0001564590-22-012325 | 10-K | XBRL Viewer

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Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Current assets:
Cash and cash equivalents	$ 55,912	$ 55,135
Marketable securities	164,195	136,813
Accounts receivable	1,480	878
Prepaid expenses and other current assets	23,011	13,365
Research and development tax credit receivable	30,723	17,344
Total current assets	275,321	223,535
Non-current assets:
Operating lease right-of-use-assets	24,316	29,815
Property and equipment, net	4,767	4,781
Restricted cash	4,266	4,266
Intangible assets, net	4,149	3,076
Other assets	9,590	15,464
Total non-current assets	47,088	57,402
Total assets	322,409	280,937
Current liabilities:
Accounts payable	10,008	8,823
Accrued expenses and other current liabilities	24,318	28,943
Deferred revenue	346
Operating lease liabilities	7,335	8,934
Notes payable, current	786	4,861
Total current liabilities	42,793	51,561
Notes payable, long-term	32,086	20,204
Deferred revenue, net of current portion	12,519
Operating lease liabilities, net of current portion	19,278	24,168
Other long-term liabilities	5,783	6,570
Total liabilities	112,459	102,503
Commitments and contingencies (Note 18)
Shareholders’ equity:
Ordinary shares, £0.10 par value, authority to allot up to a maximum nominal value of £13,023,851.50 of shares at December 31, 2021 and 2020, respectively; 125,674,095 and 98,283,603 shares issued and outstanding at December 31, 2021 and 2020, respectively.	16,253	12,507
Additional paid-in capital	940,675	771,194
Accumulated other comprehensive income	3,246	373
Accumulated deficit	(750,224)	(605,640)
Total shareholders’ equity	209,950	178,434
Total liabilities and shareholders’ equity	$ 322,409	$ 280,937

Consolidated Balance Sheets (Parenthetical) - GBP (£)	Dec. 31, 2021	Dec. 31, 2020
Statement Of Financial Position [Abstract]
Ordinary Shares, Par Value	£ 0.10	£ 0.10
Ordinary Shares, Authorized	£ 13,023,851.50	£ 13,023,851.50
Ordinary Shares, Issued	125,674,095	98,283,603
Ordinary Shares, Outstanding	125,674,095	98,283,603

Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Total revenues	$ 1,675	$ 2,595
Costs and operating expenses
Cost of product sales	226	$ 857
Type of Cost, Good or Service [Extensible List]		Product Sales, Net [Member]
Research and development	86,977	$ 93,730
Selling, general and administrative	54,905	64,986
Total costs and operating expenses	142,108	159,573
Loss from operations	(140,433)	(156,978)
Other (expense) income:
Interest income	412	3,185
Interest expense	(2,497)	(2,328)
Other (expense) income, net	(1,238)	3,411
Total other (expense) income, net	(3,323)	4,268
Net loss before income tax	(143,756)	(152,710)
Income tax (expense) benefit	(828)	731
Net loss attributable to ordinary shareholders	$ (144,584)	$ (151,979)
Net loss per share attributable to ordinary shareholders, basic and diluted	$ (1.17)	$ (1.53)
Weighted average number of ordinary shares outstanding, basic and diluted	123,963,762	99,445,874
Other comprehensive income (loss)
Foreign currency translation adjustment	$ 3,124	$ (1,485)
Unrealized loss on marketable debt securities	(251)	(184)
Total other comprehensive income (loss)	2,873	(1,669)
Total comprehensive loss	(141,711)	(153,648)
Product Sales, Net [Member]
Total revenues	700	$ 2,595
Collaboration Revenue [Member]
Total revenues	$ 975

Consolidated Statements of Shareholders' Equity - USD ($) $ in Thousands	Total	Ordinary Shares	Additional Paid-in Capital	Accumulated Other Comprehensive Income (loss)	Accumulated Deficit
Balance at Dec. 31, 2019	$ 299,193	$ 12,331	$ 738,481	$ 2,042	$ (453,661)
Balance, Shares at Dec. 31, 2019		96,923,729
Share-based compensation expense	27,962		27,962
Exercise of share options	3,465	$ 149	3,316
Exercise of share options, Shares		1,154,441
Issuance of ESPP shares	671	$ 14	657
Issuance of ESPP shares, Shares		107,262
Ordinary shares issued as part of consulting agreement		$ 3	(3)
Ordinary shares issued as part of consulting agreement, Shares		22,758
Ordinary shares issued as part of license agreement	791	$ 10	781
Ordinary shares issued as part of license agreements, Shares		75,413
Foreign currency translation adjustment	(1,485)			(1,485)
Unrealized gain (loss) on marketable debt securities	(184)			(184)
Net loss	(151,979)				(151,979)
Balance at Dec. 31, 2020	178,434	$ 12,507	771,194	373	(605,640)
Balance, Shares at Dec. 31, 2020		98,283,603
Share-based compensation expense	22,536		22,536
Exercise of share options	$ 2,739	$ 224	2,515
Exercise of share options, Shares	1,727,254	1,727,254
Issuance of ESPP shares	$ 564	$ 30	534
Issuance of ESPP shares, Shares		232,340
Vesting of restricted share units, net of shares withheld for taxes	(392)	$ 9	(401)
Vesting of restricted share units, net of shares withheld for taxes, shares		64,647
Sale of voting and non-voting ordinary shares, net of issuance costs	143,645	$ 3,310	140,335
Sale of voting and non-voting ordinary shares, net of issuance costs, Shares		24,115,755
Ordinary shares issued as part of consulting agreement		$ 3	(3)
Ordinary shares issued as part of consulting agreement, Shares		22,758
Ordinary shares issued as part of collaboration agreement	4,135	$ 170	3,965
Ordinary shares issued as part of collaboration agreement, Shares		1,227,738
Foreign currency translation adjustment	3,124			3,124
Unrealized gain (loss) on marketable debt securities	(251)			(251)
Net loss	(144,584)				(144,584)
Balance at Dec. 31, 2021	$ 209,950	$ 16,253	$ 940,675	$ 3,246	$ (750,224)
Balance, Shares at Dec. 31, 2021		125,674,095

Consolidated Statements of Shareholders' Equity (Parenthetical) $ in Thousands	12 Months Ended
	Dec. 31, 2021 USD ($)
Statement Of Stockholders Equity [Abstract]
Sale of voting and non-voting ordinary shares, issuance costs	$ 6,355

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Cash flows from operating activities
Net loss attributable to ordinary shareholders	$ (144,584)	$ (151,979)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization	2,327	2,004
Share-based compensation	22,536	27,962
Impairment of long-lived assets		5,650
Non-cash interest expense	392	500
Amortization of provision on loss contract	(1,037)	(2,413)
Non-cash consideration for licenses and milestones		791
Deferred income taxes	1,131	(2,257)
Amortization of premium on marketable securities	1,514	770
Unrealized foreign currency and other non-cash adjustments	9,687	(3,674)
Changes in operating assets and liabilities:
Accounts receivable	(624)	582
Research and development tax credit receivable	(13,920)	11,674
Prepaid expenses, other current assets, and other assets	(5,209)	(5,070)
Operating leases, right-of-use-assets	5,938	5,863
Accounts payable, accrued expenses, and other current liabilities	(9,452)	(12,278)
Deferred revenue	13,122
Other long-term liabilities	34	2,570
Operating lease liabilities	(6,952)	(6,969)
Net cash used in operating activities	(125,097)	(126,274)
Cash flows from investing activities
Proceeds from sales and maturities of marketable securities	234,732	281,433
Purchases of marketable securities	(263,878)	(113,262)
Payment of construction deposit		(10,000)
Receipt of funds from construction deposit	216	1,876
Payments on intangible assets	(887)
Purchases of property and equipment	(2,348)	(2,668)
Net cash (used in) provided by investing activities	(32,165)	157,379
Cash flows from financing activities
Proceeds from modification of credit facility, net of debt issuance costs paid	7,375
Proceeds from employee equity plans	3,303	3,936
Payment of taxes on restricted stock vesting	(392)
Proceeds from issuance of shares as part of collaboration agreement	4,135
Proceeds from the issuance of ordinary shares in private placement	150,000
Payment of placement agent fees and offering costs	(6,355)
Net cash provided by financing activities	158,066	3,936
Effect of exchange rate changes on cash	(27)	1,043
Net increase in cash, cash equivalents and restricted cash	777	36,084
Cash, cash equivalents, and restricted cash —beginning of year	59,401	23,317
Cash, cash equivalents, and restricted cash —end of year	60,178	59,401
Supplemental disclosure of non-cash investing and financing activities
Intangible assets and property and equipment in accounts payable and accrued expenses	2,589	3,096
Shares issued in consideration of license agreements		791
Employee equity plan proceeds received after year-end		200
Supplemental disclosure of cash flow information
Lease assets obtained in exchange for new operating lease liabilities	552	17,486
Cash paid for interest	2,103	1,828
Cash paid for taxes	$ 1,651	$ 1,007

Nature of Business and Basis of Presentation

12 Months Ended

Dec. 31, 2021

Organization Consolidation And Presentation Of Financial Statements [Abstract]

Nature of Business and Basis of Presentation

1. Nature of Business and Basis of Presentation

Orchard Therapeutics plc (the “Company”) is a global gene therapy company dedicated to transforming the lives of people affected by severe diseases through the development of innovative, potentially curative gene therapies. The Company’s ex vivo autologous hematopoietic stem cell (“HSC”) gene therapy approach utilizes genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. The Company’s gene therapy product candidate pipeline spans multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

The Company is a public limited company incorporated pursuant to the laws of England and Wales. The Company has American Depositary Shares (“ADSs”) registered with the U.S. Securities and Exchange Commission (the “SEC”) and has been listed on the Nasdaq Global Select Market since October 31, 2018. The Company’s ADSs each represent one ordinary share of the Company.

In December 2020, the Company received standard marketing authorization from the European Commission for Libmeldy™ (atidarsagene autotemcel), for the treatment of early onset metachromatic leukodystrophy (“MLD”), characterized by biallelic mutations in the arylsulfatase-A (ARSA) gene leading to a reduction of the ARSA enzymatic activity in children with (i) late infantile or early juvenile forms, without clinical manifestations of the disease, or (ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline.

On February 9, 2021, the Company issued and sold (i) 20,900,321 ordinary shares, nominal value £0.10 per share, at a purchase price of $6.22 per share (the “Purchase Price”), which was the closing sale price of the Company’s ADSs on the Nasdaq Global Select Market on February 4, 2021, and (ii) 3,215,434 non-voting ordinary shares, nominal value £0.10 per share, at the Purchase Price (together (i) and (ii) the “Private Placement”). The Private Placement resulted in net proceeds to the Company of $143.6 million after deducting placement agent fees of $6.0 million and other issuance costs of $0.4 million. The ordinary shares and non-voting ordinary shares were sold pursuant to a securities purchase agreement entered into between the Company and the purchasers named therein on February 4, 2021. At December 31, 2021, all outstanding non-voting shares have been converted to voting ordinary shares.

The Company’s business is subject to risks and uncertainties common to development-stage companies in the biotechnology industry. There can be no assurance that the Company’s research and development will be successfully completed, that adequate protection for the Company’s technology will be obtained, that any products developed will obtain necessary government regulatory approval or that any products, if approved, will be commercially viable. The Company operates in an environment of rapid technological innovation and substantial competition from pharmaceutical and biotechnology companies. In addition, the Company is dependent upon the services of its employees, consultants and service providers. Even if the Company’s product development efforts are successful in gaining regulatory approval, it is uncertain when, if ever, the Company will realize significant revenue from product sales. The future developments of the COVID-19 pandemic may also directly or indirectly impact the Company’s business, including impacts due to quarantines, border closures, increased border controls, travel restrictions, shelter-in-place orders and shutdowns, business closures, cancellations of public gatherings and other measures.

The accompanying consolidated financial statements have been prepared on the basis of continuity of operations, realization of assets and the satisfaction of liabilities and commitments in the ordinary course of business. Through December 31, 2021, the Company funded its operations primarily with proceeds from the sale of convertible preferred shares, and ADSs in the IPO and follow-on offering. The Company has incurred recurring losses since its inception, including net losses of $144.6 million and $152.0 million for the years ended December 31, 2021 and 2020, respectively. As of December 31, 2021, the Company had an accumulated deficit of $750.2 million. The Company expects to continue to generate operating losses for the foreseeable future. The Company expects that its cash, cash equivalents, and marketable securities on hand as of December 31, 2021 of $220.1 million will be sufficient to fund its operations and capital expenditure requirements for at least the next twelve months. The Company will seek additional funding through private or public equity financings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements. The Company may not be able to obtain financing on acceptable terms, or at all, and the Company may not be able to enter into collaborations or other arrangements. The terms of any financing may adversely affect the holdings or the rights of the Company's stockholders. The future viability of the Company is dependent on its ability to raise additional capital to finance its

operations. If the Company is unable to obtain funding, the Company will be forced to delay, reduce or eliminate some or all of its research and development programs, product portfolio expansion or commercialization efforts, which could adversely affect its business prospects, or the Company may be unable to continue operations. Although management continues to pursue these plans, there is no assurance that the Company will be successful in obtaining sufficient funding on terms acceptable to the Company to fund continuing operations, if at all.

Basis of presentation

The accompanying consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”) and include the accounts of the Company and its wholly owned subsidiaries, after elimination of all intercompany accounts and transactions.

Amounts reported are based in thousands, except percentages, per share amounts or as otherwise noted. As a result, certain totals may not sum due to rounding.

Summary of Significant Accounting Policies

12 Months Ended

Dec. 31, 2021

Accounting Policies [Abstract]

Summary of Significant Accounting Policies

2. Summary of Significant Accounting Policies

Principles of consolidation

The accompanying consolidated financial statements include the accounts of the Company and its wholly owned subsidiaries. All intercompany balances and transactions have been eliminated in consolidation.

Use of estimates

The preparation of consolidated financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of the consolidated financial statements and the reported amounts of revenue and expenses during the reporting periods. Significant estimates and assumptions reflected in these consolidated financial statements include, but are not limited to, the accrual for research and development expenses, the research and development tax credit receivable, share-based compensation, collaboration agreement milestones, operating lease assets and liabilities, and income taxes. Estimates are periodically reviewed in light of changes in circumstances, facts and experience. Actual results could differ from the Company’s estimates.

Concentration of credit risk

The Company has no significant off-balance sheet risk, such as foreign currency contracts, options contracts, or other foreign hedging arrangements. Financial instruments that potentially expose the Company to concentrations of credit risk consist primarily of cash, cash equivalents, marketable securities, and receivables. The Company maintains deposits in accredited financial institutions in excess of federally insured limits. The Company deposits its cash in financial institutions that it believes have high credit quality and has not experienced any losses on such accounts and does not believe it is exposed to any unusual credit risk beyond the normal credit risk associated with commercial banking relationships or entities for which it has a receivable.

Foreign currency

The financial statements of the Company’s subsidiaries with functional currencies other than the U.S. Dollar are translated into U.S. Dollars using period-end exchange rates for assets and liabilities, historical exchange rates for shareholders’ equity and weighted average exchange rates for operating results. Translation gains and losses are included in accumulated other comprehensive income (loss) in shareholders’ equity. Foreign currency transaction gains and losses are included in other income (expense), net in the results of operations. The Company recorded realized and unrealized foreign currency transaction losses of $1.2 million, and gains of $3.4 million for the years ended December 31, 2021, and 2020, respectively, which is included in other income (expense) in the statements of operations and comprehensive loss.

Segment information

The Company operates in a single segment, focusing on researching, developing and commercializing potentially curative gene therapies. Consistent with its operational structure, its chief operating decision maker manages and allocates resources at a global, consolidated level. Therefore, results of the Company's operations are reported on a consolidated basis for purposes of segment reporting. All material long-lived assets of the Company reside in the United States or United Kingdom. The Company had property and equipment of $3.6 million and $1.2 million located in the United Kingdom and United States, respectively, as of December 31, 2021. The Company had property and equipment of $3.7 million and $1.1 million located in the United Kingdom and United States, respectively, as of December 31, 2020. The Company had right-of-use assets in the United States and United Kingdom and European Union of $12.5 million and $11.8 million, respectively, as of December 31, 2021. The Company had right-of-use assets in the United States and United Kingdom and European Union of $14.2 million and $15.6 million, respectively, as of December 31, 2020.

Cash equivalents

The Company considers all highly liquid investments purchased with original maturities of 90 days or less at the date of acquisition to be cash equivalents.

Marketable securities

Marketable securities consist of investments with original maturities greater than ninety days at the date of acquisition. The Company has classified its investments with maturities beyond one year as short term, based on their highly liquid nature and because such marketable securities represent the investment of cash that is available for current operations. The Company considers its investment portfolio of investments as available-for-sale. Accordingly, these investments are recorded at fair value, which is based on quoted market prices or other observable inputs. Unrealized gains and losses are recorded as a component of other comprehensive income (loss). Realized gains and losses are determined on a specific identification basis and are included in other income (loss). Amortization and accretion of discounts and premiums is also recorded in other income (loss).

When the fair value is below the amortized cost of the asset an estimate of expected credit losses is made, the estimate is limited to the amount by which fair value is less than amortized cost. The credit-related impairment amount is recognized in the consolidated statements of operations; the remaining impairment amount and unrealized gains are reported as a component of accumulated other comprehensive income (loss) in shareholders’ equity. Credit losses are recognized through the use of an allowance for credit losses account and subsequent improvements in expected credit losses are recognized as a reversal of the allowance account. If the Company has the intent to sell the security or it is more likely than not that the Company will be required to sell the security prior to recovery of its amortized cost basis the allowance for credit loss is written off and the excess of the amortized cost basis of the asset over its fair value is recorded in the consolidated statements of operation.

Restricted cash and construction deposits

Cash and cash equivalents that are restricted as to withdrawal or use under the terms of certain contractual agreements are recorded as restricted cash on our consolidated balance sheet. The Company has an outstanding letter of credit for $3.0 million associated with a lease, and is required to hold this amount in a standalone bank account at December 31, 2021 and 2020. The Company is also contractually required to maintain a cash collateral account associated with corporate credit cards and other leases in the amount of $1.3 million at December 31, 2021 and 2020.

The Company includes the restricted cash balance in cash and cash equivalents when reconciling beginning-of-period and end-of-period total amounts shown on the consolidated statements of cash flows. The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported in the consolidated balance sheet that sum to the total of the amounts reported in the consolidated statement of cash flows:

	As of December 31,
	2021		2020
Cash and cash equivalents	$	55,912	$	55,135
Restricted cash		4,266		4,266
Total cash, cash equivalents and restricted cash shown in the statement of cash flows	$	60,178	$	59,401

The Company also has $7.9 million in an escrow account associated with the construction of the Company’s leased facility in Fremont, California, which the Company has ceased construction and build-out, and has subleased the facility to a third-party who intends to perform construction and build-out of the facility. Subject to the terms of the lease and reduction provisions, this escrow amount may be decreased to nil over time upon qualifying construction expenditures, or will be returned in late 2022 to the extent funds are not used. The Company deposited $10.0 million into the account in the first quarter of 2020 and has received $2.1 million in receipts from the escrow funds for work performed to date. Of the $7.9 million remaining in the escrow account, the entire balance is classified within other prepaid expenses and other current assets on the consolidated balance sheets based on the timing of when the Company expects to receive the cash from the escrow agent.

Inventory

Inventory is stated at the lower of cost or estimated net realizable value with cost determined on a first-in, first-out basis. Inventory costs include raw materials, third-party contract manufacturing, third-party packaging services, and freight. Raw and intermediate materials that may be utilized for either research and development or commercial purposes are classified as inventory. Amounts in inventory that are used for research and development purposes are charged to research and development expense when the product enters the research and development process and can no longer be used for commercial purposes and, therefore, does not have an “alternative future use” as defined in authoritative guidance. The Company performs an assessment of the recoverability of capitalized inventory during each reporting period and, if needed, writes down any excess and obsolete inventory to its estimated net realizable value in the period it is identified. If they occur, such impairment charges are recorded as a component of cost of goods sold in the consolidated statements of operations and comprehensive income (loss). Inventory is included in prepaid expenses and other current assets on the consolidated balance sheets and the amount was not significant as of December 31, 2021.

Prior to the initial date that regulatory approval is received, costs related to the production of inventory are recorded as research and development expense on the Company’s consolidated statements of operations and comprehensive income (loss) in the period incurred. In connection with the acquisition of Strimvelis in April 2018, and with the EMA approval of Libmeldy in December 2020, the Company subsequently began capitalizing inventory manufactured or purchased after these dates.

Intangible assets, net

Intangible assets, net consist milestones associated with the Company’s approved products, net of accumulated amortization. The Company amortizes its intangible assets using the straight-line method over their estimated economic lives and periodically reviews for impairment. The Company has not recognized any impairment charges related to intangible assets to date.

Property and equipment

Property and equipment are recorded at cost and depreciated or amortized using the straight-line method over the following estimated useful lives.

Property and equipment:		Estimated useful life
Lab equipment		5-10 years
Leasehold improvements		Shorter of lease term or estimated useful life
Furniture and fixtures		4 years
Office and computer equipment		3-5 years

Repairs and maintenance expenditures, which are not considered improvements and do not extend the useful life of property and equipment, are expensed as incurred. Upon retirement or sale, the cost of assets disposed of and the related accumulated depreciation are removed from the accounts, and any resulting gain or loss is included in the consolidated statements of operations and other comprehensive loss.

Impairment of long-lived assets

Long-lived assets consist of property and equipment and operating lease right-of-use assets. Long-lived assets to be held and used are tested for recoverability whenever events or changes in business circumstances indicate that the carrying amount of the assets may not be fully recoverable. Factors that the Company considers in deciding when to perform an impairment review include significant underperformance of the business in relation to expectations, significant negative industry or

economic trends and significant changes or planned changes in the use of the assets. If an impairment review is performed to evaluate a long-lived asset group for recoverability, the Company compares forecasts of undiscounted cash flows expected to result from the use and eventual disposition of the long-lived asset group to its carrying value. An impairment loss would be recognized when estimated undiscounted future cash flows expected to result from the use of an asset group are less than its carrying amount. The impairment loss would be based on the excess of the carrying value of the impaired asset group over its fair value, as determined in accordance with the related accounting literature.

Research and development costs

Research and development costs are expensed as incurred. Research and development expenses consist of costs incurred in performing research and development activities, including salaries, share-based compensation and benefits, facilities costs, depreciation, third-party license fees, certain milestone payments, and external costs of outside vendors engaged to conduct clinical development activities and clinical trials, the purchase of in-process research and development assets, as well as costs to develop a manufacturing process, perform analytical testing and manufacture clinical trial materials. Non-refundable prepayments for goods or services that will be used or rendered for future research and development activities are recorded as prepaid expenses. Such amounts are recognized as an expense as the goods are delivered or the related services are performed, or until it is no longer expected that the goods will be delivered, or the services rendered. In addition, funding from research grants is recognized as an offset to research and development expense on the basis of costs incurred on the research program. Royalties to third parties associated with our research grants will be accrued when they become probable.

Research contract costs and accruals

The Company has entered into various research and development contracts. These agreements are cancelable, and related costs are recorded as research and development expenses as incurred. When billing terms under these contracts do not coincide with the timing of when the work is performed, the Company is required to make estimates of outstanding obligations as of period end to those third parties. Any accrual estimates are based on a number of factors, including the Company’s knowledge of the progress towards completion of the research and development activities, invoicing to date under the contracts, communication from the research institution or other companies of any actual costs incurred during the period that have not yet been invoiced, and the costs included in the contracts. Significant judgments and estimates may be made in determining the accrued balances at the end of any reporting period. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense. Actual results could differ from the estimates made by the Company. The historical accrual estimates made by the Company have not been materially different from the actual costs.

Share-based compensation

The Company measures share-based awards granted to employees, consultants and directors based on the fair value of the shares and options on the date of the grant and recognizes compensation expense for those awards over the requisite service period, which is the vesting period of the respective award. Forfeitures are accounted for as they occur.

Comprehensive loss

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

Leases

The Company determines if an arrangement is a lease at contract inception. Operating lease assets represent a right to use an underlying asset for the lease term and operating lease liabilities represent an obligation to make lease payments arising from the lease. Operating lease liabilities with a term greater than one year and their corresponding right-of-use assets are recognized on the balance sheet at the commencement date of the lease based on the present value of lease payments over the expected lease term. Certain adjustments to the right-of-use asset may be required for items such as initial direct costs paid or incentives received. The Company made an accounting policy election to not record a right-of-use asset or lease liability for leases with a term of one year or less. To date, the Company has not identified any material short-term leases, either individually or in the aggregate.

As the Company’s leases do not provide an implicit rate, the Company utilized the appropriate incremental borrowing rate, which is the rate incurred to borrow on a collateralized basis over a similar term as the lease an amount equal to the lease payments in a similar economic environment. The Company estimated the incremental borrowing rate based on the

Company’s currently outstanding credit facility as inputs to the analysis to calculate a spread, adjusted for factors that reflect the profile of secured borrowing over the expected term of the lease.

The components of a lease should be split into three categories: lease components (e.g., land, building, etc.), non-lease components (e.g., common area maintenance, utilities, performance of manufacturing services, purchase of inventory, etc.), and non-components (e.g., property taxes, insurance, etc.). Then the fixed contract consideration (including any related to non-components) must be allocated based on fair values to the lease components and non-lease components. Although separation of lease and non-lease components is required, certain accounting policy elections are available to entities. Entities can elect accounting policies that would not separate lease and non-lease components. Rather, they would account for each lease component and the related non-lease component together as a single component. The Company has elected not to apply the accounting policy with respect to its lease of manufacturing space at a contract manufacturing organization, the Company has allocated the consideration between the lease and non-lease components of the contract based on the respective fair values of the lease and non-lease components. The Company calculated the fair value of the lease and non-lease components using financial information readily available as part of its master services arrangement and other representative data indicative of fair value.

The Company accounts for sublease income on a straight-line basis over the respective lease period and records an unbilled rent receivable for sublease income incurred but not yet paid. The Company periodically performs a collectability assessment associated with any unbilled rent receivables. The Company recognizes the sublease income as a reduction to the related operating expense associated with the head lease.

Strimvelis loss provision

As part of the GSK transaction, the Company is required to maintain commercial availability of Strimvelis in the European Union until such time that an alternative gene therapy is available (see Note 15). Strimvelis is not currently expected to generate sufficient cash flows to overcome the costs of maintaining the product and certain regulatory commitments; therefore, the Company initially recorded a liability associated with the loss contract of $18.4 million in 2018. The Company recognizes the amortization of the loss provision on a diminishing balance basis based on the actual net loss incurred associated with the Strimvelis program and the expected future net losses to be generated until such time as Strimvelis is no longer commercially available. The amortization of the provision is recorded as a credit to research and development expense. The Company has made an estimate of the expected future losses associated with Strimvelis and will adjust this estimate as facts and circumstances change regarding the commercial availability and costs of maintaining and selling Strimvelis. The Company does not update the accrued loss provision for any subsequent adjustment of the future losses, however, the timing of recognizing the amortization of what was originally recorded is adjusted for the updated future losses.

The following table below outlines the changes to the Strimvelis loss provision for the periods ended December 31, 2021 and 2020:

	Year Ended December 31,
	2021			2020
Balance at beginning of period	$	4,482		$	6,790
Provisions		—			—
Amortization of loss provision		(1,037	)		(2,413	)
Foreign currency translation		(26	)		105
Balance at end of period	$	3,419		$	4,482

As of December 31, 2021, $0.7 million of the Strimvelis loss provision was classified as current, and $2.7 million was classified as non-current. As of December 31, 2020, $0.9 million of the Strimvelis loss provision was classified as current, and $3.6 million was classified as non-current.

United Kingdom Research and development income tax credits

As a company that carries out research and development activities, the Company is able to submit tax credit claims from two UK research and development tax relief programs, the SME program and the RDEC program depending on eligibility. Qualifying expenditures largely comprise employment costs for research staff, consumables and certain internal overhead costs incurred as part of research projects for which the Company does not receive income.

Each reporting period, management evaluates which tax relief programs the Company is expected to be eligible for and records a reduction to research and development expense for the portion of the expense that it expects to qualify under the

programs, that it plans to submit a claim for, and it has reasonable assurance that the amount will ultimately be realized. Based on criteria established by HM Revenue and Customs (“HMRC”), management of the Company expects a proportion of expenditures being undertaken in relation to its pipeline research, clinical trials management and manufacturing development activities to be eligible for the research and development tax relief programs for the year ended December 31, 2021. The Company has qualified under the more favorable SME regime for the year ended December 31, 2020 and expects to qualify under the SME regime for the year ending December 31, 2021.

The RDEC and SME credits are not dependent on the Company generating future taxable income or on the ongoing tax status or tax position of the Company. The Company has assessed its research and development activities and expenditures to determine whether the nature of the activities and expenditures will qualify for credit under the tax relief programs and whether the claims will ultimately be realized based on the allowable reimbursable expense criteria established by the UK government which are subject to interpretation. At each period end, the Company estimates the reimbursement available to the Company based on available information at the time.

The Company recognizes credits from the research and development incentives when the relevant expenditure has been incurred and there is reasonable assurance that the reimbursement will be received. Such credits are accounted for as reductions in research and development expense. The following table outlines the changes to the research and development tax credit receivable, including amount recognized as an offset to research and development expense during the years ended December 31, 2021 and 2020:

	Year Ended December 31,
	2021			2020
Balance at beginning of period	$	17,344		$	28,644
Recognition of credit claims as offset to research and development expense		13,920			21,130
Receipt of credit claims		—			(33,771	)
Foreign currency translation		(541	)		1,341
Balance at end of period	$	30,723		$	17,344

During the year ended December 31, 2020, the Company recorded $4.8 million of additional tax credits related to a change in estimate associated with its UK research and development tax credit receivable claim for fiscal year 2019. The change in estimate was based on the results of a tax credit analysis associated with the Company’s qualified projects and research and development expenditures completed during the third quarter to finalize the 2019 UK tax return.

As of December 31, 2021, the Company’s tax credit receivable from the UK was $30.7 million, all of which was classified as current. As of December 31, 2020, the Company’s tax incentive receivable from the UK was $17.3 million, all of which was classified as current.

Income taxes

The Company is primarily subject to corporation taxes in the United Kingdom and the United States. The calculation of the Company’s tax provision involves the application of both United Kingdom and United States tax law and requires judgement and estimates.

The Company accounts for income taxes in accordance with ASC Topic 740, Accounting for Income Taxes, which provides for deferred taxes using an asset and liability approach. 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. The Company determines its deferred tax assets and liabilities based on differences between financial reporting and tax bases of assets and liabilities, which are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. Valuation allowances are provided if, based upon the weight of available evidence, it is more likely than not that some or all of the net deferred tax assets will not be realized.

The Company accounts for uncertainty in income taxes by applying a two-step process to determine the amount of tax benefit to be recognized. First, the tax position must be evaluated to determine the likelihood that it will be sustained upon external examination by the taxing authorities. If the tax position is deemed more-likely-than-not to be sustained, the tax position is then assessed as the amount of benefit to recognize in the consolidated financial statements. The amount of benefits that may be used is the largest amount that has a greater than 50% likelihood of being realized upon ultimate settlement. The provision for income taxes includes the effects of any resulting tax reserves, or unrecognized tax benefits, that are considered appropriate, as well as the related net interest and penalties.

Product sales

The Company’s product sales in 2021 and 2020 consist of sales of Strimvelis, which is distributed exclusively at the San Raffaele Hospital in Milan, Italy. San Raffaele Hospital will purchase and pay for Strimvelis and submit a claim to the payer. The Company’s contracted sales with San Raffaele Hospital contain a single performance obligation and the Company recognizes revenue from product sales when the Company has satisfied its performance obligation by transferring control of Strimvelis to San Raffaele Hospital. Control of the product generally transfers upon the completion of the scheduled Strimvelis treatment. The Company’s product sales represent total net product sales of Strimvelis. The Company evaluated the variable consideration under Accounting Standards Codification (ASC) 606, Revenue from Contracts with Customers, and there is currently no variable consideration included in the transaction price for Strimvelis. Costs to manufacture and deliver the product and those associated with administering the therapy are included in cost of product sales. As the product is sold in direct relation to a scheduled treatment, the Company estimates that there is limited risk of product return, including the risk of product expiration. During the years ended December 31, 2021 and 2020, the Company has $0.7 and $2.6 million in sales of Strimvelis, respectively.

Collaboration revenue

The terms of the Company’s collaboration agreements may include consideration such as non-refundable license fees, funding of research and development services, payments due upon the achievement of clinical and preclinical performance-based development milestones, regulatory milestones, manufacturing services, sales-based milestones and royalties on product sales.

The Company first evaluates collaboration arrangements to determine whether the arrangement (or part of the arrangement) represents a collaborative arrangement pursuant to ASC Topic 808, Collaborative Arrangements, based on the risks and rewards and activities of the parties pursuant to the contractual arrangement. The Company accounts for any collaborative arrangement or elements within the contract that are deemed to be a collaborative arrangement, and not a customer relationship, in accordance with ASC 808. Through December 31, 2021, the Company entered into one agreement with Pharming Group N.V. (the “Pharming Agreement”, see Note 16) that is accounted for pursuant to ASC 606.

Under ASC 606, an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the entity expects to receive in exchange for those goods or services. To determine the appropriate amount of revenue to be recognized for arrangements determined to be within the scope of ASC 606, the Company performs the following five steps: (i) identification of the contract(s) with the customer, (ii) identification of the promised goods or services in the contract and determination of whether the promised goods or services are performance obligations, (iii) measurement of the transaction price, (iv) allocation of the transaction price to the performance obligations, and (v) recognition of revenue when (or as) the Company satisfies each performance obligation. The Company only applies the five-step model to contracts when it is probable that the entity will collect consideration it is entitled to in exchange for the goods or services it transfers to the customer.

The Company recognizes the transaction price allocated to upfront license payments as revenue upon delivery of the license to the customer and resulting ability of the customer to use and benefit from the license, if the license is determined to be distinct from the other performance obligations identified in the contract. If the license is considered to not be distinct from other performance obligations, the Company utilizes judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied (i) at a point in time, but only for licenses determined to be distinct from other performance obligations in the contract, or (ii) over time, and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue from license payments. The Company evaluates the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition.

The Pharming Agreement entitles the Company to additional payments upon the achievement of performance-based milestones. These milestones are generally categorized into three types: development milestones, regulatory milestones, and sales-based milestones. The Company is also eligible to receive from Pharming tiered royalty payments on worldwide net sales. The Company evaluates whether it is probable that the consideration associated with each milestone will not be subject to a significant reversal in the cumulative amount of revenue recognized. Amounts that meet this threshold are included in the transaction price using the most likely amount method, whereas amounts that do not meet this threshold are considered constrained and excluded from the transaction price until they meet this threshold. Milestones tied to regulatory approval, and therefore not within the Company’s control, are considered constrained until such approval is received. Upfront and ongoing development milestones per the collaboration agreements are not subject to refund if the development activities are not successful. At the end of each subsequent reporting period, the Company re-evaluates the probability of a significant reversal of the cumulative revenue recognized for the milestones, and, if necessary, adjusts the estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect revenues from collaborators in

the period of adjustment. The Company may enter into an agreement that includes sales-based milestone payments and royalties in exchange for a license of intellectual property. The Company considers the underlying facts and circumstances of these agreements, noting whether the future payments are contingent upon future sales and whether they are dependent on a third party’s ability to successfully commercialize a product using the licensed intellectual property. The Company also considers whether the license is the only, or predominant, item to which the milestone payments and royalties relate. If the Company concludes the license is the predominant item in the agreement, therefore the primary driver of value, the Company excludes sales-based milestone payments and royalties from the transaction price until the sale occurs (or, if later, until the underlying performance obligation to which some or all of the royalty has been allocated has been satisfied or partially satisfied). Currently, the Company has not recognized any royalty revenue resulting from the Pharming Agreement.

ASC 606 requires the Company to allocate the arrangement consideration on a relative standalone selling price basis for each performance obligation after determining the transaction price of the contract and identifying the performance obligations to which that amount should be allocated. The relative standalone selling price is defined in ASC 606 as the price at which an entity would sell a promised good or service separately to a customer. If other observable transactions in which the Company has sold the same performance obligation separately are not available, the Company is required to estimate the standalone selling price of each performance obligation. Key assumptions to determine the standalone selling price may include forecasted revenues, development timelines, reimbursement rates for personnel costs, discount rates and probabilities of technical and regulatory success.

Whenever the Company determines that a contract should be accounted for as a combined performance obligation, which is recognized over time, it will utilize the cost-to-cost input method. Revenue will be recognized over time using the cost-to-cost input method, based on the total estimated costs to fulfill the obligations. The Company will recognize revenue as services are delivered. Significant management judgment is required in determining the estimate of total costs required under an arrangement and the period over which the Company is expected to complete its performance obligations under an arrangement.

Consideration that does not meet the requirements to satisfy the above revenue recognition criteria is a contract liability and is recorded as deferred revenue in the consolidated balance sheets. Short-term deferred revenue consists of amounts that are expected to be recognized as revenue in the next 12 months. Amounts that the Company expects will not be recognized within the next 12 months are classified as long-term deferred revenue.

The Company recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) each performance obligation is satisfied, either at a point in time or over time. In particular, for the Company’s collaborations with Pharming, revenue attributable to research services is recognized as those services are provided, based on the costs incurred to date.

Net loss per share

Basic net loss per share is computed by dividing the net loss by the weighted average number of ordinary shares outstanding for the period. Diluted net loss is computed by adjusting net loss based on the potential impact of dilutive securities. Diluted net loss per share is computed by dividing the diluted net loss by the weighted average number of ordinary shares outstanding for the period, including potential dilutive ordinary shares. For purpose of this calculation, outstanding options and unvested restricted shares are considered potential dilutive ordinary shares. Since the Company was in a loss position for all periods presented, basic net loss per share is the same as diluted net loss per share for all periods as the inclusion of all potential ordinary share equivalents outstanding would have been anti-dilutive.

The following securities, presented based on amounts outstanding at each period end, are considered to be ordinary share equivalents, but were not included in the computation of diluted net loss per ordinary share because to do so would have been anti-dilutive:

	As of December 31,
	2021		2020
Share options		14,042,781		11,071,555
Unvested shares from share plan and consulting agreement		512,908		816,316
		14,555,689		11,887,871

Recent accounting pronouncements

In November 2021, the FASB issued ASU No. 2020-10, Government Assistance (Topic 832): Disclosures by Business Entities about Government Assistance, which requires increased transparency in the disclosures about government assistant in the notes to the financial statements. This ASU is effective for the Company beginning January 1, 2022, and interim periods within that year, with early adoption permitted. The Company does not expect this amendment to have a significant effect on its financial statement disclosures.

Fair Value Measurements and Marketable Securities

12 Months Ended

Dec. 31, 2021

Fair Value Disclosures [Abstract]

Fair Value Measurements and Marketable Securities

3. Fair Value Measurements and Marketable Securities

The following tables present information about the Company’s financial assets that have been measured at fair value as of December 31, 2021 and 2020, and indicate the fair value of the hierarchy of the valuation inputs utilized to determine such fair value. In general, fair values determined by Level 1 inputs utilize quoted prices (unadjusted) in active markets for identical assets or liabilities. Fair value determined by Level 2 inputs utilize observable inputs other than Level 1 prices, such as quoted prices for similar assets or liabilities, quoted market 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 related assets or liabilities. Fair values determined by Level 3 inputs are unobservable data points for the asset or liability, and include situations where there is little, if any, market activity for the asset or liability. During the years ended December 31, 2021 and 2020, there were no transfers between Level 1 and Level 2 financial assets.

The following table summarizes the Company’s cash equivalents and marketable securities as of December 31, 2021:

	Fair Value Measurements as of December 31, 2021 Using:
	Level 1		Level 2		Level 3		Total
Cash equivalents
Money market funds	$	21,085	$	—	$	—	$	21,085
Corporate bonds		—		7,321		—		7,321
Commercial paper		—		13,198		—		13,198
Total cash equivalents	$	21,085	$	20,519	$	—	$	41,604
Marketable securities
Corporate bonds	$	—	$	94,794	$	—	$	94,794
Commercial paper		—		69,401		—		69,401
Total marketable securities	$	—	$	164,195	$	—	$	164,195
Total	$	21,085	$	184,714	$	—	$	205,799

The following table summarizes the Company’s cash equivalents and marketable securities as of December 31, 2020:

	Fair Value Measurements as of December 31, 2020 Using:
	Level 1		Level 2		Level 3		Total
Cash equivalents
Money market funds	$	6,650	$	—	$	—	$	6,650
U.S. government securities		—		3,001		—		3,001
Commercial paper		—		2,999		—		2,999
Total cash equivalents	$	6,650	$	6,000	$	—	$	12,650
Marketable securities
US government securities	$	—	$	2,997	$	—	$	2,997
Corporate bonds		—		93,358		—		93,358
Commercial paper		—		40,458		—		40,458
Total marketable securities	$	—	$	136,813	$	—	$	136,813
Total	$	6,650	$	142,813	$	—	$	149,463

The carrying amount reflected in the consolidated balance sheets for research and development tax incentive receivable, trade receivables, other receivables, accounts payable, and accrued expenses approximate fair value due to their short-term maturities. The carrying value of the Company’s outstanding notes payable approximates fair value (a Level 2 fair value measurement), reflecting interest rates currently available to the Company.

Marketable Securities

The following table summarizes the Company’s cash equivalents and marketable securities as of December 31, 2021:

	Fair Value Measurements as of December 31, 2021 Using:
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Credit Losses		Fair Value
Corporate bonds	$	102,224	$	—	$	(109	)	$	—	$	102,115
Commercial paper		82,657		—		(58	)		—		82,599
Total	$	184,881	$	—	$	(167	)	$	—	$	184,714

The following table summarizes the Company’s cash equivalents and marketable securities as of December 31, 2020:

	Fair Value Measurements as of December 31, 2020 Using:
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Credit Losses		Fair Value
U.S. government securities	$	3,000	$	—	$	(4	)	$	—		2,996
Corporate bonds		96,259		133		(32	)		—		96,360
Commercial paper		43,469		1		(13	)		—		43,457
Total	$	142,728	$	134	$	(49	)	$	—	$	142,813

The following table summarizes the Company’s available-for-sale marketable debt securities by contractual maturity, as of December 31, 2021 and 2020:

	2021		2020
Maturities in one year or less	$	172,575	$	132,056
Maturities between one and three years		12,139		10,757
Total	$	184,714	$	142,813

- Definition

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

+ References + Details

Revenue Recognition

12 Months Ended

Dec. 31, 2021

Revenue From Contract With Customer [Abstract]

Revenue Recognition

4. Product sales

During the years ended December 31, 2021 and 2020, the Company recorded sales for one commercial-stage therapy, Strimvelis, for the treatment of ADA-SCID. Strimvelis is currently distributed exclusively at the San Raffaele Hospital in Milan, Italy. San Raffaele Hospital will purchase and pay for Strimvelis and submit a claim to the payer. The Company’s contracted sales with San Raffaele Hospital contain a single performance obligation and the Company recognizes revenue from product sales when the Company has satisfied its performance obligation by transferring control of Strimvelis to San Raffaele Hospital. Control of the product generally transfers upon the completion of the scheduled Strimvelis treatment. The Company’s product sales represent total net product sales of Strimvelis. The Company evaluated the variable consideration under Accounting Standards Codification (ASC) 606, Revenue from Contracts with Customers, and there is currently no variable consideration included in the transaction price for Strimvelis. Costs to manufacture and deliver the product and those associated with administering the therapy are included in cost of product sales. As the product is sold in direct relation to a scheduled treatment, the Company estimates that there is limited risk of product return, including the risk of product expiration.

Payment terms and conditions generally require payment for Strimvelis sales within 60 days of treatment. Strimvelis is currently distributed exclusively at the San Raffaele Hospital, and there is currently no variable consideration included in the transaction price of Strimvelis.

- Definition

The entire disclosure of revenue from contract with customer to transfer good or service and to transfer nonfinancial asset. Includes, but is not limited to, disaggregation of revenue, credit loss recognized from contract with customer, judgment and change in judgment related to contract with customer, and asset recognized from cost incurred to obtain or fulfill contract with customer. Excludes insurance and lease contracts.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-URI http://asc.fasb.org/topic&trid=49130388

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 10
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130551-203045

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 13
-Subparagraph (b)(2)
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130556-203045

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (b)
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130554-203045

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 9
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130550-203045

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (e)
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130554-203045

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (a)
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130554-203045

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (d)
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130554-203045

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 15
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130558-203045

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (c)
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130554-203045

+ Details

Prepaid Expenses and Other Current Assets

12 Months Ended

Dec. 31, 2021

Prepaid Expense And Other Assets Current [Abstract]

Prepaid Expenses and Other Current Assets

5. Prepaid expenses and other current assets

Prepaid expenses and other current assets consist of the following:

	December 31,
	2021		2020
Prepaid external research and development expenses	$	2,438	$	1,421
Inventories		2,016		665
Other prepayments		6,128		4,930
VAT receivable		1,169		2,780
Construction deposit - current		7,909		1,552
Non-trade receivables		3,351		2,017
Total prepaid expenses and other current assets	$	23,011	$	13,365

Property and Equipment

12 Months Ended

Dec. 31, 2021

Property Plant And Equipment [Abstract]

Property and Equipment

6. Property and equipment

Property and equipment consist of the following:

	December 31,
	2021			2020
Property and equipment:
Lab equipment	$	5,937		$	5,114
Leasehold improvements		2,450			2,522
Furniture and fixtures		303			304
Office and IT equipment		2,023			763
Construction-in-progress		211			302
Property and equipment	$	10,924		$	9,005
Less: accumulated depreciation		(6,157	)		(4,224	)
Property and equipment, net	$	4,767		$	4,781

Depreciation expense for the years ended December 31, 2021 and 2020 was $2.2 million and $2.0 million, respectively.

Intangible Assets, Net

12 Months Ended

Dec. 31, 2021

Goodwill And Intangible Assets Disclosure [Abstract]

Intangible Assets, Net

7. Intangible assets, net

Intangible assets, net of accumulated amortization, consisted of the following:

	As of December 31, 2021							As of December 31, 2020
	Cost		Accumulated Amortization			Net		Cost		Accumulated Amortization		Net
License intangibles	$	4,329	$	(180	)	$	4,149	$	3,076	$	—		3,076
Total	$	4,329	$	(180	)	$	4,149	$	3,076	$	-	$	3,076

License intangibles consist of capitalized milestone payments or accruals of payments the Company has deemed probable upon receiving regulatory approval of Libmeldy in the EU. The license intangibles are being amortized on a straight-line basis over the remaining useful life of the related patents of approximately twelve years. For year ended December 31, 2021, amortization of intangible assets totaled $0.2 million. For the year ended December 31, 2020, amortization of intangible assets was nil. The effect of foreign currency translation on the net carrying value of intangible assets during 2021 was not material.

The following table summarizes the estimated future amortization for intangible assets for the next five years and thereafter:

2022			364
2023			364
2024			364
2025			364
2026			364
Thereafter			2,329
Total			4,149

Other Assets

12 Months Ended

Dec. 31, 2021

Other Assets Noncurrent Disclosure [Abstract]

Other Assets

8. Other assets

Other assets consist of the following:

	December 31,
	2021		2020
Deferred tax assets		4,086		5,219
Deposits		1,404		1,144
Deferred financing costs		693		975
Other non-current assets		3,407		1,554
Construction deposits - long-term		—		6,572
Total other assets	$	9,590	$	15,464

Accrued Expenses and Other Liabilities

12 Months Ended

Dec. 31, 2021

Accrued Liabilities And Other Liabilities [Abstract]

Accrued Expenses and Other Liabilities

9. Accrued expenses and other liabilities

Accrued expenses and other current liabilities consisted of the following:

	December 31,
	2021		2020
Accrued external research and development expenses	$	9,273	$	8,878
Accrued payroll and related expenses		8,521		11,881
Accrued milestone payments		2,058		2,252
Accrued professional fees		854		791
Accrued other		2,941		4,225
Strimvelis liability - current portion		671		916
Total accrued expenses and other current liabilities	$	24,318	$	28,943

Restructuring Charges

12 Months Ended

Dec. 31, 2021

Restructuring And Related Activities [Abstract]

Restructuring Charges

10. Restructuring charges

In May 2020, the Company committed to a new strategic plan and restructuring intended to enable the Company to advance its corporate strategy while reducing overall operating expenses, including ceasing construction and build-out of its Fremont, California manufacturing facility, closing its office in Menlo Park, California, reducing its workforce by approximately 25% across the Company, eliminating a number of future positions expected to be recruited in 2020 and 2021, reducing its investment in the future development for certain programs, and other cost-saving measures (collectively, the “Restructuring”). The workforce reductions took place primarily during the second and third quarters of 2020, and concluded in the fourth quarter of 2020.

Cash restructuring charges

Accrued restructuring and severance costs are included in Accrued expenses and other current liabilities in the consolidated balance sheet. Activity for the fiscal year is summarized as follows:

	Year Ended December 31,
	2020
Balance at beginning of period	$	—
Charged to expense		1,854
Payments made		(1,848	)
Balance at end of period	$	6

There were no restructuring costs during the year ended December 31, 2021.

Impairment of long-lived assets

During the second quarter of 2020, the Company also took the following non-cash charges to research and development expense associated with the impairment of construction-in-process associated with the Fremont manufacturing facility, partial impairment of the right-of-use asset for the Fremont manufacturing facility lease (the “Fremont ROU asset”), and a write-down of laboratory equipment from the Company’s Menlo Park, CA facility:


	Asset write-down
Operating lease right-of-use asset	$	2,605
Construction-in-progress		2,285
Laboratory equipment		760
Charge included in research and development expense	$	5,650

The Company assessed the Fremont construction-in-process for impairment in May 2020 upon the Restructuring. The construction-in-process related to design costs, and was determined to have no potential future value, and an impairment charge of $2.3 million was taken for the full value of the construction-in-process asset.

The Company assessed the Fremont ROU asset for impairment in May 2020 upon the Restructuring when the carrying value of the asset was $13.8 million. The Fremont ROU asset represented the asset group for the impairment assessment. Upon failing the first step of the long-lived asset impairment model where the undiscounted cash flows were less than the carrying value of the Fremont ROU asset, the Company performed the second step by comparing the fair value of the Fremont ROU asset to its carrying value. The fair value of the Fremont ROU asset is a non-recurring fair value measurement that was measured using a probability-weighted discounted cash flow approach, which estimated the present value of potential sublease income to be generated by the facility, less costs incurred to sublease the facility. The significant assumptions inherent in estimating the various probability weighted scenarios included the undiscounted forecasted sublease income less costs incurred, which included assumptions of the expected income and timing of entering into a future sublease, and a market-participant discount rate that reflects a potential discount rate. The Company selected the assumptions used in the fair value estimate using current market data associated with the potential sublease income and market participant discount rates. The undiscounted cash flows utilized in the fair value estimate ranged from $11.7 million to $19.1 million to be generated over the remainder of the lease term. The market-participant discount rate utilized in the fair value estimate was 4.6%. These assumptions represent level 3 inputs of the fair value hierarchy (see Note 3).

As of the assessment date, the fair value of the Fremont ROU asset was $11.2 million, and the Company recorded a $2.6 million impairment charge related to the asset. The remaining carrying value of the Fremont ROU asset is being amortized over the remaining lease term on a straight-line basis. In December 2020, the Company executed a sublease for the Fremont manufacturing facility with an unrelated third-party for the remaining lease term (see Note 11). No further impairment was necessary as a result of the sublease. The occurrence of a triggering event for the Fremont ROU asset in future periods could result in additional impairment charges if the estimated fair value of the asset is determined to be lower than the carrying value.

Leases

12 Months Ended

Dec. 31, 2021

Leases [Abstract]

Leases

11. Leases

Operating leases

In November 2017 and January 2019, the Company entered into lease agreements for office and laboratory space in Menlo Park, California, United States. The leases terminated in December 2020. The combined annual rental payments, including variable payments, under both leases with the same landlord were nil in 2021 and $1.9 million in 2020. The Company was provided with one month of free rent in connection with the first lease. The lease agreement included annual rent escalation provisions.

In January 2018 and December 2018, the Company entered into lease agreements for office space in London, United Kingdom, both of which terminate in January 2023. The combined annual rental payments, including variable payments, under the lease agreements were $1.8 million in 2021 and $1.7 million in 2020. The Company also rented lab spaces in London in 2021, for which it made $0.2 million in payments in 2021.

In March 2018, the Company entered into a lease agreement for office space in Boston, Massachusetts, United States, which terminates in September 2022. The annual rental payments, including variable payments, were $0.4 million in 2021 and

2020. The lease agreement includes annual rent escalation provisions. The Company has subleased the space in August 2021, and recognized $0.1 million in sublease income in 2021.

In July 2019, the Company entered into a lease agreement for office space in Boston, Massachusetts, United States, which commences for accounting purposes in January 2020. The lease terminates in September 2026. The annual rental payments, including variable payments, were $1.1 million and $0.9 million in 2021 and 2020, respectively. The lease agreement includes annual rent escalation provisions.

As of December 31, 2021, the carrying value of the operating lease right-of-use assets in Boston and London was $4.1 million and the lease liabilities was $4.3 million. As of December 31, 2020, the carrying value of the operating lease right-of-use assets in Boston and London was $5.4 million and the lease liabilities was $5.7 million.

Fremont operating lease and sublease agreements

In December 2018, the Company leased manufacturing, laboratory, and office space in Fremont, California (the “Fremont facility” and the “Head Lease”) which terminates in May 2030. In May 2020, the Company committed to a restructuring plan (see Note 10) whereby we ceased construction and build-out of the Fremont facility. In December 2020, the Company entered into a sublease agreement (the “Sublease”) with an unrelated third-party (the “subtenant”) whereby the Company subleased the entire Fremont facility to the subtenant. The Company accounts for the Head Lease and Sublease as two separate contracts. Both the Head Lease and Sublease were determined to be operating leases.

The Head Lease annual rental payments, including variable payments, were $3.1 million in 2021 and 2020. The Head Lease includes annual rent escalation provisions. The Company was provided with 8 months of free rent. Subject to the terms of the Head Lease agreement, the Company executed a $3.0 million letter of credit upon signing the lease, which may be reduced by 25% subject to reduction requirements specified therein. This amount is classified as restricted cash on the consolidated balance sheets.

As of December 31, 2021, the carrying value of the Fremont Head Lease right-of-use asset was $9.5 million and the lease liability was $13.1 million. The Head Lease provides for up to $5.3 million in tenant improvement allowances to be reimbursed to the Company by the landlord. These tenant improvement allowances have been included in the calculation of the operating lease liability and is currently expected to be received in 2022. The Company continues to assess the expected receipt of the tenant improvement allowances and may remeasure the right-of-use asset and liability from time to time as facts and circumstances may change.

The Sublease commenced in December 2020 and is in force for the remainder of the Head Lease term, through May 2030. The Sublease provides for 12 months of free rent until December 2021. The sublease provides for an initial annual cash base rent of $2.2 million, with annual rent escalation provisions. The subtenant is also responsible for paying all operating expenses associated with the Head Lease. The Sublease also includes pass-through of up to $5.3 million in tenant improvement allowances to the subtenant, subject to the Company being reimbursed for the allowances per the terms of the Head Lease. The Subtenant provided the Company with a $2.6 million security deposit, which may be converted to a letter of credit upon providing evidence of $2.6 million in construction expenditures. The Company accounts for the security deposit within other long-term liabilities.

The Company has $7.9 million in an escrow account associated with construction on the Fremont facility, for which the Company has ceased construction and build-out. Subject to the terms of the Head Lease and reduction provisions, this amount may be returned to the Company upon qualifying construction expenditure, or will be returned in late 2022 (the “Sunset Date”) to the extent construction expenses have not been incurred. The Company deposited $10.0 million into the account in the first quarter of 2020 and has received $2.1 million in receipts from the escrow funds for costs incurred to date. The escrow balance is all classified within other current assets on the consolidated balance sheets based on the timing of when the Company expects funds to be returned from the escrow agent. Future receipts from the escrow deposit will be dependent upon the timing of the subtenant construction spend through the Sunset Date.

Embedded operating lease arrangement

The Company is party to a manufacturing agreement for research and development and commercial production with AGC Biologics, S.p.A. (formerly MolMed S.p.A.) (“AGC”) pursuant to which AGC will develop, manufacture and supply certain viral vectors and conduct cell processing activities for certain Company development and commercial programs. A manufacturing agreement with AGC was novated to the Company as part of the GSK Agreement (see Note 15). On July 2, 2020 (the “Effective Date”), the Company entered into a new manufacturing and technology development master agreement with AGC (the “AGC Agreement”) which superseded the novated agreement.

The Company determined that the AGC Agreement contains an embedded lease as it includes provision of manufacturing suites designated for the Company’s exclusive use during the term of the agreement. The AGC Agreement has an initial term of five years, beginning on the Effective Date and ending July 2, 2025. The agreement may be extended for an additional two years by mutual agreement of the Company and AGC. The AGC Agreement contains payments associated with lease and non-lease components. The contractual annual rental payments associated with the lease that are considered a lease component amount to €2.7 million per contract year. The non-lease components of the agreement consist of minimum manufacturing purchase requirements and dedicated manufacturing and development services (see Note 18).

As of December 31, 2021, the carrying value of the embedded operating lease right-of-use asset was $10.7 million and the lease liability was $9.3 million. As of December 31, 2020, the carrying value of the embedded operating lease right-of-use asset was $13.9 million and the lease liability was $13.1 million. The Company may terminate the AGC Agreement and the use of the exclusive manufacturing suites, with 12-months’ notice, and beginning no earlier than July 2, 2022. AGC may terminate the AGC Agreement with 24-months’ notice. The AGC Agreement provides for an option to reserve one additional exclusive manufacturing suite any time prior to January 1, 2022 for a one-time option fee plus annual rental fee. The AGC Agreement extends until July 2, 2025.

Summary of all lease costs recognized under ASC 842

Our facility leases described above generally contain customary provisions allowing the landlords to terminate the leases if we fail to remedy a breach of any of our obligations under any such lease within specified time periods, or upon our bankruptcy or insolvency. The leases do not include any restrictions or covenants that had to be accounted for under the lease guidance. The following table contains a summary of the lease-related costs recognized within operating expenses, and other information pertaining to the Company’s operating leases as of December 31, 2021 and 2020:

	2021			2020
Fixed lease cost	$	7,701		$	7,593
Impairment of right-of-use assets		—			2,781
Variable lease cost		1,696			2,131
Sublease income		(2,746	)		(181	)
Total lease cost	$	6,651		$	12,324

Other information
Operating cash flows used for operating leases		7,989			8,447
Weighted-average remaining lease term (years)		6.0			6.6
Weighted-average discount rate		8.7	%		8.6	%

Fixed lease cost represents the ASC 842 rent expense associated with the amortization of our right-of-use assets and lease liabilities. Impairment of right-of-use assets relates to discrete impairment charges taken when, in the Company’s estimation, the fair value of a right-of-use asset is below the carrying value. Variable lease cost are the amounts owed by the Company to a lessor that are not fixed, such as reimbursement for common area maintenance and utilities costs, and are not included in the calculation of the Company’s operating lease right of use assets or operating lease liabilities and are expensed when incurred. Sublease income represents the straight-line recognition of base rent sublease income over the term of the Sublease, and recognition of pass-through operating expense costs per the terms of the Sublease.

During the year ended December 31, 2021, the Company obtained right of use assets valued at $0.6 million in exchange for

lease liabilities of $0.6 million. During the year ended December 31, 2020 the Company obtained $17.5 million in right of use assets in exchange for $17.5 million in lease liabilities.

As of December 31, 2021, future minimum base rent commitments under ASC 842 under the Company’s property leases were as follows:

Due in:	Gross lease payments			Gross sublease receipts			Net lease payments
2022		7,326			(2,334	)		4,992
2023		6,773			(2,246	)		4,527
2024		6,799			(2,313	)		4,486
2025		5,361			(2,382	)		2,979
2026		3,720			(2,454	)		1,266
Thereafter		11,332			(8,960	)		2,372
Total future minimum lease payments		41,311			(20,689	)		20,622
Less: imputed interest		(14,698	)
Total operating lease payments	$	26,613

*Tabular disclosure above for leases denominated in GBP have been translated at a rate of £1.00 to $1.35, and leases denominated in Euro have been translated at a rate of €1.00 to $1.13.

Notes Payable

12 Months Ended

Dec. 31, 2021

Debt Disclosure [Abstract]

Notes Payable

12. Notes Payable

In May 2019, the Company entered into a senior term facilities agreement, which was amended in April 2020 (the “Original Credit Facility”) with MidCap Financial (Ireland) Limited (“MidCap Financial”), as agent, and additional lenders from time to time (together with MidCap Financial, the “Lenders”), to borrow up to $75.0 million in term loans.

In May 2021, the Company amended and restated the Original Credit Facility (the “Amended Credit Facility”). Under the Amended Credit Facility, the Lenders agreed to make term loans available to the Company in the aggregate amount of $100.0 million, including increasing the principal on the initial term loan to $33.0 million, from $25.0 million. To date, the Company has borrowed $33.0 million under the amended initial term loan. The remaining $67.0 million under the Amended Credit Facility may be drawn down in the form of a second and third term loan, the second term loan being a $33.0 million term loan available no earlier than July 1, 2022 and no later than July 1, 2023 upon certain regulatory approvals and evidence of the Company having $100 million in cash and cash equivalent investments; and the third term loan being a $34.0 million term loan available no earlier than July 1, 2023 and no later than July 1, 2024 upon evidence of the Company having $100 million in cash and cash equivalent investments and attaining a pre-specified trailing 12-month revenue target.

Prior to execution of the Amended Credit Facility, each term loan under the Original Credit Facility bore interest at an annual rate equal to 6.0% plus LIBOR. The Company was required to make interest-only payments on the term loan for all payment dates prior to 24 months following the date of the Original Credit Facility, unless the third tranche was drawn, in which case for all payment dates prior to 36 months following the date of the Original Credit Facility. The term loans prior to the Amended Credit Facility were to begin amortizing on either the 24-month or the 36-month anniversary of the Original Credit Facility (as applicable), with equal monthly payments of principal plus interest to be made by the Borrower to the Lenders in consecutive monthly installments until the loan maturity date. In addition, a final payment of 4.5% was due on the loan maturity date. The Company accrued the final payment amount of $1.1 million associated with the first term loan of the Original Credit Facility, to outstanding debt by charges to interest expense using the effective-interest method from the date of issuance through the date of the Amended Credit Facility. Upon execution of the Amended Credit Facility, the Company was required to make a payment of $0.5 million for the accrued final payment associated with the Original Credit Facility, which was netted against proceeds from the additional initial term loan.

Each term loan under the Amended Credit Facility bears interest at an annual rate equal to 5.95% plus LIBOR. The Company is required to make interest-only payments on the term loan for 18 months following the date of the Amended Credit Facility, unless the Company is eligible for the second tranche, in which case the Company may elect to make interest-only payments for 30 months following the date of the Amended Credit Facility. The term loans under to the Amended Credit Facility begin amortizing on either the 18-month or the 30-month anniversary of the Amended Credit Facility (as applicable), with equal monthly payments of principal plus interest to be made by the Company to the Lenders in consecutive monthly installments until the loan maturity date. In addition, a final payment of 3.5% is due on the loan maturity date. The Company is accruing the final payment amount of $1.2 million associated with the first term loan of the Amended Credit Facility, to outstanding

debt by charges to interest expense using the effective-interest method from the date of issuance through the loan maturity date.

The Amended Credit Facility includes affirmative and negative covenants. The affirmative covenants include, among others, covenants requiring the Company to maintain their legal existence and governmental approvals, deliver certain financial reports, maintain insurance coverage, maintain property, pay taxes, satisfy certain requirements regarding accounts and comply with laws and regulations. The negative covenants include, among others, restrictions on the Company transferring collateral, incurring additional indebtedness, engaging in mergers or acquisitions, paying dividends or making other distributions, making investments, creating liens, amending material agreements and organizational documents, selling assets, changing the nature of the business and undergoing a change in control, in some cases subject to certain exceptions. The Company is also subject to an ongoing minimum cash financial covenant in which the Company must maintain unrestricted cash in an amount not less than $20.0 million following the utilization of the second term loan and not less than $35.0 million following the utilization of the third term loan.

As of December 31, 2021, and December 31, 2020, notes payable consist of the following:

	December 31,
	2021			2020
Notes payable, net of issuance costs	$	32,669		$	24,659
Less: current portion		(786	)		(4,861	)
Notes payable, net of current portion		31,883			19,798
Accretion related to final payment		203			406
Notes payable, long term	$	32,086		$	20,204

As of December 31, 2021, the future principal payments due are as follows:

	Aggregate Minimum Payments
2022		786
2023		9,429
2024		9,429
2025		9,429
2026		5,082
Thereafter		—
Total		34,155
Less current portion		(786	)
Less unamortized portion of final payment		(952	)
Less unamortized debt issuance costs		(331	)
Notes payable, long term	$	32,086

During the years ended December 31, 2021 and 2020, the Company recognized $2.5 million and $2.3 million of interest expense related to the term loan, respectively. The effective annual interest rate as of December 31, 2021 on the outstanding debt under the Term Loan was approximately 8.4%.

- Definition

The entire disclosure for information about short-term and long-term debt arrangements, which includes amounts of borrowings under each line of credit, note payable, commercial paper issue, bonds indenture, debenture issue, own-share lending arrangements and any other contractual agreement to repay funds, and about the underlying arrangements, rationale for a classification as long-term, including repayment terms, interest rates, collateral provided, restrictions on use of assets and activities, whether or not in compliance with debt covenants, and other matters important to users of the financial statements, such as the effects of refinancing and noncompliance with debt covenants.

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+ Details

Shareholders' Equity and Convertible Preferred Shares

12 Months Ended

Dec. 31, 2021

Shareholders Equity And Convertible Preferred Shares [Abstract]

Shareholders' Equity and Convertible Preferred Shares

13. Shareholders’ Equity and Convertible Preferred Shares

Ordinary shares

As of December 31, 2021, and 2020, each holder of ordinary shares and ADSs is entitled to one vote per ordinary share and to receive dividends when and if such dividends are recommended by the board of directors and declared by the shareholders. As of December 31, 2021, and 2020, the Company has not declared any dividends.

As of December 31, 2021, and 2020, the Company had authority to allot ordinary shares up to a maximum nominal value of £13,023,851.50 with a nominal value of £0.10 per share.

Ordinary share issuances

In April 2020, the Company issued 75,413 ordinary shares to Oxford BioMedica pursuant to the terms of our license agreement (see Note 15).

In December 2020, the Company issued 22,758 ordinary shares pursuant to a consulting agreement (see Note 18) with a non-employee advisor.

In February 2021, the Company issued and sold (i) 20,900,321 ordinary shares, nominal value £0.10 per share, at a purchase price of $6.22 per share (the “Purchase Price”), which was the closing sale price of the Company’s ADSs on the Nasdaq Global Select Market on February 4, 2021, and (ii) 3,215,434 non-voting ordinary shares, nominal value £0.10 per share, at the Purchase Price (together (i) and (ii) the “Private Placement”). The Private Placement resulted in net proceeds to the Company of $143.6 million after deducting placement agent fees of $6.0 million and other issuance costs of $0.4 million. The ordinary shares and non-voting ordinary shares were sold pursuant to a securities purchase agreement entered into between the Company and the purchasers named therein on February 4, 2021. All non-voting ordinary shares have been converted to ordinary shares as of December 31, 2021.

In July 2021 the Company issued 1,227,738 ordinary shares to Pharming Group N.V. for total consideration of $7.5 million. The consideration is payment for the fair value of ordinary shares with a fair value of $4.1 million plus a $3.4 million premium on the fair value of the Company’s ordinary shares, which was allocated to the license and collaboration agreement (see Note 16).

In December 2021, the Company issued 22,758 ordinary shares pursuant to a consulting agreement (see Note 18) with a non-employee advisor

- Definition

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

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+ Details

Share-based Compensation

12 Months Ended

Dec. 31, 2021

Disclosure Of Compensation Related Costs Sharebased Payments [Abstract]

Share-based Compensation

14. Share-based Compensation

The Company maintains four equity compensation plans; the Orchard Therapeutics Limited Employee Share Option Plan with Non-Employee Sub-Plan and U.S. Sub-Plan (the “2016 Plan”), the Orchard Therapeutics plc 2018 Share Option and Incentive Plan (the “2018 Plan”), the 2018 Employee Share Purchase Plan (the “ESPP”), and the 2020 Inducement Equity Plan (the “Inducement Plan”). The number of shares of common stock that may be issued under the 2018 Plan is subject to increase by the number of shares forfeited under any options forfeited and not exercised under the 2018 Plan or 2016 Plan. The board of directors has determined not to make any further awards under the 2016 plan. As of December 31, 2021, 6,934,474 shares remained available for grant under the 2018 Plan, 721,500 remained available under the Inducement Plan, and 1,197,399 shares remained available for grant under the ESPP.

Prior to the Company’s IPO, the Company granted options to United States employees and non-employees at exercise prices deemed by the board of directors to be equal to the fair value of the ordinary share at the time of grant, and granted options to United Kingdom and European Union employees and non-employees at an exercise price equal to the par value of the ordinary shares of £0.00001. After the IPO, options are now granted at exercise prices equal to the fair value of the Company’s ordinary shares on the grant date for all employees. The vesting period is determined by the board of directors, which is generally four years. An option’s maximum term is ten years.

Share options

The fair value of each stock option award is determined on the date of grant using the Black-Scholes option-pricing model. The risk-free interest rate is based on a U.S. treasury instrument whose term is consistent with the expected term of the stock options. The expected term of the Company’s options has been determined utilizing the “simplified” method for awards that qualify as “plain-vanilla” options. The expected volatility is based on the historical volatility of a representative group of companies with similar characteristics to the Company, including those in the early stages of product development with a similar and therapeutic focus. For these analyses, the Company selects companies with comparable characteristics to its own including enterprise value, risk profiles, position within the industry, and with historical share price information sufficient to meet the expected term of the options. The relevant data used to determine the value of stock option awards are as follows:

	Year Ended December 31,
	2021	2020
Risk-free interest rate	0.5 - 1.3%	0.3 - 1.7%
Expected term (in years)	5.3 - 6.1	5.5 - 6.1
Expected volatility	74.2 - 78.7%	70.7 - 75.2%
Expected dividend rate	0.00%	0.00%

The following table summarizes option activity under the plans for the year ended December 31, 2021:

	Shares			Weighted Average Exercise Price per Share		Weighted Average Remaining Contractual Life (Years)		Aggregate Intrinsic Value
Outstanding at December 31, 2020		13,895,643		$	7.96		7.16	$	91,133
Granted		8,489,856			4.75
Exercised		(1,727,254	)		1.59
Forfeited		(3,357,505	)		10.30
Outstanding and expected to vest at December 31, 2021		17,300,740		$	6.57		7.83	$	2,842
Exercisable, as of December 31, 2021		7,880,668		$	6.90		6.59	$	2,685

The aggregate intrinsic value of options is calculated as the difference between the exercise price of the options and the fair value of the Company’s ordinary shares for those options that had exercise prices lower than the fair value of the Company’s ordinary shares. During the years ended December 31, 2021 and 2020, the total intrinsic value of share options exercised was $7.4 million and $5.0 million, respectively. During the years ended December 31, 2021 and 2020, the total proceeds to the Company from share options exercised was $2.7 million and $3.9 million, respectively. As of December 31, 2021, and 2020, there was $nil and $0.2 million in employee equity plan proceeds received after year-end, respectively.

The weighted average grant date fair value of the options granted during the years ended December 31, 2021 and 2020 was $3.10 per share and $7.22 per share, respectively.

Restricted Share Units

Performance-based share units

The Company has issued performance-based restricted share units (“RSUs”) to certain executives and members of its senior management, with vesting linked to the achievement of three specific regulatory and research and development milestones and one market condition based upon the volume weighted-average price (“VWAP”) of the Company’s ADSs for a certain period. Upon achievement of any of the aforementioned milestones, one third of the RSUs will vest, and the award will become fully vested upon achievement of three of the four performance conditions. 89,667 performance-based share units vested during the years ended December 31, 2021. At December 31, 2021, the remaining 179,333 performance-based share units outstanding under the scheme were cancelled.

The fair value associated with the performance-based conditions is recognized when achievement of the milestones becomes probable, if at all. In the fourth quarter of 2020, the Company determined that a performance milestone was probable upon

approval of Libmeldy by the European Commission in December 2020, and recognized $1.2 million in compensation cost. The shares associated with recognition of this performance milestone vested and were issued in January 2021.

CEO Award

The Company granted 195,000 performance-based RSUs with a total grant date fair value of $1.4 million to its Chief Executive Officer, Bobby Gaspar, M.D., Ph.D., in April 2020. The award vests on January 2, 2024 as to 1/3 of the award for each of the first three to occur of four milestones, if each such milestone is achieved by the Company on or before December 31, 2023 and Dr. Gaspar remains continuously employed with the Company through January 2, 2024. The milestones relate to achievement of specific clinical and regulatory milestones. No performance-based share unit performance conditions associated with the CEO award were deemed probable and none vested during the year ended December 31, 2021.

Time-based restricted share units

Time-based restricted share units vest in equal annual installments over a three-year period.

The following table summarizes restricted share unit award activity for the year-end December 31, 2021:

	Performance-based RSUs			Time-based RSUs			Weighted Average Grant Date Fair Value per Share
Unvested at December 31, 2020		464,000			180,000		$	8.75
Granted		—			47,500			4.94
Vested		(89,667	)		(41,667	)		9.94
Forfeited		(179,333	)		(62,500	)		10.32
Unvested at December 31, 2021		195,000			123,333		$	6.41

Share-based compensation

Share-based compensation expense related to share options, restricted share unit awards, and the employee stock purchase plan was classified in the consolidated statements of operations and comprehensive loss as follows:

	Year Ended December 31,
	2021		2020
Research and development	$	9,214	$	11,679
Selling, general and administrative		13,322		16,283
Total	$	22,536	$	27,962

The Company had 9,420,072 unvested options outstanding as of December 31, 2021. As of December 31, 2021, total unrecognized compensation cost related to unvested stock option grants and time-based RSUs was approximately $37.1 million. This amount is expected to be recognized over a weighted average period of approximately 2.77 years. As of December 31, 2021, the total unrecognized compensation cost related to performance-based RSUs is a maximum of $1.4 million, the timing of recognition will be dependent upon achievement of milestones.

License and Research Agreements

12 Months Ended

Dec. 31, 2021

License And Research Arrangements [Abstract]

License and Research Arrangements

15. License and Research Arrangements

GSK asset purchase and license agreement

In April 2018, the Company completed an asset purchase and license agreement (the “GSK Agreement”) with subsidiaries of GSK to acquire a portfolio of autologous ex vivo gene therapy assets and licenses, for rare diseases and option rights on three additional programs in preclinical development from Telethon Foundation and San Raffaele Hospital (“Telethon-OSR”). The portfolio of programs and options acquired consisted of:

•

Two late-stage clinical gene therapy programs in ongoing registrational trials for MLD and WAS;

•

One earlier stage clinical gene therapy program for TDT;

•

Strimvelis, the first autologous ex vivo gene therapy for ADA-SCID which was approved for marketing by the European Medicines Agency in 2016; and

•

Option rights exercisable upon completion of clinical proof of concept studies for three additional earlier-stage development programs, which option rights have all subsequently lapsed.

The Company accounted for the GSK Agreement as an asset acquisition, since the asset purchase and licensing arrangement did not meet the definition of a business pursuant to ASC 805, Business Combinations. Total consideration was £94.2 million ($133.6 million at the acquisition date), which included an upfront payment of £10.0 million ($14.2 million at the acquisition date) and 12,455,252 convertible preferred shares of the Company issued to GSK at an aggregate value of £65.8 million ($93.4 million at the acquisition date), a loss contract on the Strimvelis program valued at £12.9 million ($18.4 million), an inventory purchase liability valued at £4.9 million ($6.9 million) and transaction costs of £0.6 million ($0.8 million). The Company allocated £94.2 million ($133.6 million) to in-process research and development expense (based on the fair value of the underlying programs in development). The convertible preferred shares were converted to ordinary shares as part of our IPO in November 2018.

The Company is required to use commercially reasonable efforts to obtain a Priority Review Voucher (“PRV”) from the United States Food and Drug Administration for each of the programs for MLD, WAS and TDT, the first of which GSK retained beneficial ownership over. GSK also has an option to acquire, at a price pursuant to an agreed upon formula, any PRV granted to the Company thereafter for MLD, WAS and TDT. If GSK does not exercise this option to purchase any PRV, the Company may sell the PRV to a third party and must share any proceeds in excess of a specified sale price equally with GSK. For accounting purposes, as of December 31, 2021, the Company does not consider the attainment of a PRV from the United States Food and Drug Administration to be probable.

As part of the GSK Agreement the Company is required to use its best endeavors to make Strimvelis commercially available in the European Union until such time as an alternative gene therapy is commercially available for patients in Italy, and at all times at the San Raffaele Hospital in Milan, provided that a minimum number of patients continue to be treated at this site. Strimvelis is not currently expected to generate sufficient cash flows to overcome the costs of maintaining the product and certain regulatory commitments; therefore, the Company recorded a liability associated with the loss contract of £12.9 million ($18.4 million at the acquisition date) associated with the loss expected due to this obligation. This liability is being amortized over the remaining period of expected sales of Strimvelis as a credit to research and development expenses (see Note 2).

The Company will pay GSK non-refundable royalties and milestone payments in relation to the gene therapy programs. The Company will pay a flat mid-single digit percentage royalty on the combined annual net sales of ADA-SCID products, which includes Strimvelis. The Company will also pay tiered royalty rates at a percentage beginning in the mid-teens up to twenty percent for the MLD and WAS products, upon marketing approval, calculated as percentages of aggregate cumulative net sales of the MLD and WAS products, respectively. The Company will pay a tiered royalty at a percentage from the high single-digits to low double-digit for the TDT product, upon marketing approval, calculated as percentages of aggregate annual net sales of the TDT product. These royalties owed to GSK are in addition to any royalties owed to other third parties under various license agreements for the GSK programs. In aggregate, the Company may pay up to £90.0 million in milestone payments upon achievement of certain sales milestones applicable to GSK. The Company’s royalty obligations with respect to MLD and WAS may be deferred for a certain period in the interest of prioritizing available capital to develop each product. The Company’s royalty obligations are subject to reduction on a product-by-product basis in the event of market control by biosimilars and will expire in April 2048. Other than Strimvelis, these royalty and milestone payments were not determined to be probable and estimable at the date of the acquisition and are not included as part of consideration.

The Company and GSK also separately executed a Transition Services Agreement (“TSA”) as well as an Inventory Sale Agreement, in April 2018. The TSA outlined several activities that the Company had requested GSK to assist with during the transition period, including but not limited to utilizing GSK to sell, market and distribute Strimvelis, and assist with regulatory, clinical and non-clinical activities for the other non-commercialized products which were ongoing at the date of the GSK Agreement. The TSA expired in December 2018.

In connection with the Company’s entering into the GSK Agreement, GSK assigned rights and obligations to certain contracts, which include among others, the original license agreement with Telethon-OSR and an ongoing manufacturing agreement (see Note 18).

Telethon-OSR research and development collaboration and license agreements

In connection with the Company’s entering into the GSK Agreement, the Company also acquired and assumed agreements with Telethon Foundation and San Raffaele Hospital, together referred to as Telethon-OSR, for the research, development and commercialization of autologous ex vivo gene therapies for ADA-SCID, WAS, MLD, TDT, as well as options over three additional earlier-stage development programs. The Company’s options under the agreement with Telethon-OSR with respect to the earlier-stage programs have lapsed.

As consideration for the licenses, the Company will be required to make payments to Telethon-OSR upon achievement of certain product development milestones. Additionally, the Company will be required to pay to Telethon-OSR a tiered mid-single to low-double digit royalty percentage on annual sales of licensed products covered by patent rights on a country-by-country basis, as well as a low double-digit percentage of sublicense income received from any certain third-party sublicenses of the collaboration programs. These royalties are in addition to those payable to GSK under the GSK Agreement. The Company may pay up to an aggregate of approximately €31.0 million ($35.0 million at December 31, 2021) in milestone payments upon achievement of certain product development milestones for the program.

In May 2019, the Company entered into a license agreement with Telethon-OSR, under which Telethon-OSR granted to the Company an exclusive worldwide license for the research, development, manufacture and commercialization of Telethon-OSR’s ex vivo autologous HSC lentiviral based gene therapy for the treatment of mucopolysaccharidosis type I (“MPS-I”), including the Hurler variant. To date, Telethon-OSR received €17.0 million in upfront and milestone payments from the Company upon entering into the agreement and shortly thereafter, resulting in $19.4 million in in-process research and development expense. The Company is also required to make milestone payments contingent upon certain development, regulatory and commercial milestones are achieved and may pay up to €28.0 million ($31.7 million at December 31, 2021). Additionally, the Company will be required to pay Telethon a tiered mid-single to low-double digit royalty percentage on annual net sales of licensed products.

UCLB/UCLA License Agreement

In February 2016, and amended in July 2017, the Company completed the UCLB/UCLA license agreement, under which the Company has been granted exclusive and non-exclusive, sublicensable licenses under certain intellectual property rights controlled by UCLB and UCLA to develop and commercialize gene therapy products in certain fields and territories.

In exchange for these rights, in 2016, the Company made upfront cash payments consisting of $0.8 million for the license to the joint UCLB/UCLA technology and $1.1 million for the license to the UCLB technology and manufacturing technology. The Company also issued an aggregate of 4,665,384 ordinary shares to UCLB, of which 1,224,094, and 3,441,290 ordinary shares were issued in 2017 and 2016, respectively. The Company recorded research and development expense based on the fair value of the ordinary shares as of the time the agreement was executed or modified. The Company was also obligated to make an additional cash payment for clinical data. In 2017, the Company paid $0.8 million in relation to clinical data acquired. The Company recorded the payments to research and development expense.

Under the UCLB/UCLA License Agreement, the Company is also obligated to pay an annual administration fee of $0.1 million on the first, second and third anniversary of the agreement date. Additionally, the Company may become obligated to make payments to the parties of up to an aggregate of £19.9 million ($26.8 million at December 31, 2021) upon the achievement of specified regulatory milestones as well as royalties ranging from low to mid-single-digit percentage on net sales of the applicable gene therapy product.

The Company recorded nil and $0.1 million of research and development costs in respect of the UCLB/UCLA license agreement associated with the annual administrative fee for the years ended December 31, 2021 and 2020.

In June 2021, the Company terminated the license to its OTL-101 program for ADA-SCID, which was granted pursuant to the UCLB/UCLA license agreement. Except for the termination of such license, the UCLB/UCLA license agreement continues in full force and effect.

Unless terminated earlier by either party, the UCLB/UCLA license agreement will expire on the 25^th anniversary of the agreement.

Oxford BioMedica license, development and supply agreement

In November 2016, and as amended in June 2017, May 2018, July 2018, September 2018, May 2019 and April 2020, the Company entered into an arrangement with Oxford BioMedica whereby Oxford BioMedica granted an exclusive intellectual property license to the Company for the purposes of research, development, and commercialization of collaboration products, and will provide process development services, and manufacture clinical and commercial GMP-grade lentiviral vectors to the Company (“Oxford BioMedica Agreement”). As part of the consideration to rights and licenses granted under the Oxford BioMedica Agreement, the Company issued 588,220 ordinary shares to Oxford BioMedica. The Company is also obligated to make certain development milestone payments in the form of issuance of additional ordinary shares if the milestones are achieved. In November 2017, the first milestone was achieved, and the Company was committed to issue another 150,826 ordinary shares, and issued these shares in 2018. In September 2018, the second and fourth milestones were achieved, and the Company issued 150,826 ordinary shares. In April 2020, the fifth milestone was deemed to have been met upon execution of the amended agreement in April 2020, and the Company issued 75,413 ordinary shares to Oxford BioMedica with a total value of $0.8 million, which was expensed to research and development expense. No milestones were met during the year ended December 31, 2021.

The Company may also pay low single-digit percentage royalties on annual net sales of collaborated product generated under the Oxford BioMedica Agreement.

16. Collaboration agreement with Pharming Group N.V.

Overview

On July 1, 2021, the Company entered into a strategic collaboration with Pharming Group N.V. (“Pharming”) to research, develop, manufacture, and commercialize OTL-105, an investigational ex vivo autologous HSC gene therapy for the treatment of hereditary angioedema (HAE), a life-threatening rare disorder that causes recurring swelling attacks in the face, throat, extremities and abdomen (the “Collaboration Agreement”).

Under the terms of the Collaboration Agreement, Pharming was granted worldwide rights to OTL-105 and will be responsible for clinical development, regulatory filings and commercialization of the investigational gene therapy, including associated costs. The Company will lead the completion of IND-enabling activities and oversee manufacturing of OTL-105 during preclinical and clinical development, which will be funded by Pharming. In addition, both the Company and Pharming will explore the application of non-toxic conditioning regimen for use with OTL-105 administration.

The Company received an upfront payment of $10.0 million in cash from Pharming. The Company is also eligible to receive up to $189.5 million in development, regulatory and sales milestones as well as mid-single to low double-digit percentage royalty payments on future worldwide sales.

Share Purchase Agreement

The Company also entered into a Share Purchase Agreement with Pharming on July 1, 2021 (the “SPA”), pursuant to which the Company issued 1,227,738 ordinary shares to Pharming for total consideration of $7.5 million. The consideration is payment for the fair value of ordinary shares with a fair value of $4.1 million plus a $3.4 million premium on the fair value of the Company’s ordinary shares.

The “Collaboration Agreement” and the “SPA” are referred to together as the “Pharming Agreements.”

Accounting Analysis

At the commencement of the arrangement, two units of accounting were identified, which are the issuance of 1,227,738 of the Company’s ordinary shares as part of the SPA, and the license and collaboration agreement, which conveys the license and provides for the Company to provide research, development, manufacturing services for OTL-105. The Pharming Agreements were entered into concurrently as part of a single commercial objective, and the Company considers them a

single arrangement for accounting purposes. The total upfront payments of $17.5 million are comprised of $4.1 million attributed to the equity sold to Pharming and $13.4 million attributed to the Collaboration Agreement. In determining the fair value of the common stock issued to Pharming as part of the SPA, the Company used an option pricing valuation model to take into consideration certain holding period restrictions on the shares. The fair value of the Company’s common shares was considered a level 2 fair value measurement within the fair value hierarchy. The most significant assumptions within the model are the Company’s stock price, the term of the restrictions and the stock price volatility, which is based upon historical volatility of the Company’s stock. Based on the fair value adjustments made by management, the fair value of the shares issued was determined to be $4.1 million with the excess proceeds of $3.4 million being allocation to the Collaboration Agreement.

The Company recognizes revenue under Accounting Standards Codification (“ASC”) 606, Revenue from Contracts with Customer (“ASC 606”). The Company has concluded that the conveyance of the license for the HAE program and the provision of research, development, and manufacturing services for the HAE program represent a series of distinct services that are accounted for as a single performance obligation within the Collaboration Agreement. The Company determined that the transaction price includes: the non-refundable up-front payment of $10.0 million, the $3.4 million in premium associated with the SPA, and the variable consideration for estimated reimbursement payments at agreed upon contractual rates to be received from Pharming for the Company’s on-going research, development, and manufacturing services. The potential future variable consideration is associated with the reimbursement for research, development, and manufacturing services provided by the Company to Pharming at agreed upon contractual rates which is the only remaining unsatisfied performance obligation. The milestone payments included in the Collaboration Agreement are fully constrained, as a result of the uncertainty regarding whether any of the associated milestones will be achieved and therefore, the Company determined that it could not assert that it was probable that a significant reversal in the amount of cumulative revenue recognized will not occur. The total estimated cost of the research and development services reflect the nature of the services to be performed and the Company’s best estimate of the length of time required to perform the services. The Company re-evaluates the transaction price as of the end of each reporting period.

The Company also considered the existence of any significant financing component within the Pharming Agreements given their upfront payment structure. Based upon this assessment, the Company concluded that the up-front payments were provided for valid business reasons and not for the purpose of providing financing. Accordingly, the Company has concluded that the upfront payment structure of the Pharming Agreements does not result in the existence of a significant financing component.

The Company recognizes revenue associated with the performance obligation as the research, development and manufacturing services are provided using an input method, based on the cumulative costs incurred compared to the total estimated costs expected to be incurred to satisfy the performance obligation. The transfer of control to the customer occurs over the time period that the research, development and manufacturing services are to be provided by the Company, and this cost-to-cost method is, in management’s judgment, the best measure of progress towards satisfying the performance obligation. Reimbursement for research, development, and manufacturing services are recognized as the costs are incurred consistent with the cost-to-cost method. The Company's continuing obligations to provide research, development, and manufacturing services is based on the results of such efforts, and the estimated costs associated with the remaining efforts required to complete the performance obligations may change, which may materially impact revenue recognition. The Company regularly evaluates and, when necessary, updates the costs associated with the remaining effort under the Collaboration Agreement. Accordingly, revenue may fluctuate from period to period due to revisions to estimated costs, resulting in a change in the measure of progress for the performance obligation, or if the transaction price changes due to inclusion of any milestone payments that become unconstrained.

The following table summarizes research and development costs incurred and collaboration revenue recognized in connection with the Company’s performance under the Collaboration Agreement:

	Year Ended December 31,
	2021		2020
Reimbursement revenue	$	843	$	—
Upfront and milestone payment revenue		132		—
Total	$	975	$	—

The Company had $0.8 million and nil due from Pharming included in accounts receivable as of December 31, 2021 and December 31, 2020, respectively.

As of December 31, 2021, the Company had contract liabilities of $12.9 million, which is classified as either current or long-term deferred revenue in the consolidated balance sheets based on the period over which this is expected to be recognized. The deferred revenue balance represents the portion of the upfront payments received related to the performance obligation that remains partially unsatisfied as of December 31, 2021.

Collaboration Agreement with Pharming Group N.V.

12 Months Ended

Dec. 31, 2021

Collaborative Arrangement [Abstract]

License and Research Arrangements

15. License and Research Arrangements

GSK asset purchase and license agreement

•

Two late-stage clinical gene therapy programs in ongoing registrational trials for MLD and WAS;

•

One earlier stage clinical gene therapy program for TDT;

•

Strimvelis, the first autologous ex vivo gene therapy for ADA-SCID which was approved for marketing by the European Medicines Agency in 2016; and

•

Option rights exercisable upon completion of clinical proof of concept studies for three additional earlier-stage development programs, which option rights have all subsequently lapsed.

Telethon-OSR research and development collaboration and license agreements

UCLB/UCLA License Agreement

Unless terminated earlier by either party, the UCLB/UCLA license agreement will expire on the 25^th anniversary of the agreement.

Oxford BioMedica license, development and supply agreement

The Company may also pay low single-digit percentage royalties on annual net sales of collaborated product generated under the Oxford BioMedica Agreement.

16. Collaboration agreement with Pharming Group N.V.

Overview

Share Purchase Agreement

The “Collaboration Agreement” and the “SPA” are referred to together as the “Pharming Agreements.”

Accounting Analysis

The following table summarizes research and development costs incurred and collaboration revenue recognized in connection with the Company’s performance under the Collaboration Agreement:

	Year Ended December 31,
	2021		2020
Reimbursement revenue	$	843	$	—
Upfront and milestone payment revenue		132		—
Total	$	975	$	—

The Company had $0.8 million and nil due from Pharming included in accounts receivable as of December 31, 2021 and December 31, 2020, respectively.

Income Taxes

12 Months Ended

Dec. 31, 2021

Income Tax Disclosure [Abstract]

Income Taxes

17. Income Taxes

The components of net loss before income taxes for the years ended December 31, 2021 and 2020 are as follows:

	December 31,
	2021			2020
U.K.	$	(147,337	)	$	(155,614	)
Non-U.K.		3,581			2,904
Net loss before income taxes	$	(143,756	)	$	(152,710	)

The provision for (benefit from) income taxes for the years ended December 31, 2021 and 2020 are as follows:

	December 31,
	2021			2020
Current (benefit) provision
Federal—United States	$	(1,025	)	$	1,107
State—United States		334			189
Other foreign		388			230
United Kingdom		—			—
Total current (benefit) provision		(303	)		1,526
Deferred provision (benefit)
Federal—United States		1,099			(1,774	)
State—United States		(312	)		(103	)
United Kingdom		—			—
Other foreign		344			(380	)
Total deferred provision (benefit)		1,131			(2,257	)
Total provision (benefit) for income taxes	$	828		$	(731	)

The following table presents a reconciliation of income tax expense (benefit) computed at the UK statutory income tax rate to the effective income tax rate as reflected in the consolidated financial statements:

	December 31,
	2021			2020
Income taxes at United Kingdom statutory rate	$	(27,313	)	$	(29,015	)
Change in valuation allowance		59,691			29,302
Reduction in research expense for credits granted		6,674			8,435
Change in tax rates		(38,785	)		(8,105	)
Tax credits		(2,232	)		(1,369	)
U.S. Deduction for foreign derived intangible income		(196	)		(1,254	)
Permanent differences, including share-based compensation deduction shortfalls		2,863			1,265
U.S. state income taxes		17			68
Foreign rate differential		109			(58	)
Total provision (benefit) for income taxes	$	828		$	(731	)

The Company’s income tax expense for the year ended December 31, 2021, compared to the year ended December 31, 2020, increased primarily related to shortfalls related to share-based compensation that is not deductible for tax purposes and a reduction of the U.S. deduction for foreign derived intangible income (“FDII”), offset by an increase in the benefit from U.S. federal research and development tax credits.

During 2021, the U.K. Government announced that from April 1, 2023, the corporation tax rate would increase to 25%. This new law was enacted on June 10, 2021. The overall effect of the change was an increase in net deferred tax assets by $38.8 million and an increase in valuation allowance by an equal amount.

The Company accounts for income taxes in accordance with ASC Topic 740. Deferred income tax assets and liabilities are determined based upon temporary differences between the financial reporting and tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. The following table presents the principal components of the Company’s deferred tax assets and liabilities as of December 31, 2021 and 2020:

	December 31,
	2021			2020
Deferred tax assets
Net operating loss carryforwards	$	126,563		$	75,502
Amortization		25,206			22,599
Research and development credits		2,449			1,564
Share-based compensation		9,353			7,400
Accruals		798			1,001
Lease liability		6,444			6,805
Property and equipment		1,022			523
Other		—			3
Total deferred tax assets		171,835			115,397
Valuation allowance		(161,573	)		(103,890	)
Fixed assets and right-of-use asset		(6,176	)		(6,288	)
Other non-current assets (net deferred tax assets and liabilities)	$	4,086		$	5,219

For the years ended December 31, 2021 and 2020, the Company had cumulative tax-effected UK net operating loss carryforwards of approximately $126.6 million and $75.1 million, respectively. UK losses not surrendered may be carried forward indefinitely, subject to numerous utilization criteria and restrictions and are fully offset by a valuation allowance. For the years ended December 31, 2021 and 2020, the Company also had U.S. federal orphan drug tax credits of $0.6 million and $0, respectively, and U.S. state research and development tax credits of $2.4 million and $2.0 million. The U.S. federal orphan drug tax credits expire in 2041, while the U.S. state research and development credits may be carried forward indefinitely and are offset by a valuation allowance.

In measuring the Company’s deferred tax assets, the Company considers all available evidence, both positive and negative, to determine whether, based on the weight of that evidence, a valuation allowance is needed for all or some portion of the deferred tax assets. Significant judgment is required in considering the relative impact of the negative and positive evidence, and weight given to each category of evidence is commensurate with the extent to which it can be objectively verified. The more negative evidence that exists, the more positive evidence is necessary, and the more difficult it is to support a conclusion that a valuation allowance is not needed. Additionally, the Company utilizes the "more likely than not" criteria established in FASB ASC Topic 740 to determine whether the future tax benefit from the deferred tax assets should be recognized. As a result, the Company has established valuation allowances on the deferred tax assets in jurisdictions that have incurred net operating losses and in which it is more likely than not that such losses will not be utilized in the foreseeable future.

As of each reporting date, the Company considers new evidence, both positive and negative, that could impact the Company’s view with regard to future realization of our deferred tax assets. Management has considered the Company’s history of cumulative net losses in the UK, along with estimated future taxable income and has concluded that it is more likely than not that the Company will not realize the benefits of its UK deferred tax assets and U.S. state research and development tax credits. Accordingly, the Company has maintained a full valuation allowance against these net deferred tax assets as of December 31, 2021 and 2020, respectively.

Changes in the valuation allowance for deferred tax assets during the years ended December 31, 2021 and 2020 related primarily to the increase in UK net operating loss carryforwards as follows:

	December 31,
	2021			2020
Valuation allowance as of beginning of year	$	(103,890	)	$	(70,153	)
Increases recorded to income tax provision		(59,691	)		(29,302	)
Effect of foreign currency translation		2,008			(4,435	)
Valuation allowance as of end of year	$	(161,573	)	$	(103,890	)

The Company applies the authoritative guidance on accounting for and disclosure of uncertainty in tax positions, which requires the Company to determine whether a tax position of the Company is more likely than not to be sustained upon examination, including resolution of any related appeals of litigation processes, based on the technical merits of the position. For tax positions meeting the more likely than not threshold, the tax amount recognized in the financial statements is reduced by the largest benefit that has a greater than fifty percent likelihood of being realized upon the ultimate settlement with the relevant taxing authority. There were no material uncertain tax positions as of December 31, 2021 and 2020.

The Company will recognize interest and penalties related to uncertain tax positions in income tax expense. As of December 31, 2021, and 2020, the Company had no accrued interest or penalties related to uncertain tax positions and no amounts have been recognized in the Company’s statement of operations.

The Company and its subsidiaries file income tax returns in the UK, the U.S., and various foreign jurisdictions. Generally, the tax years 2017 through 2021 remain open to examination by the major taxing jurisdictions to which the Company is subject. 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 federal, state, or foreign tax authorities, if such tax attributes are utilized in a future period.

- Definition

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

+ References

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+ Details

Commitments and Contingencies

12 Months Ended

Dec. 31, 2021

Commitments And Contingencies Disclosure [Abstract]

Commitments and Contingencies

18. Commitments and Contingencies

Lease commitments

The Company leases office and laboratory space and has an embedded lease at AGC. Refer to Note 11, Leases, for further information on the terms of the lease agreements.

Manufacturing and technology development master agreement with AGC

On July 2, 2020, the Company entered into the AGC Agreement, pursuant to which AGC will develop, manufacture and supply certain viral vectors and conduct cell processing activities for certain Company development and commercial programs. Under the terms of the AGC Agreement, the Company is obligated to pay AGC for a minimum product manufacturing commitment, dedicated manufacturing and development resources, and for a lease component associated with the right of use of exclusive manufacturing suites within AGC’s existing facilities. The following table outlines the annual commitments associated with the contract, as of December 31, 2021:

Due in:	Product manufacturing commitments (1)		Dedicated manufacturing and development resources (2)		Exclusive transduction suites (3)		Total AGC Commitment
2022		2,627		8,379		2,626	$	13,632
2023		3,051		7,831		3,079		13,961
2024		3,051		7,831		3,079		13,961
2025		1,525		3,915		1,539		6,979
2026		—		—		—		—
Thereafter		—		—		—		—
Total manufacturing commitments	$	10,254	$	27,956	$	10,323	$	48,533

*Tabular disclosure above has been translated to U.S. Dollar, from Euro, using an exchange rate of €1.00 to $1.13.

(1) The minimum product manufacturing commitments may be increased to the mid-seven figures per contract year upon achievement of certain milestones.

(2) The Company may increase or decrease the usage of dedicated development services on a rolling basis with between six and 12-months’ prior written notice to AGC. The above table assumes continued usage of dedicated development services at current rates.

(3) Refer to Note 11 for further information on the embedded operating lease agreement

The AGC Agreement has an initial term of five years, beginning on the Effective Date and ending July 2, 2025. The AGC Agreement may be extended for an additional two years by mutual agreement of the Company and AGC. The Company has the right to terminate the AGC Agreement at its discretion upon 12-month’s prior written notice to AGC, and beginning no earlier than July 2, 2022, AGC has the right to terminate the AGC Agreement at its discretion upon 24-month’s prior written notice to the Company. Each party may terminate the AGC Agreement upon prior notice to the other party for an uncured material breach that the breaching party does not cure within the notice period.

Other funding commitments

The Company has entered into several license agreements (see Note 15). In connection with these agreements the Company is required to make milestone payments and annual license maintenance payments or royalties on future sales of specified products.

Consulting Agreement

In December 2019, the Company entered into a consulting agreement with non-employee advisor whereby the Company is obligated to make cash payments of $0.1 million per year and to issue up to 91,034 ordinary shares, which vest annually over a four-year period, and 92,035 ordinary shares upon attainment of certain clinical development and regulatory milestones. In December 2021 and 2020, the Company issued 22,758 ordinary shares associated with the service condition.

During the years ended December 31, 2021 and 2020, the Company recorded $0.3 million and $0.3 million in research and development expense associated with the share-based awards with service conditions. During the years ended December 31, 2021 and 2020, no expense was recorded associated with the performance-based conditions.

Legal proceedings

The Company is not a party to any litigation and does not have contingency reserves established for any litigation liabilities.

Benefit Plans

12 Months Ended

Dec. 31, 2021

Compensation And Retirement Disclosure [Abstract]

Benefit Plans

19. Benefit Plans

The Company makes contributions to private defined contribution pension plans on behalf of its employees. The Company matches its employee contributions up to six percent of each employee’s annual salary based on the jurisdiction the employees are located. The Company paid $1.7 million and $1.6 million, in matching contributions for the years ended December 31, 2021 and 2020, respectively.

- Definition

The entire disclosure for retirement benefits.

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+ Details

Related-Party Transactions

12 Months Ended

Dec. 31, 2021

Related Party Transactions

20. Related-party Transactions

GSK

In April 2018, the Company completed the GSK Agreement with subsidiaries of GSK (See Note 14). As consideration under the agreement the Company paid an upfront fee of $14.2 million, purchased inventory of $6.9 million, paid $0.8 million in transaction costs, and issued 12,455,252 convertible preferred shares valued at $93.4 million. Additionally, as part of the GSK Agreement, the Company obtained, and is responsible for maintaining the commercial availability of Strimvelis. The Company recorded a loss provision of $18.4 million associated with the agreement, as the costs to maintain Strimvelis are expected to significantly exceed revenues. The issuance of the convertible preferred shares made GSK a principal shareholder in the Company. As of June 16, 2021, GSK no longer had a right to nominate and appoint a designee to the Company’s board of directors, and GSK is no longer considered a related party.

As of December 31, 2020, the Company had accounts payable and accrued expenses due to GSK of $0.1 million. During the year-ended December 31, 2020, the Company entered into a global license agreement with GSK for use of their lentiviral stable cell line technology whereby the Company recorded $1.2 million of in-process research and development expense

associated with upfront payments made to GSK. During the year-ended December 31, 2020, the Company made $5.8 million in payments on accounts payable due to GSK associated with milestones, clinical inventory, and royalties.

Subsequent Events

12 Months Ended

Dec. 31, 2021

Subsequent Events [Abstract]

Subsequent Events

21. Subsequent events

On March 30, 2022, the Company announced a proposed reduction of its workforce of approximately 30%, subject to a consultation process with certain employees in the United Kingdom. The Company estimates that it will incur aggregate charges of approximately $2.5 million in the first and second quarters of 2022 as a result of the restructuring, consisting of one-time cash expenditures for severance and employee termination-related costs. The Company also announced that it would discontinue its investment in and seek alternatives for OTL-102 for treatment of X-CGD, OTL-103 for treatment of WAS and Strimvelis.

Summary of Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2021

Accounting Policies [Abstract]

Principles of consolidation

Use of estimates

Concentration of credit risk

Foreign currency

Segment information

Cash equivalents

The Company considers all highly liquid investments purchased with original maturities of 90 days or less at the date of acquisition to be cash equivalents.

Marketable securities

Restricted cash and construction deposits

	As of December 31,
	2021		2020
Cash and cash equivalents	$	55,912	$	55,135
Restricted cash		4,266		4,266
Total cash, cash equivalents and restricted cash shown in the statement of cash flows	$	60,178	$	59,401

Inventory

Intangible assets

Intangible assets, net

Property and equipment

Property and equipment are recorded at cost and depreciated or amortized using the straight-line method over the following estimated useful lives.

Property and equipment:		Estimated useful life
Lab equipment		5-10 years
Leasehold improvements		Shorter of lease term or estimated useful life
Furniture and fixtures		4 years
Office and computer equipment		3-5 years

Impairment of long-lived assets

Research and development costs

Research contract costs and accruals

Share-based compensation

Comprehensive loss

Leases

Strimvelis loss provision

The following table below outlines the changes to the Strimvelis loss provision for the periods ended December 31, 2021 and 2020:

	Year Ended December 31,
	2021			2020
Balance at beginning of period	$	4,482		$	6,790
Provisions		—			—
Amortization of loss provision		(1,037	)		(2,413	)
Foreign currency translation		(26	)		105
Balance at end of period	$	3,419		$	4,482

United Kingdom Research and development income tax credits

	Year Ended December 31,
	2021			2020
Balance at beginning of period	$	17,344		$	28,644
Recognition of credit claims as offset to research and development expense		13,920			21,130
Receipt of credit claims		—			(33,771	)
Foreign currency translation		(541	)		1,341
Balance at end of period	$	30,723		$	17,344

Income taxes

Product sales

Collaboration Revenue

Collaboration revenue

Net loss per share

	As of December 31,
	2021		2020
Share options		14,042,781		11,071,555
Unvested shares from share plan and consulting agreement		512,908		816,316
		14,555,689		11,887,871

Recent accounting pronouncements

Summary of Significant Accounting Policies (Tables)

12 Months Ended

Dec. 31, 2021

Accounting Policies [Abstract]

Schedule of Reconciliation of Cash, Cash Equivalents and Restricted Cash

The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported in the consolidated balance sheet that sum to the total of the amounts reported in the consolidated statement of cash flows:

	As of December 31,
	2021		2020
Cash and cash equivalents	$	55,912	$	55,135
Restricted cash		4,266		4,266
Total cash, cash equivalents and restricted cash shown in the statement of cash flows	$	60,178	$	59,401

Schedule of Estimated Useful Lives of Property and Equipment

Property and equipment are recorded at cost and depreciated or amortized using the straight-line method over the following estimated useful lives.

Property and equipment:		Estimated useful life
Lab equipment		5-10 years
Leasehold improvements		Shorter of lease term or estimated useful life
Furniture and fixtures		4 years
Office and computer equipment		3-5 years

Schedule of Changes in Loss Provision [Table Text Block]

The following table below outlines the changes to the Strimvelis loss provision for the periods ended December 31, 2021 and 2020:

	Year Ended December 31,
	2021			2020
Balance at beginning of period	$	4,482		$	6,790
Provisions		—			—
Amortization of loss provision		(1,037	)		(2,413	)
Foreign currency translation		(26	)		105
Balance at end of period	$	3,419		$	4,482

Summary of Amounts Recognized to Offset Research and Development Expense

The following table outlines the changes to the research and development tax credit receivable, including amount recognized as an offset to research and development expense during the years ended December 31, 2021 and 2020:

	Year Ended December 31,
	2021			2020
Balance at beginning of period	$	17,344		$	28,644
Recognition of credit claims as offset to research and development expense		13,920			21,130
Receipt of credit claims		—			(33,771	)
Foreign currency translation		(541	)		1,341
Balance at end of period	$	30,723		$	17,344

Securities Excluded in the Computation of Diluted Net Loss Per Ordinary Share

	As of December 31,
	2021		2020
Share options		14,042,781		11,071,555
Unvested shares from share plan and consulting agreement		512,908		816,316
		14,555,689		11,887,871

Fair Value Measurements and Marketable Securities (Tables)

12 Months Ended

Dec. 31, 2021

Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Abstract]

Schedule of Cash Equivalents and Marketable Securities

The following table summarizes the Company’s cash equivalents and marketable securities as of December 31, 2021:

	Fair Value Measurements as of December 31, 2021 Using:
	Level 1		Level 2		Level 3		Total
Cash equivalents
Money market funds	$	21,085	$	—	$	—	$	21,085
Corporate bonds		—		7,321		—		7,321
Commercial paper		—		13,198		—		13,198
Total cash equivalents	$	21,085	$	20,519	$	—	$	41,604
Marketable securities
Corporate bonds	$	—	$	94,794	$	—	$	94,794
Commercial paper		—		69,401		—		69,401
Total marketable securities	$	—	$	164,195	$	—	$	164,195
Total	$	21,085	$	184,714	$	—	$	205,799

The following table summarizes the Company’s cash equivalents and marketable securities as of December 31, 2020:

	Fair Value Measurements as of December 31, 2020 Using:
	Level 1		Level 2		Level 3		Total
Cash equivalents
Money market funds	$	6,650	$	—	$	—	$	6,650
U.S. government securities		—		3,001		—		3,001
Commercial paper		—		2,999		—		2,999
Total cash equivalents	$	6,650	$	6,000	$	—	$	12,650
Marketable securities
US government securities	$	—	$	2,997	$	—	$	2,997
Corporate bonds		—		93,358		—		93,358
Commercial paper		—		40,458		—		40,458
Total marketable securities	$	—	$	136,813	$	—	$	136,813
Total	$	6,650	$	142,813	$	—	$	149,463

Schedule of Cash Equivalents and Marketable Securities

The following table summarizes the Company’s cash equivalents and marketable securities as of December 31, 2021:

	Fair Value Measurements as of December 31, 2021 Using:
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Credit Losses		Fair Value
Corporate bonds	$	102,224	$	—	$	(109	)	$	—	$	102,115
Commercial paper		82,657		—		(58	)		—		82,599
Total	$	184,881	$	—	$	(167	)	$	—	$	184,714

The following table summarizes the Company’s cash equivalents and marketable securities as of December 31, 2020:

	Fair Value Measurements as of December 31, 2020 Using:
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Credit Losses		Fair Value
U.S. government securities	$	3,000	$	—	$	(4	)	$	—		2,996
Corporate bonds		96,259		133		(32	)		—		96,360
Commercial paper		43,469		1		(13	)		—		43,457
Total	$	142,728	$	134	$	(49	)	$	—	$	142,813

Schedule of Available-for-Sale Debt Marketable Securities by contractual Maturity

The following table summarizes the Company’s available-for-sale marketable debt securities by contractual maturity, as of December 31, 2021 and 2020:

	2021		2020
Maturities in one year or less	$	172,575	$	132,056
Maturities between one and three years		12,139		10,757
Total	$	184,714	$	142,813

Prepaid Expenses and Other Current Assets (Tables)

12 Months Ended

Dec. 31, 2021

Prepaid Expense And Other Assets Current [Abstract]

Schedule of Prepaid Expenses and Other Current Assets

Prepaid expenses and other current assets consist of the following:

	December 31,
	2021		2020
Prepaid external research and development expenses	$	2,438	$	1,421
Inventories		2,016		665
Other prepayments		6,128		4,930
VAT receivable		1,169		2,780
Construction deposit - current		7,909		1,552
Non-trade receivables		3,351		2,017
Total prepaid expenses and other current assets	$	23,011	$	13,365

Property and Equipment (Tables)

12 Months Ended

Dec. 31, 2021

Property Plant And Equipment [Abstract]

Schedule of Property and Equipment

Property and equipment consist of the following:

	December 31,
	2021			2020
Property and equipment:
Lab equipment	$	5,937		$	5,114
Leasehold improvements		2,450			2,522
Furniture and fixtures		303			304
Office and IT equipment		2,023			763
Construction-in-progress		211			302
Property and equipment	$	10,924		$	9,005
Less: accumulated depreciation		(6,157	)		(4,224	)
Property and equipment, net	$	4,767		$	4,781

Intangible Assets, Net (Tables)

12 Months Ended

Dec. 31, 2021

Goodwill And Intangible Assets Disclosure [Abstract]

Schedule of Intangible Assets Net of Accumulated Amortization

Intangible assets, net of accumulated amortization, consisted of the following:

	As of December 31, 2021							As of December 31, 2020
	Cost		Accumulated Amortization			Net		Cost		Accumulated Amortization		Net
License intangibles	$	4,329	$	(180	)	$	4,149	$	3,076	$	—		3,076
Total	$	4,329	$	(180	)	$	4,149	$	3,076	$	-	$	3,076

Schedule of Estimated Future Amortization For Intangible Assets

The following table summarizes the estimated future amortization for intangible assets for the next five years and thereafter:

2022			364
2023			364
2024			364
2025			364
2026			364
Thereafter			2,329
Total			4,149

Other Assets (Tables)

12 Months Ended

Dec. 31, 2021

Other Assets Noncurrent Disclosure [Abstract]

Schedule of Other Assets

Other assets consist of the following:

	December 31,
	2021		2020
Deferred tax assets		4,086		5,219
Deposits		1,404		1,144
Deferred financing costs		693		975
Other non-current assets		3,407		1,554
Construction deposits - long-term		—		6,572
Total other assets	$	9,590	$	15,464

Accrued Expenses and Other Liabilities (Tables)

12 Months Ended

Dec. 31, 2021

Accrued Liabilities And Other Liabilities [Abstract]

Schedule of Accrued Expenses and Other Liabilities

Accrued expenses and other current liabilities consisted of the following:

	December 31,
	2021		2020
Accrued external research and development expenses	$	9,273	$	8,878
Accrued payroll and related expenses		8,521		11,881
Accrued milestone payments		2,058		2,252
Accrued professional fees		854		791
Accrued other		2,941		4,225
Strimvelis liability - current portion		671		916
Total accrued expenses and other current liabilities	$	24,318	$	28,943

Restructuring Charges (Tables)

12 Months Ended

Dec. 31, 2021

Restructuring And Related Activities [Abstract]

Summary of Cash Restructuring Charges

Accrued restructuring and severance costs are included in Accrued expenses and other current liabilities in the consolidated balance sheet. Activity for the fiscal year is summarized as follows:

	Year Ended December 31,
	2020
Balance at beginning of period	$	—
Charged to expense		1,854
Payments made		(1,848	)
Balance at end of period	$	6

Summary of Impairment of Long Lived Assets


	Asset write-down
Operating lease right-of-use asset	$	2,605
Construction-in-progress		2,285
Laboratory equipment		760
Charge included in research and development expense	$	5,650

Leases (Tables)

12 Months Ended

Dec. 31, 2021

Leases [Abstract]

Summary of Lease Cost Under Operating Leases

The following table contains a summary of the lease-related costs recognized within operating expenses, and other information pertaining to the Company’s operating leases as of December 31, 2021 and 2020:

	2021			2020
Fixed lease cost	$	7,701		$	7,593
Impairment of right-of-use assets		—			2,781
Variable lease cost		1,696			2,131
Sublease income		(2,746	)		(181	)
Total lease cost	$	6,651		$	12,324

Other information
Operating cash flows used for operating leases		7,989			8,447
Weighted-average remaining lease term (years)		6.0			6.6
Weighted-average discount rate		8.7	%		8.6	%

Schedule of Future Minimum Base Rent Commitments Under Operating Leases

As of December 31, 2021, future minimum base rent commitments under ASC 842 under the Company’s property leases were as follows:

Due in:	Gross lease payments			Gross sublease receipts			Net lease payments
2022		7,326			(2,334	)		4,992
2023		6,773			(2,246	)		4,527
2024		6,799			(2,313	)		4,486
2025		5,361			(2,382	)		2,979
2026		3,720			(2,454	)		1,266
Thereafter		11,332			(8,960	)		2,372
Total future minimum lease payments		41,311			(20,689	)		20,622
Less: imputed interest		(14,698	)
Total operating lease payments	$	26,613

Notes Payable (Tables)

12 Months Ended

Dec. 31, 2021

Debt Disclosure [Abstract]

Summary of Notes Payable

As of December 31, 2021, and December 31, 2020, notes payable consist of the following:

	December 31,
	2021			2020
Notes payable, net of issuance costs	$	32,669		$	24,659
Less: current portion		(786	)		(4,861	)
Notes payable, net of current portion		31,883			19,798
Accretion related to final payment		203			406
Notes payable, long term	$	32,086		$	20,204

Summary of Future Principal Payments Due

As of December 31, 2021, the future principal payments due are as follows:

	Aggregate Minimum Payments
2022		786
2023		9,429
2024		9,429
2025		9,429
2026		5,082
Thereafter		—
Total		34,155
Less current portion		(786	)
Less unamortized portion of final payment		(952	)
Less unamortized debt issuance costs		(331	)
Notes payable, long term	$	32,086

Share-based Compensation (Tables)

12 Months Ended

Dec. 31, 2021

Disclosure Of Compensation Related Costs Sharebased Payments [Abstract]

Assumptions Used in Black-Scholes Option Pricing Model

The relevant data used to determine the value of stock option awards are as follows:

	Year Ended December 31,
	2021	2020
Risk-free interest rate	0.5 - 1.3%	0.3 - 1.7%
Expected term (in years)	5.3 - 6.1	5.5 - 6.1
Expected volatility	74.2 - 78.7%	70.7 - 75.2%
Expected dividend rate	0.00%	0.00%

Summary of Option Activity

The following table summarizes option activity under the plans for the year ended December 31, 2021:

	Shares			Weighted Average Exercise Price per Share		Weighted Average Remaining Contractual Life (Years)		Aggregate Intrinsic Value
Outstanding at December 31, 2020		13,895,643		$	7.96		7.16	$	91,133
Granted		8,489,856			4.75
Exercised		(1,727,254	)		1.59
Forfeited		(3,357,505	)		10.30
Outstanding and expected to vest at December 31, 2021		17,300,740		$	6.57		7.83	$	2,842
Exercisable, as of December 31, 2021		7,880,668		$	6.90		6.59	$	2,685

Summary of Award Activity

The following table summarizes restricted share unit award activity for the year-end December 31, 2021:

	Performance-based RSUs			Time-based RSUs			Weighted Average Grant Date Fair Value per Share
Unvested at December 31, 2020		464,000			180,000		$	8.75
Granted		—			47,500			4.94
Vested		(89,667	)		(41,667	)		9.94
Forfeited		(179,333	)		(62,500	)		10.32
Unvested at December 31, 2021		195,000			123,333		$	6.41

Share-based Compensation Expense

	Year Ended December 31,
	2021		2020
Research and development	$	9,214	$	11,679
Selling, general and administrative		13,322		16,283
Total	$	22,536	$	27,962

Collaboration Agreement with Pharming Group N.V. (Tables)

12 Months Ended

Dec. 31, 2021

Collaborative Arrangement [Abstract]

Summary of Research and Development Costs Incurred and Collaboration Revenue Recognized

The following table summarizes research and development costs incurred and collaboration revenue recognized in connection with the Company’s performance under the Collaboration Agreement:

	Year Ended December 31,
	2021		2020
Reimbursement revenue	$	843	$	—
Upfront and milestone payment revenue		132		—
Total	$	975	$	—

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2021

Income Tax Disclosure [Abstract]

Schedule of Components of Net Loss Before Income Taxes

The components of net loss before income taxes for the years ended December 31, 2021 and 2020 are as follows:

	December 31,
	2021			2020
U.K.	$	(147,337	)	$	(155,614	)
Non-U.K.		3,581			2,904
Net loss before income taxes	$	(143,756	)	$	(152,710	)

Schedule of Provision for (Benefit from) Income Taxes

The provision for (benefit from) income taxes for the years ended December 31, 2021 and 2020 are as follows:

	December 31,
	2021			2020
Current (benefit) provision
Federal—United States	$	(1,025	)	$	1,107
State—United States		334			189
Other foreign		388			230
United Kingdom		—			—
Total current (benefit) provision		(303	)		1,526
Deferred provision (benefit)
Federal—United States		1,099			(1,774	)
State—United States		(312	)		(103	)
United Kingdom		—			—
Other foreign		344			(380	)
Total deferred provision (benefit)		1,131			(2,257	)
Total provision (benefit) for income taxes	$	828		$	(731	)

Schedule of Reconciliation of Income Tax Expense (Benefit)

	December 31,
	2021			2020
Income taxes at United Kingdom statutory rate	$	(27,313	)	$	(29,015	)
Change in valuation allowance		59,691			29,302
Reduction in research expense for credits granted		6,674			8,435
Change in tax rates		(38,785	)		(8,105	)
Tax credits		(2,232	)		(1,369	)
U.S. Deduction for foreign derived intangible income		(196	)		(1,254	)
Permanent differences, including share-based compensation deduction shortfalls		2,863			1,265
U.S. state income taxes		17			68
Foreign rate differential		109			(58	)
Total provision (benefit) for income taxes	$	828		$	(731	)

Schedule of Deferred Tax Assets and Liabilities

The following table presents the principal components of the Company’s deferred tax assets and liabilities as of December 31, 2021 and 2020:

	December 31,
	2021			2020
Deferred tax assets
Net operating loss carryforwards	$	126,563		$	75,502
Amortization		25,206			22,599
Research and development credits		2,449			1,564
Share-based compensation		9,353			7,400
Accruals		798			1,001
Lease liability		6,444			6,805
Property and equipment		1,022			523
Other		—			3
Total deferred tax assets		171,835			115,397
Valuation allowance		(161,573	)		(103,890	)
Fixed assets and right-of-use asset		(6,176	)		(6,288	)
Other non-current assets (net deferred tax assets and liabilities)	$	4,086		$	5,219

Schedule of Changes in Valuation Allowance for Deferred Tax Assets Related Primarily to Increase in U.K. Net Operating Loss Carryforwards

Changes in the valuation allowance for deferred tax assets during the years ended December 31, 2021 and 2020 related primarily to the increase in UK net operating loss carryforwards as follows:

	December 31,
	2021			2020
Valuation allowance as of beginning of year	$	(103,890	)	$	(70,153	)
Increases recorded to income tax provision		(59,691	)		(29,302	)
Effect of foreign currency translation		2,008			(4,435	)
Valuation allowance as of end of year	$	(161,573	)	$	(103,890	)

Commitments and Contingencies (Tables)

12 Months Ended

Dec. 31, 2021

Commitments And Contingencies Disclosure [Abstract]

Schedule of Annual Commitments Associated with the Contract

The following table outlines the annual commitments associated with the contract, as of December 31, 2021:

Due in:	Product manufacturing commitments (1)		Dedicated manufacturing and development resources (2)		Exclusive transduction suites (3)		Total AGC Commitment
2022		2,627		8,379		2,626	$	13,632
2023		3,051		7,831		3,079		13,961
2024		3,051		7,831		3,079		13,961
2025		1,525		3,915		1,539		6,979
2026		—		—		—		—
Thereafter		—		—		—		—
Total manufacturing commitments	$	10,254	$	27,956	$	10,323	$	48,533

*Tabular disclosure above has been translated to U.S. Dollar, from Euro, using an exchange rate of €1.00 to $1.13.

(1) The minimum product manufacturing commitments may be increased to the mid-seven figures per contract year upon achievement of certain milestones.

(3) Refer to Note 11 for further information on the embedded operating lease agreement

Nature of Business and Basis of Presentation - Additional Information (Details) $ / shares in Units, $ in Thousands		1 Months Ended	12 Months Ended
	Feb. 09, 2021 USD ($) shares	Feb. 28, 2021 USD ($) shares	Dec. 31, 2021 USD ($)	Dec. 31, 2020 USD ($)	Dec. 31, 2021 £ / shares	Feb. 28, 2021 £ / shares	Feb. 28, 2021 $ / shares	Feb. 09, 2021 £ / shares	Feb. 09, 2021 $ / shares	Dec. 31, 2020 £ / shares
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Ordinary Shares, Par Value \| £ / shares					£ 0.10					£ 0.10
Placement agent fees			$ 6,355
Net loss			(144,584)	$ (151,979)
Accumulated deficit			750,224	$ 605,640
Cash, cash equivalents and marketable securities			$ 220,100
Securities Purchase Agreement
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Net proceeds from private placement	$ 143,600	$ 143,600
Securities Purchase Agreement \| Private Placement
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Sale of voting and non-voting ordinary shares, net of issuance costs, Shares \| shares	20,900,321	20,900,321
Ordinary Shares, Par Value \| £ / shares						£ 0.10		£ 0.10
Purchase price per share \| $ / shares							$ 6.22		$ 6.22
Closing price of share date	Feb. 04, 2021	Feb. 04, 2021
Placement agent fees	$ 6,000	$ 6,000
Other issuance costs	$ 400	$ 400
Private placement, transaction date	Feb. 04, 2021	Feb. 04, 2021
Securities Purchase Agreement \| Private Placement \| Non-voting Ordinary Shares
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Sale of voting and non-voting ordinary shares, net of issuance costs, Shares \| shares	3,215,434	3,215,434
Ordinary Shares, Par Value \| £ / shares						£ 0.10		£ 0.10

Summary of Significant Accounting Policies - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2021	Dec. 31, 2020	Mar. 31, 2020
Summary Of Significant Accounting Policies [Line Items]
Description of significant off-balance sheet risk		The Company has no significant off-balance sheet risk, such as foreign currency contracts, options contracts, or other foreign hedging arrangements.
Foreign currency transaction gain (loss)		$ (1,200)	$ 3,400
Property and equipment		4,767	4,781
Right-of-use assets		24,316	29,815
Proceeds from lines of credit		3,000	3,000
Cash collateral associated with corporate credit cards and other leases		1,300	1,300
Liability associated with the loss contract	$ 18,400
Strimvelis loss provision current		700	900
Strimvelis loss provision non current		2,700	3,600
Tax incentive receivable, current		30,723	17,344
Sales of strimvelis		$ 1,675	2,595
Change in accounting principle, accounting standards update, adopted		true
Change in accounting principle, accounting standards update, adoption date		Jan. 01, 2022
New accounting pronouncement or change in accounting principle, description		ASU No. 2020-10
Product Sales, Net [Member]
Summary Of Significant Accounting Policies [Line Items]
Sales of strimvelis		$ 700	2,595
Fremont Lease Agreement [Member]
Summary Of Significant Accounting Policies [Line Items]
Right-of-use assets		9,500
Proceeds from lines of credit	$ 3,000
Escrow Deposit		7,900	7,900	$ 10,000
Increase Decrease In Escrow Deposit		2,100	(2,100)
Fremont Lease Agreement [Member] \| Prepaid Expenses and Other Current Assets [Member]
Summary Of Significant Accounting Policies [Line Items]
Escrow Deposit		7,900
United Kingdom
Summary Of Significant Accounting Policies [Line Items]
Property and equipment		3,600	3,700
Tax incentive receivable			17,300
Tax incentive receivable, current		$ 30,700
Incremental percentage of taxable profits		50.00%
United Kingdom \| Research and Development Expense
Summary Of Significant Accounting Policies [Line Items]
Foreign currency transaction gain (loss)		$ (541)	1,341
Additional income tax credits			4,800
US
Summary Of Significant Accounting Policies [Line Items]
Property and equipment		1,200	1,100
Right-of-use assets		12,500	14,200
United Kingdom and European Union
Summary Of Significant Accounting Policies [Line Items]
Right-of-use assets		$ 11,800	$ 15,600

Summary of Significant Accounting Policies - Schedule of Reconciliation of Cash, Cash Equivalents and Restricted Cash (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Summary Of Significant Accounting Policies [Abstract]
Cash and cash equivalents	$ 55,912	$ 55,135
Restricted cash	4,266	4,266
Total cash, cash equivalents and restricted cash shown in the statement of cash flows	$ 60,178	$ 59,401	$ 23,317

Summary of Significant Accounting Policies - Schedule of Estimated Useful Lives of Property and Equipment (Details)	12 Months Ended
	Dec. 31, 2021
Leasehold Improvements
Property Plant And Equipment [Line Items]
Property and equipment useful life, term	Shorter of lease term or estimated useful life
Furniture and Fixtures
Property Plant And Equipment [Line Items]
Property and equipment useful life	4 years
Minimum \| Lab Equipment
Property Plant And Equipment [Line Items]
Property and equipment useful life	5 years
Minimum \| Office and Computer Equipment
Property Plant And Equipment [Line Items]
Property and equipment useful life	3 years
Maximum \| Lab Equipment
Property Plant And Equipment [Line Items]
Property and equipment useful life	10 years
Maximum \| Office and Computer Equipment
Property Plant And Equipment [Line Items]
Property and equipment useful life	5 years

Summary of Significant Accounting Policies - Schedule of Changes in Loss Provision (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Summary Of Significant Accounting Policies [Abstract]
Balance at beginning of period	$ 4,482	$ 6,790
Amortization of loss provision	(1,037)	(2,413)
Foreign currency translation	(26)	105
Balance at end of period	$ 3,419	$ 4,482

Summary of Significant Accounting Policies - Summary of Amounts recognized to Offset Research and Development Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Summary Of Significant Accounting Policies [Line Items]
Receipt of credit claims	$ (2,232)	$ (1,369)
Foreign currency translation	(1,200)	3,400
United Kingdom \| Research and Development Expense
Summary Of Significant Accounting Policies [Line Items]
Balance at beginning of period	17,344	28,644
Recognition of credit claims as offset to research and development expense	13,920	21,130
Receipt of credit claims		(33,771)
Foreign currency translation	(541)	1,341
Balance at end of period	$ 30,723	$ 17,344

Summary of Significant Accounting Policies - Securities Excluded in the Computation of Diluted Net Loss Per Ordinary Share (Details) - shares	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common shares attributable to anti-dilutive shares	14,555,689	11,887,871
Share options
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common shares attributable to anti-dilutive shares	14,042,781	11,071,555
Unvested Shares from Share Plan and Consulting Agreement
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common shares attributable to anti-dilutive shares	512,908	816,316

Fair Value Measurements and Marketable Securities - Additional Information (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Fair Value Disclosures [Abstract]
Fair value of financial assets transfers between level 1 to level 2	$ 0	$ 0
Fair value of financial assets transfers between level 2 to level 1	$ 0	$ 0

Fair Value Measurements and Marketable Securities - Schedule of Cash Equivalents and Marketable Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Cash equivalents
Total cash equivalents	$ 41,604	$ 12,650
Marketable securities
Total marketable securities	164,195	136,813
Total	205,799	149,463
Level 1
Cash equivalents
Total cash equivalents	21,085	6,650
Marketable securities
Total	21,085	6,650
Level 2
Cash equivalents
Total cash equivalents	20,519	6,000
Marketable securities
Total marketable securities	164,195	136,813
Total	184,714	142,813
Money Market Funds
Cash equivalents
Total cash equivalents	21,085	6,650
Money Market Funds \| Level 1
Cash equivalents
Total cash equivalents	21,085	6,650
Corporate Bonds
Cash equivalents
Total cash equivalents	7,321
Marketable securities
Total marketable securities	94,794	93,358
Corporate Bonds \| Level 2
Cash equivalents
Total cash equivalents	7,321
Marketable securities
Total marketable securities	94,794	93,358
Commercial Paper
Cash equivalents
Total cash equivalents	13,198	2,999
Marketable securities
Total marketable securities	69,401	40,458
Commercial Paper \| Level 2
Cash equivalents
Total cash equivalents	13,198	2,999
Marketable securities
Total marketable securities	$ 69,401	40,458
U.S. Government Securities
Cash equivalents
Total cash equivalents		3,001
Marketable securities
Total marketable securities		2,997
U.S. Government Securities \| Level 2
Cash equivalents
Total cash equivalents		3,001
Marketable securities
Total marketable securities		$ 2,997

Fair Value Measurements and Marketable Securities - Schedule of Level 2 Cash Equivalents and Marketable Securities (Details) - Level 2 - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	$ 184,881	$ 142,728
Gross Unrealized Gains		134
Gross Unrealized Losses	(167)	(49)
Fair Value	184,714	142,813
U.S. Government Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost		3,000
Gross Unrealized Losses		(4)
Fair Value		2,996
Corporate Bonds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	102,224	96,259
Gross Unrealized Gains		133
Gross Unrealized Losses	(109)	(32)
Fair Value	102,115	96,360
Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	82,657	43,469
Gross Unrealized Gains		1
Gross Unrealized Losses	(58)	(13)
Fair Value	$ 82,599	$ 43,457

Fair Value Measurements and Marketable Securities - Schedule of Available-for-Sale Marketable Debt Securities by contractual Maturity (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Fair Value Disclosures [Abstract]
Maturities in one year or less	$ 172,575	$ 132,056
Maturities between one and three years	12,139	10,757
Total	$ 184,714	$ 142,813

Revenue Recognition - Additional Information (Details)	12 Months Ended
Revenue Recognition - Additional Information (Details)	Dec. 31, 2021
Revenue From Contract With Customer [Abstract]
General payment terms, maximum	60 days

Prepaid Expenses and Other Current Assets - Schedule of Prepaid Expenses and Other Current Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Prepaid Expense And Other Assets Current [Abstract]
Prepaid external research and development expenses	$ 2,438	$ 1,421
Inventories	2,016	665
Other prepayments	6,128	4,930
VAT receivable	1,169	2,780
Construction deposit - current	7,909	1,552
Non-trade receivables	3,351	2,017
Total prepaid expenses and other current assets	$ 23,011	$ 13,365

Property and Equipment - Schedule of Property and Equipment (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Property Plant And Equipment [Line Items]
Property and equipment	$ 10,924	$ 9,005
Less: accumulated depreciation	(6,157)	(4,224)
Property and equipment, net	4,767	4,781
Lab Equipment
Property Plant And Equipment [Line Items]
Property and equipment	5,937	5,114
Leasehold Improvements
Property Plant And Equipment [Line Items]
Property and equipment	2,450	2,522
Furniture and Fixtures
Property Plant And Equipment [Line Items]
Property and equipment	303	304
Office and IT Equipment
Property Plant And Equipment [Line Items]
Property and equipment	2,023	763
Construction-In-Progress
Property Plant And Equipment [Line Items]
Property and equipment	$ 211	$ 302

Property and Equipment - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Property Plant And Equipment [Abstract]
Depreciation expense	$ 2.2	$ 2.0

Intangible Assets, Net - Schedule of Intangible Assets Net of Accumulated Amortization (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Finite Lived Intangible Assets [Line Items]
Intangible Assets, Cost	$ 4,329	$ 3,076
Intangible Assets, Accumulated Amortized	(180)
Intangible Assets, Net	4,149	3,076
License Intangibles
Finite Lived Intangible Assets [Line Items]
Intangible Assets, Cost	4,329	3,076
Intangible Assets, Accumulated Amortized	(180)
Intangible Assets, Net	$ 4,149	$ 3,076

Intangible Assets, Net - Additional Information (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2021 USD ($)
Goodwill And Intangible Assets Disclosure [Abstract]
Intangible asset, useful life	12 years
Amortization of intangible assets	$ 180

Intangible Assets, Net - Schedule of Estimated Future Amortization For Intangible Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Goodwill And Intangible Assets Disclosure [Abstract]
2022	$ 364
2023	364
2024	364
2025	364
2026	364
Thereafter	2,329
Intangible Assets, Net	$ 4,149	$ 3,076

Other Assets - Schedule of Other Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Other Assets Noncurrent Disclosure [Abstract]
Deferred tax assets	$ 4,086	$ 5,219
Deposits	1,404	1,144
Deferred financing costs	693	975
Other non-current assets	3,407	1,554
Construction deposits - long-term		6,572
Total other assets	$ 9,590	$ 15,464

Accrued Expenses and Other Liabilities - Schedule of Accrued Expenses and Other Current Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Accrued Liabilities And Other Liabilities [Abstract]
Accrued external research and development expenses	$ 9,273	$ 8,878
Accrued payroll and related expenses	8,521	11,881
Accrued milestone payments	2,058	2,252
Accrued professional fees	854	791
Accrued other	2,941	4,225
Strimvelis liability - current portion	671	916
Total accrued expenses and other current liabilities	$ 24,318	$ 28,943

Restructuring Charges - Additional Information (Details) - USD ($)	1 Months Ended		3 Months Ended	12 Months Ended
	Dec. 31, 2020	May 31, 2020	Jun. 30, 2020	Dec. 31, 2021	Dec. 31, 2020
Restructuring Cost And Reserve [Line Items]
Restructuring costs				$ 0	$ 1,854,000
Construction-in-process, impairment charges			$ 2,285,000
Operating lease right-of-use-assets	$ 29,815,000			24,316,000	29,815,000
Undiscounted cash flow estimate				$ 14,698,000
Right of use asset, impairment charge			$ 2,605,000		$ 2,781,000
Menlo Park, California
Restructuring Cost And Reserve [Line Items]
Number of positions eliminated, percent		25.00%
Fremont, California
Restructuring Cost And Reserve [Line Items]
Construction-in-process, impairment charges		$ 2,300,000
Operating lease right-of-use-assets		$ 13,800,000
Discount rate		4.60%
Fair value of ROU asset		$ 11,200,000
Right of use asset, impairment charge	$ 0	2,600,000
Fremont, California \| Minimum
Restructuring Cost And Reserve [Line Items]
Undiscounted cash flow estimate		11,700,000
Fremont, California \| Maximum
Restructuring Cost And Reserve [Line Items]
Undiscounted cash flow estimate		$ 19,100,000

Restructuring Charges - Summary of Cash Restructuring Charges (Details) - USD ($)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Restructuring And Related Activities [Abstract]
Balance at beginning of period	$ 6,000
Charged to expense	$ 0	$ 1,854,000
Payments made		(1,848,000)
Balance at end of period		$ 6,000

Restructuring Charges - Summary of Impairment of Long Lived Assets (Details) - USD ($) $ in Thousands	3 Months Ended	12 Months Ended
	Jun. 30, 2020	Dec. 31, 2020
Restructuring And Related Activities [Abstract]
Operating lease right-of-use asset	$ 2,605	$ 2,781
Construction-in-progress	2,285
Laboratory equipment, Asset write-downs	760
Charge included in research and development expense	$ 5,650	$ 5,650

Leases - Additional Information (Details) $ in Thousands, € in Millions	1 Months Ended						12 Months Ended
	Jul. 31, 2019	Jan. 31, 2019	Dec. 31, 2018 USD ($)	Mar. 31, 2018	Jan. 31, 2018	Nov. 30, 2017	Dec. 31, 2021 USD ($)	Dec. 31, 2020 USD ($)	Dec. 31, 2021 EUR (€)	Mar. 31, 2020 USD ($)
Operating Leases [Line Items]
Operating leases expiration term							Jul. 02, 2025
Sublease income							$ 2,746	$ 181
Operating lease right-of-use-assets							24,316	29,815
Operating lease liabilities							26,613
Proceeds from lines of credit							3,000	3,000
Operating lease, liability, noncurrent							19,278	24,168
Operating lease, right-of-use asset obtained in exchange for lease liabilities							600	17,500
Rental Lab Space [Member]
Operating Leases [Line Items]
Annual rental payment							200
Office Space Menlo Park Lease Agreement [Member]
Operating Leases [Line Items]
Operating leases expiration term						Dec. 31, 2020
Operating lease duration for free rent						1 month
Laboratory Space Menlo Park Lease Agreement [Member]
Operating Leases [Line Items]
Operating leases expiration term		Dec. 31, 2020
Office and Laboratory Space Menlo Park Lease Agreement [Member]
Operating Leases [Line Items]
Annual rental payment								1,900
Five Years Lease Term Terminates In January 2023 [Member] \| Office Space London United Kingdom Lease Agreement [Member]
Operating Leases [Line Items]
Operating leases expiration term			Jan. 31, 2023		Jan. 31, 2023
Annual rental payment							1,800	1,700
Lease Term Terminates in September 2022 [Member] \| Office Space Boston Lease Agreement [Member]
Operating Leases [Line Items]
Operating leases expiration term				Sep. 30, 2022
Annual rental payment								400
Sublease income							100
Lease Term Terminates in September 2026 [Member] \| Office Space Boston Lease Agreement [Member]
Operating Leases [Line Items]
Operating leases expiration term	Sep. 30, 2026
Annual rental payment							1,100	900
Operating leases Commenced term	Jan. 31, 2020
Boston and London Office Space Lease Agreements [Member]
Operating Leases [Line Items]
Operating lease right-of-use-assets							4,100	4,300
Operating lease liabilities							5,400	5,700
Fremont Lease Agreement [Member]
Operating Leases [Line Items]
Operating leases expiration term			May 31, 2030
Annual rental payment							3,100	3,100
Operating lease duration for free rent			8 months
Operating lease right-of-use-assets							9,500
Reduction of standby letter of credit amount percentage			25.00%
Proceeds from lines of credit			$ 3,000
Operating lease, liability, noncurrent							13,100
Escrow Deposit							7,900	7,900		$ 10,000
Increase decrease in escrow deposit							(2,100)	2,100
Fremont Lease Agreement [Member] \| Maximum [Member]
Operating Leases [Line Items]
Tenant improvements allowance							5,300
Fremont Sublease Agreement
Operating Leases [Line Items]
Annual rental payment								$ 2,200
Operating lease duration for free rent								12 months
Fremont Sublease Agreement \| Other Long-Term Liabilities [Member]
Operating Leases [Line Items]
Security deposit								$ 2,600
Fremont Sublease Agreement \| Maximum [Member]
Operating Leases [Line Items]
Tenant improvements allowance								$ 5,300
G S K Agreement
Operating Leases [Line Items]
Operating leases expiration term								Jul. 02, 2025
Operating lease right-of-use-assets							10,700	$ 13,900
Operating lease, liability, noncurrent							$ 9,300	$ 13,100
Operating lease term							5 years		5 years
Lessee, operating lease, option to extend							The agreement may be extended for an additional two years by mutual agreement of the Company and AGC
Lessee, operating Lease, existence of option to extend [true false]							true
Operating lease extended term							2 years
Lease component manufacturing suites commitment amount per contract year \| €									€ 2.7

Leases - Summary of Lease Cost Under Operating Leases (Details) - USD ($) $ in Thousands	3 Months Ended	12 Months Ended
	Jun. 30, 2020	Dec. 31, 2021	Dec. 31, 2020
Leases [Abstract]
Fixed lease cost		$ 7,701	$ 7,593
Impairment of right-of-use assets	$ 2,605		2,781
Variable lease cost		1,696	2,131
Sublease income		(2,746)	(181)
Total lease cost		6,651	12,324
Operating cash flows used for operating leases		$ 7,989	$ 8,447
Weighted-average remaining lease term (years)		6 years	6 years 7 months 6 days
Weighted-average discount rate		8.70%	8.60%

Leases - Schedule of Future Minimum Base Rent Commitments Under Operating Leases (Details) $ in Thousands	Dec. 31, 2021 USD ($)
Gross lease payments
2022	$ 7,326
2023	6,773
2024	6,799
2025	5,361
2026	3,720
Thereafter	11,332
Total future minimum lease payments	41,311
Less: imputed interest	(14,698)
Total operating lease payments	26,613
Gross sublease receipts
2022	(2,334)
2023	(2,246)
2024	(2,313)
2025	(2,382)
2026	(2,454)
Thereafter	(8,960)
Total future minimum lease payments	(20,689)
Net lease payments
2022	4,992
2023	4,527
2024	4,486
2025	2,979
2026	1,266
Thereafter	2,372
Total future minimum lease payments	$ 20,622

Leases - Schedule of Future Minimum Base Rent Commitments Under Operating Leases (Parenthetical) (Details)	Dec. 31, 2021
Operating Leases [Line Items]
Lease translation rate	1.13
GBP
Operating Leases [Line Items]
Lease translation rate	1.35
Euro
Operating Leases [Line Items]
Lease translation rate	1.13

Notes Payable - Additional Information (Details) - USD ($)	1 Months Ended		12 Months Ended
	May 31, 2021	May 31, 2019	Dec. 31, 2021	Dec. 31, 2020
Debt Instrument [Line Items]
Line of credit facility agreement date		May 31, 2019
Credit facility maximum borrowings	$ 100,000,000.0	$ 75,000,000.0
Proceeds from lines of credit			$ 3,000,000.0	$ 3,000,000.0
Credit facility, remaining borrowings	$ 67,000,000.0
Line of credit facility interest payments term	18 months	24 months
Line of credit facility amortization term		36 months
Line of credit facility, frequency of payments			monthly payments
Line of credit facility, percentage of final payment	3.50%	4.50%
Final payment amount	$ 1,200,000	$ 1,100,000
Repayment of line of credit		$ 500,000
Line of credit facility interest rate description			Prior to execution of the Amended Credit Facility, each term loan under the Original Credit Facility bore interest at an annual rate equal to 6.0% plus LIBOR. The Company was required to make interest-only payments on the term loan for all payment dates prior to 24 months following the date of the Original Credit Facility, unless the third tranche was drawn, in which case for all payment dates prior to 36 months following the date of the Original Credit Facility. The term loans prior to the Amended Credit Facility were to begin amortizing on either the 24-month or the 36-month anniversary of the Original Credit Facility (as applicable), with equal monthly payments of principal plus interest to be made by the Borrower to the Lenders in consecutive monthly installments until the loan maturity date. In addition, a final payment of 4.5% was due on the loan maturity date.
Line of credit facility covenants description			The Company is also subject to an ongoing minimum cash financial covenant in which the Company must maintain unrestricted cash in an amount not less than $20.0 million following the utilization of the second term loan and not less than $35.0 million following the utilization of the third term loan
Term Loan
Debt Instrument [Line Items]
Debt instrument, interest expense			$ 2,500,000	$ 2,300,000
Debt instrument, effective annual interest rate			8.40%
LIBOR
Debt Instrument [Line Items]
Debt instrument, annual interest rate	5.95%	6.00%
Minimum
Debt Instrument [Line Items]
Line of credit facility amortization term	18 months
Minimum \| Second Tranche (Term Loan Available from July 1, 2022 to July 1, 2023)
Debt Instrument [Line Items]
Line of credit facility minimum cash financial covenant	$ 20,000,000.0
Minimum \| TThird Tranche (Term Loan Available from July 1, 2023 to July 1, 2024)
Debt Instrument [Line Items]
Line of credit facility minimum cash financial covenant	$ 35,000,000.0
Maximum
Debt Instrument [Line Items]
Line of credit facility amortization term	30 months
Initial Term Loan
Debt Instrument [Line Items]
Credit facility maximum borrowings	$ 33,000,000.0	$ 25,000,000.0
Proceeds from lines of credit	33,000,000.0
Second Tranche (Term Loan Available from July 1, 2022 to July 1, 2023)
Debt Instrument [Line Items]
Credit facility maximum borrowings	$ 33,000,000.0
Line of Credit Facility, Covenant Terms			upon certain regulatory approvals and evidence of the Company having $100 million in cash and cash equivalent investments
Line of credit facility interest payments term	30 months
Second Tranche (Term Loan Available from July 1, 2022 to July 1, 2023) \| Minimum
Debt Instrument [Line Items]
Cash and cash equivalent investments	$ 100,000,000
Third Tranche (Term Loan Available from July 1, 2023 to July 1, 2024)
Debt Instrument [Line Items]
Credit facility maximum borrowings	$ 34,000,000.0
Line of Credit Facility, Covenant Terms			upon evidence of the Company having $100 million in cash and cash equivalent investments and attaining a pre-specified trailing 12-month revenue target
Line of credit facility interest payments term	30 months
Third Tranche (Term Loan Available from July 1, 2023 to July 1, 2024) \| Minimum
Debt Instrument [Line Items]
Cash and cash equivalent investments	$ 100,000,000

Notes Payable - Summary of Notes Payable (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Long Term Notes And Loans [Abstract]
Notes payable, net of issuance costs	$ 32,669	$ 24,659
Less: current portion	(786)	(4,861)
Notes payable, net of current portion	31,883	19,798
Accretion related to final payment	203	406
Notes payable, long term	$ 32,086	$ 20,204

Notes Payable - Summary of Future Principal Payments Due (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Long Term Debt By Maturity [Abstract]
2022	$ 786
2023	9,429
2024	9,429
2025	9,429
2026	5,082
Total	34,155
Less current portion	(786)
Less unamortized portion of final payment	(952)
Less unamortized debt issuance costs	(331)
Notes payable, long term	$ 32,086	$ 20,204

Shareholders' Equity and Convertible Preferred Shares - Additional Information (Details)			1 Months Ended		12 Months Ended
	Jul. 01, 2021 USD ($) shares	Feb. 09, 2021 USD ($) shares	Jul. 31, 2021 USD ($) shares	Feb. 28, 2021 USD ($) shares	Dec. 31, 2021 USD ($) VotingRight	Dec. 31, 2020 USD ($) VotingRight	Dec. 31, 2021 GBP (£) £ / shares shares	Feb. 28, 2021 £ / shares	Feb. 28, 2021 $ / shares	Feb. 09, 2021 £ / shares	Feb. 09, 2021 $ / shares	Dec. 31, 2020 GBP (£) £ / shares shares	Apr. 30, 2020 shares	Nov. 30, 2018 shares	Sep. 30, 2018 shares
Class Of Stock [Line Items]
Ordinary shares voting rights description					each holder of ordinary shares and ADSs is entitled to one vote per ordinary share
Ordinary shares dividends declared					$ 0	$ 0
Number of ordinary voting rights \| VotingRight					1	1
Ordinary Shares, Par Value \| £ / shares							£ 0.10					£ 0.10
Ordinary Shares, Issued \| shares							125,674,095					98,283,603
Nominal value of shares issued and sold \| £ / shares							£ 0.10					£ 0.10
Placement agent fees					$ 6,355,000
Total consideration					$ 143,645,000
Consulting Agreement \| Advisor
Class Of Stock [Line Items]
Ordinary Shares, Issued \| shares							22,758					22,758
Oxford BioMedica License, Development and Supply Agreement
Class Of Stock [Line Items]
Ordinary Shares, Issued \| shares							588,220						75,413	150,826	150,826
Securities Purchase Agreement
Class Of Stock [Line Items]
Net proceeds from private placement		$ 143,600,000		$ 143,600,000
Securities Purchase Agreement \| Private Placement
Class Of Stock [Line Items]
Ordinary Shares, Par Value \| £ / shares								£ 0.10		£ 0.10
Number of ordinary shares issued and sold \| shares		20,900,321		20,900,321
Nominal value of shares issued and sold \| £ / shares								0.10		0.10
Purchase price per share \| $ / shares									$ 6.22		$ 6.22
Closing price of share date		Feb. 04, 2021		Feb. 04, 2021
Placement agent fees		$ 6,000,000.0		$ 6,000,000.0
Other issuance costs		$ 400,000		$ 400,000
Private placement, transaction date		Feb. 04, 2021		Feb. 04, 2021
Securities Purchase Agreement \| Private Placement \| Non-voting Ordinary Shares
Class Of Stock [Line Items]
Ordinary Shares, Par Value \| £ / shares								0.10		0.10
Number of ordinary shares issued and sold \| shares		3,215,434		3,215,434
Nominal value of shares issued and sold \| £ / shares								£ 0.10		£ 0.10
Share Purchase Agreement with Pharming
Class Of Stock [Line Items]
Number of ordinary shares issued and sold \| shares	1,227,738		1,227,738
Total consideration	$ 7,500,000		$ 7,500,000
Common stock consideration	4,100,000		4,100,000
Premium consideration	$ 3,400,000		$ 3,400,000
Maximum
Class Of Stock [Line Items]
Ordinary shares maximum nominal value \| £							£ 13,023,851.50					£ 13,023,851.50

Share-based Compensation - Additional Information (Details) $ / shares in Units, $ in Thousands	1 Months Ended	3 Months Ended	12 Months Ended
	Apr. 30, 2020 USD ($) shares	Dec. 31, 2020 USD ($)	Dec. 31, 2021 USD ($) $ / shares shares	Dec. 31, 2020 USD ($) $ / shares	Dec. 31, 2021 £ / shares
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Exercise price of option \| £ / shares					£ 0.00001
Award vesting period			4 years
Maximum term of option			10 years
Total intrinsic value of share options exercised \| $			$ 7,400	$ 5,000
Total proceeds from share options exercised \| $			2,700	3,900
Employee equity plan proceeds received after year end \| $		$ 200		$ 200
Weighted average grant date fair value of share options granted \| $ / shares			$ 3.10	$ 7.22
Compensation cost recognized \| $			$ 22,536	$ 27,962
Unvested options outstanding			9,420,072
Total unrecognized compensation cost of stock option and time-based RSUs \| $			$ 37,100
Compensation cost expected to be recognized weighted average period			2 years 9 months 7 days
Total unrecognized compensation cost of performance-based RSUs \| $			$ 1,400
Performance-based Restricted Share Units ("RSUs")
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Number of shares vested			89,667
Remaining performance based share units outstanding			179,333
Performance-based Restricted Share Units ("RSUs") \| Chief Executive Officer
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Number of shares granted	195,000
Total grant date fair value \| $	$ 1,400
Performance-based Restricted Share Units ("RSUs") \| Chief Executive Officer \| Achievement of At Least Three of Four Milestones
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Vesting rights			The award vests on January 2, 2024 as to 1/3 of the award for each of the first three to occur of four milestones, if each such milestone is achieved by the Company on or before December 31, 2023
Performance-based Restricted Share Units ("RSUs") \| Libmeldy
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Compensation cost recognized \| $		$ 1,200
Time-based Restricted Share Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Award vesting period			3 years
Number of shares vested			41,667
Remaining performance based share units outstanding			62,500
Number of shares granted			47,500
2018 Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Remaining shares available for issuance			6,934,474
2018 ESPP
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Remaining shares available for issuance			1,197,399
Inducement Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Remaining shares available for issuance			721,500

Share-based Compensation - Assumptions Used in Black-Scholes Option Pricing Model (Details)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Risk-free interest rate, minimum	0.50%	0.30%
Risk-free interest rate, maximum	1.30%	1.70%
Expected volatility, minimum	74.20%	70.70%
Expected volatility, maximum	78.70%	75.20%
Expected dividend rate	0.00%	0.00%
Minimum
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expected term (in years)	5 years 3 months 18 days	5 years 6 months
Maximum
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expected term (in years)	6 years 1 month 6 days	6 years 1 month 6 days

Share-based Compensation - Summary of Option Activity (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Disclosure Of Compensation Related Costs Sharebased Payments [Abstract]
Number of Options, Outstanding at December 31, 2020	13,895,643
Number of Options, Granted	8,489,856
Number of Options, Exercised	(1,727,254)
Number of Options, Forfeited	(3,357,505)
Number of Options, Outstanding and expected to vest at December 31, 2021	17,300,740	13,895,643
Number of Options, Exercisable as of December 31, 2021	7,880,668
Weighted Average Exercise Price per Share, Outstanding at December 31, 2020	$ 7.96
Weighted Average Exercise Price per Share, Granted	4.75
Weighted Average Exercise Price per Share, Exercised	1.59
Weighted Average Exercise Price per Share, Forfeited	10.30
Weighted Average Exercise Price per Share, Outstanding and expected to vest at December 31,2021	6.57	$ 7.96
Weighted Average Exercise Price per Share, Exercisable as of December 31,2021	$ 6.90
Weighted Average Remaining Contractual Life, Outstanding at December 31, 2020		7 years 1 month 28 days
Weighted Average Remaining Contractual Life, Outstanding and expected to vest at December 31, 2021	7 years 9 months 29 days
Weighted Average Remaining Contractual Life, Exercisable as of December 31, 2021	6 years 7 months 2 days
Aggregate Intrinsic Value, Outstanding	$ 2,842	$ 91,133
Aggregate Intrinsic Value, Exercisable as of December 31, 2021	$ 2,685

Share-based Compensation - Summary of Award Activity (Details)	12 Months Ended
	Dec. 31, 2021 $ / shares shares
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Weighted Average Grant Date Fair Value per share, Unvested at December 31, 2020 \| $ / shares	$ 8.75
Weighted Average Grant Date Fair Value per Share, Granted \| $ / shares	4.94
Weighted Average Grant Date Fair Value per share, Vested \| $ / shares	9.94
Weighted Average Grant Date Fair Value per share, Forfeited \| $ / shares	10.32
Weighted Average Grant Date Fair Value per Share, Unvested at December 31, 2021 \| $ / shares	$ 6.41
Performance-based RSUs
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
RSUs, Unvested at December 31, 2020	464,000
RSUs, Vested	(89,667)
RSUs, Forfeited	(179,333)
RSUs, Unvested at December 31, 2021	195,000
Time-based Restricted Share Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
RSUs, Unvested at December 31, 2020	180,000
Number of shares granted	47,500
RSUs, Vested	(41,667)
RSUs, Forfeited	(62,500)
RSUs, Unvested at December 31, 2021	123,333

Share-based Compensation - Share-based Compensation Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Total share-based compensation	$ 22,536	$ 27,962
Research and Development
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Total share-based compensation	9,214	11,679
Selling General and Administrative
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Total share-based compensation	$ 13,322	$ 16,283

License and Research Agreements - Additional Information (Details) € in Millions		1 Months Ended		12 Months Ended						32 Months Ended
	Apr. 30, 2020 USD ($) shares	Apr. 30, 2018 USD ($) Program shares	Apr. 30, 2018 GBP (£) Program shares	Dec. 31, 2021 USD ($) shares	Dec. 31, 2021 GBP (£)	Dec. 31, 2020 USD ($) shares	Dec. 31, 2019 USD ($) Milestone	Dec. 31, 2017 USD ($) shares	Dec. 31, 2016 USD ($) shares	Dec. 31, 2021 USD ($) shares	Dec. 31, 2021 EUR (€)	Dec. 31, 2021 GBP (£) shares	Dec. 31, 2021 EUR (€) shares	Dec. 31, 2018 shares	Nov. 30, 2018 shares	Sep. 30, 2018 shares	Apr. 30, 2018 GBP (£)
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Remaining liability				$ 3,419,000		$ 4,482,000	$ 6,790,000			$ 3,419,000
Ordinary shares issued \| shares				125,674,095		98,283,603				125,674,095		125,674,095	125,674,095
Research and development				$ 86,977,000		$ 93,730,000
GSK Asset Purchase and License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Number of earlier stage clinical gene therapy program \| Program		2	2
Number of earlier stage clinical gene therapy program \| Program		1	1
Number of additional earlier-stage development programs \| Program		3	3
Total consideration		$ 133,600,000	£ 94,200,000
Upfront payment		14,200,000	10,000,000.0
Remaining liability		18,400,000															£ 12,900,000
Inventory purchase liability		6,900,000															4,900,000
Transaction costs		800,000	600,000
In-process research and development expense		$ 133,600,000	£ 94,200,000
Payment of tiered royalty, maximum percentage				20.00%						20.00%		20.00%	20.00%
Milestone payments payable upon achievement of certain sales milestones				$ 35,000,000.0						$ 35,000,000.0		£ 90,000,000.0	€ 31.0
Upfront payment description				In May 2019, the Company entered into a license agreement with Telethon-OSR, under which Telethon-OSR granted to the Company an exclusive worldwide license for the research, development, manufacture and commercialization of Telethon-OSR’s ex vivo autologous HSC lentiviral based gene therapy for the treatment of mucopolysaccharidosis type I (“MPS-I”), including the Hurler variant. To date, Telethon-OSR received €17.0 million in upfront and milestone payments from the Company upon entering into the agreement and shortly thereafter, resulting in $19.4 million in in-process research and development expense.	In May 2019, the Company entered into a license agreement with Telethon-OSR, under which Telethon-OSR granted to the Company an exclusive worldwide license for the research, development, manufacture and commercialization of Telethon-OSR’s ex vivo autologous HSC lentiviral based gene therapy for the treatment of mucopolysaccharidosis type I (“MPS-I”), including the Hurler variant. To date, Telethon-OSR received €17.0 million in upfront and milestone payments from the Company upon entering into the agreement and shortly thereafter, resulting in $19.4 million in in-process research and development expense.
GSK Asset Purchase and License Agreement \| Convertible Preferred Shares
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Shares issued for asset acquisition \| shares		12,455,252	12,455,252
Aggregate value of shares issued for asset acquisition		$ 93,400,000															£ 65,800,000
Telethon O S R License Agreements
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront and milestone payments \| €											€ 17.0
In-process research and development expense for upfront and milestone payments										19,400,000
Milestone payments payable upon achievement of certain development regulatory and commercial milestones				$ 31,700,000						$ 31,700,000			€ 28.0
UCLB/UCLA Technology
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront cash payments									$ 800,000
UCLB Technology and Manufacturing Technology
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront cash payments									$ 1,100,000
UCLB License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Ordinary shares issued \| shares								1,224,094	3,441,290					4,665,384
UCLB/UCLA License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Payments to acquire clinical data								$ 800,000
Annual administration fee				100,000
Payments upon achievement of specified regulatory milestones				$ 26,800,000	£ 19,900,000
Research and development						$ 100,000
Oxford BioMedica License, Development and Supply Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Ordinary shares issued \| shares	75,413			588,220						588,220		588,220	588,220		150,826	150,826
Number of milestones met \| Milestone							0
Oxford BioMedica License, Development and Supply Agreement \| Research and Development Expense
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payment	$ 800,000

Collaboration Agreement with Pharming Group N.V. - Additional Information (Details) - USD ($)		1 Months Ended	12 Months Ended
	Jul. 01, 2021	Jul. 31, 2021	Dec. 31, 2021	Dec. 31, 2020
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total consideration			$ 143,645,000
Shares issued as part of license agreement				$ 791,000
Strategic Collaboration Agreement with Pharming
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Cash upfront payment received	$ 10,000,000.0
Non-refundable up-front payment	10,000,000.0
Strategic Collaboration Agreement with Pharming \| Maximum
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments receivable	189,500,000
Share Purchase Agreement with Pharming
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total consideration	$ 7,500,000	$ 7,500,000
Issuance of ordinary shares	1,227,738	1,227,738
Common stock consideration	$ 4,100,000	$ 4,100,000
Premium consideration	3,400,000	$ 3,400,000
Pharming Agreements
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total upfront payments	17,500,000
Upfront payments attributed to equity sold	4,100,000
Upfront payments attributed to research activities	13,400,000
Shares issued as part of license agreement	4,100,000
Excess proceeds from fair value of shares issued allocated to collaboration agreement	$ 3,400,000
Collaborative Arrangement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Contract liabilities			12,900,000
Collaborative Arrangement \| Accounts Receivable
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Accounts receivable			$ 800,000	$ 800,000

Collaboration Agreement with Pharming Group N.V. - Summary of Research and Development Costs Incurred and Collaboration Revenue Recognized (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total revenues	$ 1,675	$ 2,595
Collaborative Arrangement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total revenues	975
Collaborative Arrangement \| Reimbursement Revenue
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total revenues	843
Collaborative Arrangement \| Upfront and Milestone Payment Revenue
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total revenues	$ 132

- Definition

Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.

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

Income Taxes - Schedule of Components of Net Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Income Tax Disclosure [Abstract]
U.K.	$ (147,337)	$ (155,614)
Non-U.K.	3,581	2,904
Net loss before income tax	$ (143,756)	$ (152,710)

- Definition

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

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

Income Taxes - Schedule of Provision for (Benefit from) Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Current (benefit) provision
Federal—United States	$ (1,025)	$ 1,107
State—United States	334	189
Other foreign	388	230
Total current (benefit) provision	(303)	1,526
Deferred provision (benefit)
Federal—United States	1,099	(1,774)
State—United States	(312)	(103)
Other foreign	344	(380)
Total deferred provision (benefit)	1,131	(2,257)
Total provision (benefit) for income taxes	$ 828	$ (731)

Income Taxes - Schedule of Reconciliation of Income Tax Expense (Benefit) (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Income Tax Disclosure [Abstract]
Income taxes at United Kingdom statutory rate	$ (27,313)	$ (29,015)
Change in valuation allowance	59,691	29,302
Reduction in research expense for credits granted	6,674	8,435
Change in tax rates	(38,785)	(8,105)
Tax credits	(2,232)	(1,369)
U.S. Deduction for foreign derived intangible income	(196)	(1,254)
Permanent differences, including share-based compensation deduction shortfalls	2,863	1,265
U.S. state income taxes	17	68
Foreign rate differential	109	(58)
Total provision (benefit) for income taxes	$ 828	$ (731)

Income Taxes - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Operating Loss Carryforwards [Line Items]
Accrued interest or penalties related to uncertain tax positions	$ 0	$ 0
Earliest Tax Year
Operating Loss Carryforwards [Line Items]
Income tax year open to examination	2017
Latest Tax Year
Operating Loss Carryforwards [Line Items]
Income tax year open to examination	2021
United Kingdom
Operating Loss Carryforwards [Line Items]
Corporation tax rate percentage	25.00%
Increase in net deferred tax assets	$ 38,800,000
Increase in valuation allowance	38,800,000
Operating loss carryforwards	126,600,000	75,100,000
US \| Federal \| Orphan Drug
Operating Loss Carryforwards [Line Items]
Tax credits carryforward, amount	600,000	0
US \| State \| Research and Development
Operating Loss Carryforwards [Line Items]
Tax credits carryforward, amount	$ 2,400,000	$ 2,000,000.0
Tax credit carryforward expiration year	2041

Income Taxes - Schedule of Deferred Tax Assets and Liabilities Taxes (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Deferred tax assets
Net operating loss carryforwards	$ 126,563	$ 75,502
Amortization	25,206	22,599
Research and development credits	2,449	1,564
Share-based compensation	9,353	7,400
Accruals	798	1,001
Lease liability	6,444	6,805
Property and equipment	1,022	523
Other		3
Total deferred tax assets	171,835	115,397
Valuation allowance	(161,573)	(103,890)	$ (70,153)
Fixed assets and right-of-use asset	(6,176)	(6,288)
Other non-current assets (net deferred tax assets and liabilities)	$ 4,086	$ 5,219

Income Taxes - Schedule of Changes in Valuation Allowance for Deferred Tax Assets Related Primarily to Increase in U.K. Net Operating Loss Carryforwards (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Income Tax Disclosure [Abstract]
Valuation allowance as of beginning of year	$ (103,890)	$ (70,153)
Increases recorded to income tax provision	(59,691)	(29,302)
Effect of foreign currency translation	2,008	(4,435)
Valuation allowance as of end of year	$ (161,573)	$ (103,890)

Commitments and Contingencies - Schedule of Annual Commitments Associated with the Contract (Details) $ in Thousands	Dec. 31, 2021 USD ($)
Other Commitments [Line Items]
2022	$ 13,632
2023	13,961
2024	13,961
2025	6,979
Total manufacturing commitments	48,533
Product Manufacturing Commitments
Other Commitments [Line Items]
2022	2,627
2023	3,051
2024	3,051
2025	1,525
Total manufacturing commitments	10,254
Dedicated Manufacturing and Development Resources
Other Commitments [Line Items]
2022	8,379
2023	7,831
2024	7,831
2025	3,915
Total manufacturing commitments	27,956
Exclusive Transduction Suites
Other Commitments [Line Items]
2022	2,626
2023	3,079
2024	3,079
2025	1,539
Total manufacturing commitments	$ 10,323

Commitments and Contingencies - Schedule of Annual Commitments Associated with the Contract (Parenthetical) (Details)	Dec. 31, 2021
Commitments And Contingencies Disclosure [Abstract]
Exchange rate, Euro to U.S. Dollar	1.13

Commitments and Contingencies - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Other Commitments [Line Items]
Shares, vest	4 years
Ordinary Shares, Issued	125,674,095	98,283,603
Research and development	$ 86,977,000	$ 93,730,000
Compensation cost recognized	$ 22,536,000	$ 27,962,000
Consulting Agreement \| Advisor
Other Commitments [Line Items]
Cash payments			$ 100,000
Shares, issued			91,034
Shares, vest			4 years
Ordinary Shares, Issued	22,758	22,758
Research and development	$ 300,000	$ 300,000
Compensation cost recognized	$ 0	$ 0
Agreement
Other Commitments [Line Items]
Initial term of agreement	5 years
Agreement maturity date	Jul. 02, 2025
Agreement extension term	2 years
Clinical Development And Regulatory Milestone \| Consulting Agreement \| Advisor
Other Commitments [Line Items]
Shares, issued			92,035
Ordinary Shares, Issued	22,758	22,758

Benefit Plans - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Compensation And Retirement Disclosure [Abstract]
Contribution expenses	$ 1.7	$ 1.6
Maximum annual contribution employer matches per employee, percent	6.00%

Related Party Transactions - Additional Information (Details) $ in Thousands, £ in Millions	1 Months Ended		12 Months Ended
	Apr. 30, 2018 USD ($) shares	Apr. 30, 2018 GBP (£)	Dec. 31, 2021 USD ($)	Dec. 31, 2020 USD ($)	Dec. 31, 2018 USD ($)
Related Party Transaction [Line Items]
Loss provision associated with contract					$ 18,400
Research and development			$ 86,977	$ 93,730
GSK Asset Purchase and License Agreement
Related Party Transaction [Line Items]
Transaction costs	$ 800	£ 0.6
GSK
Related Party Transaction [Line Items]
License upfront fee	14,200
Inventory purchased	6,900
Transaction costs	$ 800
Due to related party transactions, accounts payable				100
Due to related party transactions, accrued expenses				100
Payments on accounts payable				5,800
GSK \| GSK Asset Purchase and License Agreement
Related Party Transaction [Line Items]
Research and development				$ 1,200
GSK \| Convertible Preferred Shares
Related Party Transaction [Line Items]
Ordinary shares Issuable Upon Conversion \| shares	12,455,252
Preferred stock, Value	$ 93,400
Loss provision associated with contract	$ 18,400

Subsequent Events - Additional Information (Details) - Subsequent Events - United Kingdom $ in Millions	Mar. 30, 2022 USD ($)
Subsequent Event [Line Items]
Number of positions eliminated, percent	30.00%
Estimated aggregate restructuring charges in first half of 2022	$ 2.5