Adverum Biotechnologies (ADVM) 10-K 30 Mar 23 2022 FY Annual report Financial data

Cover Page

Cover Page - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Mar. 17, 2023	Jun. 30, 2022
Cover [Abstract]
Document Type	10-K
Document Annual Report	true
Document Period End Date	Dec. 31, 2022
Current Fiscal Year End Date	--12-31
Document Transition Report	false
Entity File Number	001-36579
Entity Registrant Name	Adverum Biotechnologies, Inc.
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	20-5258327
Entity Address, Address Line One	100 Cardinal Way
Entity Address, City or Town	Redwood City
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	94063
City Area Code	650
Local Phone Number	656-9323
Title of 12(b) Security	Common Stock, par value $0.0001 per share
Trading Symbol	ADVM
Security Exchange Name	NASDAQ
Entity Well-known Seasoned Issuer	No
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Filer Category	Non-accelerated Filer
Entity Small Business	true
Entity Emerging Growth Company	false
ICFR Auditor Attestation Flag	false
Entity Shell Company	false
Entity Public Float			$ 114.9
Entity Common Stock, Shares Outstanding		100,559,291
Documents Incorporated by Reference	Portions of the definitive proxy statement (the Proxy Statement) for the 2023 Annual Meeting of Stockholders of the registrant are incorporated by reference into Part III of this Annual Report on Form 10-K. If the Proxy Statement is not filed by May 1, 2023, then the registrant will file an amendment to this Form 10-K on Form 10-K/A to include the Part III information in this Form 10-K.
Amendment Flag	false
Document Fiscal Year Focus	2022
Document Fiscal Period Focus	FY
Entity Central Index Key	0001501756

Audit Information

Audit Information	12 Months Ended
	Dec. 31, 2022
Audit Information [Abstract]
Auditor Name	Ernst & Young LLP
Auditor Firm ID	42
Auditor Location	San Jose, California

CONSOLIDATED BALANCE SHEETS

CONSOLIDATED BALANCE SHEETS - USD ($)	Dec. 31, 2022	Dec. 31, 2021
Current assets:
Cash and cash equivalents	$ 68,431,000	$ 34,195,000
Short-term investments	117,158,000	270,993,000
Lease incentive receivable	0	5,709,000
Prepaid expenses and other current assets	5,006,000	6,248,000
Total current assets	190,595,000	317,145,000
Operating lease right-of-use assets	78,934,000	86,000,000
Property and equipment, net	34,927,000	33,060,000
Restricted cash	2,503,000	2,503,000
Deferred rent receivable	0	769,000
Deposit and other non-current assets	1,413,000	250,000
Total assets	308,372,000	439,727,000
Current liabilities:
Accounts payable	2,238,000	1,387,000
Accrued expenses and other current liabilities	16,767,000	18,047,000
Lease liability, current portion	13,241,000	1,886,000
Total current liabilities	32,246,000	21,320,000
Long-term liabilities:
Lease liability, net of current portion	93,561,000	101,108,000
Other non-current liabilities	1,047,000	1,114,000
Total liabilities	126,854,000	123,542,000
Commitments and contingencies (Note 7)
Stockholders’ equity:
Preferred stock, $0.0001 par value, 5,000 shares authorized; no shares issued and outstanding	0	0
Common stock, $0.0001 par value, 300,000 shares authorized at December 31, 2022: 100,117 and 98,381 shares issued and outstanding at December 31, 2022 and 2021, respectively	10,000	10,000
Additional paid-in capital	985,651,000	964,965,000
Accumulated other comprehensive loss	(1,531,000)	(714,000)
Accumulated deficit	(802,612,000)	(648,076,000)
Total stockholders’ equity	181,518,000	316,185,000
Total liabilities and stockholders’ equity	$ 308,372,000	$ 439,727,000

CONSOLIDATED BALANCE SHEETS (Pa

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2022	Dec. 31, 2021
Statement of Financial Position [Abstract]
Preferred stock, par value (in USD per share)	$ 0.0001	$ 0.0001
Preferred stock, shares authorized (in shares)	5,000,000	5,000,000
Preferred stock, shares issued (in shares)	0	0
Preferred stock, shares outstanding (in shares)	0	0
Common stock, par value (in USD per share)	$ 0.0001	$ 0.0001
Common stock, shares authorized (in shares)	300,000,000	300,000,000
Common stock, shares issued (in shares)	100,117,000	98,381,000
Common stock, shares outstanding (in shares)	100,117,000	98,381,000

CONSOLIDATED STATEMENTS OF OPER

CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS - USD ($) shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Income Statement [Abstract]
Collaboration and license revenue	$ 0	$ 7,500
Operating expenses:
Research and development	99,277	89,181
General and administrative	57,858	64,441
Total operating expenses	157,135	153,622
Operating loss	(157,135)	(146,122)
Other income, net	2,673	582
Net loss before income taxes	(154,462)	(145,540)
Income tax provision	(74)	0
Net loss	(154,536)	(145,540)
Other comprehensive loss:
Net unrealized loss on marketable securities	(788)	(428)
Foreign currency translation adjustment	(29)	(25)
Comprehensive loss	$ (155,353)	$ (145,993)
Net loss per share - basic (in dollars per share)	$ (1.56)	$ (1.48)
Net loss per share - diluted (in dollars per share)	$ (1.56)	$ (1.48)
Weighted-average common shares outstanding - basic (in shares)	99,251	98,039
Weighted-average common shares outstanding - diluted (in shares)	99,251	98,039

CONSOLIDATED STATEMENTS OF STOC

CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY - USD ($) shares in Thousands, $ in Thousands	Total	Common Stock	Additional Paid-In Capital	Accumulated Other Comprehensive Loss	Accumulated Deficit
Beginning balance (in shares) at Dec. 31, 2020		97,549
Beginning balance at Dec. 31, 2020	$ 434,347	$ 10	$ 937,134	$ (261)	$ (502,536)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock net of issuance costs (in shares)		121
Issuance of common stock net of issuance costs	1,685	$ 0	1,685
Stock-based compensation expense	$ 25,194		25,194
Common stock issued upon exercise of stock options, shares (in shares)	9	9
Common stock issued upon exercise of stock options	$ 51		51
Common stock issued under employee stock purchase plan (in shares)		397
Common stock issued under employee stock purchase plan	901		901
Common stock issued upon release of restricted stock units (in shares)		305
Net unrealized loss on marketable securities	(428)			(428)
Foreign currency translation adjustment	(25)			(25)
Net loss	$ (145,540)				(145,540)
Ending balance (in shares) at Dec. 31, 2021	98,381	98,381
Ending balance at Dec. 31, 2021	$ 316,185	$ 10	964,965	(714)	(648,076)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Stock-based compensation expense	$ 20,079		20,079
Common stock issued upon exercise of stock options, shares (in shares)	15	15
Common stock issued upon exercise of stock options	$ 3		3
Common stock issued under employee stock purchase plan (in shares)		886
Common stock issued under employee stock purchase plan	604		604
Common stock issued upon release of restricted stock units (in shares)		835
Net unrealized loss on marketable securities	(788)			(788)
Foreign currency translation adjustment	(29)			(29)
Net loss	$ (154,536)				(154,536)
Ending balance (in shares) at Dec. 31, 2022	100,117	100,117
Ending balance at Dec. 31, 2022	$ 181,518	$ 10	$ 985,651	$ (1,531)	$ (802,612)

CONSOLIDATED STATEMENTS OF ST_2

CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY (Parenthetical) $ in Thousands	12 Months Ended
	Dec. 31, 2021 USD ($)
Statement of Stockholders' Equity [Abstract]
Issuance costs	$ 9

CONSOLIDATED STATEMENTS OF CASH

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Cash flows from operating activities:
Net loss	$ (154,536)	$ (145,540)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization	6,528	4,645
Stock-based compensation expense	20,079	25,194
Net (accretion) amortization of (discount) premium on marketable securities, net	(880)	2,770
Loss on disposal of property and equipment	122	0
Impairment of long-lived assets	2,124	1,063
Other	(1,417)	(25)
Changes in operating assets and liabilities:
Prepaid expenses and other current assets	1,653	(2,257)
Deposit and other long-term assets and deferred rent receivable	(394)	(990)
Operating lease right-of-use assets	4,040	2,719
Accounts payable	845	(1,612)
Accrued expenses, other current and non-current liabilities	64	3,274
Other non-current liabilities	74	0
Lease liability	13,607	2,928
Net cash used in operating activities	(108,091)	(107,831)
Cash flows from investing activities:
Purchases of marketable securities	(104,363)	(407,514)
Maturities of marketable securities	257,899	492,356
Sales of marketable securities	0	8,990
Purchases of property and equipment	(11,816)	(15,123)
Net cash provided by investing activities	141,720	78,709
Cash flows from financing activities:
Proceeds from offering of common stock, net of issuance costs	0	1,685
Proceeds from issuance of common stock pursuant to option exercises	3	51
Proceeds from employee stock purchase plan	604	901
Repayment of BPI loan	0	(240)
Net cash provided by financing activities	607	2,397
Net increase (decrease) in cash, cash equivalents and restricted cash	34,236	(26,725)
Cash, cash equivalents and restricted cash at beginning of period	36,698	63,423
Cash, cash equivalents and restricted cash at end of period	70,934	36,698
Cash and cash equivalents	68,431	34,195
Restricted cash	2,503	2,503
Cash, cash equivalents and restricted cash at end of period	70,934	36,698
Supplemental schedule of noncash investing information
Right-of-use assets obtained in exchange for lease liability	0	84,005
Decrease in right-of-use asset and lease liability due to termination	0	15,768
Remeasurement of right-of-use asset on lease modification	2,842	2,052
Fixed assets in accounts payable and current liabilities	$ 64	$ 1,402

Description of the business

Description of the business	12 Months Ended
	Dec. 31, 2022
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Description of the Business	Description of the business Nature of Business —Adverum Biotechnologies, Inc. (the “Company” or “Adverum”) was incorporated in Delaware on July 17, 2006 and is headquartered in Redwood City, California. The Company aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases. The Company develops gene therapy product candidates intended to provide durable efficacy by inducing sustained expression of a therapeutic protein. The Company has not generated any revenue from the sale of products since its inception. The Company has experienced net losses since its inception and had an accumulated deficit of $802.6 million as of December 31, 2022. The Company expects to incur losses and have negative net cash flows from operating activities as it engages in further research and development activities. As of December 31, 2022, the Company had cash, cash equivalents and short-term investments of $185.6 million, which the Company believes will be sufficient to fund its operations into 2025.

Summary of Significant Accounti

Summary of Significant Accounting Policies	12 Months Ended
	Dec. 31, 2022
Accounting Policies [Abstract]
Summary of Significant Accounting Policies	Summary of significant accounting policies Basis of Presentation and Principles of Consolidation — The Company’s consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”) and pursuant to the rules and regulations of the Securities and Exchange Commission (“SEC”). The consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries. All intercompany transactions and balances have been eliminated in consolidation. Use of Estimates —The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets, liabilities, and the disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of income and expenses during the reporting period. The Company bases estimates and assumptions on historical experience when available and on various factors that it believes to be reasonable under the circumstances. The Company evaluates its estimates and assumptions, including those related to research and development expense accruals, stock-based compensation expense, income taxes, fair values of financial instruments, and incremental borrowing rate. The Company’s actual results may differ from these estimates under different assumptions or conditions. There have been no significant changes from the Company’s original estimates in any periods presented. Foreign Currency —Assets and liabilities of non-U.S. subsidiaries that operate in a local currency environment, where the local currency is the functional currency, are translated to U.S. dollars at exchange rates in effect at the balance sheet date, with the resulting translation adjustments directly recorded to a separate component of accumulated other comprehensive loss. Upon sale or upon complete or substantially complete liquidation of an investment in a foreign entity, the amount attributable to that entity and accumulated in the translation adjustment component of equity is removed from the separate component of equity and reported as part of the gain or loss on sale or liquidation of the investment for the period during which the sale or liquidation occurs. Income and expense accounts are translated at average exchange rates for the period. Transactions which are not in the functional currency of the entity are remeasured into the functional currency and gains or losses resulting from the remeasurement recorded in other income (expense). Cash and Cash Equivalents —The Company considers all highly liquid investments purchased with original maturities of three months or less at the date of purchase to be cash equivalents. Cash and cash equivalents include cash held in banks, money market accounts and highly liquid debt securities. Cash equivalents are stated at fair value. Restricted Cash —Restricted cash primarily consists of cash collateral to letter of credit provided to the landlord in relation to a lease agreement (see Note 5). Short-Term Investments —All short-term investments in debt securities have been classified as “available for sale” and are carried at fair value. Unrealized gains and losses, net of any related tax effects, are excluded from earnings and are included in other comprehensive loss and reported as a separate component of stockholders’ equity until realized. Realized gains and losses and declines in value judged to be other than temporary, if any, on available-for-sale securities are included in other income (expense), net in the Company’s consolidated statements of operations and comprehensive loss. The cost of securities sold is based on the specific-identification method. The amortized cost of securities is adjusted for amortization of premiums and accretion of discounts to maturity. Interest on short-term investments is included in other income, net in the Company’s consolidated statements of operations and comprehensive loss. In accordance with the Company’s investment policy, management invests to diversify credit risk and only invests in securities with high credit quality, including U.S. government securities. The Company periodically evaluates whether declines in the fair value of its investments below their cost are other than temporary. The evaluation includes consideration of the cause of the impairment, including the creditworthiness of the security issuers, the number of securities in an unrealized loss position, the severity and duration of the unrealized losses, whether the Company has the intent to sell the securities, and whether it is more likely than not that the Company will be required to sell the securities before the recovery of their amortized cost basis. If the Company determines that the decline in fair value of an investment is below its accounting basis and this decline is other than temporary, the Company would reduce the carrying value of the security it holds and records a loss for the amount of such decline. The Company has not recorded any realized losses or declines in value judged to be other than temporary on its investments. Segment Reporting —The Company operates and manages its business as one reporting and operating segment, which is the business of developing and commercializing gene therapeutics. The Company’s chief executive officer, who is the chief operating decision maker, reviews financial information on an aggregate basis for purposes of allocating resources and evaluating financial performance. Concentrations of Credit Risk and Other Uncertainties —Financial instruments that potentially subject the Company to significant concentrations of credit risk consist primarily of cash, cash equivalents and short-term investments. Risks associated with cash, cash equivalents, short-term investments are mitigated by the Company’s investment policy, which limits the Company’s investing to securities having specified credit ratings. Management believes that the Company is not exposed to significant credit risk. The Company is subject to certain risks and uncertainties, including, but not limited to changes in any of the following areas that the Company believes could have a material adverse effect on future financial position or results of operations: the ability to obtain future financing; regulatory approval and market acceptance of, and reimbursement for, the Company’s product candidates; performance of third-party clinical research organizations and manufacturers; development of sales channels; protection of intellectual property; litigation or claims against the Company based on intellectual property, patent, product, regulatory or other factors; and the Company’s ability to attract and retain employees necessary to support growth. As of December 31, 2022, the Company held cash deposits at Silicon Valley Bank (“SVB”) in excess of government insured limits. On March 10, 2023, SVB was closed by the California Department of Financial Protection and Innovation, and the Federal Deposit Insurance Corporation (“FDIC”) was appointed as receiver. On March 12, 2023, the U.S. Treasury Department, the Federal Reserve and the FDIC jointly announced enabling actions that fully protect all SVB depositors’ insured and uninsured deposits, and that such depositors would have access to all of their funds starting March 13, 2023. On March 13, 2023, the Company was able to access its deposits with SVB. As such, no losses have been incurred by the Company on deposits that were held at SVB. Management believes that the Company is not currently exposed to significant credit risk as the Company’s investments are held in custody at a third-party financial institution. Subsequent to March 13, 2023, the Company transferred most of the cash in SVB to a third-party financial institution. As of March 24, 2023, the Company has a remaining $2.5 million deposit with SVB, which secures a letter of credit on a lease. Property and Equipment —Property and equipment are recorded at cost, net of accumulated depreciation and amortization. Depreciation is recorded using the straight-line method over the estimated useful lives of the assets, generally three Valuation of Long-Lived Assets and Purchased Intangible Assets —The Company evaluates the carrying value of amortizable long‑lived assets whenever events, or changes in business circumstances or the planned use of long‑lived assets indicate that their carrying amounts may not be fully recoverable or that their useful lives are no longer appropriate. If these facts and circumstances exist, the Company assesses for recovery by comparing the carrying values of long‑lived assets with their future undiscounted net cash flows. If the comparison indicates that impairment exists, long‑lived assets are written down to their respective fair values based on discounted cash flows. Significant management judgment is required in the forecasting of future operating results that is used in the preparation of expected undiscounted cash flows. If management’s assumptions about future operating results were to change as a result of events or circumstances, the Company may be required to record an impairment loss on these assets. The Company recorded within research and development expense in the consolidated statements of operations and comprehensive loss an impairment charge of $2.1 million as result of an impairment analysis (see Note 6) for the year ended December 31, 2022. Leases — For long-term operating leases, the Company recognizes a right-of-use asset and a lease liability on the Company's consolidated balance sheets. The lease liability is determined as the present value of future lease payments reduced by lease incentives, if any, using an estimated rate of interest that it would pay to borrow equivalent funds on a collateralized basis at the lease commencement date. In order to determine the incremental borrowing rate, the Company estimates its credit rating, adjusts the credit rating for the nature of the collateral, and benchmarks the borrowing rate against observable yields on comparable securities with a similar term. It bases the right-of-use lease asset on the lease liability adjusted for any prepaid or deferred rent. The Company determines the lease term at the commencement date by considering whether renewal options and termination options are reasonably assured of exercise. Rent expense for operating leases is recognized on a straight-line basis over the lease term and is included in operating expenses on the statements of operations and comprehensive loss. The variable lease payments primarily consist of common area maintenance and other operating costs. Sublease income for operating leases is classified as a reduction of rent expense in operating expenses. The difference between sublease income recorded and cash received from the subtenant accrues as a deferred rent receivable. During the year ended December 31, 2022, the Company reassessed the probability of collection of the deferred rent receivable from the subtenant over the remaining term of a sublease. The Company assessed the collectability to be less than probable and recognized an adjustment to eliminate the deferred rent receivable as a current period adjustment to sublease income, resulting in an increase in general and administrative expenses during the year ended December 31, 2022. As a result of the adjustment to eliminate the deferred rent receivable, sublease income for the year ended December 31, 2022 was a negative $0.3 million. The deferred rent receivable as of December 31, 2022 and 2021 was zero and $0.8 million, respectively. Revenue Recognition —The Company has primarily generated revenue through license, research and collaboration arrangements with its strategic partners. Under Topic 606, the Company recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the Company expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that the Company determines are within the scope of ASC 606, the Company performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the Company satisfies a performance obligation. At contract inception, once the contract is determined to be within the scope of ASC 606, the Company assesses the goods or services promised within each contract and determines those that are performance obligations. The Company then recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied. Research and Development Expenses —Research and development expenses are charged to expense as incurred. Research and development expenses include primarily personnel-related costs, stock-based compensation expense, laboratory supplies, consulting costs, external contract research and development expenses, including expenses incurred under agreements with CROs, the cost of acquiring, developing and manufacturing clinical trial materials, and overhead expenses, such as rent, equipment depreciation, insurance and utilities. Advance payments for goods or services for future research and development activities are deferred and expensed as the goods are delivered or the related services are performed. The Company estimates research and clinical trial expenses based on the services performed pursuant to contracts with research institutions and clinical research organizations that conduct and manage nonclinical studies and clinical trials on the Company’s behalf. In accruing service fees, the Company estimates the time period over which services will be performed and the level of effort to be expended in each period. These estimates are based on communications with the third-party service providers and the Company’s estimates of accrued expenses and on information available at each balance sheet date. If the actual timing of the performance of services or the level of effort varies from the estimate, the Company adjusts the accrual accordingly. Fair Value Measurements —Fair value is defined as the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. As such, fair value is a market-based measurement that should be determined based on assumptions that market participants would use in pricing an asset or liability. The carrying amounts of the Company’s financial instruments, including cash equivalents, prepaid and other current assets, accounts payable, accrued expenses and other current liabilities approximate their fair values due to their short-term maturities. Refer to Note 3 for the methodologies and assumptions used in valuing financial instruments. Stock-based Compensation Expense —Stock-based compensation expense related to stock awards to employees is measured at fair value of the award on the date of the grant. The Company estimates the grant-date fair value, and the resulting stock-based compensation expense, using the Black-Scholes valuation model for stock options and employee stock purchase and using intrinsic value, which is the closing price of its common stock on the date of the grant, for restricted stock units (“RSUs”) and performance stock units (“PSUs”). Expense recognition of PSU and performance-based options commences when the associated performance-based criteria are determined to be probable. The fair value of the award that is ultimately expected to vest is recognized as expense on a straight-line basis over the requisite service period, which is generally the vesting period. The Black-Scholes valuation model requires the use of following assumptions: Expected Term —The expected term assumption represents the period that the Company’s stock-based awards are expected to be outstanding and is determined using the simplified method. Expected Volatility —Expected volatility is based on the Company’s historical stock price volatility. Expected Dividend —The Black-Scholes valuation model calls for a single expected dividend yield as an input. The Company has never paid dividends and has no plans to pay dividends. Risk-Free Interest Rate —The risk-free interest rate is based on the U.S. Treasury zero-coupon issues in effect at the time of grant for periods corresponding with the expected term of option. Income Taxes —The Company accounts for income taxes using the asset and liability method. The Company recognizes deferred tax assets and liabilities for the expected future tax consequences of events that have been included in the financial statements or tax returns. Deferred tax assets and liabilities are determined based on the difference between the financial statement and tax basis of assets and liabilities using enacted tax rates in effect for the year in which the differences are expected to reverse. In evaluating the ability to recover its deferred income tax assets, the Company considers all available positive and negative evidence, including its operating results, ongoing tax planning and forecasts of future taxable income on a jurisdiction-by-jurisdiction basis. In the event the Company determines that it would be able to realize its deferred income tax assets in the future in excess of their net recorded amount, it would make an adjustment to the valuation allowance that would reduce the provision for income taxes. Conversely, in the event that all or part of the net deferred tax assets are determined not to be realizable in the future, an adjustment to the valuation allowance would be charged to earnings in the period when such determination is made. As of December 31, 2022 and 2021, the Company has recorded a full valuation allowance on its deferred tax assets. Tax benefits related to uncertain tax positions are recognized when it is more likely than not that a tax position will be sustained upon examination. Interest and penalties related to unrecognized tax liabilities are included within the provision for income tax. Comprehensive Loss —Comprehensive loss comprises net loss and other comprehensive loss. Other comprehensive loss consists of foreign currency translation adjustments and unrealized loss on marketable securities. Basic and Diluted Net Loss Per Share — Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding for the period. Diluted net loss per share is computed by giving effect to all potential dilutive common stock equivalents outstanding for the period using the treasury stock method. Outstanding stock options, RSUs, and employee stock purchase plan (“ESPP”) are considered to be common stock equivalents and are only included in the calculation of diluted net loss per share when their effect is dilutive. Recent Accounting Pronouncements In June 2016, the Financial Accounting Standards Board (“FASB”) issued Accounting Standards Update (“ASU”) 2016-13, Financial Instruments – Credit Losses: Measurement of Credit Losses on Financial Instruments (“Topic 326”) and also issued subsequent amendments to the initial guidance: ASU 2018-19, ASU 2019-04, ASU 2019-05, and ASU 2019-11. The standard requires that financial assets measured at amortized cost be presented at the net amount expected to be collected. The measurement of expected credit losses is based on historical experience, current conditions, and reasonable and supportable forecasts that affect collectability. Topic 326 also eliminates the concept of “other-than-temporary” impairment when evaluating available-for-sale debt securities and instead focuses on determining whether any impairment is a result of a credit loss or other factors. An entity will recognize an allowance for credit losses on available-for-sale debt securities rather than an other-than-temporary impairment that reduces the cost basis of the investment. The Company adopted Topic 326 on January 1, 2023, which had no material impact on the Company’s financial statements and related disclosures.

Fair Value Measurements and Fai

Fair Value Measurements and Fair Value of Financial Instruments	12 Months Ended
	Dec. 31, 2022
Fair Value Disclosures [Abstract]
Fair Value Measurements and Fair Value of Financial Instruments	Fair Value Measurements and Fair Value of Financial Instruments The authoritative guidance on fair value measurements establishes a three-tier fair value hierarchy for disclosure of fair value measurements as follows: Level 1: Quoted prices in active markets for identical assets or liabilities. Level 2: Observable inputs other than Level 1 prices, such as quoted prices for similar assets or liabilities, quoted prices in markets that are not active, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities. Level 3: Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the assets or liabilities. Assets and liabilities measured at fair value are classified in their entirety based on the lowest level of input that is significant to the fair value measurement. The Company’s assessment of the significance of a particular input to the fair value measurement in its entirety requires management to make judgments and consider factors specific to the asset or liability. The fair value of Level 1 securities is determined using quoted prices in active markets for identical assets. Level 1 securities consist of highly liquid money market funds. Financial assets and liabilities are considered Level 2 when their fair values are determined using inputs that are observable in the market or can be derived principally from or corroborated by observable market data such as pricing for similar securities, recently executed transactions, cash flow models with yield curves, and benchmark securities. In addition, Level 2 financial instruments are valued using comparisons to like-kind financial instruments and models that use readily observable market data as their basis. U.S. government and agency securities, commercial paper, corporate bonds and certificates of deposit are valued primarily using market prices of comparable securities, bid/ask quotes, interest rate yields and prepayment spreads and are included in Level 2. The following is a summary of the Company’s cash equivalents and short-term investments (in thousands): December 31, 2022 Amortized Unrealized Unrealized Estimated Level 1 Money market funds $ 10,235 $ — $ — $ 10,235 Level 2 U.S. government and agency securities 59,487 — (824) 58,663 Commercial paper 102,722 — (246) 102,476 Corporate bonds 2,059 — (35) 2,024 Total cash equivalents and short-term investments 174,503 — (1,105) 173,398 Less: Cash equivalents (56,256) — 16 (56,240) Total short-term investments $ 118,247 $ — $ (1,089) $ 117,158 December 31, 2021 Amortized Unrealized Unrealized Estimated Level 1 Money market funds $ 10,311 $ — $ — $ 10,311 Level 2 U.S. government and agency securities 62,268 — (218) 62,050 Commercial paper 177,215 1 (61) 177,155 Corporate bonds 47,323 — (39) 47,284 Total cash equivalents and short-term investments 297,117 1 (318) 296,800 Less: Cash equivalents (25,808) — 1 (25,807) Total short-term investments $ 271,309 $ 1 $ (317) $ 270,993 As the Company may sell these securities at any time for use in current operations even if the securities have not yet reached maturity, all marketable securities are classified as current assets in the Company’s consolidated balance sheet. Management regularly reviews all of the Company’s investments for other-than-temporary declines in estimated fair value. The aggregate fair value of the marketable securities in an unrealized loss position as of December 31, 2022 was $155.5 million, which are highly liquid securities with high credit ratings that have final maturity of less than two years from date of purchase. Management determined that the gross unrealized losses on the Company’s marketable securities as of December 31, 2022 were temporary in nature and none were in continuous loss position for 12 months or more. Management concluded that none of the Company’s marketable securities were other-than-temporarily impaired as of December 31, 2022. As of December 31, 2022, $5.0 million of marketable securities had remaining maturities between one During the year ended December 31, 2022, the Company performed an impairment test to measure certain laboratory equipment at fair value. The assets are measured at fair value using Level 3 inputs on a non-recurring basis as a result of the occurrence of certain triggering events indicating the carrying value of the assets may not be recoverable. See Note 6, Balance Sheet Components for additional information.

Revenue

Revenue	12 Months Ended
	Dec. 31, 2022
Revenue from Contract with Customer [Abstract]
Revenue	Revenue Lexeo — On January 25, 2021, the Company and Lexeo Therapeutics, Inc (“Lexeo”) entered into a License Agreement pursuant to which the Company granted Lexeo an exclusive, worldwide, royalty-bearing license to certain of the Company's intellectual property to develop, manufacture, and commercialize a gene therapy product to treat cardiomyopathy due to Friedreich's Ataxia. Upon execution of the agreement, Lexeo paid the Company a one-time, non-creditable and non-refundable upfront payment of $7.5 million. Under the terms of the agreement, the Company is eligible to receive additional payments upon the achievement of certain milestones. Additionally, the Company will receive royalty payments on net sales subject to a cap and reductions based on patent expiry, anti-stacking, and a defined royalty floor percentage. Under Topic 606, the initial transaction price is the $7.5 million the Company received for the license granted. As described above, the arrangement provides for additional payments to the Company when certain development and commercial milestones are achieved. Because these milestone payments are not within the control of the Company and are not considered probable of being achieved until the events occur, the Company did not include them in the transaction price. The Company recognized $7.5 million of license revenue during the year ended December 31, 2021.

Leases

Leases	12 Months Ended
	Dec. 31, 2022
Leases [Abstract]
Leases	Leases Redwood City As of December 31, 2022, the Company has a lease for facilities in Redwood City, which provided a total of tenant improvement allowances of $6.8 million. Related to the Redwood City lease, the Company provided the landlord with a letter of credit in the amount of $2.5 million, which is classified as restricted cash under long term assets on the Company's consolidated balance sheets. The Redwood City lease expires in December 2031, with an option to extend for a period of eight years. On November 1, 2021, the Company entered into an amendment to terminate the lease of one of its Redwood City premises under the existing lease and paid a termination fee of $0.4 million. Concurrently, the Company entered into an agreement to sublease a portion of such premises at $0.1 million monthly base rent through June 30, 2022. For short-term leases the Company does not recognize a right-of-use asset and lease liability and recognizes the lease expense over the term of the lease on a straight-line basis. North Carolina On January 8, 2021, the Company entered into an operating lease agreement for a building in North Carolina (“NC Premises”). The lease commenced in April 2021 when the Company obtained control of the NC Premises, and the lease term expires in October 2037 with two options to extend the lease term for a period of five years each. On October 26, 2021, the Company entered into a sublease agreement with a subtenant for the North Carolina property through October 2037, the remainder of the lease term. The remainder of the tenant improvement allowance under the original lease of approximately $22.7 million was transferred to the subtenant. This change in the Company’s payment terms with the landlord at the time of the sublease was considered to be a lease modification and the Company remeasured the lease liability on the modification date. The base annual rental rates, payment schedules and amounts under the sublease agreement are substantially the same as the original payment terms by Adverum to the landlord. Sublease income for operating leases is classified as a reduction of rent expense in operating expenses. The difference between sublease income recorded and cash received from the subtenant accrues as a deferred rent receivable. During the year ended December 31, 2022, management reassessed the probability of collection of the deferred rent receivable from the subtenant over the remaining term of a sublease. Management assessed the collectability to be less than probable and the Company recognized an adjustment to eliminate the deferred rent receivable as a current period adjustment to sublease income, resulting in an increase in general and administrative expenses during the year ended December 31, 2022. The deferred rent receivable as of December 31, 2022 and 2021 was zero and $0.8 million, respectively. As of December 31, 2022, the weighted-average remaining lease term was 10.2 years for the Company's leases and the weighted-average Incremental Borrowing Rate (“IBR”) was 9.9%. IBR is an estimated rate of interest used to determine present value of future lease payments in order to measure lease liability, which rate is what the Company would pay to borrow equivalent funds on a collateralized basis at the lease commencement date. In order to determine the IBR, the Company estimates its credit rating, adjusts the credit rating for the nature of the collateral, and benchmarks the borrowing rate against observable yields on comparable securities with a similar term. On March 24, 2023, the Company entered into an agreement to terminate the lease of one of its Redwood City premises, which will be effective September 30, 2023. As of December 31, 2022, including the effect of this subsequent event, the undiscounted future non-cancellable lease payments under the lease agreements are as follows (in thousands): December 31, Operating Leases Sublease Payment Receivable 2023 $ 11,484 $ 5,844 2024 11,857 6,019 2025 12,242 6,200 2026 12,639 6,385 2027 13,050 6,577 Thereafter 104,410 76,174 Total undiscounted lease payments 165,682 107,199 Less: Present value adjustments (74,766) Total $ 90,916 Rent expense for the years ended December 31, 2022, and 2021 was $17.2 million and $12.8 million, respectively, which includes variable lease costs for utilities, parking, maintenance, and real estate taxes. Variable lease expenses for the years ended December 31, 2022 and 2021 were $2.3 million and $1.8 million, respectively. Cash paid for amounts included in the measurement of lease liabilities for the twelve months ended December 31, 2022 and 2021 was $6.0 million and $5.2 million, respectively. Sublease income was $(0.3) million and $1.2 million for the years ended December 31, 2022 and 2021, respectively, which was classified as a general and administrative expense or reduction in general and administrative expense, respectively.

Balance Sheet Components

Balance Sheet Components	12 Months Ended
	Dec. 31, 2022
Balance Sheet Related Disclosures [Abstract]
Balance Sheet Components	Balance Sheet Components Property and Equipment, Net Property and equipment, net consists of the following: December 31, 2022 2021 (In thousands) Computer equipment and software $ 1,325 $ 1,224 Laboratory equipment 14,382 12,778 Furniture and fixtures 868 1,136 Leasehold improvements 34,336 26,701 Construction in progress 1,010 4,395 Total property and equipment 51,921 46,234 Less accumulated depreciation and amortization (16,994) (13,174) Property and equipment, net $ 34,927 $ 33,060 The Company performed an impairment analysis for certain laboratory equipment assets based on the identification of impairment indicators during the year ended December 31, 2022. The analysis determined that the fair value of the assets, which was determined using a market approach, was lower than the carrying value. As a result of the evaluation, an impairment charge of $2.1 million was recognized for the year ended December 31, 2022. The assets indicated as impaired were written down to their estimated fair value. Accrued Expenses and Other Current Liabilities Accrued expenses and other current liabilities consist of the following: December 31, 2022 2021 (In thousands) Compensation expense $ 8,710 $ 9,209 Accrued professional fees 532 550 Accrued nonclinical costs 1,162 2,895 Accrued clinical and process development costs 5,692 2,058 State taxes payable 254 1,318 Other 417 2,017 Total accrued expenses and other current liabilities $ 16,767 $ 18,047

Commitments and Contingencies

Commitments and Contingencies	12 Months Ended
	Dec. 31, 2022
Commitments and Contingencies Disclosure [Abstract]
Commitments and Contingencies	Commitments and Contingencies License Agreements The Company is a party to various agreements, principally relating to licensed technology that requires future payments relating to milestones or royalties on future sales of specified products. Through December 31, 2022, none of the goals had been achieved under the license agreements and no milestones were accrued or payable. Because the achievement of these milestones is not fixed and determinable, such commitments have not been included on the Company’s consolidated balance sheets.

Stock Plans

Stock Plans	12 Months Ended
	Dec. 31, 2022
Share-Based Payment Arrangement [Abstract]
Stock Plans	Stock Plans On December 26, 2006, the Company adopted the 2006 Equity Incentive Plan, which was amended by the board of directors on November 15, 2012 (the “2006 Plan”). The 2006 Plan allowed for the granting of incentive stock options (“ISOs”) and non-qualified stock options (“NSOs”) to the employees, members of the board of directors and consultants of the Company. ISOs were granted only to the Company’s employees, including officers and directors who are also employees. NSOs were granted to employees and consultants. In July 2014, the Company’s board of directors and its stockholders approved the establishment of the 2014 Equity Incentive Award Plan (the “2014 Plan”). Options may no longer be issued under the 2006 Plan after July 30, 2014. In addition, the 2014 Plan provides for annual increases in the number of shares available for issuance thereunder on the first business day of each fiscal year, beginning with the year ended December 31, 2015, equal to four percent (4%) of the number of shares of the Company’s common stock outstanding as of such date or a lesser number of shares as determined by the Company’s board of directors. In October 2017, the Company adopted the 2017 Inducement Plan (the “Inducement Plan”). The Company reserved 600,000 shares for issuance pursuant to stock options and RSUs under the Inducement Plan. The only persons eligible to receive grants of stock options and RSUs under Inducement Plan are individuals who satisfy the standards for inducement grants under Nasdaq guidance that is, generally, a person not previously an employee or director of Adverum, or following a bona fide period of non-employment, as an inducement material to the individual's entering into employment with Adverum. The 2006 Plan, 2014 Plan and Inducement Plan are referred to collectively as the Plans. As of December 31, 2022, a total of 37,900,792 shares of common stock were reserved for issuance and 3,202,937 shares were available for future grants under the Plans. Stock Options Stock options under the 2014 Plan and the Inducement Plan may be granted for periods of up to 10 years and at prices no less than 100% of the estimated fair value of the shares on the date of grant as determined by the board of directors, provided, however, that the exercise price of an ISO and NSO granted to a 10% stockholder may not be less than 110% of the estimated fair value of the shares on the date of grant. Stock options granted to employees and non-employees generally vest ratably over four years. The following table summarizes stock option activity under the Company’s stock plans and related information: (In thousands, except exercise prices and years) Options Weighted- Weighted- Aggregate Intrinsic Value (a) Balance at December 31, 2020 10,432 $ 7.19 8.2 $ 31,626 Granted 8,231 7.04 Exercised (9) 5.86 Cancelled/forfeited (5,366) 10.32 Balance at December 31, 2021 13,288 $ 5.83 6.9 $ 145 Granted 10,933 1.24 Exercised (15) 0.19 Cancelled/forfeited (4,886) 5.29 Balance at December 31, 2022 19,320 $ 3.38 8.0 $ 29 Vested and expected to vest as of December 31, 2022 19,320 $ 5.79 8.0 $ 29 Exercisable at December 31, 2022 6,102 $ 11.03 6.4 $ 29 (a) The aggregate intrinsic value is calculated as the difference between the stock option exercise price and the closing price of the Company’s common stock as quoted on a national exchange. The total intrinsic value of stock options exercised during the years ended December 31, 2022 and 2021 was $18,000 and $0.1 million, respectively. Options granted during the year ended December 31, 2022 include 2.5 million shares of performance-based stock options with both performance and service vesting conditions. The fair value of each stock option issued was estimated at the date of grant using the Black-Scholes valuation model with the following weighted-average assumptions: Options Employee Stock Purchase Plan Years ended December 31, Years ended December 31, 2022 2021 2022 2021 Expected volatility 89% 91% 77% 122% Expected term (in years) 6.0 6.0 1.2 1.2 Expected dividend yield — — — — Risk-free interest rate 2.6% 1.0% 3.0% 0.1% The weighted-average fair values of options granted during the years ended December 31, 2022 and 2021 were $0.93 and $5.18, respectively. As of December 31, 2022, there was $30.4 million of unrecognized stock-based compensation expense related to stock options that is expected to be recognized over a weighted-average period of 2.6 years. RSUs RSUs are share awards that entitle the holder to receive freely tradable shares of the Company’s common stock upon vesting. The fair value of RSUs is based upon the closing sales price of the Company’s common stock on the grant date. RSUs granted to employees generally vest over a 2–4 year period. The following table summarizes the RSU activity under the Company’s stock plans and related information: (In thousands, except grant date fair value and years) Number of Weighted- Weighted- Balance at December 31, 2020 540 $ 6.41 0.8 Granted 2,585 3.90 Vested and released (305) 5.26 Forfeited (694) 5.68 Balance at December 31, 2021 2,126 3.76 1.4 Granted 857 1.43 Vested and released (835) 3.41 Forfeited (455) 3.21 Balance at December 31, 2022 1,693 $ 2.90 1.2 RSUs granted during the year ended December 31, 2022 include 0.4 million shares of performance stock units with both performance and service vesting conditions. During the years ended December 31, 2022 and 2021, total fair value of RSUs vested was $2.8 million and $1.6 million, respectively. The number of RSUs vested includes shares of common stock that the Company withheld on behalf of employees or sold to cover to satisfy the minimum statutory tax withholding requirements. As of December 31, 2022, there was $1.6 million of unrecognized compensation cost related to unvested RSUs that is expected to be recognized over a weighted-average period of 1.5 years. ESPP In July 2014, the Company approved the establishment of the 2014 Employee Stock Purchase Plan (the “ESPP”). The Company reserved 208,833 shares of its common stock for issuance and provided for annual increases in the number of shares available for issuance on the first business day of each fiscal year, beginning in 2015, equal to the lesser of one percent (1%) of the number of the Company’s common stock shares outstanding as of such date or a number of shares as determined by the Company’s board of directors. During the year ended December 31, 2022, 887,061 shares were issued under the ESPP. As of December 31, 2022, a total of 7,043,481 shares of common stock were available for future issuance under the ESPP. As of December 31, 2022, there was $0.6 million of unrecognized compensation cost related to the ESPP. Stock-Based Compensation Recognized in the Consolidated Statement of Operations and Comprehensive Loss The following table presents the Company’s stock-based compensation expense: Years ended December 31, 2022 2021 (In thousands) Research and development $ 7,108 $ 8,875 General and administrative 12,971 16,319 Total share-based compensation expense $ 20,079 $ 25,194

401(k) Savings Plan

401(k) Savings Plan	12 Months Ended
	Dec. 31, 2022
Retirement Benefits [Abstract]
401(k) Savings Plan	401(k) Savings PlanThe Company established a defined-contribution savings plan under Section 401(k) of the Code. 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 amount of contributions that the Company made to the 401(k) Plan during the years ended December 31, 2022 and 2021 was $1.1 million and $1.0 million, respectively.

Restructuring

Restructuring	12 Months Ended
	Dec. 31, 2022
Restructuring and Related Activities [Abstract]
Restructuring	10. Restructuring In July 2022, the Company implemented a restructuring of operations, including reductions in both headcount and expenses, to prioritize its clinical development of ixoberogene soroparvovec (“Ixo-vec”), formerly referred to as ADVM-022, and focus its pipeline strategy on certain highly prevalent ocular diseases. Under the restructuring plan, the Company reduced its workforce by 75 employees (approximately 37%) as of July 6, 2022. Below is a summary of restructuring costs during the year ended December 31, 2022: Severance and Benefits Costs Stock-Based Compensation Total (In thousands) Charges $ 4,632 $ 53 $ 4,685 Cash payments made (4,632) — (4,632) Non-cash — (53) (53) Balance at December 31, 2022 $ — $ — $ — In the year ended December 31, 2022, the Company recorded $4.7 million of restructuring costs, of which $3.7 million was classified as research and development expenses and $1.0 million was classified as general and administrative expenses. The Company completed the restructuring in the fourth quarter of 2022.

Income Taxes

Income Taxes	12 Months Ended
	Dec. 31, 2022
Income Tax Disclosure [Abstract]
Income Taxes	Income Taxes The following table presents domestic and foreign components of loss before provision for income taxes: Years ended December 31, 2022 2021 (In thousands) U.S. $ (154,002) $ (145,375) Foreign (460) (165) Loss before income taxes $ (154,462) $ (145,540) The components of the Company’s income tax provision were as follows: Years ended December 31, 2022 2021 (In thousands) Current: Foreign $ 74 $ — Total current tax provision 74 — Deferred Foreign — — Total deferred tax provision — — Total income tax provision $ 74 $ — Income tax provision for the years ended December 31, 2022 and 2021 differed from the amounts computed by applying the statutory federal income tax rate of 21% to pretax loss as a result of the following: Years ended December 31, 2022 2021 (In thousands) Federal income tax expense at statutory rate $ (32,437) $ (30,563) Stock compensation 3,414 1,662 Non-deductible expenses 52 28 Research and development tax credits (2,529) (2,672) Change in valuation allowance 31,542 41,324 Foreign rate differential (46) (9) Impact of internal reorganization 103 (9,763) Other (25) (7) Total tax provision $ 74 $ — Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. The following table presents significant components of the Company’s deferred tax assets and liabilities: As of December 31, 2022 2021 (In thousands) Deferred tax assets: Net operating loss carryforwards $ 111,709 $ 105,509 Accruals, reserve and other 2,053 2,272 Tax credit carryforwards 21,439 16,838 Stock-based compensation 10,705 9,741 Property and equipment 279 — Intangibles 1,562 1,613 Lease obligation 26,241 24,224 Capital losses 9,850 9,850 Capitalized costs 23,697 — Total deferred tax assets before valuation allowance 207,535 170,047 Valuation allowance (188,141) (148,440) Total deferred tax assets 19,394 21,607 Deferred tax liabilities: Right-of-use assets (19,394) (20,227) Property and equipment — (1,380) Total deferred tax liabilities $ (19,394) $ (21,607) Net deferred tax assets $ — $ — 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 operating losses, the Company has concluded that it is more likely than not that the benefit of its deferred tax assets will not be realized. Accordingly, the Company has provided a full valuation allowance for deferred tax assets as of December 31, 2022 and 2021. The valuation allowance increased approximately $39.7 million and $53.8 million during the years ended December 31, 2022 and 2021, respectively. As of December 31, 2022, the Company had U.S. federal net operating losses (“NOLs”) carryforwards of approximately $418.9 million to offset any future federal income. Approximately $57.3 million of NOLs expire at various years beginning with 2036. As of December 31, 2022, the Company also had U.S. state NOL carryforwards of approximately $239.9 million to offset any future state income. U.S. state NOLs expire at various years beginning with 2037. At December 31, 2022, the Company also had approximately $49.0 million of foreign net operating loss carryforwards which may be available to offset future foreign income; these carryforwards do not expire. As of December 31, 2022, the Company had federal research and development tax credit carryforwards of approximately $17.5 million available to reduce future tax liabilities which expire at various years beginning with 2036. As of December 31, 2022, the Company had state credit carryforwards of approximately $15.5 million available to reduce future tax liabilities which do not expire. Effective January 1, 2022, the Tax Cuts and Jobs Act (“TCJA”) eliminated the option to deduct research and development expenditures in the current year and requires taxpayers to capitalize such expenses pursuant to Internal Revenue Code Section 174. The capitalized expenses are amortized over a 5-year period for domestic expenses and a 15-year period for foreign expenses. As a result of this provision of the TCJA, deferred tax assets related to capitalized research expenses increased by $23.7 million, net of amortization on research expenses capitalized in current year. Under Section 382 and 383 of the Code, our ability to utilize NOL carryforwards or other tax attributes such as research tax credits, in any taxable year may be limited if we have experienced an “ownership change.” Generally, a Section 382 ownership change occurs if there is a cumulative increase of more than 50 percentage points in the stock ownership of one or more stockholders or groups of stockholders who own at least 5% of a corporation’s stock within a specified testing period. Similar rules may apply under state tax laws. Due to a June 30, 2020 ownership change, we determined that certain NOLs and research and development tax credits for both federal and state purposes are subject to the 382 limitation; however, it was determined that there should be no material impact to the ability of the utilization before expiration. The Company files income tax returns in the U.S. federal, state, and foreign jurisdictions. The federal, state and foreign income tax returns are open under the statute of limitations subject to tax examinations for the tax years ended December 31, 2017 through December 31, 2021. To the extent the Company has tax attribute carryforwards, the tax years in which the attribute was generated may still be adjusted upon examination by the Internal Revenue Service, state or foreign tax authorities to the extent utilized in a future period. The Company has total unrecognized tax benefits as of December 31, 2022 and 2021 of approximately $24.7 million and $21.9 million, respectively. As of December 31, 2022, the total amount of unrecognized tax benefits that would affect the Company's effective tax rate, if recognized, is $1.0 million. The Company does not anticipate a significant change to its unrecognized tax benefits over the next twelve months. A reconciliation of the unrecognized tax benefits is as follows: Years ended December 31, 2022 2021 (In thousands) Unrecognized tax benefits as of the beginning of the year $ 21,944 $ 8,677 Increase related to prior year tax provisions 274 10,656 Increase related to current year tax provisions 2,527 2,611 Unrecognized tax benefits as of the end of the year $ 24,745 $ 21,944 The Company recognizes interest and penalties related to uncertain tax positions in income tax expense. As of December 31, 2022 and 2021, the Company accrued interest and penalties related to uncertain tax positions of $0.3 million. There are no ongoing examinations by taxing authorities at this time.

Net Loss per Share

Net Loss per Share	12 Months Ended
	Dec. 31, 2022
Earnings Per Share [Abstract]
Net Loss per Share	Net Loss per Share The following common stock equivalents outstanding at the end of the periods presented were excluded from the calculation of diluted net loss per share for the periods indicated because including them would have had an anti-dilutive effect: As of December 31, 2022 2021 (In thousands) Stock options 19,320 13,288 Restricted stock units 1,693 2,126 ESPP 307 148 21,320 15,562

Summary of Significant Accoun_2

Summary of Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2022
Accounting Policies [Abstract]
Basis of Presentation and Principles of Consolidation	Basis of Presentation and Principles of Consolidation — The Company’s consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”) and pursuant to the rules and regulations of the Securities and Exchange Commission (“SEC”). The consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries. All intercompany transactions and balances have been eliminated in consolidation.
Use of Estimates	Use of Estimates —The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets, liabilities, and the disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of income and expenses during the reporting period. The Company bases estimates and assumptions on historical experience when available and on various factors that it believes to be reasonable under the circumstances. The Company evaluates its estimates and assumptions, including those related to research and development expense accruals, stock-based compensation expense, income taxes, fair values of financial instruments, and incremental borrowing rate. The Company’s actual results may differ from these estimates under different assumptions or conditions. There have been no significant changes from the Company’s original estimates in any periods presented.
Foreign Currency	Foreign Currency —Assets and liabilities of non-U.S. subsidiaries that operate in a local currency environment, where the local currency is the functional currency, are translated to U.S. dollars at exchange rates in effect at the balance sheet date, with the resulting translation adjustments directly recorded to a separate component of accumulated other comprehensive loss. Upon sale or upon complete or substantially complete liquidation of an investment in a foreign entity, the amount attributable to that entity and accumulated in the translation adjustment component of equity is removed from the separate component of equity and reported as part of the gain or loss on sale or liquidation of the investment for the period during which the sale or liquidation occurs. Income and expense accounts are translated at average exchange rates for the period. Transactions which are not in the functional currency of the entity are remeasured into the functional currency and gains or losses resulting from the remeasurement recorded in other income (expense).
Cash and Cash Equivalents	Cash and Cash Equivalents —The Company considers all highly liquid investments purchased with original maturities of three months or less at the date of purchase to be cash equivalents. Cash and cash equivalents include cash held in banks, money market accounts and highly liquid debt securities. Cash equivalents are stated at fair value.
Restricted Cash	Restricted Cash —Restricted cash primarily consists of cash collateral to letter of credit provided to the landlord in relation to a lease agreement (see Note 5).
Short-Term Investments	Short-Term Investments —All short-term investments in debt securities have been classified as “available for sale” and are carried at fair value. Unrealized gains and losses, net of any related tax effects, are excluded from earnings and are included in other comprehensive loss and reported as a separate component of stockholders’ equity until realized. Realized gains and losses and declines in value judged to be other than temporary, if any, on available-for-sale securities are included in other income (expense), net in the Company’s consolidated statements of operations and comprehensive loss. The cost of securities sold is based on the specific-identification method. The amortized cost of securities is adjusted for amortization of premiums and accretion of discounts to maturity. Interest on short-term investments is included in other income, net in the Company’s consolidated statements of operations and comprehensive loss. In accordance with the Company’s investment policy, management invests to diversify credit risk and only invests in securities with high credit quality, including U.S. government securities. The Company periodically evaluates whether declines in the fair value of its investments below their cost are other than temporary. The evaluation includes consideration of the cause of the impairment, including the creditworthiness of the security issuers, the number of securities in an unrealized loss position, the severity and duration of the unrealized losses, whether the Company has the intent to sell the securities, and whether it is more likely than not that the Company will be required to sell the securities before the recovery of their amortized cost basis. If the Company determines that the decline in fair value of an investment is below its accounting basis and this decline is other than temporary, the Company would reduce the carrying value of the security it holds and records a loss for the amount of such decline. The Company has not recorded any realized losses or declines in value judged to be other than temporary on its investments.
Segment Reporting	Segment Reporting —The Company operates and manages its business as one reporting and operating segment, which is the business of developing and commercializing gene therapeutics. The Company’s chief executive officer, who is the chief operating decision maker, reviews financial information on an aggregate basis for purposes of allocating resources and evaluating financial performance.
Concentrations of Credit Risk and Other Uncertainties	Concentrations of Credit Risk and Other Uncertainties —Financial instruments that potentially subject the Company to significant concentrations of credit risk consist primarily of cash, cash equivalents and short-term investments. Risks associated with cash, cash equivalents, short-term investments are mitigated by the Company’s investment policy, which limits the Company’s investing to securities having specified credit ratings. Management believes that the Company is not exposed to significant credit risk. The Company is subject to certain risks and uncertainties, including, but not limited to changes in any of the following areas that the Company believes could have a material adverse effect on future financial position or results of operations: the ability to obtain future financing; regulatory approval and market acceptance of, and reimbursement for, the Company’s product candidates; performance of third-party clinical research organizations and manufacturers; development of sales channels; protection of intellectual property; litigation or claims against the Company based on intellectual property, patent, product, regulatory or other factors; and the Company’s ability to attract and retain employees necessary to support growth. As of December 31, 2022, the Company held cash deposits at Silicon Valley Bank (“SVB”) in excess of government insured limits. On March 10, 2023, SVB was closed by the California Department of Financial Protection and Innovation, and the Federal Deposit Insurance Corporation (“FDIC”) was appointed as receiver. On March 12, 2023, the U.S. Treasury Department, the Federal Reserve and the FDIC jointly announced enabling actions that fully protect all SVB depositors’ insured and uninsured deposits, and that such depositors would have access to all of their funds starting March 13, 2023. On March 13, 2023, the Company was able to access its deposits with SVB. As such, no losses have been incurred by the Company on deposits that were held at SVB. Management believes that the Company is not currently exposed to significant credit risk as the Company’s investments are held in custody at a third-party financial institution. Subsequent to March 13, 2023, the Company transferred most of the cash in SVB to a third-party financial institution. As of March 24, 2023, the Company has a remaining $2.5 million deposit with SVB, which secures a letter of credit on a lease.
Property and Equipment	Property and Equipment —Property and equipment are recorded at cost, net of accumulated depreciation and amortization. Depreciation is recorded using the straight-line method over the estimated useful lives of the assets, generally three
Valuation of Long-Lived Assets and Purchased Intangible Assets	Valuation of Long-Lived Assets and Purchased Intangible Assets —The Company evaluates the carrying value of amortizable long‑lived assets whenever events, or changes in business circumstances or the planned use of long‑lived assets indicate that their carrying amounts may not be fully recoverable or that their useful lives are no longer appropriate. If these facts and circumstances exist, the Company assesses for recovery by comparing the carrying values of long‑lived assets with their future undiscounted net cash flows. If the comparison indicates that impairment exists, long‑lived assets are written down to their respective fair values based on discounted cash flows. Significant management judgment is required in the forecasting of future operating results that is used in the preparation of expected undiscounted cash flows. If management’s assumptions about future operating results were to change as a result of events or circumstances, the Company may be required to record an impairment loss on these assets. The Company recorded within research and development expense in the consolidated statements of operations and comprehensive loss an impairment charge of $2.1 million as result of an impairment analysis (see Note 6) for the year ended December 31, 2022.
Leases	Leases — For long-term operating leases, the Company recognizes a right-of-use asset and a lease liability on the Company's consolidated balance sheets. The lease liability is determined as the present value of future lease payments reduced by lease incentives, if any, using an estimated rate of interest that it would pay to borrow equivalent funds on a collateralized basis at the lease commencement date. In order to determine the incremental borrowing rate, the Company estimates its credit rating, adjusts the credit rating for the nature of the collateral, and benchmarks the borrowing rate against observable yields on comparable securities with a similar term. It bases the right-of-use lease asset on the lease liability adjusted for any prepaid or deferred rent. The Company determines the lease term at the commencement date by considering whether renewal options and termination options are reasonably assured of exercise. Rent expense for operating leases is recognized on a straight-line basis over the lease term and is included in operating expenses on the statements of operations and comprehensive loss. The variable lease payments primarily consist of common area maintenance and other operating costs. Sublease income for operating leases is classified as a reduction of rent expense in operating expenses. The difference between sublease income recorded and cash received from the subtenant accrues as a deferred rent receivable. During the year ended December 31, 2022, the Company reassessed the probability of collection of the deferred rent receivable from the subtenant over the remaining term of a sublease. The Company assessed the collectability to be less than probable and recognized an adjustment to eliminate the deferred rent receivable as a current period adjustment to sublease income, resulting in an increase in general and administrative expenses during the year ended December 31, 2022. As a result of the adjustment to eliminate the deferred rent receivable, sublease income for the year ended December 31, 2022 was a negative $0.3 million. The deferred rent receivable as of December 31, 2022 and 2021 was zero and $0.8 million, respectively.
Revenue Recognition	Revenue Recognition —The Company has primarily generated revenue through license, research and collaboration arrangements with its strategic partners. Under Topic 606, the Company recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the Company expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that the Company determines are within the scope of ASC 606, the Company performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the Company satisfies a performance obligation. At contract inception, once the contract is determined to be within the scope of ASC 606, the Company assesses the goods or services promised within each contract and determines those that are performance obligations. The Company then recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied.
Research and Development Expenses	Research and Development Expenses —Research and development expenses are charged to expense as incurred. Research and development expenses include primarily personnel-related costs, stock-based compensation expense, laboratory supplies, consulting costs, external contract research and development expenses, including expenses incurred under agreements with CROs, the cost of acquiring, developing and manufacturing clinical trial materials, and overhead expenses, such as rent, equipment depreciation, insurance and utilities. Advance payments for goods or services for future research and development activities are deferred and expensed as the goods are delivered or the related services are performed.
Fair Value Measurements	Fair Value Measurements —Fair value is defined as the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. As such, fair value is a market-based measurement that should be determined based on assumptions that market participants would use in pricing an asset or liability. The carrying amounts of the Company’s financial instruments, including cash equivalents, prepaid and other current assets, accounts payable, accrued expenses and other current liabilities approximate their fair values due to their short-term maturities. Refer to Note 3 for the methodologies and assumptions used in valuing financial instruments.
Stock-based Compensation Expense	Stock-based Compensation Expense —Stock-based compensation expense related to stock awards to employees is measured at fair value of the award on the date of the grant. The Company estimates the grant-date fair value, and the resulting stock-based compensation expense, using the Black-Scholes valuation model for stock options and employee stock purchase and using intrinsic value, which is the closing price of its common stock on the date of the grant, for restricted stock units (“RSUs”) and performance stock units (“PSUs”). Expense recognition of PSU and performance-based options commences when the associated performance-based criteria are determined to be probable. The fair value of the award that is ultimately expected to vest is recognized as expense on a straight-line basis over the requisite service period, which is generally the vesting period. The Black-Scholes valuation model requires the use of following assumptions: Expected Term —The expected term assumption represents the period that the Company’s stock-based awards are expected to be outstanding and is determined using the simplified method. Expected Volatility —Expected volatility is based on the Company’s historical stock price volatility. Expected Dividend —The Black-Scholes valuation model calls for a single expected dividend yield as an input. The Company has never paid dividends and has no plans to pay dividends. Risk-Free Interest Rate —The risk-free interest rate is based on the U.S. Treasury zero-coupon issues in effect at the time of grant for periods corresponding with the expected term of option.
Income Taxes	Income Taxes —The Company accounts for income taxes using the asset and liability method. The Company recognizes deferred tax assets and liabilities for the expected future tax consequences of events that have been included in the financial statements or tax returns. Deferred tax assets and liabilities are determined based on the difference between the financial statement and tax basis of assets and liabilities using enacted tax rates in effect for the year in which the differences are expected to reverse. In evaluating the ability to recover its deferred income tax assets, the Company considers all available positive and negative evidence, including its operating results, ongoing tax planning and forecasts of future taxable income on a jurisdiction-by-jurisdiction basis. In the event the Company determines that it would be able to realize its deferred income tax assets in the future in excess of their net recorded amount, it would make an adjustment to the valuation allowance that would reduce the provision for income taxes. Conversely, in the event that all or part of the net deferred tax assets are determined not to be realizable in the future, an adjustment to the valuation allowance would be charged to earnings in the period when such determination is made. As of December 31, 2022 and 2021, the Company has recorded a full valuation allowance on its deferred tax assets. Tax benefits related to uncertain tax positions are recognized when it is more likely than not that a tax position will be sustained upon examination. Interest and penalties related to unrecognized tax liabilities are included within the provision for income tax.
Comprehensive Loss	Comprehensive Loss—Comprehensive loss comprises net loss and other comprehensive loss. Other comprehensive loss consists of foreign currency translation adjustments and unrealized loss on marketable securities.
Basic and Diluted Net Loss Per Share	Basic and Diluted Net Loss Per Share — Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding for the period. Diluted net loss per share is computed by giving effect to all potential dilutive common stock equivalents outstanding for the period using the treasury stock method. Outstanding stock options, RSUs, and employee stock purchase plan (“ESPP”) are considered to be common stock equivalents and are only included in the calculation of diluted net loss per share when their effect is dilutive.
Recent Accounting Pronouncements	Recent Accounting Pronouncements In June 2016, the Financial Accounting Standards Board (“FASB”) issued Accounting Standards Update (“ASU”) 2016-13, Financial Instruments – Credit Losses: Measurement of Credit Losses on Financial Instruments (“Topic 326”) and also issued subsequent amendments to the initial guidance: ASU 2018-19, ASU 2019-04, ASU 2019-05, and ASU 2019-11. The standard requires that financial assets measured at amortized cost be presented at the net amount expected to be collected. The measurement of expected credit losses is based on historical experience, current conditions, and reasonable and supportable forecasts that affect collectability. Topic 326 also eliminates the concept of “other-than-temporary” impairment when evaluating available-for-sale debt securities and instead focuses on determining whether any impairment is a result of a credit loss or other factors. An entity will recognize an allowance for credit losses on available-for-sale debt securities rather than an other-than-temporary impairment that reduces the cost basis of the investment. The Company adopted Topic 326 on January 1, 2023, which had no material impact on the Company’s financial statements and related disclosures.

Fair Value Measurements and F_2

Fair Value Measurements and Fair Value of Financial Instruments (Tables)	12 Months Ended
	Dec. 31, 2022
Fair Value Disclosures [Abstract]
Schedule of Cash Equivalents and Short-term Investments	The following is a summary of the Company’s cash equivalents and short-term investments (in thousands): December 31, 2022 Amortized Unrealized Unrealized Estimated Level 1 Money market funds $ 10,235 $ — $ — $ 10,235 Level 2 U.S. government and agency securities 59,487 — (824) 58,663 Commercial paper 102,722 — (246) 102,476 Corporate bonds 2,059 — (35) 2,024 Total cash equivalents and short-term investments 174,503 — (1,105) 173,398 Less: Cash equivalents (56,256) — 16 (56,240) Total short-term investments $ 118,247 $ — $ (1,089) $ 117,158 December 31, 2021 Amortized Unrealized Unrealized Estimated Level 1 Money market funds $ 10,311 $ — $ — $ 10,311 Level 2 U.S. government and agency securities 62,268 — (218) 62,050 Commercial paper 177,215 1 (61) 177,155 Corporate bonds 47,323 — (39) 47,284 Total cash equivalents and short-term investments 297,117 1 (318) 296,800 Less: Cash equivalents (25,808) — 1 (25,807) Total short-term investments $ 271,309 $ 1 $ (317) $ 270,993

Leases (Tables)

Leases (Tables)	12 Months Ended
	Dec. 31, 2022
Leases [Abstract]
Schedule of Undiscounted Future Lease Payments under Operating Lease	As of December 31, 2022, including the effect of this subsequent event, the undiscounted future non-cancellable lease payments under the lease agreements are as follows (in thousands): December 31, Operating Leases Sublease Payment Receivable 2023 $ 11,484 $ 5,844 2024 11,857 6,019 2025 12,242 6,200 2026 12,639 6,385 2027 13,050 6,577 Thereafter 104,410 76,174 Total undiscounted lease payments 165,682 107,199 Less: Present value adjustments (74,766) Total $ 90,916

Balance Sheet Components (Table

Balance Sheet Components (Tables)	12 Months Ended
	Dec. 31, 2022
Balance Sheet Related Disclosures [Abstract]
Schedule of Property and Equipment, Net	Property and equipment, net consists of the following: December 31, 2022 2021 (In thousands) Computer equipment and software $ 1,325 $ 1,224 Laboratory equipment 14,382 12,778 Furniture and fixtures 868 1,136 Leasehold improvements 34,336 26,701 Construction in progress 1,010 4,395 Total property and equipment 51,921 46,234 Less accumulated depreciation and amortization (16,994) (13,174) Property and equipment, net $ 34,927 $ 33,060
Schedule of Accrued Expenses and Other Current Liabilities	Accrued expenses and other current liabilities consist of the following: December 31, 2022 2021 (In thousands) Compensation expense $ 8,710 $ 9,209 Accrued professional fees 532 550 Accrued nonclinical costs 1,162 2,895 Accrued clinical and process development costs 5,692 2,058 State taxes payable 254 1,318 Other 417 2,017 Total accrued expenses and other current liabilities $ 16,767 $ 18,047

Stock Plans (Tables)

Stock Plans (Tables)	12 Months Ended
	Dec. 31, 2022
Share-Based Payment Arrangement [Abstract]
Schedule of Stock Options Activity	The following table summarizes stock option activity under the Company’s stock plans and related information: (In thousands, except exercise prices and years) Options Weighted- Weighted- Aggregate Intrinsic Value (a) Balance at December 31, 2020 10,432 $ 7.19 8.2 $ 31,626 Granted 8,231 7.04 Exercised (9) 5.86 Cancelled/forfeited (5,366) 10.32 Balance at December 31, 2021 13,288 $ 5.83 6.9 $ 145 Granted 10,933 1.24 Exercised (15) 0.19 Cancelled/forfeited (4,886) 5.29 Balance at December 31, 2022 19,320 $ 3.38 8.0 $ 29 Vested and expected to vest as of December 31, 2022 19,320 $ 5.79 8.0 $ 29 Exercisable at December 31, 2022 6,102 $ 11.03 6.4 $ 29 (a) The aggregate intrinsic value is calculated as the difference between the stock option exercise price and the closing price of the Company’s common stock as quoted on a national exchange.
Schedule of Fair Value of Option Issued Valuation Assumptions	The fair value of each stock option issued was estimated at the date of grant using the Black-Scholes valuation model with the following weighted-average assumptions: Options Employee Stock Purchase Plan Years ended December 31, Years ended December 31, 2022 2021 2022 2021 Expected volatility 89% 91% 77% 122% Expected term (in years) 6.0 6.0 1.2 1.2 Expected dividend yield — — — — Risk-free interest rate 2.6% 1.0% 3.0% 0.1%
Schedule of Restricted Stock Units Activity	The following table summarizes the RSU activity under the Company’s stock plans and related information: (In thousands, except grant date fair value and years) Number of Weighted- Weighted- Balance at December 31, 2020 540 $ 6.41 0.8 Granted 2,585 3.90 Vested and released (305) 5.26 Forfeited (694) 5.68 Balance at December 31, 2021 2,126 3.76 1.4 Granted 857 1.43 Vested and released (835) 3.41 Forfeited (455) 3.21 Balance at December 31, 2022 1,693 $ 2.90 1.2
Schedule of Stock-based Compensation Expense	The following table presents the Company’s stock-based compensation expense: Years ended December 31, 2022 2021 (In thousands) Research and development $ 7,108 $ 8,875 General and administrative 12,971 16,319 Total share-based compensation expense $ 20,079 $ 25,194

Restructuring (Tables)

Restructuring (Tables)	12 Months Ended
	Dec. 31, 2022
Restructuring and Related Activities [Abstract]
Schedule of Restructuring Cost	Below is a summary of restructuring costs during the year ended December 31, 2022: Severance and Benefits Costs Stock-Based Compensation Total (In thousands) Charges $ 4,632 $ 53 $ 4,685 Cash payments made (4,632) — (4,632) Non-cash — (53) (53) Balance at December 31, 2022 $ — $ — $ —

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2022
Income Tax Disclosure [Abstract]
Schedule of Components of Loss Before Income Taxes	The following table presents domestic and foreign components of loss before provision for income taxes: Years ended December 31, 2022 2021 (In thousands) U.S. $ (154,002) $ (145,375) Foreign (460) (165) Loss before income taxes $ (154,462) $ (145,540)
Schedule of Components of Income Tax Provision	The components of the Company’s income tax provision were as follows: Years ended December 31, 2022 2021 (In thousands) Current: Foreign $ 74 $ — Total current tax provision 74 — Deferred Foreign — — Total deferred tax provision — — Total income tax provision $ 74 $ —
Schedule of Reconciliation of Income Tax Expense Computed Statutory Federal Income Tax and Financial Statements	Income tax provision for the years ended December 31, 2022 and 2021 differed from the amounts computed by applying the statutory federal income tax rate of 21% to pretax loss as a result of the following: Years ended December 31, 2022 2021 (In thousands) Federal income tax expense at statutory rate $ (32,437) $ (30,563) Stock compensation 3,414 1,662 Non-deductible expenses 52 28 Research and development tax credits (2,529) (2,672) Change in valuation allowance 31,542 41,324 Foreign rate differential (46) (9) Impact of internal reorganization 103 (9,763) Other (25) (7) Total tax provision $ 74 $ —
Schedule of Deferred Tax Assets	The following table presents significant components of the Company’s deferred tax assets and liabilities: As of December 31, 2022 2021 (In thousands) Deferred tax assets: Net operating loss carryforwards $ 111,709 $ 105,509 Accruals, reserve and other 2,053 2,272 Tax credit carryforwards 21,439 16,838 Stock-based compensation 10,705 9,741 Property and equipment 279 — Intangibles 1,562 1,613 Lease obligation 26,241 24,224 Capital losses 9,850 9,850 Capitalized costs 23,697 — Total deferred tax assets before valuation allowance 207,535 170,047 Valuation allowance (188,141) (148,440) Total deferred tax assets 19,394 21,607 Deferred tax liabilities: Right-of-use assets (19,394) (20,227) Property and equipment — (1,380) Total deferred tax liabilities $ (19,394) $ (21,607) Net deferred tax assets $ — $ —
Schedule of Unrecognized Tax Benefits	A reconciliation of the unrecognized tax benefits is as follows: Years ended December 31, 2022 2021 (In thousands) Unrecognized tax benefits as of the beginning of the year $ 21,944 $ 8,677 Increase related to prior year tax provisions 274 10,656 Increase related to current year tax provisions 2,527 2,611 Unrecognized tax benefits as of the end of the year $ 24,745 $ 21,944

Net Loss per Share (Tables)

Net Loss per Share (Tables)	12 Months Ended
	Dec. 31, 2022
Earnings Per Share [Abstract]
Schedule of Antidilutive Common Stock Equivalents Excluded from Calculation of Diluted Net Loss Per Share	The following common stock equivalents outstanding at the end of the periods presented were excluded from the calculation of diluted net loss per share for the periods indicated because including them would have had an anti-dilutive effect: As of December 31, 2022 2021 (In thousands) Stock options 19,320 13,288 Restricted stock units 1,693 2,126 ESPP 307 148 21,320 15,562

Description of the business - A

Description of the business - Additional Information (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Accumulated deficit	$ 802,612	$ 648,076
Cash, cash equivalents, and short-term investments	$ 185,600

Summary of Significant Accoun_3

Summary of Significant Accounting Policies - Additional Information (Details)	2 Months Ended	12 Months Ended
	Mar. 13, 2023 USD ($)	Dec. 31, 2022 USD ($) segment	Dec. 31, 2021 USD ($)	Mar. 24, 2023 USD ($)
Summary Of Significant Accounting Policies [Line Items]
Number of reportable segments | segment		1
Number of operating segments | segment		1
Deposits		$ 185,600,000
Impairment of long-lived assets		2,124,000	$ 1,063,000
Negative sublease income		300,000	(1,200,000)
Deferred rent receivable		$ 0	$ 769,000
Subsequent Event | Silicon Valley Bank
Summary Of Significant Accounting Policies [Line Items]
Losses incurred on deposits	$ 0
Deposits				$ 2,500,000
Minimum
Summary Of Significant Accounting Policies [Line Items]
Estimated useful life of assets (in years)		3 years
Maximum
Summary Of Significant Accounting Policies [Line Items]
Estimated useful life of assets (in years)		5 years

Fair Value Measurements and F_3

Fair Value Measurements and Fair Value of Financial Instruments - Schedule of Cash Equivalents and Short-term Investments (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Debt Securities, Available-for-sale [Line Items]
Amortized Cost Basis	$ 118,247	$ 271,309
Unrealized Gains	0	1
Unrealized Losses	(1,089)	(317)
Estimated Fair Value	117,158	270,993
Less: Cash equivalents, amortized cost basis	(56,256)	(25,808)
Less: Cash equivalents	0	0
Less: Cash equivalents, unrealized losses	16	1
Less: Cash equivalents, estimated fair value	(56,240)	(25,807)
Total cash equivalents and short-term investments
Debt Securities, Available-for-sale [Line Items]
Amortized Cost Basis	174,503	297,117
Unrealized Gains	0	1
Unrealized Losses	(1,105)	(318)
Estimated Fair Value	173,398	296,800
Level 1 | Money market funds
Debt Securities, Available-for-sale [Line Items]
Amortized Cost Basis	10,235	10,311
Unrealized Gains	0	0
Unrealized Losses	0	0
Estimated Fair Value	10,235	10,311
Level 2 | U.S. government and agency securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost Basis	59,487	62,268
Unrealized Gains	0	0
Unrealized Losses	(824)	(218)
Estimated Fair Value	58,663	62,050
Level 2 | Commercial paper
Debt Securities, Available-for-sale [Line Items]
Amortized Cost Basis	102,722	177,215
Unrealized Gains	0	1
Unrealized Losses	(246)	(61)
Estimated Fair Value	102,476	177,155
Level 2 | Corporate bonds
Debt Securities, Available-for-sale [Line Items]
Amortized Cost Basis	2,059	47,323
Unrealized Gains	0	0
Unrealized Losses	(35)	(39)
Estimated Fair Value	$ 2,024	$ 47,284

Fair Value Measurements and F_4

Fair Value Measurements and Fair Value of Financial Instruments - Additional Information (Details)	Dec. 31, 2022 USD ($)
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Fair value of marketable securities in an unrealized loss position	$ 155,500,000
Marketable securities other-than-temporarily impaired	0
Marketable securities	$ 5,000,000
Minimum
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Marketable securities term (in years)	1 year
Maximum
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Marketable securities term (in years)	2 years

Revenue - Additional Informatio

Revenue - Additional Information (Details) - USD ($) $ in Thousands		12 Months Ended
	Jan. 25, 2021	Dec. 31, 2022	Dec. 31, 2021
Disaggregation of Revenue [Line Items]
Collaboration and license revenue	$ 7,500	$ 0	$ 7,500
Lexeo Therapeutics, Inc
Disaggregation of Revenue [Line Items]
Collaboration and license revenue	$ 7,500

Leases - Additional Information

Leases - Additional Information (Details)			12 Months Ended
	Nov. 01, 2021 USD ($)	Jan. 08, 2021 segment	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Oct. 26, 2021 USD ($)
Lessee, Lease, Description [Line Items]
Restricted cash			$ 2,503,000	$ 2,503,000
Deferred rent receivable			0	769,000
Rent expense			17,200,000	12,800,000
Variable lease costs			2,300,000	1,800,000
Operating lease, payments			6,000,000	5,200,000
Negative sublease income			300,000	$ (1,200,000)
Terminated Lease
Lessee, Lease, Description [Line Items]
Lease termination fees	$ 400,000
Lease monthly base rent	$ 100,000
Building
Lessee, Lease, Description [Line Items]
Leasehold improvement allowance			6,800,000
Restricted cash			$ 2,500,000
Lease renewal term (in years)			8 years
Manufacturing Facility
Lessee, Lease, Description [Line Items]
Leasehold improvement allowance					$ 22,700,000
Lease renewal term (in years)		5 years
Number of renewal contracts | segment		2
Weighted-average remaining lease term (in years)			10 years 2 months 12 days
Weighted-average IBR (as percent)			9.90%

Leases - Schedule of Future Non

Leases - Schedule of Future Non-cancellable Lease Payments under Operating Lease (Details) $ in Thousands	Dec. 31, 2022 USD ($)
Operating Leases
2023	$ 11,484
2024	11,857
2025	12,242
2026	12,639
2027	13,050
Thereafter	104,410
Total undiscounted lease payments	165,682
Less: Present value adjustments	(74,766)
Total	90,916
Sublease Payment Receivable
2023	5,844
2024	6,019
2025	6,200
2026	6,385
2027	6,577
Thereafter	76,174
Total undiscounted lease payments	$ 107,199

Balance Sheet Components - Sche

Balance Sheet Components - Schedule of Property and Equipment, Net (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 51,921	$ 46,234
Less accumulated depreciation and amortization	(16,994)	(13,174)
Property and equipment, net	34,927	33,060
Computer equipment and software
Property, Plant and Equipment [Line Items]
Total property and equipment	1,325	1,224
Laboratory equipment
Property, Plant and Equipment [Line Items]
Total property and equipment	14,382	12,778
Furniture and fixtures
Property, Plant and Equipment [Line Items]
Total property and equipment	868	1,136
Leasehold improvements
Property, Plant and Equipment [Line Items]
Total property and equipment	34,336	26,701
Construction in progress
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 1,010	$ 4,395

Balance Sheet Components - Sc_2

Balance Sheet Components - Schedule of Accrued Expenses and Other Current Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Balance Sheet Related Disclosures [Abstract]
Compensation expense	$ 8,710	$ 9,209
Accrued professional fees	532	550
Accrued nonclinical costs	1,162	2,895
Accrued clinical and process development costs	5,692	2,058
State taxes payable	254	1,318
Other	417	2,017
Total accrued expenses and other current liabilities	$ 16,767	$ 18,047

Commitments and Contingencies -

Commitments and Contingencies - Additional Information (Details)	Dec. 31, 2022 USD ($)
Commitments and Contingencies Disclosure [Abstract]
Accrued royalties	$ 0

Stock Plans - Additional Inform

Stock Plans - Additional Information (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Oct. 31, 2017
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total intrinsic value of stock options exercised	$ 18	$ 100
Granted (in shares)	10,933,000	8,231,000
Weighted-average fair values of options granted (in USD per share)	$ 0.93	$ 5.18
Unrecognized stock-based compensation expense related to awards	$ 30,400
Unrecognized stock-based compensation, weighted-average period (in years)	2 years 7 months 6 days
Stock-based compensation expense		$ 1,600
Stock-Based Compensation
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Common stock shares authorized for issuance (in shares)	37,900,792
Shares available for future grants (in shares)	3,202,937
Options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Award price as a percentage of grant date fair value, minimum	100%
Incentive Stock Options (ISOs) and Non-Qualified Stock Options (NSOs)
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Award price as a percentage of grant date fair value, minimum	110%
Significant stockholder threshold ownership percentage	10%
Performance Shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares of performance units both performance and service vesting conditions (in shares)	400,000
Restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized stock-based compensation, weighted-average period (in years)	1 year 6 months
Shares of performance units both performance and service vesting conditions (in shares)	857,000	2,585,000
Total fair values of RSUs vested	$ 2,800	$ 1,600
Unrecognized compensation cost	$ 1,600
Restricted stock units | Minimum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Awards granted to employees and non-employees vesting period (in years)	2 years
Restricted stock units | Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Awards granted to employees and non-employees vesting period (in years)	4 years
2014 Equity Incentive Award Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Number of shares available for future issuance (as percent)	4%
2017 Inducement Plan | Stock Options and Restricted Stock Units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Common stock shares available for future grant (in shares)			600,000
2014 Plan And Inducement Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Awards granted to employees and non-employees vesting period (in years)	4 years
2014 Plan And Inducement Plan | Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock options granted period	10 years
2014 Plan And Inducement Plan | Performance Shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Granted (in shares)	2,500,000
2014 Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Common stock shares available for future grant (in shares)	208,833
Shares available for future grants (in shares)	7,043,481
Unrecognized compensation cost	$ 600
Percentage increase in shares issued	1%
Common stock issued (in shares)	887,061

Stock Plans - Schedule of Stock

Stock Plans - Schedule of Stock Options Activity (Details) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Options Outstanding
Beginning Balance (in shares)	13,288	10,432
Granted (in shares)	10,933	8,231
Exercised (in shares)	(15)	(9)
Cancelled/forfeited (in shares)	(4,886)	(5,366)
Ending Balance (in shares)	19,320	13,288	10,432
Vested and expected to vest (in shares)	19,320
Exercisable (in shares)	6,102
Weighted- Average Exercise Price
Beginning Balance (in USD per share)	$ 5.83	$ 7.19
Granted (in USD per share)	1.24	7.04
Exercised (in USD per share)	0.19	5.86
Cancelled/forfeited (in USD per share)	5.29	10.32
Ending Balance (in USD per share)	3.38	$ 5.83	$ 7.19
Vested and expected to vest (in USD per share)	5.79
Exercisable (in USD per share)	$ 11.03
Weighted- Average Remaining Contract Life (in years)
Weighted- Average Remaining Contract Life (in years)	8 years	6 years 10 months 24 days	8 years 2 months 12 days
Vested and expected to vest	8 years
Exercisable	6 years 4 months 24 days
Outstanding, Aggregate Intrinsic Value	$ 29	$ 145	$ 31,626
Vested and expected to vest, Aggregate Intrinsic Value	29
Exercisable, Aggregate Intrinsic Value	$ 29

Stock Plans - Schedule of Fair

Stock Plans - Schedule of Fair Value of Option Issued Valuation Assumptions (Details)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected volatility	89%	91%
Expected term (in years)	6 years	6 years
Expected dividend yield	0%	0%
Risk-free interest rate	2.60%	1%
Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected volatility	77%	122%
Expected term (in years)	1 year 2 months 12 days	1 year 2 months 12 days
Expected dividend yield	0%	0%
Risk-free interest rate	3%	0.10%

Stock Plans - Schedule of Restr

Stock Plans - Schedule of Restricted Stock Units Activity (Details) - Restricted stock units - $ / shares shares in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Number of Units
Beginning Balance (in shares)	2,126	540
Granted (in shares)	857	2,585
Vested and released (in shares)	(835)	(305)
Forfeited (in shares)	(455)	(694)
Ending Balance (in shares)	1,693	2,126	540
Weighted- Average Grant Date Fair Value
Beginning Balance (in USD per share)	$ 3.76	$ 6.41
Granted (in USD per share)	1.43	3.90
Vested and released (in USD per share)	3.41	5.26
Forfeited (in USD per share)	3.21	5.68
Ending Balance (in USD per share)	$ 2.90	$ 3.76	$ 6.41
Weighted- Average Remaining Contractual Term (in years)
Weighted- Average Remaining Contractual Term (in years)	1 year 2 months 12 days	1 year 4 months 24 days	9 months 18 days

Stock Plans - Schedule of Sto_2

Stock Plans - Schedule of Stock-based Compensation Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Share-based Payment Arrangement, Expensed and Capitalized, Amount [Line Items]
Total share-based compensation expense	$ 20,079	$ 25,194
Research and development
Share-based Payment Arrangement, Expensed and Capitalized, Amount [Line Items]
Total share-based compensation expense	7,108	8,875
General and administrative
Share-based Payment Arrangement, Expensed and Capitalized, Amount [Line Items]
Total share-based compensation expense	$ 12,971	$ 16,319

401(k) Savings Plan - Additiona

401(k) Savings Plan - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Retirement Benefits [Abstract]
Contribution by company	$ 1.1	$ 1

Restructuring - Additional info

Restructuring - Additional information (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2022 USD ($)	Jul. 06, 2022 employee
Restructuring Cost and Reserve [Line Items]
Number of employees | employee		75
Number of employees (as percent)		37%
Restructuring charges	$ 4,685
Research and development
Restructuring Cost and Reserve [Line Items]
Restructuring charges	3,700
General and administrative
Restructuring Cost and Reserve [Line Items]
Restructuring charges	$ 1,000

Restructuring - Schedule of Res

Restructuring - Schedule of Restructuring Costs (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2022 USD ($)
Restructuring Cost and Reserve [Line Items]
Charges	$ 4,685
Cash payments made	(4,632)
Non-cash	(53)
Total restructuring costs	0
Severance and Benefits Costs
Restructuring Cost and Reserve [Line Items]
Charges	4,632
Cash payments made	(4,632)
Non-cash	0
Total restructuring costs	0
Stock-Based Compensation
Restructuring Cost and Reserve [Line Items]
Charges	53
Cash payments made	0
Non-cash	(53)
Total restructuring costs	$ 0

Income Taxes - Schedule of Comp

Income Taxes - Schedule of Components of Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
U.S.	$ (154,002)	$ (145,375)
Foreign	(460)	(165)
Net loss before income taxes	$ (154,462)	$ (145,540)

Income Taxes- Schedule of Compo

Income Taxes- Schedule of Components of Income Tax Provision (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Current:
Foreign	$ 74	$ 0
Total current tax provision	74	0
Deferred
Foreign	0	0
Total deferred tax provision	0	0
Total income tax provision	$ 74	$ 0

Income Taxes - Schedule of Reco

Income Taxes - Schedule of Reconciliation of Income Tax Expense Computed Statutory Federal Income Tax and Financial Statements (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Federal income tax expense at statutory rate	$ (32,437)	$ (30,563)
Stock compensation	3,414	1,662
Non-deductible expenses	52	28
Research and development tax credits	(2,529)	(2,672)
Change in valuation allowance	31,542	41,324
Foreign rate differential	(46)	(9)
Impact of internal reorganization	103	(9,763)
Other	(25)	(7)
Total income tax provision	$ 74	$ 0

Income Taxes - Schedule of Defe

Income Taxes - Schedule of Deferred Tax Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Deferred tax assets:
Net operating loss carryforwards	$ 111,709	$ 105,509
Accruals, reserve and other	2,053	2,272
Tax credit carryforwards	21,439	16,838
Stock-based compensation	10,705	9,741
Property and equipment	279	0
Intangibles	1,562	1,613
Lease obligation	26,241	24,224
Capital losses	9,850	9,850
Capitalized costs	23,697	0
Total deferred tax assets before valuation allowance	207,535	170,047
Valuation allowance	(188,141)	(148,440)
Total deferred tax assets	19,394	21,607
Deferred tax liabilities:
Right-of-use assets	(19,394)	(20,227)
Property and equipment	0	(1,380)
Total deferred tax liabilities	(19,394)	(21,607)
Net deferred tax assets	$ 0	$ 0

Income Taxes - Additional Infor

Income Taxes - Additional Information (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Income Taxes [Line Items]
Increase in valuation allowance due to net operating loss	$ 39,700	$ 53,800
Capitalized costs	23,697	0
Unrecognized tax benefits	24,745	21,944	$ 8,677
Unrecognized tax benefits, if recognized would effective annual tax rate	1,000
Accrued interest or penalties related to uncertain tax positions	300	$ 300
Domestic tax authority
Income Taxes [Line Items]
NOL carryforwards	418,900
NOL carryforwards subject to expiration	57,300
Domestic tax authority | Research Tax Credit Carryforward
Income Taxes [Line Items]
Tax credit carryforwards	17,500
State credit carryforwards
Income Taxes [Line Items]
NOL carryforwards	239,900
State credit carryforwards | Research Tax Credit Carryforward
Income Taxes [Line Items]
Tax credit carryforwards	15,500
Foreign Tax Authority
Income Taxes [Line Items]
NOL carryforwards	$ 49,000

Income Taxes - Schedule of Unre

Income Taxes - Schedule of Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Reconciliation of Unrecognized Tax Benefits [Roll Forward]
Unrecognized tax benefits as of the beginning of the year	$ 21,944	$ 8,677
Increase related to prior year tax provisions	274	10,656
Increase related to current year tax provisions	2,527	2,611
Unrecognized tax benefits as of the end of the year	$ 24,745	$ 21,944

Net Loss per Share - Schedule o

Net Loss per Share - Schedule of Antidilutive Common Stock Equivalents Excluded from Calculation of Diluted Net Loss Per Share (Details) - shares shares in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive common stock equivalents excluded from calculation of diluted net loss per share (in shares)	21,320	15,562
Stock options
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive common stock equivalents excluded from calculation of diluted net loss per share (in shares)	19,320	13,288
Restricted stock units
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive common stock equivalents excluded from calculation of diluted net loss per share (in shares)	1,693	2,126
ESPP
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive common stock equivalents excluded from calculation of diluted net loss per share (in shares)	307	148