quarter of 2021 and, in connection therewith, received a payment of $12.5 million in December 2021. As of December 31, 2022, the Company is eligible to receive remaining potential future milestones of $775.0 million under the 2019 Collaboration Agreement.

In April 2021, the Company and Vertex agreed to amend and restate the JDA and entered into an Amended and Restated Joint Development and Commercialization Agreement, or the “A&R Vertex JDCA,” pursuant to which the parties agreed to, among other things, (a) adjust the governance structure for the collaboration and adjust the responsibilities of each party thereunder, whereby Vertex shall lead and have all decision making (i.e., control) in relation to the exa-cel program prospectively; (b) adjust the allocation of net profits and net losses between the parties with respect to exa-cel (formerly known as CTX001) only, which will be allocated 40% to the Company and 60% to Vertex, prospectively; and (c) exclusively license (subject to the Company’s reserved rights to conduct certain activities) certain intellectual property rights to Vertex relating to the specified product candidates and products (including exa-cel) that may be researched, developed, manufactured and commercialized on a worldwide basis under such agreement. The transaction contemplated by the A&R Vertex JDCA closed in the second quarter of 2021. The Company is providing certain specified transition services to Vertex in connection with the agreement.

In connection with the closing of the transaction contemplated by the A&R Vertex JDCA, the Company received a $900.0 million up-front payment from Vertex. Additionally, the Company is eligible to receive a one-time $200.0 million milestone payment upon receipt by Vertex of the first marketing approval of the initial product candidate from the U.S. Food and Drug Administration or the European Commission. With respect to exa-cel only, the net profits and net losses, as applicable, incurred under the A&R Vertex JDCA through July 1, 2021 in connection with the initial shared product (i.e., exa-cel) were shared equally between the Company and Vertex, and beginning July 1, 2021, the net profits and net losses, as applicable, incurred under the A&R Vertex JDCA are allocated 40% to the Company and 60% to Vertex. Additionally, the A&R Vertex JDCA allows the Company to defer a portion of its share of costs under the arrangement if spending on the exa-cel program exceeds specified amounts. Any deferred amounts are only payable to Vertex as an offset against future profitability of the exa-cel program and the amounts payable are capped at a specified maximum amount per year.

Accounting for the Vertex Agreements

The 2015 Collaboration Agreement, Amendment No. 1, and JDA are collectively the “2015 Agreements” and the 2019 Collaboration Agreement and Amendment No. 2. are collectively the “2019 Agreements.” The 2015 Collaboration Agreement, Amendment No. 1, Amendment No. 2, JDA, A&R Vertex JDCA and 2019 Collaboration Agreement are collectively the “Vertex Agreements.”

The Vertex Agreements include components of a customer-vendor relationship as defined under ASC 606, collaborative arrangements as defined under ASC 808 and research and development costs as defined under ASC 730, Research and Development, or ASC 730.

Accounting Analysis Under ASC 606

Accounting for the A&R Vertex JDCA

Identification of the Contract

The A&R Vertex JDCA represented a contractual modification to the JDA. For accounting purposes, the A&R Vertex JDCA was treated as a separate contract.

Identification of Performance Obligations

The Company concluded the A&R Vertex JDCA contained a single material promise, an exclusive worldwide license granting Vertex an additional 10% economic interest in the exa-cel program and the right to control development and commercialization of exa-cel, or the “Exa-cel Exclusive License.” The Company concluded the Exa-cel Exclusive License was both capable of being distinct and distinct within the context of the A&R Vertex JDCA, and the Exa-cel Exclusive License was sold at its estimated standalone selling price, or “ESSP.” As such, the Exa-cel Exclusive License represented a separate performance obligation.

Determination of Transaction Price

The transaction price was comprised of the upfront payment of $900.0 million. The Company determined that all other possible variable consideration resulting from milestones and royalties discussed above was fully constrained at the time of the transaction. The Company will reevaluate the transaction price in each reporting period.

Allocation of Transaction Price to Performance Obligations

The selling price of the performance obligation was determined based on the Company’s ESSP. The Company developed the ESSP for the Exa-cel Exclusive License 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 ESSP for the Exa-cel Exclusive License was determined to be approximately $900.0 million. The ESSP was determined based on 10% of the probability and present value adjusted cash flows from projected worldwide net profit for exa-cel based on probability assessments, projections based on internal forecasts, industry data, and information from other guideline companies within the same industry and other relevant factors. As the Company determined the Exa-cel Exclusive License was the only performance obligation, the entire transaction price was allocated to the Exa-cel Exclusive License. The aforementioned ESSP reflects the level of risk and expected probability of success inherent in the nature of the associated research area.

Recognition of Revenue

The Company determined that the Exa-cel Exclusive License represented functional intellectual property, as the intellectual property provides Vertex with the ability to perform a function or task in the form of research and development, manufacturing and commercialization. As such, the revenue related to the Exa-cel Exclusive License was recognized at the point in time, which was upon transfer in the second quarter of 2021.

Accounting for the 2019 Agreements

The 2019 Agreements represented a contract modification to the 2015 Agreements. As a result, the 2019 Agreements and the 2015 Agreements are combined for accounting purposes and treated as a single arrangement. Transactions under the 2019 Agreements were not material for the twelve months ended December 31, 2022 and 2020. For the twelve months ended December 31, 2021, the Company recognized $12.0 million in revenue related to a milestone under the 2019 Agreements.

The Company determined that all other possible variable consideration remaining under the 2019 Agreements resulting from milestones and royalties discussed above was fully constrained as of December 31, 2022. The Company will re-evaluate the transaction price in each reporting period.

Revenue recognized in connection with the Vertex Agreements

Revenue recognized under the Vertex Agreements for the year ended December 31, 2022 was not material. Revenue recognized under the Vertex Agreements for the year ended December 31, 2021 was $913.1 million and was comprised of (i) revenue related to the exclusive worldwide license for exa-cel of $900.0 million, (ii) revenue related to the second DM1 milestone under the 2019 Agreements of $12.0 million, and (iii) revenue recognized in connection with research and development services. Revenue recognized under the Vertex Agreements for the year ended December 31, 2020 was not material.

As of December 31, 2022 and 2021 there was no current deferred revenue related to the collaboration with Vertex, respectively. As of December 31, 2022 and 2021, there was $12.3 million of non-current deferred revenue, respectively, related to the collaboration with Vertex. The transaction price allocated to the remaining performance obligations was $12.3 million.

Future Milestones under the Vertex Agreements

The Company has evaluated the milestones that may be received in connection with the Vertex Agreements. As discussed above, the Company is eligible to receive up to $410.0 million in additional development, regulatory and commercial milestones and royalties on net product sales for each of the three collaboration targets that Vertex licensed in the fourth quarter of 2019. Each milestone is payable only once per collaboration target, regardless of the number of products directed to such collaboration target that achieve the relevant milestone event.

The Company is eligible to receive additional potential future payments of up to $775.0 million based upon the successful achievement of specified development, regulatory and commercial milestones for the DMD and DM1 programs. The Company is also eligible to receive tiered royalties on future net sales on any products that may result from this collaboration; however, the Company has the option to forego the DM1 milestones and royalties to co-develop and co-commercialize all DM1 products globally.

The Company is eligible to receive additional potential future payments of up to $200.0 million upon receipt by Vertex of the first marketing approval of the initial product candidate from the U.S. Food and Drug Administration or the European Commission. In addition, the Company has the option to conduct research at their own cost in certain defined areas that, if beneficial to the exa-cel program and exa-cel ultimately achieves regulatory approval in such areas, then the Company could be entitled to certain milestone payments aggregating to high eight digits from Vertex.

Each of the remaining milestones are fully constrained as of December 31, 2022. There is uncertainty that the events to obtain the research and developmental milestones will be achieved given the nature of clinical development and the stage of the CRISPR/Cas9 technology. The remaining research, development and regulatory milestones will be constrained until it is probable that a significant revenue reversal will not occur. Commercial milestones and royalties relate predominantly to a license of intellectual property and are determined by sales or usage-based thresholds. The commercial milestones and royalties are accounted for under the royalty recognition constraint and will be accounted for as constrained variable consideration. The Company applies the royalty recognition constraint for each commercial milestone and will not recognize revenue for each until the subsequent sale of a licensed product (achievement of each) occurs.

Accounting Analysis under ASC 808

In connection with the Vertex Agreements, the Company identified the following collaborative elements, which are accounted for under ASC 808: (i) development and commercialization services for shared products, including any transition services related to exa-cel under the A&R Vertex JDCA; (ii) R&D Services for follow-on products; and (iii) committee participation. The related impact of the cost sharing is included within collaboration expense, net, in the consolidated statements of operations and comprehensive (loss) income.

During the years ended December 31, 2022, 2021 and 2020, the Company recognized $110.3 million, $101.2 million, and $48.0 million of collaboration expense, net, related to the Vertex Agreements, respectively. Research and development expense for the years ended December 31, 2022, 2021 and 2020 is net of $37.8 million, $47.4 million, and $27.6 million of reimbursements from Vertex, respectively.

Under the A&R Vertex JDCA, the Company has an option to defer its portion of specified costs on the exa-cel program in excess of $110.3 million for the years ended December 31, 2022, 2023 and 2024. Vertex may only recover any such deferred amounts as an offset against future profitability of the exa-cel program, determined on an annual basis in accordance with the A&R Vertex JDCA. Any such deferred amounts are capped at a specified maximum amount per year. For the year ended December 31, 2022, the Company exercised its option to defer $36.1 million of its share of costs incurred under the A&R Vertex JDCA. These deferred costs will be recognized by the Company when recoverability of such deferred amounts by Vertex is probable and the amount can be reasonably estimated. As of December 31, 2022, no such deferred amounts have been recognized.

Share Capital

12 Months Ended

Dec. 31, 2022

Equity [Abstract]

Share Capital

10. Share Capital

The Company had 150,347,467 and 145,364,335 authorized common shares as of December 31, 2022 and 2021, respectively, with a par value of CHF 0.03 per share. Share Capital consisted of the following:


		As of December 31,
Type of Share Capital	Conditional Capital	2022		2021
Common shares	Registered share capital		82,028,328		80,321,227
Common shares	Authorized share capital		39,316,975		39,316,975
Common shares	Conditional share capital - Bonds or similar debt instruments		8,202,832		4,919,700
Common shares	Conditional share capital - Employee benefit plans		20,799,332		20,806,433
	Total		150,347,467		145,364,335

Included in registered share capital are 5,025,897 shares registered, of which 4,845,581 shares are held by the Company and its subsidiaries and are reserved for future issuance for financings and 180,316 shares held by the Company and its subsidiaries as treasury shares.

Common Share Issuances

Recent Public Offerings

In July 2020, the Company sold 7.4 million common shares through an underwritten public offering (inclusive of shares sold pursuant to the exercise of the underwriters’ option to purchase additional shares) at a public offering price of $70.00 per share for aggregate net proceeds of $484.8 million, which were net of equity issuance costs and stamp tax of $32.5 million.

At-the-Market Offerings

In August 2019, the Company entered into an Open Market Sale AgreementSM with Jefferies LLC, or Jefferies, under which the Company was able to offer and sell, from time to time at its sole discretion through Jefferies, as its sales agent, its common shares, or the August 2019 Sales Agreement. In August 2019, the Company filed a prospectus supplement with the SEC to offer and sell, from time to time, common shares having aggregate gross proceeds of up to $200.0 million, or the 2019 ATM. During the year ended December 31, 2020, the Company issued and sold an aggregate of 2.2 million common shares under the 2019 ATM at an average price of $89.47 per share for aggregate proceeds of $195.5 million, which were net of equity issuance costs of $4.5 million.

In December 2020, in connection with the August 2019 Sales Agreement, the Company filed a prospectus supplement with the SEC to offer and sell, from time to time, common shares having aggregate gross proceeds of up to $350.0 million, or the 2020 ATM. During the year ended December 31, 2020, the Company issued and sold an aggregate of 1.8 million common shares under the 2020 ATM at an average price of $169.57 per share for aggregate proceeds of $298.0 million, which were net of equity issuance costs of $4.5 million. Additional equity issuance costs for stamp taxes related to shares sold in 2020 related to the 2019 ATM and 2020 ATM were $4.9 million, of which $4.0 million was accrued as of December 31, 2020 and paid in 2021.

In January 2021, the Company issued and sold under the 2020 ATM an aggregate of 0.3 million common shares at an average price of $162.46 per share with aggregate proceeds of $46.7 million, which were net of equity issuance costs of $0.7 million. An additional $0.5 million of stamp taxes related to this amount was paid in 2021.

In January 2021, in connection with the August 2019 Sales Agreement, the Company filed a prospectus supplement with the SEC to offer and sell, from time to time, common shares having aggregate gross proceeds of up to $600.0 million. In July 2021, the Company filed a new prospectus supplement with the SEC, which replaced the previous prospectus supplement filed in January 2021, to offer and sell, from time to time, the common shares remaining under the original prospectus supplement having aggregate gross proceeds of up to $419.8 million, or, together with the January 2021 prospectus supplement, the 2021 ATM.

As of December 31, 2021, the Company issued and sold an aggregate of 1.1 million common shares under the 2021 ATM at an average price of $169.82 per share for aggregate proceeds of $177.8 million, which were net of equity issuance costs of $2.4 million. An additional $1.8 million of stamp taxes related to this amount was paid in 2021.

As of December 31, 2022, the Company has issued and sold an aggregate of 1.1 million common shares under the 2021 ATM at an average price of $168.79 per share for aggregate proceeds of $178.8 million, which were net of equity issuance costs of $2.4 million.

The Common Shares have the following characteristics:

Voting Rights

The holders of common shares are entitled to one vote for each common share held at all meetings of shareholders.

Dividends

The holders of common shares are entitled to receive dividends, if and when resolved upon by the general meeting of shareholders based on a respective proposal by the Board of Directors and provided that the Company disposes of sufficient freely distributable reserves. As of December 31, 2022, no dividends have been declared or paid since the Company’s inception.

Liquidation

The holders of the common shares are entitled to share ratably in the Company’s assets available for distribution to shareholders in the event of any voluntary or involuntary liquidation, dissolution or winding up of the Company or upon the occurrence of a deemed liquidation event.

- Definition

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

+ References

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+ Details

Equity-based Compensation

12 Months Ended

Dec. 31, 2022

Share-Based Payment Arrangement [Abstract]

Equity-based Compensation

11. Equity-based Compensation

Option and Grant Plans

In April 2015, the Company’s shareholders approved the 2015 Stock Option and Grant Plan, or the 2015 Plan, and in July 2016, the Company’s shareholders approved the 2016 Stock Option and Incentive Plan, or the 2016 Plan. In May 2018, the Company’s shareholders approved the 2018 Stock Option and Incentive Plan, or the 2018 Plan (collectively, the “Plans”). Subsequent to the IPO, no further options were granted under the 2015 Plan. The Plans provide for the issuance of equity awards in the form of restricted shares, options to purchase common shares which may constitute incentive stock options, or ISOs, or non-statutory stock options, or NSOs, unrestricted stock unit grants, and qualified performance and market-based awards to eligible employees, officers, directors, non-employee consultants and other key personnel. Terms of the equity awards, including vesting requirements, are determined by the Company’s board of directors, subject to the provisions of the Plans. Options granted by the Company typically vest over four years and have a contractual life of ten years. Restricted stock unit grants typically vest over two to four years. At December 31, 2022, the Company had 26,705,365 common shares authorized for issuance under the 2018 Plan and 10,338,717 common shares available for future grant under the 2018 Plan.

Equity-Based Compensation Expense

The Company recognized stock-based compensation expense totaling $97.9 million, $102.4 million, and $66.0 million during the years ended December 31, 2022, 2021 and 2020, respectively. Stock‑based compensation expense by classification within the consolidated statements of operations and comprehensive (loss) income is as follows (in thousands):


	Years Ended December 31,
	2022		2021		2020
Research and development	$	53,956	$	59,683	$	35,120
General and administrative		43,991		42,707		30,898
Total	$	97,947	$	102,390	$	66,018

As of December 31, 2022, there was $107.9 million and $67.8 million of unrecognized compensation expense related to unvested stock options and restricted stock units, respectively, that is expected to be recognized over a weighted-average period of 2.4 and 2.3 years, respectively.

Stock Options

The fair value of each option issued to employees was estimated at the date of grant using the Black-Scholes option pricing model with the following weighted-average assumptions:


	Years Ended December 31,
	2022			2021			2020
Options granted		1,492,589			1,616,255			2,182,773
Weighted-average exercise price	$	60.19		$	124.32		$	68.91
Weighted-average grant date fair value	$	38.54		$	77.38		$	42.28
Assumptions:
Expected volatility		70.2	%		70.3	%		69.2	%
Expected term (in years)		6.0			6.0			6.0
Risk-free interest rate		2.6	%		1.0	%		0.6	%
Expected dividend yield		0.0	%		0.0	%		0.0	%

The following table summarizes stock option activity under the Company’s equity award plans (intrinsic value in thousands):


	Shares			Weighted- Average Exercise Price		Weighted- Average Remaining Contractual Term (years)		Aggregate Intrinsic Value
Outstanding at December 31, 2021		7,812,982		$	58.07		7.4	$	219,103
Granted		1,492,589			60.19
Exercised		(1,235,528	)		29.66
Cancelled or forfeited		(839,810	)		85.13
Outstanding at December 31, 2022		7,230,233		$	60.22		7.0	$	32,131
Exercisable at December 31, 2022		4,769,450		$	51.76		6.2	$	30,915
Vested and expected to vest at December 31, 2022		7,230,233		$	60.22		7.0	$	32,131

The total intrinsic value (the amount by which the fair market value exceeded the exercise price) of stock options exercised during the year ended December 31, 2022, 2021 and 2020 was $40.8 million, $119.5 million, and $104.2 million, respectively.

As of December 31, 2022, options to purchase 1,048,911 common shares subject to performance-based vesting conditions were vested, as performance conditions were satisfied in prior years, and there were 170,652 options to purchase common shares subject to performance-based vesting conditions outstanding. Activity related to stock options subject to performance-based vesting conditions is included in the table above.

As of December 31, 2022, options to purchase 150,000 common shares subject to market-based vesting conditions were vested, as market conditions were satisfied in prior years. 150,000 options to purchase common shares subject to market-based vesting conditions were outstanding as of December 31, 2022. Activity related to stock options subject to market-based vesting conditions is included in the table above.

The Company did not grant stock options subject to performance-based or market-based vesting conditions during 2022, 2021, and 2020.

Restricted Stock Units

The following table summarizes the restricted stock unit activity under the Company’s equity award plans:


	Shares			Weighted- Average Grant Date Fair Value
Unvested balance at December 31, 2021		934,175		$	100.14
Granted		853,326			62.31
Vested		(237,932	)		83.88
Cancelled or forfeited		(224,384	)		91.69
Unvested balance at December 31, 2022		1,325,185		$	80.13

During the years ended December 31, 2022, 2021 and 2020, the total fair value of restricted stock units vested was $14.3 million, $45.3 million, and $21.6 million, respectively.

During 2022, the Company granted 150,000 performance stock units with market-based vesting conditions in which the recipient is eligible to receive between zero and 150,000 common shares at the end of a three-year service period based upon achieving a specified average stock price. Expense for these awards is being recognized over the requisite service period. As of December 31, 2022, 150,000 of the performance stock units were unvested. Activity related to stock units subject to market-based vesting conditions is included in the table above.

The Company did not grant stock units subject to performance-based or market-based vesting conditions during 2021 and 2020.

Award modifications

Equity award modifications for certain equity awards held by departing employees for the years ended December 31, 2022, 2021 and 2020 were not material to the Company's stock-based compensation expense.

Employee Stock Purchase Plan

On July 19, 2016, the Company’s board of directors adopted its 2016 Employee Stock Purchase Plan, or the ESPP Plan, which was subsequently approved by its shareholders and became effective on October 19, 2016. The ESPP Plan authorizes the initial issuance of up to a total of 0.4 million shares of the Company’s common stock to participating employees. The Company activated its ESPP Plan on January 1, 2020. The Company issued 36,559 and 21,590 shares under the ESPP Plan during the years ended December 31, 2022 and 2021, respectively.

Net (Loss) Income Per Share Attributable to Common Shareholders

12 Months Ended

Dec. 31, 2022

Earnings Per Share [Abstract]

Net (Loss) Income Per Share Attributable to Common Shareholders

12. Net (Loss) Income Per Share Attributable to Common Shareholders

Basic net (loss) income per share is calculated by dividing net (loss) income attributable to common shareholders by the weighted-average number of common shares outstanding during the period. Diluted net (loss) income per share is calculated by dividing the net (loss) income attributable to common shareholders by the weighted-average number of common share equivalents outstanding for the period, including any dilutive effect from outstanding stock options and warrants using the treasury stock method. The Company’s net (loss) income is net (loss) income attributable to common shareholders for all periods presented.

The following table sets forth the computation of basic and diluted net (loss) income per share for the periods ended (in thousands, except share and per share amounts):


	Year ended December 31,
	2022			2021		2020

Net (loss) income	$	(650,175	)	$	377,661	$	(348,865	)
Basic weighted-average common shares outstanding		77,746,575			75,948,686		65,949,672
Effect of potentially dilutive securities:
Outstanding options		—			3,990,579		—
Unvested restricted common shares		—			454,231		—
Diluted weighted-average common shares outstanding		77,746,575			80,393,496		65,949,672
Net (loss) income per common share — basic	$	(8.36	)	$	4.97	$	(5.29	)
Net (loss) income per common share — diluted	$	(8.36	)	$	4.70	$	(5.29	)

The Company did not include the securities in the following table in the computation of the net (loss) income per share calculations because the effect would have been anti-dilutive during each period:


	Year ended December 31,
	2022		2021		2020
Outstanding options		7,230,233		1,765,881		8,101,980
Unvested restricted common shares		1,325,185		225,904		894,092
ESPP		19,105		6,671		11,257
Total		8,574,523		1,998,456		9,007,329

401 (k) Savings Plan

12 Months Ended

Dec. 31, 2022

Retirement Benefits [Abstract]

401(k) Savings Plan

13. 401(k) Savings Plan

The Company established a defined‑contribution savings plan under Section 401(k) of the Internal Revenue Code (the “401(k) Plan”) in November 2016. The 401(k) Plan covers all employees who meet defined minimum age and service requirements and allows participants to defer a portion of their annual compensation on a pretax basis. The Company contributed $3.2 million, $3.4 million, and $1.9 million to the 401(k) Plan for the years ended December 31, 2022, 2021 and 2020, respectively.

- Definition

The entire disclosure for retirement benefits.

+ References

Reference 1: http://www.xbrl.org/2003/role/exampleRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 55
-Paragraph 17
-URI https://asc.fasb.org/extlink&oid=123450688&loc=d3e4179-114921

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
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+ Details

Income Taxes

12 Months Ended

Dec. 31, 2022

Income Tax Disclosure [Abstract]

Income Taxes

14. Income Taxes

The Company is subject to U.S. federal and various state corporate income taxes as well as taxes in foreign jurisdictions for the foreign parent and where foreign subsidiaries have been established.

Net (loss) income before taxes

For the years ended December 31, 2022, 2021 and 2020, the (loss) income before provision for income taxes consist of the following (in thousands):


	Years Ended December 31,
	2022			2021		2020
Domestic	$	1,321		$	4,569	$	7,630
Foreign		(651,821	)		374,962		(355,686	)
Total	$	(650,500	)	$	379,531	$	(348,056	)

The benefit from (provision for) income taxes consist of the following (in thousands):


		Years Ended December 31,


	2022			2021			2020
Current income taxes:
Federal	$	(444	)	$	(80	)	$	(248	)
State		(241	)		(42	)		(151	)
Foreign		—			—			(1	)
Total current income taxes		(685	)		(122	)		(400	)
Deferred income taxes:
Federal		1,010			(1,748	)		(409	)
State		—			—			—
Foreign		—			—			—
Total deferred income taxes		1,010			(1,748	)		(409	)
Total income tax benefit (provision)	$	325		$	(1,870	)	$	(809	)

A reconciliation of income tax expense computed at the statutory corporate income tax rate to the effective income tax rate for the years ended December 31, 2022, 2021 and 2020 is as follows:


	Years Ended December 31,
	2022			2021			2020
Income tax expense at statutory rate		11.9	%		11.9	%		11.9	%
State income tax, net of federal benefit		1.2	%		(1.0	)%		1.0	%
Nondeductible expenses		(0.2	)%		0.7	%		0.1	%
Foreign rate differential		(0.1	)%		0.6	%		(0.1	%)
Statutory to US GAAP permanent differences		0.0	%		0.0	%		0.0	%
Stock-based compensation		(0.2	)%		(2.5	%)		2.3	%
Impact of deferred rate change		(0.1	)%		0.0	%		0.0	%
Research credits		3.3	%		(4.2	)%		3.3	%
Change in valuation allowance		(15.8	)%		(5.0	)%		(18.7	%)
Effective income tax rate		—			0.5	%		(0.2	%)

The federal statutory rate reflects the Switzerland mixed company service rate.

Deferred taxes are recognized for temporary differences between the basis of assets and liabilities for financial statement and income tax purposes. The significant components of the Company’s deferred tax assets are comprised of the following (in thousands):


	Years Ended December 31,
	2022			2021
Deferred tax assets:
Net operating loss carryforwards	$	118,432		$	47,190
Accruals and reserves		4,782			5,878
Operating lease liabilities		66,436			61,476
Other deferred tax assets		10,154			6,362
Stock-based compensation		18,034			14,042
Research credit		63,416			37,878
Total deferred tax assets		281,254			172,826
Less valuation allowance		(198,279	)		(98,649	)
Net deferred tax assets		82,975			74,177
Deferred tax liabilities:
Depreciation		(41,206	)		(28,579	)
Operating lease assets		(42,678	)		(47,521	)
Intangible assets		(18	)		(31	)
Other deferred tax liabilities		(209	)		(192	)
Total deferred tax liabilities		(84,111	)		(76,323	)
Long term deferred taxes	$	(1,136	)	$	(2,146	)

The Company has evaluated the positive and negative evidence bearing upon the realizability of its deferred tax assets. Based on the Company’s history of worldwide operating losses, the Company has concluded that it is more-likely-than-not that the benefit of its U.S. and non-U.S. deferred tax assets will not be realized. Accordingly, as of December 31, 2022 and 2021, the Company has provided a full valuation allowance against its net deferred tax assets in Switzerland and the United Kingdom. The Company has also provided a valuation allowance against the U.S. deferred tax assets that cannot be realized by existing deferred tax liabilities based upon when they are scheduled to reverse. The valuation allowance increased by $99.6 million during 2022, which is primarily attributable to increase in net operating loss carryforwards as a result of current year net loss.

As of December 31, 2022, the Company had no available U.S. federal net operating loss carryforwards. As of December 31, 2022, the Company had available non-U.S. net operating loss carryforwards of $1,979.7 million of which $988.4 million relate to Switzerland, $988.4 million relate to the Canton of Zug, and $2.9 million relate to the Company’s wholly-owned subsidiary in the United Kingdom. The net operating losses generated in Switzerland and the Canton of Zug begin to expire in 2027 and the net operating losses generated in the United Kingdom can be carried forward indefinitely.

As of December 31, 2022, the Company had U.S. domestic federal research and development credit carryforwards of $27.3 million that begin to expire in 2039 for federal purposes, which are net of uncertain tax positions of $13.9 million. As of December 31, 2022, the Company had U.S. domestic federal orphan drug credit carryforwards of $22.7 million which begin to expire in 2040 for federal purposes, which are net of uncertain tax positions of $9.8 million. As of December 31, 2022, the Company had U.S. domestic state research and development credit carryforwards of $16.9 million which begin to expire in 2035, which are net of uncertain tax positions of $10.9 million.

ASC 740 clarifies the accounting for uncertainty in income taxes recognized in an enterprise’s financial statement by prescribing the minimum recognition threshold and measurement of a tax position taken or expected to be taken in a tax return.

As of December 31, 2022, the Company had gross unrecognized tax benefits of $34.5 million of which $32.3 million would favorably impact the effective tax rate if recognized. The Company will recognize interest and penalties related to uncertain tax positions in income tax expense. As of December 31, 2022, 2021 and 2020, the Company had no accrued interest or penalties related to uncertain tax positions and no amounts have been recognized in the Company’s consolidated statements of operations and comprehensive loss.

The aggregate changes in gross unrecognized tax benefits were as follows (in thousands):


	Years Ended December 31,
	2022		2021			2020
Balance at beginning of year	$	21,395	$	11,967		$	5,231
Increases for tax positions taken during current period		10,439		9,911			7,004
Increases for tax positions taken in prior periods		2,702		—			—
Decreases for tax positions taken during current period		—		—			—
Decreases for tax positions taken in prior periods		—		(483	)		(268	)
Balance at end of year	$	34,536	$	21,395		$	11,967

The Company files income tax returns in the U.S. federal jurisdiction, Massachusetts, California and certain non-U.S. jurisdictions. The Company is subject to U.S. federal, Massachusetts, California and non-U.S. income tax examinations by authorities for tax years ending after December 31, 2018. Research credits generated in prior tax years that are closed for examination may still be adjusted upon future examination if they have or will be used in a future period. The Company is subject to income tax examinations by authorities in its non-U.S. jurisdictions for all years.

- Definition

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

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section 50
-Paragraph 21
-URI https://asc.fasb.org/extlink&oid=121826272&loc=d3e32857-109319

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section S99
-Paragraph 2
-Subparagraph (SAB Topic 11.C)
-URI https://asc.fasb.org/extlink&oid=122134291&loc=d3e330215-122817

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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-Paragraph 17
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=121826272&loc=d3e32809-109319

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section S99
-Paragraph 1
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-URI https://asc.fasb.org/extlink&oid=122134291&loc=d3e330036-122817

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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Reference 6: http://www.xbrl.org/2003/role/disclosureRef
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Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
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Reference 9: http://www.xbrl.org/2003/role/disclosureRef
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-URI https://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

+ Details

Summary of Significant Accounting Policies and Basis of Presentation (Policies)

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Basis of Presentation and Use of Estimates

Segment Information

Foreign Currency Translation and Transactions

Cash and Cash Equivalents

Restricted Cash

Marketable Securities

Other Receivables

Concentrations of Credit Risk and Off-balance Sheet Risk

Fair Value of Financial Instruments

Level 1 — Quoted prices in active markets that are accessible at the market date for identical unrestricted 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.

Property and Equipment


Asset		Estimated useful life
Computer equipment		3 years
Furniture, fixtures and other		5 years
Laboratory equipment		5 years
Leasehold improvements		Shorter of useful life or remaining lease term

Impairment of Long-lived Assets

Revenue Recognition

1) Identify the contract with the customer

2) Identify the performance obligations in the contract

3) Determine the transaction price

4) Allocate the transaction consideration to performance obligations in the contract

5) Recognize revenue when or as the Company satisfies a performance obligation

Contract Balances

Collaboration Arrangements

Research and Development Expenses

Leases

Equity-Based Compensation Expense

Equity Based Compensation Expense

The Company expenses restricted stock unit awards to employees based on the fair value of the award on a straight-line basis over the associated service period of the award.

Patent Costs

Income Taxes

Comprehensive (Loss) Income

Net (Loss) Income Per Share Attributable to Common Shareholders

New Accounting Pronouncements

Summary of Significant Accounting Policies and Basis of Presentation (Tables)

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Schedule of Estimated Useful Lives of Assets

Depreciation is recorded using the straight-line method over the estimated useful lives of the respective assets, which are as follows:


Asset		Estimated useful life
Computer equipment		3 years
Furniture, fixtures and other		5 years
Laboratory equipment		5 years
Leasehold improvements		Shorter of useful life or remaining lease term

Marketable Securities (Tables)

12 Months Ended

Dec. 31, 2022

Investments, Debt and Equity Securities [Abstract]

Summary of Cash Equivalents and Marketable Securities Recorded at Fair Value


December 31, 2022	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Fair Value
Cash equivalents:
Money market funds	$	17,766	$	—	$	—		$	17,766
Corporate debt securities		2,151		—		(2	)		2,149
Certificates of deposit		—		—		—			—
Commercial paper		32,675		—		—			32,675
Total cash equivalents		52,592		—		(2	)		52,590
Marketable securities:
U.S. Treasury securities		—		—		—			—
Corporate debt securities		1,236,770		615		(15,006	)		1,222,379
Certificates of deposit		92,417		—		—			92,417
Government-sponsored enterprise securities		79,746		11		(712	)		79,045
Commercial paper		263,231		—		(509	)		262,722
Total marketable securities		1,672,164		626		(16,227	)		1,656,563
Total cash equivalents and marketable securities	$	1,724,756	$	626	$	(16,229	)	$	1,709,153


December 31, 2021	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Fair Value

Cash equivalents:
Money market funds	$	507,386	$	—	$	—		$	507,386
Corporate debt securities		—							—
Certificates of deposit		—		—		—			—
Commercial paper		9,997		—		(1	)		9,996
Total cash equivalents		517,383		—		(1	)		517,382
Marketable securities:
U.S. Treasury securities		16,238		6		(52	)		16,192
Corporate debt securities		1,173,659		10		(4,903	)		1,168,766
Certificates of deposit		45,164		—		—			45,164
Government-sponsored enterprise securities		13,334		—		(77	)		13,257
Commercial paper		212,805		—		(86	)		212,719
Total marketable securities		1,461,200		16		(5,118	)		1,456,098
Total cash equivalents and marketable securities	$	1,978,583	$	16	$	(5,119	)	$	1,973,480

Fair Value Measurement (Tables)

12 Months Ended

Dec. 31, 2022

Fair Value Disclosures [Abstract]

Schedule of Financial Assets Measured at Fair Value on Recurring Basis


	Fair Value Measurements at
	December 31, 2022
	Total		Level 1		Level 2		Level 3
Cash and cash equivalents:
Cash	$	159,295	$	159,295	$	—	$	—
Money market funds		17,766		17,766		—		—
Corporate debt securities		2,149		—		2,149		—
Certificates of deposit		—		—		—		—
Commercial paper		32,675		—		32,675		—
Marketable securities:
U.S. Treasury securities		—		—		—		—
Corporate debt securities		1,222,379		—		1,222,379		—
Certificates of deposit		92,417		—		92,417		—
Government-sponsored enterprise securities		79,045		—		79,045		—
Commercial paper		262,722		—		262,722		—
Other non-current assets		2,212		—		—		2,212
Total	$	1,870,660	$	177,061	$	1,691,387	$	2,212


	Fair Value Measurements at
	December 31, 2021
	Total		Level 1		Level 2		Level 3
Cash and cash equivalents:
Cash	$	405,648	$	405,648	$	—	$	—
Money market funds		507,386		507,386		—		—
Corporate debt securities		—		—		—		—
Certificates of deposit		—		—		—		—
Commercial paper		9,997		—		9,997		—
Marketable securities:
U.S. Treasury securities		16,192		—		16,192		—
Corporate debt securities		1,168,766		—		1,168,766		—
Certificates of deposit		45,164		—		45,164		—
Government-sponsored enterprise securities		13,257		—		13,257		—
Commercial paper		212,719		—		212,719		—
Other non-current assets		2,212		—		—		2,212
Total	$	2,381,341	$	913,034	$	1,466,095	$	2,212

Property and Equipment, net (Tables)

12 Months Ended

Dec. 31, 2022

Property, Plant and Equipment [Abstract]

Summary of Property and Equipment, Net

Property and equipment, net, consists of the following (in thousands):


	As of December 31,
	2022			2021
Computer equipment	$	3,618		$	1,757
Furniture, fixtures, and other		8,109			4,371
Laboratory equipment		37,897			30,123
Leasehold improvements		141,680			86,735
Construction work in process		6,162			52,396
Total property and equipment, gross		197,466			175,382
Accumulated Depreciation		(33,832	)		(37,807	)
Total property and equipment, net	$	163,634		$	137,575

Accrued Expenses (Tables)

12 Months Ended

Dec. 31, 2022

Payables and Accruals [Abstract]

Schedule of Accrued Expenses

Accrued expenses consist of the following (in thousands):


	As of December 31,
	2022		2021
Payroll and employee-related costs	$	19,241	$	23,661
Research costs		46,187		47,986
Licensing fees		983		138
Professional fees		4,927		4,720
Intellectual property costs		3,936		6,120
Accrued property and equipment		1,244		7,113
Other		1,164		1,265
Total	$	77,682	$	91,003

Leases (Tables)

12 Months Ended

Dec. 31, 2022

Leases [Abstract]

Summary of Lease Assets and Liabilities

The following table summarizes the lease assets and liabilities as of December 31, 2022 and 2021 (in thousands):


	As of December 31,
	2022		2021
Assets
Operating lease assets	$	156,921	$	174,460
Total lease assets		156,921		174,460
Liabilities
Current
Operating lease liabilities		15,842		12,158
Non-current
Operating lease liabilities, net of current portion		228,179		212,872
Total lease liabilities	$	244,021	$	225,030

Summary of Operating Lease Costs Included in Research and Development and General and Administrative Expense, as well as Sublease Income


	Years Ended December 31,
	2022		2021			2020
Operating lease costs	$	34,896	$	22,520		$	14,342
Short-term lease costs		824		11,087			7,339
Variable lease costs		11,882		8,402			6,368
Sublease income		—		(5,253	)		(587	)
Net lease cost	$	47,602	$	36,756		$	27,462

Summary of Maturity of Undiscounted Payments Due under Lease Liabilities and Present Value of Those Liabilities

The following table summarizes the maturity of undiscounted payments due under lease liabilities and the present value of those liabilities as of December 31, 2022 (in thousands):


	Total
2023		29,270
2024		26,526
2025		26,251
2026		26,745
2027		25,927
Thereafter		205,495
Total	$	340,214
Present value adjustment		(96,193	)
Present value of lease liabilities	$	244,021

Summary of Lease Term and Discount Rate

The following table summarizes the lease term (in years) and discount rate for operating leases as of December 31, 2022 and 2021:


	As of December 31,
	2022			2021
Weighted-average remaining lease term		11.8			12.4
Weighted-average discount rate		5.9	%		5.9	%

Lessee, Operating Lease Cash Flow Payments

The following table summarizes the cash paid for amounts included in the measurement of lease liabilities for the years ended December 31, 2022, 2021 and 2020 (in thousands):


	Years Ended December 31,
	2022			2021			2020
Cash paid for amounts included in measurement of lease liabilities:
Operating cash flows used in operating leases	$	(17,004	)	$	(19,753	)	$	(13,161	)
Operating lease non-cash items:
Right-of-use assets (decreased) increased through lease modifications and reassessments		1,208			(14,230	)		3,169
Right-of-use assets obtained in exchange for operating lease liabilities		—			152,486			13,956
Leasehold improvements paid directly by landlord		19,252			30,500			—

Share Capital (Tables)

12 Months Ended

Dec. 31, 2022

Equity [Abstract]

Schedule of Share Capital

Share Capital consisted of the following:


		As of December 31,
Type of Share Capital	Conditional Capital	2022		2021
Common shares	Registered share capital		82,028,328		80,321,227
Common shares	Authorized share capital		39,316,975		39,316,975
Common shares	Conditional share capital - Bonds or similar debt instruments		8,202,832		4,919,700
Common shares	Conditional share capital - Employee benefit plans		20,799,332		20,806,433
	Total		150,347,467		145,364,335

- Definition

Tabular disclosure of an entity's stock, including par or stated value per share, number and dollar amount of share subscriptions, shares authorized, shares issued, shares outstanding, number and dollar amount of shares held in an employee trust, dividend per share, total dividends, share conversion features, par value plus additional paid in capital, the value of treasury stock and other information necessary to a fair presentation, and EPS information. Stock by class includes common, convertible, and preferred stocks which are not redeemable or redeemable solely at the option of the issuer. Includes preferred stock with redemption features that are solely within the control of the issuer and mandatorily redeemable stock if redemption is required to occur only upon liquidation or termination of the reporting entity. If more than one issue is outstanding, state the title of each issue and the corresponding dollar amount; dollar amount of any shares subscribed but unissued and the deduction of subscriptions receivable there from; number of shares authorized, issued, and outstanding.

+ References

Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef
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-Name Accounting Standards Codification
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Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef
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-Name Accounting Standards Codification
-Topic 210
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-Subparagraph (SX 210.5-02(28))
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Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef
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Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef
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Reference 9: http://fasb.org/us-gaap/role/ref/legacyRef
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-Name Accounting Standards Codification
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Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef
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+ Details

Equity-based Compensation (Tables)

12 Months Ended

Dec. 31, 2022

Share-Based Payment Arrangement [Abstract]

Schedule of Stock-Based Compensation Expense

Stock‑based compensation expense by classification within the consolidated statements of operations and comprehensive (loss) income is as follows (in thousands):


	Years Ended December 31,
	2022		2021		2020
Research and development	$	53,956	$	59,683	$	35,120
General and administrative		43,991		42,707		30,898
Total	$	97,947	$	102,390	$	66,018

Fair Value of Each Option Issued to Employees Estimated Using Black-Scholes Option-Pricing Model

The fair value of each option issued to employees was estimated at the date of grant using the Black-Scholes option pricing model with the following weighted-average assumptions:


	Years Ended December 31,
	2022			2021			2020
Options granted		1,492,589			1,616,255			2,182,773
Weighted-average exercise price	$	60.19		$	124.32		$	68.91
Weighted-average grant date fair value	$	38.54		$	77.38		$	42.28
Assumptions:
Expected volatility		70.2	%		70.3	%		69.2	%
Expected term (in years)		6.0			6.0			6.0
Risk-free interest rate		2.6	%		1.0	%		0.6	%
Expected dividend yield		0.0	%		0.0	%		0.0	%

Summary of Stock Option Activity

The following table summarizes stock option activity under the Company’s equity award plans (intrinsic value in thousands):


	Shares			Weighted- Average Exercise Price		Weighted- Average Remaining Contractual Term (years)		Aggregate Intrinsic Value
Outstanding at December 31, 2021		7,812,982		$	58.07		7.4	$	219,103
Granted		1,492,589			60.19
Exercised		(1,235,528	)		29.66
Cancelled or forfeited		(839,810	)		85.13
Outstanding at December 31, 2022		7,230,233		$	60.22		7.0	$	32,131
Exercisable at December 31, 2022		4,769,450		$	51.76		6.2	$	30,915
Vested and expected to vest at December 31, 2022		7,230,233		$	60.22		7.0	$	32,131

Summary of Restricted Stock Activity

The following table summarizes the restricted stock unit activity under the Company’s equity award plans:


	Shares			Weighted- Average Grant Date Fair Value
Unvested balance at December 31, 2021		934,175		$	100.14
Granted		853,326			62.31
Vested		(237,932	)		83.88
Cancelled or forfeited		(224,384	)		91.69
Unvested balance at December 31, 2022		1,325,185		$	80.13

Net Income (Loss) Per Share Attributable to Common Shareholders (Tables)

12 Months Ended

Dec. 31, 2022

Earnings Per Share [Abstract]

Schedule of Computation of Basic and Diluted Net Income (Loss) per Share

The following table sets forth the computation of basic and diluted net (loss) income per share for the periods ended (in thousands, except share and per share amounts):


	Year ended December 31,
	2022			2021		2020

Net (loss) income	$	(650,175	)	$	377,661	$	(348,865	)
Basic weighted-average common shares outstanding		77,746,575			75,948,686		65,949,672
Effect of potentially dilutive securities:
Outstanding options		—			3,990,579		—
Unvested restricted common shares		—			454,231		—
Diluted weighted-average common shares outstanding		77,746,575			80,393,496		65,949,672
Net (loss) income per common share — basic	$	(8.36	)	$	4.97	$	(5.29	)
Net (loss) income per common share — diluted	$	(8.36	)	$	4.70	$	(5.29	)

Schedule of Antidilutive Securities not Include in Computation of Net Income (Loss) per Share


	Year ended December 31,
	2022		2021		2020
Outstanding options		7,230,233		1,765,881		8,101,980
Unvested restricted common shares		1,325,185		225,904		894,092
ESPP		19,105		6,671		11,257
Total		8,574,523		1,998,456		9,007,329

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2022

Income Tax Disclosure [Abstract]

Schedule of (Loss) Income Before Provision for Income Taxes

For the years ended December 31, 2022, 2021 and 2020, the (loss) income before provision for income taxes consist of the following (in thousands):


	Years Ended December 31,
	2022			2021		2020
Domestic	$	1,321		$	4,569	$	7,630
Foreign		(651,821	)		374,962		(355,686	)
Total	$	(650,500	)	$	379,531	$	(348,056	)

Schedule of Benefit (Provision for) from Income Taxes

The benefit from (provision for) income taxes consist of the following (in thousands):


		Years Ended December 31,


	2022			2021			2020
Current income taxes:
Federal	$	(444	)	$	(80	)	$	(248	)
State		(241	)		(42	)		(151	)
Foreign		—			—			(1	)
Total current income taxes		(685	)		(122	)		(400	)
Deferred income taxes:
Federal		1,010			(1,748	)		(409	)
State		—			—			—
Foreign		—			—			—
Total deferred income taxes		1,010			(1,748	)		(409	)
Total income tax benefit (provision)	$	325		$	(1,870	)	$	(809	)

Schedule of Reconciliation of Income Tax Expense Computed at Statutory Corporate Income Tax Rate to Effective Income Tax Rate

A reconciliation of income tax expense computed at the statutory corporate income tax rate to the effective income tax rate for the years ended December 31, 2022, 2021 and 2020 is as follows:


	Years Ended December 31,
	2022			2021			2020
Income tax expense at statutory rate		11.9	%		11.9	%		11.9	%
State income tax, net of federal benefit		1.2	%		(1.0	)%		1.0	%
Nondeductible expenses		(0.2	)%		0.7	%		0.1	%
Foreign rate differential		(0.1	)%		0.6	%		(0.1	%)
Statutory to US GAAP permanent differences		0.0	%		0.0	%		0.0	%
Stock-based compensation		(0.2	)%		(2.5	%)		2.3	%
Impact of deferred rate change		(0.1	)%		0.0	%		0.0	%
Research credits		3.3	%		(4.2	)%		3.3	%
Change in valuation allowance		(15.8	)%		(5.0	)%		(18.7	%)
Effective income tax rate		—			0.5	%		(0.2	%)

Schedule of Significant Components of Company's Deferred Tax Assets


	Years Ended December 31,
	2022			2021
Deferred tax assets:
Net operating loss carryforwards	$	118,432		$	47,190
Accruals and reserves		4,782			5,878
Operating lease liabilities		66,436			61,476
Other deferred tax assets		10,154			6,362
Stock-based compensation		18,034			14,042
Research credit		63,416			37,878
Total deferred tax assets		281,254			172,826
Less valuation allowance		(198,279	)		(98,649	)
Net deferred tax assets		82,975			74,177
Deferred tax liabilities:
Depreciation		(41,206	)		(28,579	)
Operating lease assets		(42,678	)		(47,521	)
Intangible assets		(18	)		(31	)
Other deferred tax liabilities		(209	)		(192	)
Total deferred tax liabilities		(84,111	)		(76,323	)
Long term deferred taxes	$	(1,136	)	$	(2,146	)

Schedule of Aggregate Changes in Gross Unrecognized Tax Benefits

The aggregate changes in gross unrecognized tax benefits were as follows (in thousands):


	Years Ended December 31,
	2022		2021			2020
Balance at beginning of year	$	21,395	$	11,967		$	5,231
Increases for tax positions taken during current period		10,439		9,911			7,004
Increases for tax positions taken in prior periods		2,702		—			—
Decreases for tax positions taken during current period		—		—			—
Decreases for tax positions taken in prior periods		—		(483	)		(268	)
Balance at end of year	$	34,536	$	21,395		$	11,967

Organization and Operations - Additional Information (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Company incorporation date	Oct. 31, 2013
Accumulated deficit	$ (846,090)	$ (195,915)
Cash, cash equivalents and marketable securities	$ 1,868,400

Summary of Significant Accounting Policies and Basis of Presentation - Additional Information (Detail)	12 Months Ended
	Dec. 31, 2022 USD ($) Segment	Dec. 31, 2021 USD ($)	Dec. 31, 2020 USD ($)
Summary Of Significant Accounting Policies [Line Items]
Number of operating segments \| Segment	1
Cash and cash equivalents	$ 211,885,000	$ 923,031,000	$ 1,168,620,000
Marketable securities	159,300,000	405,600,000
Contract liabilities	12,300,000	12,300,000
Significant uncertain tax positions	$ 0	0	0
Minimum [Member]
Summary Of Significant Accounting Policies [Line Items]
Marketable securities maturity period	1 year
Vertex and Casebia [Member] \| Collaborative Arrangement [Member]
Summary Of Significant Accounting Policies [Line Items]
Other receivables	$ 11,200,000	8,400,000
Prepaid Expenses and Other Current Assets [Member]
Summary Of Significant Accounting Policies [Line Items]
Letters of credit secured by cash held in restricted depository account	540,000	0	$ 0
Marketable Securities [Member]
Summary Of Significant Accounting Policies [Line Items]
Marketable securities	1,656,600,000	1,456,100,000
Letter of Credit [Member]
Summary Of Significant Accounting Policies [Line Items]
Letters of credit secured by cash held in restricted depository account	12,200,000	16,900,000
Letter of Credit [Member] \| Prepaid Expenses and Other Current Assets [Member]
Summary Of Significant Accounting Policies [Line Items]
Letters of credit secured by cash held in restricted depository account	500,000	0.0
Letter of Credit [Member] \| Restricted Cash Noncurrent [Member]
Summary Of Significant Accounting Policies [Line Items]
Letters of credit secured by cash held in restricted depository account	$ 11,600,000	$ 16,900,000

Summary of Significant Accounting Policies and Basis of Presentation - Schedule of Estimated Useful Lives of Assets (Detail)	12 Months Ended
	Dec. 31, 2022
Computer Equipment [Member]
Property Plant And Equipment [Line Items]
Estimated useful lives of assets	3 years
Furniture, Fixtures, and Other [Member]
Property Plant And Equipment [Line Items]
Estimated useful lives of assets	5 years
Laboratory Equipment [Member]
Property Plant And Equipment [Line Items]
Estimated useful lives of assets	5 years
Leasehold Improvements [Member]
Property Plant And Equipment [Line Items]
Leasehold improvements	Shorter of useful life or remaining lease term

Marketable Securities - Additional Information (Detail) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Marketable Securities [Line Items]
Marketable securities	$ 159,300,000	$ 405,600,000
Marketable securities unrealized loss, Less than twelve months	628,400,000	1,311,600,000
Marketable securities unrealized loss, more than twelve months	619,200,000	4,600,000
Marketable securities, non-current	53,130,000	0
Available-for-sale debt securities remaining maturities greater than thirty months	0
Other Comprehensive Income (Loss) [Member]
Marketable Securities [Line Items]
Unrealized loss, net	$ 10,500,000	$ 5,000,000.0

Marketable Securities - Summary of Cash Equivalents and Marketable Securities Recorded at Fair Value (Detail) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Marketable Securities [Line Items]
Cash equivalents, amortized cost	$ 52,592	$ 517,383
Cash equivalents, gross unrealized gains	0	0
Cash equivalents, gross unrealized losses	(2)	(1)
Cash equivalents, fair value	52,590	517,382
Marketable securities, amortized cost	1,672,164	1,461,200
Marketable securities, gross unrealized gains	626	16
Marketable securities, gross unrealized losses	(16,227)	(5,118)
Marketable securities, fair value	1,656,563	1,456,098
Cash equivalents and marketable securities, amortized cost	1,724,756	1,978,583
Cash equivalents and marketable securities, gross unrealized gains	626	16
Cash equivalents and marketable securities, gross unrealized losses	(16,229)	(5,119)
Cash equivalents and marketable securities, fair value	1,709,153	1,973,480
Money Market Funds [Member]
Marketable Securities [Line Items]
Cash equivalents, amortized cost	17,766	507,386
Cash equivalents, fair value	17,766	507,386
Certificates of Deposit [Member]
Marketable Securities [Line Items]
Cash equivalents, amortized cost	0	0
Cash equivalents, fair value	0	0
Marketable securities, amortized cost	92,417	45,164
Marketable securities, fair value	92,417	45,164
Commercial Paper [Member]
Marketable Securities [Line Items]
Cash equivalents, amortized cost	32,675	9,997
Cash equivalents, gross unrealized losses	0	(1)
Cash equivalents, fair value	32,675	9,996
Marketable securities, amortized cost	263,231	212,805
Marketable securities, gross unrealized losses	(509)	(86)
Marketable securities, fair value	262,722	212,719
US Treasury Securities [Member]
Marketable Securities [Line Items]
Marketable securities, amortized cost	0	16,238
Marketable securities, gross unrealized gains		6
Marketable securities, gross unrealized losses	0	(52)
Marketable securities, fair value	0	16,192
Corporate Debt Securities [Member]
Marketable Securities [Line Items]
Cash equivalents, amortized cost	2,151	0
Cash equivalents, gross unrealized gains	0
Cash equivalents, gross unrealized losses	(2)
Cash equivalents, fair value	2,149	0
Marketable securities, amortized cost	1,236,770	1,173,659
Marketable securities, gross unrealized gains	615	10
Marketable securities, gross unrealized losses	(15,006)	(4,903)
Marketable securities, fair value	1,222,379	1,168,766
Government-sponsored Enterprise Securities [Member]
Marketable Securities [Line Items]
Marketable securities, amortized cost	79,746	13,334
Marketable securities, gross unrealized gains	11	0
Marketable securities, gross unrealized losses	(712)	(77)
Marketable securities, fair value	$ 79,045	$ 13,257

Fair Value Measurement - Schedule of Financial Assets Measured at Fair Value on Recurring Basis (Detail) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Marketable securities, fair value	$ 1,656,563	$ 1,456,098
Recurring Basis [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Other non-current assets	2,212	2,212
Total	1,870,660	2,381,341
Recurring Basis [Member] \| Cash [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and cash equivalents	159,295	405,648
Recurring Basis [Member] \| Money Market Funds [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and cash equivalents	17,766	507,386
Recurring Basis [Member] \| Corporate Debt Securities [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and cash equivalents	2,149
Marketable securities, fair value	1,222,379	1,168,766
Recurring Basis [Member] \| Certificates of Deposit [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Marketable securities, fair value	92,417	45,164
Recurring Basis [Member] \| Commercial Paper [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and cash equivalents	32,675	9,997
Marketable securities, fair value	262,722	212,719
Recurring Basis [Member] \| US Treasury Securities [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Marketable securities, fair value		16,192
Recurring Basis [Member] \| Government-sponsored Enterprise Securities [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Marketable securities, fair value	79,045	13,257
Recurring Basis [Member] \| Level 1 [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total	177,061	913,034
Recurring Basis [Member] \| Level 1 [Member] \| Cash [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and cash equivalents	159,295	405,648
Recurring Basis [Member] \| Level 1 [Member] \| Money Market Funds [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and cash equivalents	17,766	507,386
Recurring Basis [Member] \| Level 2 [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total	1,691,387	1,466,095
Recurring Basis [Member] \| Level 2 [Member] \| Corporate Debt Securities [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and cash equivalents	2,149
Marketable securities, fair value	1,222,379	1,168,766
Recurring Basis [Member] \| Level 2 [Member] \| Certificates of Deposit [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Marketable securities, fair value	92,417	45,164
Recurring Basis [Member] \| Level 2 [Member] \| Commercial Paper [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and cash equivalents	32,675	9,997
Marketable securities, fair value	262,722	212,719
Recurring Basis [Member] \| Level 2 [Member] \| US Treasury Securities [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Marketable securities, fair value		16,192
Recurring Basis [Member] \| Level 2 [Member] \| Government-sponsored Enterprise Securities [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Marketable securities, fair value	79,045	13,257
Recurring Basis [Member] \| Level 3 [Member]
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Other non-current assets	2,212	2,212
Total	$ 2,212	$ 2,212

Property and Equipment, net - Summary of Property and Equipment, Net (Detail) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Property, Plant and Equipment [Line Items]
Total property and equipment, gross	$ 197,466	$ 175,382
Accumulated Depreciation	(33,832)	(37,807)
Total property and equipment, net	163,634	137,575
Computer Equipment [Member]
Property, Plant and Equipment [Line Items]
Total property and equipment, gross	3,618	1,757
Furniture, Fixtures, and Other [Member]
Property, Plant and Equipment [Line Items]
Total property and equipment, gross	8,109	4,371
Laboratory Equipment [Member]
Property, Plant and Equipment [Line Items]
Total property and equipment, gross	37,897	30,123
Leasehold Improvements [Member]
Property, Plant and Equipment [Line Items]
Total property and equipment, gross	141,680	86,735
Construction Work in Process [Member]
Property, Plant and Equipment [Line Items]
Total property and equipment, gross	$ 6,162	$ 52,396

Property and Equipment, net - Additional Information (Detail) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Property, Plant and Equipment [Abstract]
Depreciation expense	$ 24.1	$ 17.9	$ 9.1

Accrued Expenses - Schedule of Accrued Expenses (Detail) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Accrued Liabilities, Current [Abstract]
Payroll and employee-related costs	$ 19,241	$ 23,661
Research costs	46,187	47,986
Licensing fees	983	138
Professional fees	4,927	4,720
Intellectual property costs	3,936	6,120
Accrued property and equipment	1,244	7,113
Other	1,164	1,265
Total	$ 77,682	$ 91,003

Leases - Additional Information (Detail) $ in Thousands	1 Months Ended						12 Months Ended
Leases - Additional Information (Detail) $ in Thousands	Jul. 31, 2020 USD ($) Term	May 31, 2020 Term	Dec. 31, 2019	May 31, 2019	May 31, 2016	Jun. 30, 2015	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Lessee Lease Description [Line Items]
Operating lease, right-of-use asset							$ 156,921	$ 174,460
Operating lease liability							$ 244,021	$ 225,030
2015 Lease [Member]
Lessee Lease Description [Line Items]
Lease commencement date						Nov. 15, 2015
Lessee, operating lease, option to extend							expired in 2022
Lease expiration year						2022
2016 Sublease [Member]
Lessee Lease Description [Line Items]
Lease commencement date					Dec. 23, 2016
Lease expiration year					2022
2019 Lease [Member]
Lessee Lease Description [Line Items]
Lease commencement date				Jun. 01, 2019
Lessee, operating lease, existence of option to extend				true
Lessee, operating lease, option to extend							an option to extend the term of the lease for an additional five-year period based on certain conditions within the Company’s control
Lease expiration, month and year				2026-11
Extended term of lease expiration				5 years
2019 Sublease [Member]
Lessee Lease Description [Line Items]
Lessee, operating lease, option to extend							expired in 2022
Lease expiration year			2022
Framingham Lease [Member]
Lessee Lease Description [Line Items]
Lease expiration, month and year		2036-03
Lessee, operating sublease, existence of option to extend		true
Number of additional renewal terms \| Term		2
Lease renewal term under each extension option		7 years
2020 Boston Lease [Member]
Lessee Lease Description [Line Items]
Lessee, operating lease, existence of option to extend	true
Lessee, operating lease, option to extend							an option to extend the term of the lease for two additional five-year periods
Lease expiration, month and year	2034-03
Extended term of lease expiration	5 years
Number of additional renewal terms \| Term	2
Operating lease, right-of-use asset	$ 149,800
Operating lease liability	147,900
Tenant incentives	$ 49,200

Leases - Summary of Lease Assets and Liabilities (Detail) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Assets
Operating lease assets	$ 156,921	$ 174,460
Total lease assets	156,921	174,460
Liabilities
Operating lease liabilities, current	15,842	12,158
Operating lease liabilities, net of current portion	228,179	212,872
Total lease liabilities	$ 244,021	$ 225,030

Leases - Summary of Operating Lease Costs Included in Research and Development and General and Administrative Expense, as well as Sublease Income (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Leases [Abstract]
Operating lease costs	$ 34,896	$ 22,520	$ 14,342
Short-term lease costs	824	11,087	7,339
Variable lease costs	11,882	8,402	6,368
Sublease income		(5,253)	(587)
Net lease cost	$ 47,602	$ 36,756	$ 27,462

Leases - Summary of Maturity of Undiscounted Payments Due under Lease Liabilities and Present Value of Those Liabilities (Detail) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Leases [Abstract]
2023	$ 29,270
2024	26,526
2025	26,251
2026	26,745
2027	25,927
Thereafter	205,495
Total	340,214
Present value adjustment	(96,193)
Present value of lease liabilities	$ 244,021	$ 225,030

Leases - Summary of Lease Term and Discount Rate (Detail)	Dec. 31, 2022	Dec. 31, 2021
Leases [Abstract]
Operating leases, weighted-average remaining lease term (years)	11 years 9 months 18 days	12 years 4 months 24 days
Operating leases, weighted-average discount rate	5.90%	5.90%

Leases - Summary of Cash Paid for Amounts Included in Measurement of Lease Liabilities (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Cash paid for amounts included in measurement of lease liabilities:
Operating cash flows used in operating leases	$ (17,004)	$ (19,753)	$ (13,161)
Operating lease non-cash items:
Right-of-use assets increased through lease modifications and reassessments	1,208	(14,230)	3,169
Right-of-use assets obtained in exchange for operating lease liabilities		152,486	$ 13,956
Leasehold improvements paid directly by landlord	$ 19,252	$ 30,500

Commitments and Contingencies - Additional Information (Detail) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Contingencies And Commitments [Line Items]
Deferred Finance Costs, Share Lending Arrangement, Issuance Costs	$ 36.1
Cost sharing expensed relating to patent maintenance, defense and prosecution, incurred	2.2	$ 5.8	$ 4.5
Cost sharing expensed relating to patent maintenance, defense and prosecution, accrued	1.4	$ 4.0
2015 Collaboration Agreement [Member] \| Vertex [Member]
Contingencies And Commitments [Line Items]
Milestone payment receivable	$ 395.0

Significant Contracts - Additional Information (Detail)		1 Months Ended		3 Months Ended	12 Months Ended
Significant Contracts - Additional Information (Detail)	Oct. 26, 2015 USD ($)	Apr. 30, 2021 USD ($)	Oct. 31, 2019 License	Dec. 31, 2019 USD ($)	Dec. 31, 2024 USD ($)	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($) Option	Dec. 31, 2021 USD ($)	Dec. 31, 2020 USD ($)	Jul. 01, 2021	Apr. 30, 2020 USD ($)
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Non-current deferred revenue							$ 12,323,000	$ 12,323,000
Current deferred revenue							0	1,011,000
Collaboration Expense							110,250,000	101,178,000	$ 48,025,000
Defer option amount							0
Defer option specified cost							110,300,000
Exercised option to defer amount							36,100,000
Scenario Forecast [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Defer option specified cost					$ 110,300,000	$ 110,300,000
A&R Vertex JDCA [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Percentage of net profits and net losses		40.00%								40.00%
2019 Collaboration Agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Revenue								12,000,000.0
Vertex Pharmaceuticals Incorporated and Certain of its Subsidiaries [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Nonrefundable upfront payment received	$ 75,000,000.0
Non-current deferred revenue							12,300,000	12,300,000
Transaction price allocated to remaining performance obligations							12,300,000
Revenue								913,100,000
Current deferred revenue							0	0
Maximum potential future payments							775,000,000.0
Collaboration Expense							110,300,000	101,200,000	48,000,000.0
Reimbursements from research and license agreements							37,800,000	47,400,000	$ 27,600,000
Vertex Pharmaceuticals Incorporated and Certain of its Subsidiaries [Member] \| Collaboration Target Options [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Milestone payment receivable							420,000,000.0
Milestone payment receivable							410,000,000.0
Vertex Pharmaceuticals Incorporated and Certain of its Subsidiaries [Member] \| DM1 License [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Revenue								12,000,000.0
Vertex Pharmaceuticals Incorporated and Certain of its Subsidiaries [Member] \| Exclusive License [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Revenue								900,000,000.0
Vertex Pharmaceuticals Incorporated and Certain of its Subsidiaries [Member] \| 2015 Collaboration Agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Milestone payment receivable							$ 395,000,000.0
Percentage of exchange payment of research and development costs							50.00%
Number of options would not be exercised under agreement \| Option							1
Number of remaining options under agreement \| Option							4
Vertex Pharmaceuticals Incorporated and Certain of its Subsidiaries [Member] \| 2019 Collaboration Agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Nonrefundable upfront payment received							$ 175,000,000.0
Maximum potential payments							$ 825,000,000
Percentage of exchange payment of research and development costs							50.00%
Vertex Pharmaceuticals Incorporated and Certain of its Subsidiaries [Member] \| Joint Development Agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Up-front payment received							$ 7,000,000.0
Agreement description							In connection with the JDA, the Company received a $7.0 million up-front payment from Vertex and subsequently received a one-time low seven-digit milestone payment upon the dosing of the second patient in a clinical trial with the initial product candidate.
Vertex Pharmaceuticals Incorporated and Certain of its Subsidiaries [Member] \| Exercise of Exclusive Option [Member] \| Collaboration Target Options [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Milestone payment receivable							$ 10,000,000
Vertex Pharmaceuticals Inc [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Maximum potential future payments							200,000,000.0
Vertex Pharmaceuticals Inc [Member] \| Exclusive License [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Estimated standalone selling price for single collaboration							900,000,000.0
Vertex Pharmaceuticals Inc [Member] \| A&R Vertex JDCA [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Up-front payment received		$ 900,000,000.0					$ 900,000,000.0
Milestone payment receivable		$ 200,000,000.0
Percentage of net profits and net losses		60.00%								60.00%
Additional interest of percentage							10.00%
Vertex Pharmaceuticals Inc [Member] \| 2015 Collaboration Agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Aggregate amount in option exercise payments received				$ 30,000,000.0
Number of exclusive license targets \| License			3
Vertex Pharmaceuticals Inc [Member] \| 2019 Collaboration Agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Milestone payment receivable								$ 12,500,000			$ 25,000,000.0
Remaining milestone payment receivable							$ 775,000,000.0

Share Capital - Additional Information (Detail)	1 Months Ended					12 Months Ended
Share Capital - Additional Information (Detail)	Jul. 31, 2021 USD ($)	Jan. 31, 2021 USD ($) $ / shares shares	Dec. 31, 2020 USD ($)	Jul. 31, 2020 USD ($) $ / shares shares	Aug. 31, 2019 USD ($)	Dec. 31, 2022 USD ($) $ / shares	Dec. 31, 2021 USD ($) $ / shares	Dec. 31, 2020 USD ($) $ / shares shares	Dec. 31, 2022 SFr / shares shares	Dec. 31, 2021 SFr / shares	Dec. 31, 2021 USD ($) shares
Class of Stock [Line Items]
Common stock, shares authorized \| shares									150,347,467		145,364,335
Common shares, par value \| SFr / shares									SFr 0.03	SFr 0.03
Capital reserved for future issuance \| shares									5,025,897
Capital reserved for future issuance held by the Company and its subsidiaries \| shares									4,845,581
Treasury stock, shares \| shares									180,316		180,316
Proceeds from issuance of common shares						$ 970,000	$ 213,267,000	$ 982,289,000
Common Stock, Voting Rights						one vote for each common share
Dividends declared and paid						$ 0
Underwritten Public Offering [Member]
Class of Stock [Line Items]
Common shares sold \| shares				7,400,000
Common shares price per share \| $ / shares				$ 70.00
Proceeds from issuance of common shares				$ 484,800,000
Equity issuance costs				$ 32,500,000
2019 ATM [Member] \| Sales Agreement With Jefferies LLC [Member]
Class of Stock [Line Items]
Common shares sold \| shares								2,200,000
Proceeds from issuance of common shares								$ 195,500,000
Equity issuance costs								$ 4,500,000
Average issue price of common shares \| $ / shares								$ 89.47
2019 ATM [Member] \| Sales Agreement With Jefferies LLC [Member] \| Maximum [Member]
Class of Stock [Line Items]
Aggregate estimated gross proceeds		$ 600,000,000.0			$ 200,000,000.0
2020 ATM [Member] \| Sales Agreement With Jefferies LLC [Member]
Class of Stock [Line Items]
Common shares sold \| shares								1,800,000
Common shares issued \| shares		300,000
Proceeds from issuance of common shares		$ 46,700,000						$ 298,000,000.0
Equity issuance costs		$ 700,000						4,500,000
Payments of stamp taxes related to securities							500,000	4,900,000
Payable of stamp taxes related to securities			$ 4,000,000.0					$ 4,000,000.0			$ 4,000,000.0
Average issue price of common shares \| $ / shares		$ 162.46						$ 169.57
2020 ATM [Member] \| Sales Agreement With Jefferies LLC [Member] \| Maximum [Member]
Class of Stock [Line Items]
Aggregate estimated gross proceeds			$ 350,000.0
2021 ATM [Member] \| Sales Agreement With Jefferies LLC [Member]
Class of Stock [Line Items]
Common shares issued \| shares									1,100,000		1,100,000
Proceeds from issuance of common shares						178,800,000	177,800,000
Equity issuance costs						$ 2,400,000	2,400,000
Payments of stamp taxes related to securities							$ 1,800,000
Average issue price of common shares \| $ / shares						$ 168.79	$ 169.82
2021 ATM [Member] \| Sales Agreement With Jefferies LLC [Member] \| Maximum [Member]
Class of Stock [Line Items]
Aggregate estimated gross proceeds	$ 419,800,000

Share Capital - Schedule of Share Capital (Detail) - shares	Dec. 31, 2022	Dec. 31, 2021
Class of Stock [Line Items]
Authorized share capital	150,347,467	145,364,335
Common shares [Member]
Class of Stock [Line Items]
Registered share capital	82,028,328	80,321,227
Authorized share capital	39,316,975	39,316,975
Common shares [Member] \| Employee Benefit Plans [Member]
Class of Stock [Line Items]
Conditional share capital - Bonds or similar debt instruments	20,799,332	20,806,433
Common shares [Member] \| Bonds or Similar Debt Instruments [Member]
Class of Stock [Line Items]
Conditional share capital - Bonds or similar debt instruments	8,202,832	4,919,700

Equity-based Compensation - Option and Grant Plans - Additional Information (Detail) - shares	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares granted	1,492,589	1,616,255	2,182,773
Minimum [Member] \| Restricted Stock Unit [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, vesting period	2 years
Maximum [Member] \| Restricted Stock Unit [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, vesting period	4 years
Option and Grant Plans [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, vesting period	4 years
Share-based compensation, options, contractual life	10 years
Option and Grant Plans [Member] \| IPO [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares granted	0
2018 Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Number of authorized for issuance	26,705,365
Number of shares available for future grant	10,338,717

Equity-based Compensation - Equity-Based Compensation Expense - Additional Information (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation expense	$ 97,947	$ 102,390	$ 66,018
Total unrecognized compensation expense related to stock options	107,900
Restricted Stock Units [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total unrecognized compensation expense	$ 67,800
Unrecognized compensation expense, remaining weighted-average period for recognition	2 years 3 months 18 days
Stock Options [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized compensation expense, remaining weighted-average period for recognition	2 years 4 months 24 days

Equity-based Compensation - Schedule of Stock-Based Compensation Expense (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]
Stock-based compensation expense	$ 97,947	$ 102,390	$ 66,018
Research and Development [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]
Stock-based compensation expense	53,956	59,683	35,120
General and Administrative [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]
Stock-based compensation expense	$ 43,991	$ 42,707	$ 30,898

Equity-based Compensation - Fair Value of Each Option Issued to Employees and Non-employees Estimated Using Black-Scholes Option-Pricing Model (Detail) - $ / shares	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Share-Based Payment Arrangement [Abstract]
Options granted	1,492,589	1,616,255	2,182,773
Weighted-average exercise price	$ 60.19	$ 124.32	$ 68.91
Weighted-average grant date fair value	$ 38.54	$ 77.38	$ 42.28
Expected volatility	70.20%	70.30%	69.20%
Expected term (in years)	6 years	6 years	6 years
Risk-free interest rate	2.60%	1.00%	0.60%
Expected dividend yield	0.00%	0.00%	0.00%

Equity-based Compensation - Summary of Stock Option Activity (Detail) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Additional Disclosures [Abstract]
Shares, Outstanding, Beginning Balance	7,812,982
Options granted	1,492,589	1,616,255	2,182,773
Shares, Exercised	(1,235,528)
Shares, Cancelled or forfeited	(839,810)
Shares, Outstanding, Ending Balance	7,230,233	7,812,982
Shares, Exercisable	4,769,450
Shares, Vested or expected to vest	7,230,233
Weighted-Average Exercise Price, Outstanding, Beginning Balance	$ 58.07
Weighted-Average Exercise Price, Granted	60.19	$ 124.32	$ 68.91
Weighted-Average Exercise Price, Exercised	29.66
Weighted-Average Exercise Price, Cancelled or forfeited	85.13
Weighted-Average Exercise Price, Outstanding, Ending Balance	60.22	$ 58.07
Weighted-Average Exercise Price, Exercisable	51.76
Weighted-Average Exercise Price, Vested or expected to vest	$ 60.22
Weighted-Average Remaining Contractual Term	7 years	7 years 4 months 24 days
Weighted-Average Remaining Contractual Term, Exercisable	6 years 2 months 12 days
Weighted-Average Remaining Contractual Term, Vested or expected to vest	7 years
Aggregate Intrinsic Value, Outstanding Balance	$ 32,131	$ 219,103
Aggregate Intrinsic Value, Exercisable	30,915
Aggregate Intrinsic Value, Vested or expected to vest	$ 32,131

Equity-based Compensation - Stock Options - Additional Information (Detail) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, options, outstanding	7,230,233	7,812,982
Shares granted	1,492,589	1,616,255	2,182,773
Total intrinsic value of stock options exercised	$ 40.8	$ 119.5	$ 104.2
Performance-Based [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares granted	150,000
Performance-Based [Member] \| Vesting Percentage on First Anniversary [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, options, vested	1,048,911
Share-based compensation, options, outstanding	170,652
Performance-Based [Member] \| Stock Option [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares granted	0	0	0
Market-Based [Member] \| Vesting Percentage on First Anniversary [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, options, vested	150,000
Share-based compensation, options, outstanding	150,000
Market-Based [Member] \| Stock Option [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares granted	0	0	0

Equity-based Compensation - Summary of Restricted Stock Activity (Detail) - Restricted Stock [Member]	12 Months Ended
	Dec. 31, 2022 $ / shares shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unvested, Shares, Beginning Balance \| shares	934,175
Unvested, Shares, Granted \| shares	853,326
Unvested, Shares, Vested \| shares	(237,932)
Unvested, Shares, Cancelled or forfeited \| shares	(224,384)
Unvested, Shares, Ending Balance \| shares	1,325,185
Unvested, Weighted-Average Grant Date Fair Value, Beginning Balance \| $ / shares	$ 100.14
Unvested, Weighted-Average Grant Date Fair Value, Granted \| $ / shares	62.31
Unvested, Weighted-Average Grant Date Fair Value, Vested \| $ / shares	83.88
Unvested, Weighted-Average Grant Date Fair Value, Cancelled or forfeited \| $ / shares	91.69
Unvested, Weighted-Average Grant Date Fair Value, Ending Balance \| $ / shares	$ 80.13

Equity-based Compensation - Restricted Stock - Additional Information (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation expense	$ 97,947	$ 102,390	$ 66,018
Shares granted	1,492,589	1,616,255	2,182,773
Restricted Stock [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total fair value of restricted stock vested	$ 14,300	$ 45,300	$ 21,600
Performance stock units unvested	1,325,185	934,175
Stock units granted	853,326
Performance Shares [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares granted	150,000
Performance stock units unvested	150,000
Stock units granted		0
Performance Shares [Member] \| Minimum [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share based compensation, number of shares eligible to receive	0
Performance Shares [Member] \| Maximum [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share based compensation, number of shares eligible to receive	150,000
Performance Shares [Member] \| Service [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, requisite service period	3 years
Market-Based [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock units granted			0

Equity-based Compensation - Employee Stock Purchase Plan - Additional Information (Detail) - 2016 Employee Stock Purchase Plan [Member] - shares	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Oct. 19, 2016
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share based compensation, number of shares eligible to receive	36,559	21,590
Maximum [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Number of shares authorized			400,000

Net Income (Loss) Per Share Attributable to Common Shareholders - Schedule of Computation of Basic and Diluted Net Income (Loss) per Share (Detail) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Net (loss) income	$ (650,175)	$ 377,661	$ (348,865)
Basic weighted-average common shares outstanding	77,746,575	75,948,686	65,949,672
Effect of potentially dilutive securities:
Diluted weighted-average common shares outstanding	77,746,575	80,393,496	65,949,672
Net (loss) income per common share - basic	$ (8.36)	$ 4.97	$ (5.29)
Net (loss) income per common share - diluted	$ (8.36)	$ 4.70	$ (5.29)
Outstanding Options [Member]
Effect of potentially dilutive securities:
Effect of potentially dilutive securities		3,990,579
Unvested Restricted Common Shares [Member]
Effect of potentially dilutive securities:
Effect of potentially dilutive securities		454,231

Net Income (Loss) Per Share Attributable to Common Shareholders - Schedule of Antidilutive Securities not Include in Computation of Net Income (Loss) per Share (Detail) - shares	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Anti-dilutive securities not include in computation of net income (loss) per share	8,574,523	1,998,456	9,007,329
Outstanding Options [Member]
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Anti-dilutive securities not include in computation of net income (loss) per share	7,230,233	1,765,881	8,101,980
Unvested Restricted Common Shares [Member]
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Anti-dilutive securities not include in computation of net income (loss) per share	1,325,185	225,904	894,092
ESPP [Member]
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Anti-dilutive securities not include in computation of net income (loss) per share	19,105	6,671	11,257

401(k) Savings Plan - Additional Information (Detail) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Retirement Benefits [Abstract]
Company contributions toward the plan	$ 3.2	$ 3.4	$ 1.9

Income Taxes - Schedule of (Loss) Income Before Provision for Income Taxes (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Income Tax Disclosure [Abstract]
Domestic	$ 1,321	$ 4,569	$ 7,630
Foreign	(651,821)	374,962	(355,686)
Net income (loss) before income taxes	$ (650,500)	$ 379,531	$ (348,056)

- Definition

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

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (c)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8933-108599

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 30
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8906-108599

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (f)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8933-108599

Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 940
-SubTopic 20
-Section 25
-Paragraph 1
-URI https://asc.fasb.org/extlink&oid=126941158&loc=d3e41242-110953

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 22
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8736-108599

Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 220
-SubTopic 10
-Section S99
-Paragraph 2
-Subparagraph (SX 210.5-03(10))
-URI https://asc.fasb.org/extlink&oid=126953954&loc=SL114868664-224227

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

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

Reference 9: http://www.xbrl.org/2003/role/exampleRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 31
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8924-108599

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

+ Details

Income Taxes - Schedule of (Provision for) Benefit from Income Taxes (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Current income taxes:
Federal	$ (444)	$ (80)	$ (248)
State	(241)	(42)	(151)
Foreign			(1)
Total current income taxes	(685)	(122)	(400)
Deferred income taxes:
Federal	1,010	(1,748)	(409)
Total deferred income taxes	1,010	(1,748)	(409)
Total income tax benefit (provision)	$ 325	$ (1,870)	$ (809)

- Definition

Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.

+ References + Details

Income Taxes - Schedule of Reconciliation of Income Tax Expense Computed at Statutory Corporate Income Tax Rate to Effective Income Tax Rate (Detail)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Reconciliation of Effective Income Tax Rate
Income tax expense at statutory rate	11.90%	11.90%	11.90%
State income tax, net of federal benefit	1.20%	(1.00%)	1.00%
Nondeductible expenses	(0.20%)	0.70%	0.10%
Foreign rate differential	(0.10%)	0.60%	(0.10%)
Statutory to US GAAP permanent differences	0.00%	0.00%	0.00%
Stock-based compensation	(0.20%)	(2.50%)	2.30%
Impact of deferred rate change	(0.10%)	0.00%	0.00%
Research credits	3.30%	(4.20%)	3.30%
Change in valuation allowance	(15.80%)	(5.00%)	(18.70%)
Effective income tax rate	0.00%	0.50%	(0.20%)

Income Taxes - Schedule of Significant Components of Company's Deferred Tax Assets (Detail) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Deferred tax assets:
Net operating loss carryforwards	$ 118,432	$ 47,190
Accruals and reserves	4,782	5,878
Operating lease liabilities	66,436	61,476
Other deferred tax assets	10,154	6,362
Stock-based compensation	18,034	14,042
Research credit	63,416	37,878
Total deferred tax assets	281,254	172,826
Less valuation allowance	(198,279)	(98,649)
Net deferred tax assets	82,975	74,177
Deferred tax liabilities:
Depreciation	(41,206)	(28,579)
Operating lease assets	(42,678)	(47,521)
Intangible assets	(18)	(31)
Other deferred tax liabilities	(209)	(192)
Total deferred tax liabilities	(84,111)	(76,323)
Long term deferred taxes, liabilities	$ (1,136)	$ (2,146)

Income Taxes - Additional Information (Detail) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Valuation Allowance [Line Items]
Increase in valuation allowance	$ 99,600,000
U.S. federal net operating loss carryforwards	0
Non-US Net operating loss carryforwards	$ 1,979,700,000
Operating loss carryforwards expiration period	2027
Unrecognized tax benefits, gross	$ 34,536,000	$ 21,395,000	$ 11,967,000	$ 5,231,000
Unrecognized tax benefits would favorably impact the effective tax rate if recognized	32,300,000
Accrued interest or penalties related to uncertain tax positions	0	0	0
Uncertain tax positions recognized	0	$ 0	$ 0
U.S. Domestic Federal [Member] \| Research and Development [Member]
Valuation Allowance [Line Items]
Tax credit carryforward amount	$ 27,300,000
Tax credit carryforward, expiration year	2039
Uncertain tax positions	$ 13,900,000
U.S. Domestic Federal [Member] \| Orphan Drug Credit Carryforwards [Member]
Valuation Allowance [Line Items]
Tax credit carryforward amount	$ 22,700,000
Tax credit carryforward, expiration year	2040
Uncertain tax positions	$ 9,800,000
U.S. Domestic State [Member] \| Research and Development [Member]
Valuation Allowance [Line Items]
Tax credit carryforward amount	$ 16,900,000
Tax credit carryforward, expiration year	2035
Uncertain tax positions	$ 10,900,000
Switzerland [Member]
Valuation Allowance [Line Items]
Non-US Net operating loss carryforwards	988,400,000
Canton of Zug [Member]
Valuation Allowance [Line Items]
Non-US Net operating loss carryforwards	988,400,000
United Kingdom [Member]
Valuation Allowance [Line Items]
Non-US Net operating loss carryforwards	$ 2,900,000

Income Taxes - Schedule of Aggregate Changes in Gross Unrecognized Tax Benefits (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Income Tax Disclosure [Abstract]
Balance at beginning of year	$ 21,395	$ 11,967	$ 5,231
Increases for tax positions taken during current period	10,439	9,911	7,004
Increases for tax positions taken in prior periods	2,702
Decreases for tax positions taken in prior periods		(483)	(268)
Balance at end of year	$ 34,536	$ 21,395	$ 11,967