0000950170-23-007708 | 10-K | XBRL Viewer

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Document and Entity Information - USD ($) $ in Millions	12 Months Ended
Document and Entity Information - USD ($) $ in Millions	Dec. 31, 2022	Mar. 10, 2023	Jun. 30, 2022
Cover [Abstract]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2022
Document Fiscal Year Focus	2022
Document Fiscal Period Focus	FY
Entity Registrant Name	ORCHARD THERAPEUTICS PLC
Current Fiscal Year End Date	--12-31
Entity Central Index Key	0001748907
Entity Filer Category	Non-accelerated Filer
Entity Well-known Seasoned Issuer	No
Entity Small Business	true
Entity Common Stock, Shares Outstanding		183,984,499
Entity Public Float			$ 74
Entity Shell Company	false
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Incorporation, State or Country Code	X0
Entity Address, Address Line One	245 Hammersmith Road
Entity Address, City or Town	London
Entity Address, Postal Zip Code	W6 8PW
City Area Code	44
Local Phone Number	(0) 203 808-8286
Document Annual Report	true
Document Transition Report	false
Entity File Number	001-38722
Entity Emerging Growth Company	false
Entity Tax Identification Number	00-0000000
Entity Address, Country	GB
ICFR Auditor Attestation Flag	false
Auditor Firm ID	238
Title of 12(b) Security	American Depositary Shares, each representing one ordinary share, nominal value £0.10 per share
Trading Symbol	ORTX
Security Exchange Name	NASDAQ
Auditor Name	PricewaterhouseCoopers LLP
Auditor Location	Boston, Massachusetts
Documents Incorporated by Reference	Portions of the Registrant’s definitive proxy statement for its 2023 Annual General Meeting are incorporated by reference into Part III of this Annual Report on Form 10-K where indicated.

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Current assets:
Cash and cash equivalents	$ 68,424	$ 55,912
Marketable securities	75,326	164,195
Accounts receivable	8,467	1,480
Prepaid expenses and other current assets	9,986	23,011
Research and development tax credit receivable	5,942	30,723
Total current assets	168,145	275,321
Non-current assets:
Operating lease right-of-use-assets	22,774	24,316
Property and equipment, net	8,138	4,767
Restricted cash	4,215	4,266
Intangible assets, net	3,560	4,149
Other assets	12,075	9,590
Total non-current assets	50,762	47,088
Total assets	218,907	322,409
Current liabilities:
Accounts payable	9,318	10,008
Accrued expenses and other current liabilities	34,437	24,318
Deferred revenue	959	346
Operating lease liabilities	6,424	7,335
Notes payable, current	9,429	786
Total current liabilities	60,567	42,793
Notes payable, long-term	22,991	32,086
Deferred revenue, net of current portion	10,315	12,519
Operating lease liabilities, net of current portion	19,246	19,278
Other long-term liabilities	7,524	5,783
Total liabilities	120,643	112,459
Commitments and contingencies (Note 17)
Shareholders’ equity:
Ordinary shares, GBP0.10 par value, authority to allot up to a maximum nominal value of GBP13,023,851.50 of shares at December 31, 2022 and 2021, respectively; Issued and outstanding - 126,947,225 and 125,674,095 shares at December 31, 2022 and 2021, respectively	16,419	16,253
Additional paid-in capital	956,711	940,675
Accumulated other comprehensive income	26,018	3,246
Accumulated deficit	(900,884)	(750,224)
Total shareholders’ equity	98,264	209,950
Total liabilities and shareholders’ equity	$ 218,907	$ 322,409

Consolidated Balance Sheets (Parenthetical) - GBP (£)	Dec. 31, 2022	Dec. 31, 2021
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	126,947,225	125,674,095
Ordinary Shares, Outstanding	126,947,225	125,674,095

Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Total revenues	$ 22,655	$ 1,675
Costs and operating expenses
Cost of product revenue	6,771	226
Research and development	93,847	86,977
Selling general and administrative	49,125	54,905
Total costs and operating expenses	149,743	142,108
Loss from operations	(127,088)	(140,433)
Other (expense) income:
Interest income	1,543	412
Interest expense	(3,079)	(2,497)
Other (expense) income, net	(24,410)	(1,238)
Total other (expense) income, net	(25,946)	(3,323)
Net loss before income tax	(153,034)	(143,756)
Income tax (expense) benefit	2,374	(828)
Net loss attributable to ordinary shareholders	$ (150,660)	$ (144,584)
Net loss per share attributable to ordinary shareholders, basic	$ (1.18)	$ (1.17)
Net loss per share attributable to ordinary shareholders, diluted	$ (1.18)	$ (1.17)
Weighted average number of ordinary shares outstanding, basic	127,975,062	123,963,762
Weighted average number of ordinary shares outstanding, diluted	127,975,062	123,963,762
Other comprehensive income (loss)
Foreign currency translation	$ 22,838	$ 3,124
Unrealized loss on marketable debt securities	(66)	(251)
Total other comprehensive income (loss)	22,772	2,873
Total comprehensive loss	(127,888)	(141,711)
Product Revenue, Net [Member]
Total revenues	20,610	700
Collaboration Revenue [Member]
Total revenues	$ 2,045	$ 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, 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
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	3,124			3,124
Unrealized 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
Share-based compensation expense	16,010		16,010
Exercise of share options	$ 1	$ 91	(90)
Exercise of share options, Shares	699,234	699,234
Issuance of ESPP shares	$ 211	$ 72	139
Issuance of ESPP shares, Shares		544,442
Vesting of restricted share units, net of shares withheld for taxes	(19)	$ 3	(22)
Vesting of restricted share units, net of shares withheld for taxes, shares		24,202
Ordinary shares issued as part of consulting agreement	(1)		(1)
Ordinary shares issued as part of consulting agreement, Shares		5,252
Foreign currency translation	22,838			22,838
Unrealized loss on marketable debt securities	(66)			(66)
Net loss	(150,660)				(150,660)
Balance at Dec. 31, 2022	$ 98,264	$ 16,419	$ 956,711	$ 26,018	$ (900,884)
Balance, Shares at Dec. 31, 2022		126,947,225

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, 2022	Dec. 31, 2021
Cash flows from operating activities
Net loss attributable to ordinary shareholders	$ (150,660)	$ (144,584)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization	2,741	2,327
Share-based compensation	16,010	22,536
Non-cash interest expense	372	392
Amortization of provision on loss contract	(274)	(1,037)
Deferred income taxes	(3,283)	1,131
Amortization of premium (discount) on marketable securities	(305)	1,514
Unrealized foreign currency and other non-cash adjustments	23,208	9,687
Changes in operating assets and liabilities:
Accounts receivable	(7,420)	(624)
Research and development tax credit receivable	22,568	(13,920)
Prepaid expenses, other current assets, and other assets	5,053	(5,209)
Operating leases, right-of-use-assets	5,431	5,938
Accounts payable, accrued expenses, and other current liabilities	13,642	(9,452)
Deferred revenue	(272)	13,122
Other long-term liabilities	2,154	34
Operating lease liabilities	(4,952)	(6,952)
Net cash used in operating activities	(75,987)	(125,097)
Cash flows from investing activities
Proceeds from sales and maturities of marketable securities	201,389	234,732
Purchases of marketable securities	(112,281)	(263,878)
Receipt of funds from construction deposit	7,966	216
Payments on intangible assets		(887)
Purchases of property and equipment	(6,514)	(2,348)
Net cash provided by (used in) investing activities	90,560	(32,165)
Cash flows from financing activities
Proceeds from modification of credit facility, net of debt issuance costs paid		7,375
Proceeds from employee equity plans	212	3,303
Payment of taxes on restricted stock vesting	(19)	(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	(100)	(6,355)
Repayment of notes payable	(786)
Net cash (used in) provided by financing activities	(693)	158,066
Effect of exchange rate changes on cash	(1,419)	(27)
Net increase in cash, cash equivalents and restricted cash	12,461	777
Cash, cash equivalents, and restricted cash —beginning of year	60,178	59,401
Cash, cash equivalents, and restricted cash —end of year	72,639	60,178
Supplemental disclosure of non-cash investing and financing activities
Intangible assets and property and equipment in accounts payable and accrued expenses	60	2,589
Supplemental disclosure of cash flow information
Lease assets obtained in exchange for new operating lease liabilities	4,912	552
Changes to operating lease right-of-use assets and liabilities from amendments	530
Cash paid for interest	2,648	2,103
Cash paid for taxes	$ 157	$ 1,651

Nature of the Business and Liquidity

12 Months Ended

Dec. 31, 2022

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Nature of the Business and Liquidity

1. Nature of the Business and Liquidity

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 has a portfolio that includes a commercial-stage product and research and development-stage product candidates.

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”). The ADSs were listed on the Nasdaq Global Select Market on October 31, 2018 and were transferred to the Nasdaq Capital Market on September 13, 2022. As of December 31, 2022, 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. The Company did not declared any dividends in 2022 or 2021.

Effective March 10, 2023, the Company enacted a ratio change wherein each ADS listed on the Nasdaq Capital Market is worth ten ordinary shares.

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 “2021 Private Placement”). The 2021 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. As of December 31, 2021, all outstanding non-voting shares have been converted to voting ordinary shares.

In January 2022, the Company began to generate revenue from product sales of Libmeldy™ in Europe following the approval of Libmeldy by the European Commission in December 2020 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 March 6, 2023, the Company entered into a Securities Purchase Agreement pursuant to which the Company agreed to sell ordinary shares, non-voting ordinary shares, and warrants to purchase to purchase ordinary shares or non-voting ordinary shares in an unregisterd offering (the "2023 Private Placement"). The 2023 Private Placement consists of two closings. On March 10, 2023, the Company completed the initial closing and issued and sold (i) 56,666,900 ordinary shares and non-voting ordinary shares, nominal value £0.10 per share and (ii) warrants to purchase an aggregate of 62,333,590 ordinary shares or non-voting ordinary shares, at a purchase price of $6.00 per unit, where each unit consists of ten (10) Shares and an accompanying Warrant to purchase eleven (11) Shares. The initial closing of the 2023 Private Placement resulted in gross proceeds of approximately $34.0 million. Refer to Footnote 19 for further discussion around the 2023 Private Placement.

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 travel restrictions, supply chain disruptions, business closures, and other measures.

Through December 31, 2022, the Company funded its operations with proceeds from the sale of equity securities, including ADSs in the Company’s initial public offering (“IPO”) and follow-on offering, ordinary shares in the private placement, and convertible preferred shares. The Company has also financed its operations through proceeds from the Company’s senior term facilities agreement with MidCap Financial (Ireland) Limited, research grants from the California Institute of Regenerative Medicine (“CIRM”), upfront payments from the Company’s collaboration agreement and share purchase agreement with Pharming Group N.V., proceeds from the sales of the Company's Libmeldy product, and reimbursements associated with two UK research and development tax relief programs, the Small and Medium-sized Enterprises research and

development tax credit (“SME”) program and the Research and Development Expenditure (“RDEC”) program. The Company has incurred recurring losses since its inception and 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, 2022, of $143.8 million, together with expected proceeds from sales of Libmeldy and the $34 million received in March 2023 from the 2023 Private Placement, will be sufficient to fund its operations and capital expenditure requirements for at least twelve months from the date of filing of this Annual Report on Form 10-K. 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 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.

Summary of Significant Accounting Policies

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Summary of Significant Accounting Policies

2. Summary of Significant Accounting Policies

Basis of presentation

The accompanying consolidated financial statements have been prepared in conformity with U.S. generally accepted accounting principles ("GAAP") and include the accounts of the Company and its wholly owned subsidiaries, after elimination of all intercompany accounts and transactions. Any reference in these notes to applicable guidance is meant to refer to authoritative United States generally accepted accounting principles as found in the Accounting Standards Codification (“ASC”) and as amended by Accounting Standards Updates (“ASU”) of the Financial Accounting Standards Board (“FASB”).

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.

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 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, variable consideration in revenue recognition, 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 and of significant suppliers

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 invests its excess cash, in line with its investment policy, in money market funds and high credit quality debt instruments. The Company's cash is deposited 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.

The Company is dependent upon a third-party contract manufacturer to develop, manufacture, and supply certain raw materials and conduct manufacturing activities for certain research and development and commercial programs. The disruption of the supply of raw materials and manufacturing activities could adversely affect the Company's operations. The

Company believes that its relationship with this manufacturer is satisfactory and has contingency plans in place to mitigate any adverse effects around the loss of this contract manufacturer.

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. Unrealized losses are driven primarily by intercompany balances denominated in currencies other than the functional currency of the entity with the intercompany balance, and typically fluctuates concurrently with fluctuations in the U.S. Dollar, Pounds sterling, and Euro exchange rates. 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 $24.3 million and of $1.2 million for the years ended December 31, 2022 and 2021, 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, the results of the Company's operations are reported on a consolidated basis for the 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, net, of $7.5 million and $0.6 million located in the United Kingdom and United States, respectively, as of December 31, 2022. The Company had property and equipment, net, 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 right-of-use assets in the United States and United Kingdom of $11.2 million and $11.6 million, respectively, as of December 31, 2022. 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.

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 from 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 and 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 operations.

Accounts receivable

Accounts receivable arise from product revenue and amounts due from the Company's collaboration partners and have payment terms that generally require payment within 30 to 90 days. For some Libmeldy customers, our payment terms can range from 30 days to under one year. The amount from product revenue represents amounts due from distributors in Europe, which are recorded net of reserves for trade discounts and allowances, and other incentives to the extent such amounts are payable to the customer by the Company. The Company monitors economic conditions to identify facts or circumstances that

may indicate that its receivables are at risk of collection. The Company provides reserves against accounts receivable for estimated losses, if any, that may result from a customer's inability to pay based on the composition of its accounts receivable, current economic conditions, and historical credit loss activity. Amounts determined to be uncollectible are charged or written-off against the reserve. The Company did not record any expected credit losses related to outstanding accounts receivable in 2022 and 2021.

Fair Value Measurements

Certain assets and liabilities of the Company are carried at fair value under GAAP. Financial assets and liabilities carried at fair value are to be classified and disclosed in one of the following three levels of the fair value hierarchy, of which the first two are considered observable and the last is considered unobservable:

Level 1—Valuations based on quoted prices in active markets for identical assets or liabilities that the Company has the ability to access at the measurement date.

Level 2—Valuations based on quoted prices for similar assets or liabilities in markets that are not active or for which all significant inputs are observable, either directly or indirectly, such as quoted market prices, interest rates, and yield curves.

Level 3—Valuations that require inputs that reflect the Company’s own assumptions that are both significant to the fair value measurement and unobservable.

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

The Company believes that the carrying amount reflected on the consolidated balance sheets for research and development tax incentive receivable, trade 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

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 the Company's consolidated balance sheets. 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 as of December 31, 2022 and 2021. 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 as of December 31, 2022 and 2021.

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 (in thousands):


	As of December 31,
	2022		2021
Cash and cash equivalents	$	68,424	$	55,912
Restricted cash		4,215		4,266
Total cash, cash equivalents and restricted cash shown in the statement of cash flows	$	72,639	$	60,178

Inventory

The Company began capitalizing inventory manufactured or purchased after the acquisition of Strimvelis in April 2018 and EMA approval of Libmeldy in December 2020. 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 as its balance was not significant as of December 31, 2022 or 2021 (refer to Footnote 4).

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.

Intangible assets, net

Intangible assets consist of 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.


Asset Type:		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 or asset group may not be fully recoverable. Factors that the Company considers in deciding when to perform an impairment review include significant under performance 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 or asset group to its carrying value. An impairment loss would be recognized when the 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.

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 and benefits, share-based compensation, facilities costs, depreciation, third-party license fees, certain milestone payments, external costs incurred by outside vendors engaged to conduct clinical development activities and clinical trials, the purchase of in-process research and development assets, and costs incurred 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, 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 expenses 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.

Accrued external research and development expenses

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 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 entities 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 all stock options and other stock-based awards granted based on the fair value of the award on the date of the grant and recognizes stock-based compensation expense for those awards over the requisite service period, which is generally the vesting period of the respective award. The Company has elected to recognize forfeitures as they occur. Therefore, the reversal of compensation cost previously recognized for an award that is forfeited because of a failure to satisfy a service or performance condition is recognized in the period of the forfeiture. The Company classifies stock-based compensation expense in its consolidated statements of operations and comprehensive loss in the same manner in which the award recipient’s payroll costs are classified or in which the award recipients’ service payments are classified.

The fair value of each stock option grant is estimated on the date of grant using the Black-Scholes option pricing model, which requires inputs based on certain subjective assumptions, including the fair value of the Company’s common stock, expected stock price volatility, the expected term of the stock option, the risk-free interest rate for a period that approximates the expected term of the stock option, and the Company’s expected dividend yield. 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 closing sale price per share of the Company’s common stock as reported on The Nasdaq Global Market on the date of grant is used to determine the fair value, which is then used to establish the exercise price per share of share-based awards to purchase common stock.

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

At the inception of an arrangement, the Company determines whether the arrangement is or contains a lease based on specific facts and circumstances, the existence of an identified asset(s), if any, and the Company’s control over the use of the identified asset(s), if applicable. 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. The Company recognizes a corresponding right-of-use (“ROU”) asset, initially measured as the amount of lease liability, adjusted for any initial lease costs or lease payments made before or at the commencement of the lease, and reduced by any lease incentives. 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.

The lease liability is measured at the present value of future lease payments, discounted using the discount rate as of the lease commencement date. Future lease payments may include payments that depend on an index or a rate (such as the consumer price index or other market index). The Company initially measures payments based on an index or rate by using the applicable rate at lease commencement and subsequent changes in such rates are recognized as variable lease costs. Variable payments that do not depend on a rate or index are not included in the lease liability and are recognized as they are incurred. The Company’s contracts typically do not have variable payments based on index or rate.

When readily determinable, the discount rate used to calculate the lease liability is the rate implicit in the lease. As the Company’s leases do not typically provide an implicit rate, the Company utilizes an incremental borrowing rate, which is the rate incurred to borrow an amount on a collateralized basis over a similar term as the associated lease 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 lease term used to calculate the lease liability includes options to extend or terminate the lease when it is reasonably certain that the Company will exercise that option. With limited exceptions, the nature of the Company's facility leases is such that there are no economic or other conditions that would indicate that it is reasonably certain at lease commencement that the Company will exercise options to extend the term.

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, and as a result, 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’s leases consist of only operating leases. Operating leases are recognized on the balance sheet as ROU assets, operating lease liabilities, and operating lease liabilities non-current. Fixed payments are included in the calculation of the lease balances while certain variable costs paid for certain operating and pass-through costs are excluded. Lease expense is recognized over the expected lease term on a straight-line basis.

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. 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 reduction 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 future losses, however, the timing of recognizing the amortization of what was originally recorded is adjusted for updated future losses.

The following table below outlines the changes to the Strimvelis loss provision for the periods ended December 31, 2022 and 2021 (in thousands):


	Year Ended December 31,
	2022			2021
Balance at beginning of period	$	3,419		$	4,482
Amortization of loss provision		(274	)		(1,037	)
Foreign currency translation		(326	)		(26	)
Balance at end of period	$	2,819		$	3,419

As of December 31, 2022, the entire balance of the Strimvelis loss provision was categorized as current. As of December 31, 2021, $0.7 million of the loss provision was classified as current, and $2.7 million was classified as non-current.

United Kingdom Research and development income tax credits

As the Company carries out research and development activities, it is able to submit tax credit claims from two UK research and development tax relief programs: the Small and Medium-Sized Enterprises research and development tax credit (“SME”) program and the Research and Development Expenditure Credit (“RDEC”), 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.

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. Each reporting period, the Company assesses its research and development activities and expenditures to determine whether the nature of these costs 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. The Company expects a proportion of expenditures incurred 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, 2022. The Company has qualified under the more favorable SME regime for the year ended December 31, 2021 and expects to qualify under the SME regime for the year ending December 31, 2022.

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 expenses. 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, 2022 and 2021 (in thousands):


	Year Ended December 31,
	2022			2021
Balance at beginning of period	$	30,723		$	17,344
Recognition of credit claims as offset to research and development expense		8,243			13,920
Receipt of credit claims		(30,811	)		-
Foreign currency translation		(2,213	)		(541	)
Balance at end of period	$	5,942		$	30,723

As of December 31, 2022 and 2021, the Company’s tax credit receivable was classified as current with receipt of the credit expected within twelve months of the balance sheet date.

Income taxes

The Company is primarily subject to corporation taxes in the United Kingdom, the United States, and certain European Union countries in which it has legal subsidiaries. The calculation of the Company’s tax provision involves the application of country applicable tax law and requires judgment 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 revenue, net

Libmeldy

In January 2022, the Company began generating product revenue from sales of Libmeldy in Europe following the approval of Libmeldy by the European Commission in December 2020 for the treatment of early onset MLD, characterized by biallelic mutations in the 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.

The Company recognizes revenue when control of promised goods is transferred to a customer at an amount that reflects the consideration to which the Company expects to be entitled in exchange for those goods. Control of the product transfers upon infusion of the product.

To determine revenue recognition, the Company performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price, including variable consideration, if any; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the Company satisfies the performance obligations. The Company only applies the five-step model to contracts when collectability of the consideration to which it is entitled in exchange for the goods the Company transfers to the customer is determined to be probable.

In certain regions of Europe and the Middle East, the Company utilizes distributors to act in an agent capacity including for patient identification and other related functions. The Company is exclusively responsible for product fulfillment and retains inventory risk and pricing discretion of the product. Evaluation of these key indicators supports the assertion that the Company maintains control over the product prior to delivery to the patient. The Company has concluded that it is the principal in these transactions and records the associated revenue on a gross basis with any payments to these entities being recorded as a selling expense.

Amounts are recorded as accounts receivable when the right to the consideration is unconditional. The Company does not assess whether a contract has a significant financing component if the expectation at contract inception is that the period between payment by the customer and the transfer of the promised goods or services to the customer will be one year or less. The Company expenses incremental costs of obtaining a contract as and when incurred if the expected amortization period of the asset that would have been recognized is one year or less or the amount is immaterial. As of December 31, 2022, the Company has not capitalized any costs to obtain contracts.

The Company recognizes product revenue, net of variable consideration related to certain allowances and accruals, when the customer takes control of the product, which is at a point in time once the patient has been infused. Product revenue is recorded at the net sales price, or transaction price. The Company records estimated product revenue reserves, which are classified as a reduction in product revenue, to account for the components of variable consideration. Variable consideration includes the following components: government rebates, including performance-based rebates, trade discounts and allowances, and other incentives, which are described below.

These reserves are based on estimates of the amounts earned or to be claimed on the related sales and are classified as a liability. The Company's estimates of reserves established for variable consideration are calculated based upon an application of the expected value method, which is the sum of probability-weighted amounts in a range of possible consideration amounts. These estimates reflect the Company's historical experience, current contractual and statutory requirements, specific known market events and trends, industry data, and current expectations around final pricing. The amount of variable consideration that is included in the transaction price may be subject to constraint and is included in net product revenue only to the extent that it is probable that a significant reversal in the amount of the cumulative revenue recognized will not occur in a future period. The actual amounts of consideration received may ultimately differ from the Company's estimates. If actual results vary, the Company adjusts these estimates, which could have an effect on earnings in the period of adjustment. The following is a summary of the types of variable consideration the Company records:

Government rebates: The Company is subject to statutory government rebates on sales in certain European countries as well as estimated rebates in certain European countries because final pricing has not yet been negotiated. The Company records reserves for rebates in the same period the related product revenue is recognized, resulting in a reduction of product revenue and a current liability that is included in accrued expenses on the Company’s consolidated balance sheet. The Company is also subject to potential rebates in connection with performance criteria agreed upon with certain payors. The estimate for rebates is based on statutory discount rates, industry pricing data, current expectations around final pricing to be obtained, and historical experience of the performance of the Company’s products during clinical trials. The Company classifies rebates within accrued expenses in the accompanying consolidated balance sheets.

Trade discounts and allowances: The Company may offer customers discounts, such as prompt pay discounts to remit payment in accordance with the stated terms of the invoice. These discounts are explicitly stated in the contracts and recorded in the period the related product revenue is recognized. The Company estimates which customers will earn these discounts and fees and deducts these discounts and fees in full from gross product revenue and accounts receivable at the time the Company recognizes the related revenue. The Company classifies trade discounts and allowances as a reduction of accounts receivable within the accompanying consolidated balance sheets.

Product returns: Based on the timing of revenue recognition upon treatment with the patient, the Company does not expect any returns of the Company’s products.

Other incentives: While the Company does not currently have any other incentives that have been recorded to date, the Company may enter into future arrangements that have other incentives that will be recorded as a reduction of revenue.

Strimvelis

The Company’s product sales of Strimvelis are currently distributed exclusively at the San Raffaele Hospital in Milan, Italy. The hospital will purchase and pay for the products and submit a claim to the payer. The Company’s contracted sales with the hospital contains a single performance obligation and the Company recognizes revenue from product sales when the Company has satisfied its performance obligation, which is upon transferring control of the products to the hospital. The Company evaluated the variable consideration under ASC 606 and there is currently no variable consideration included in the transaction price for the products. Costs to manufacture and deliver the product and those associated with administering the therapy are included in the cost of product sales. As the product is sold in direct relation to a scheduled treatment, the Company estimates there is limited risk of product return, including the risk of product expiration.

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 pre-clinical 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, 2022, 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 five-step model.

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 potentially dilutive ordinary shares. For the 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, the 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,
	2022		2021
Share options		13,076,959		14,042,781
Unvested restricted incentive shares		2,253,199		512,908
		15,330,158		14,555,689

Recent accounting pronouncements

In November 2021, the FASB issued ASU No. 2021-10, Government Assistance (Topic 832): Disclosures by Business Entities about Government Assistance, which requires increased transparency in the disclosures about government assistance 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 adopted and applied the amendments of this ASU to its disclosures. The application of this ASU did not have a material impact on the Company's financial position, results of operations or cash flows.

In March 2020, the FASB issued ASU 2020-04, Reference Rate Reform (Topic 848): Facilitation of the Effects of Reference Rate Reform on Financial Reporting and issued two subsequent amendments: ASU 2021-01, issued in January 2021, refines the scope of ASU and clarifies some of its guidance as part of the FASB’s monitoring of global reference rate reform activities and ASU 2022-06, issued in December 2022, which extends the effective period of the ASU through December 31, 2023 (collectively, including ASU 2020-04, “ASC 848”). ASC 848 provides temporary optional expedients and exceptions to the GAAP guidance on contract modifications and hedge accounting to ease the financial reporting burdens related to the expected market transition from the London Interbank Offered Rate (“LIBOR”) and other interbank offered rates to alternative reference rates. ASC 848 is effective for all entities as of March 12, 2020, through December 31, 2023, at which time transition is expected to be complete. The Company is currently reviewing the provisions of this pronouncement, specifically its impact on its notes payable, but does not expect this guidance will have a material impact on the Company's consolidated financial statements.

Fair Value Measurements and Marketable Securities

12 Months Ended

Dec. 31, 2022

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, 2022 and 2021, and indicate the fair value of the hierarchy of the valuation inputs utilized to determine such fair value (in thousands):


	Fair Value Measurements as of December 31, 2022
	Level 1		Level 2		Level 3		Total
Cash equivalents
Money market funds	$	1,239	$	—	$	—	$	1,239
U.S. treasuries		—		6,600		—		6,600
U.S. government securities		—		5,200		—		5,200
Commercial paper		—		14,122		—		14,122
Total cash equivalents	$	1,239	$	25,922	$	—	$	27,161
Marketable securities
U.S. government securities	$	—	$	1,984	$	—	$	1,984
Corporate bonds		—		25,475		—		25,475
Commercial paper		—		47,867		—		47,867
Total marketable securities	$	—	$	75,326	$	—	$	75,326
Total Assets	$	1,239	$	101,248	$	—	$	102,487


	Fair Value Measurements as of December 31, 2021
	Level 1		Level 2		Level 3		Total
Cash equivalents
Money market funds	$	21,085	$	—	$	—	$	21,085
U.S. government securities		—		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 Company classifies its money market funds as Level 1 assets since it measures fair value using quoted prices in active markets for identical assets. The Level 2 assets include commercial paper, U.S. government securities, U.S. treasuries, and corporate bonds and are valued based on quoted prices for similar assets in active markets and inputs other than quoted prices that are derived from observable market data. The Company did not hold any Level 3 assets during the periods presented.

The Company evaluates transfers between levels at the end of each reporting period. There were no transfers between Level 1 and Level 2 assets during the periods presented.

Marketable Securities

The following tables summarize the amortized cost and fair value of the Company's available-for-sale marketable debt securities (in thousands):


	December 31, 2022
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Credit Losses		Fair Value
U.S. government securities	$	7,188	$	1	$	(6	)	$	—	$	7,183
U.S. treasuries		6,599		1		—			—		6,600
Corporate bonds		25,656		—		(180	)		—		25,476
Commercial paper		62,038		3		(52	)		—		61,989
Total	$	101,481	$	5	$	(238	)	$	—	$	101,248


	December 31, 2021
	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 available-for-sale marketable debt securities by contractual maturity, as of December 31, 2022 and 2021 (in thousands):


	2022		2021
Maturities in one year or less	$	98,277	$	172,575
Maturities between one and three years		2,971		12,139
Total	$	101,248	$	184,714

All investments in an unrealized loss position were in this position for less than 12 months. The Company evaluated its securities for potential other-than-temporary impairment and considered the decline in market value to be primarily attributable to current economic and market conditions. Additionally, the Company does not intend to sell the securities in an unrealized loss position and does not expect it will be required to sell the securities before recovery of the unamortized cost basis. Given the Company's intent and ability to hold such securities until recovery, and the lack of a significant change in credit risk for these investments, the Company does not consider these investments to be impaired as of December 31, 2022.

There were no realized gains or losses recognized on investments for the years ended December 31, 2022 and 2021.

- Definition

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

+ References + Details

Prepaid Expenses and Other Current Assets

12 Months Ended

Dec. 31, 2022

Prepaid Expense and Other Assets, Current [Abstract]

Prepaid Expenses and Other Current Assets

4. Prepaid expenses and other current assets

Prepaid expenses and other current assets consist of the following (in thousands):


	December 31,
	2022		2021
Prepaid external research and development expenses	$	881	$	2,438
Inventories		3,400		2,016
Other prepayments		1,817		6,128
VAT receivable		1,077		1,169
Construction deposit - current		—		7,909
Non-trade receivables		1,851		3,351
Rent deposits		960		—
Total prepaid expenses and other current assets	$	9,986	$	23,011

Property and Equipment

12 Months Ended

Dec. 31, 2022

Property, Plant and Equipment [Abstract]

Property and Equipment

5. Property and equipment

Property and equipment consist of the following (in thousands):


	December 31,
	2022			2021
Property and equipment:
Lab equipment	$	6,722		$	5,937
Leasehold improvements		5,069			2,450
Furniture and fixtures		226			303
Office and computer equipment		2,153			2,023
Construction-in-progress		759			211
Property and equipment		14,929			10,924
Less: accumulated depreciation		(6,791	)		(6,157	)
Property and equipment, net	$	8,138		$	4,767

Depreciation expense for the years ended December 31, 2022 and 2021 was $2.4 million and $2.2 million, respectively.

Intangible Assets, Net

12 Months Ended

Dec. 31, 2022

Goodwill and Intangible Assets Disclosure [Abstract]

Intangible Assets, Net

6. Intangible assets, net

Intangible assets, net of accumulated amortization, consisted of the following (in thousands):


	As of December 31, 2022
	Cost		Accumulated Amortization			Net
License milestones	$	4,069	$	(509	)	$	3,560
Total	$	4,069	$	(509	)	$	3,560

	As of December 31, 2021
	Cost		Accumulated Amortization			Net
License milestones	$	4,329	$	(180	)		4,149
Total	$	4,329	$	(180	)	$	4,149

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. Amortization of intangible assets was $0.3 million and $0.2 million for the years ended December 31, 2022 and 2021, respectively. The effect of foreign currency translation on the net carrying value of intangible assets during the year ended December 31, 2022 was $0.2 million. 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 (in thousands):


2023	$	343
2024		343
2025		343
2026		343
2027		343
Thereafter		1,845
Total	$	3,560

Other Assets

12 Months Ended

Dec. 31, 2022

Other Assets, Noncurrent Disclosure [Abstract]

Other Assets

7. Other assets

Other assets consist of the following (in thousands):


	December 31,
	2022		2021
Deferred tax assets	$	7,369	$	4,086
Deposits		1,048		1,404
Deferred financing costs		462		693
Other non-current assets		3,196		3,407
Total other assets	$	12,075	$	9,590

Accrued Expenses and Other Liabilities

12 Months Ended

Dec. 31, 2022

Accrued Liabilities and Other Liabilities [Abstract]

Accrued Expenses and Other Liabilities

8. Accrued expenses and other liabilities

Accrued expenses and other current liabilities consisted of the following (in thousands):


	December 31,
	2022		2021
Accrued external research and development expenses	$	11,230	$	9,273
Accrued payroll and related expenses		12,312		8,521
Accrued milestone payments		85		2,058
Accrued professional fees		2,263		854
Accrued other		2,562		2,941
Accrued governmental rebates		2,300		—
Strimvelis liability - current portion		3,685		671
Total accrued expenses and other current liabilities	$	34,437	$	24,318

Restructuring Charges

12 Months Ended

Dec. 31, 2022

Restructuring and Related Activities [Abstract]

Restructuring Charges

9. Restructuring charges

On March 30, 2022, the Company announced its commitment to focus on severe neurometabolic diseases and early research programs, and to discontinue its investment in and seek strategic alternatives for the Company’s programs in rare primary immune deficiencies, including OTL-103 for treatment of Wiskott Aldrich syndrome (“WAS”), OTL-102 for treatment of X-linked chronic granulomatous disease (“X-CGD”), and Strimvelis for adenosine deaminase severe combined immunodeficiency (“ADA-SCID”). During the year ended December 31, 2022, the Company recognized a one-time charge during of approximately $1.7 million, which relates to employee-related termination costs, of which $1.4 million and $0.3 million was recognized in research and development expenses and selling, general, and administrative expenses, respectively, in the Company's consolidated statements of operations and comprehensive loss. Activity during the year ended December 31, 2022, was as follows (in thousands):


	Year Ended December 31,
	2022
Balance at beginning of period	$	6
Charged to expense		2,481
Non-cash adjustments and foreign currency translation		(760	)
Payments made		(1,727	)
Balance at end of period	$	-

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

Leases

12 Months Ended

Dec. 31, 2022

Leases [Abstract]

Leases

10. Leases

Operating leases- office and lab space

In January 2018, December 2018, and February 2022 the Company entered into lease agreements for office space in London, United Kingdom. The leases entered into in 2018 both terminate in January 2023 and there were no options to extend the lease term. The lease entered into in March 2022 expires in February 2032 and there are no options to extend the lease term. The combined annual rental payments, including variable payments, under the lease agreements were $1.7 million in 2022 and $1.8 million in 2021. The Company also rented lab spaces in London in 2021, for which it made $0.2 million in payments in 2022 and 2021.

In March 2018, the Company entered into a lease agreement for office space in Boston, Massachusetts, United States, which terminated in September 2022. The annual rental payments, including variable payments, were $0.3 million in 2022 and $0.4 million in 2021. The Company subleased the space starting in August 2021, and recognized $0.2 and $0.1 million in sublease income in 2022 and 2021, respectively.

In July 2019, the Company entered into a lease agreement for office space in Boston, Massachusetts, United States, which commenced in January 2020. The lease terminates in September 2026 and has no options for term extension. The annual rental payments, including variable payments, were $1.2 million and $1.1 million in 2022 and 2021, respectively. The lease agreement includes annual rent escalation provisions.

As of December 31, 2022, the carrying value of the operating lease right-of-use assets in Boston and London was $8.1 million and the lease liabilities was $8.7 million. 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.

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 whereby it 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 $3.2 million in 2022 and $3.1 million in 2021. 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, 2022, the carrying value of the Fremont Head Lease right-of-use asset was $8.8 million and the lease liability was $12.0 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 are currently expected to be received in 2023. 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. The Sublease provided for 12 months of free rent until December 2021. The sublease provides for cash base rent payments with an annual rent escalation provision. 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.

Embedded operating lease arrangement

In July 2020, the Company entered into a manufacturing and technology development master 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 ("AGC Agreement").

The Company determined that the AGC Agreement contains an embedded lease as it includes a provision for 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 Company does not deem it probable that it will exercise the option to extend as of December 31, 2022. The Company paid $2.5 million and $3.1 million in rental payments in 2022 and 2021, respectively. As of December 31, 2022, the carrying value of the embedded operating lease right-of-use asset was $5.8 million and the lease liability was $5.3 million. 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.

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, 2022 and 2021 (in thousands, where applicable):


	2022			2021
Fixed lease cost	$	7,693		$	7,701
Variable lease cost		1,602			1,696
Sublease income		(2,820	)		(2,746	)
Total lease cost	$	6,475		$	6,651

Other information
Operating cash flows used for operating leases	$	7,442		$	7,989
Weighted-average remaining lease term (years)		6.5			6.0
Weighted-average discount rate		8.5	%		8.7	%

Fixed lease cost represents the ASC 842 rent expense associated with the amortization of our right-of-use assets and lease liabilities. 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, 2022, the Company obtained right of use assets valued at $6.1 million in exchange for

lease liabilities of $6.1 million. During the year ended December 31, 2021, the Company obtained $0.6 million in right of use assets in exchange for $0.6 million in lease liabilities.

As of December 31, 2022, future minimum base rent commitments under ASC 842 under the Company’s property leases were as follows (in thousands):


Due in:	Gross lease payments			Gross sublease receipts			Net lease payments
2023	$	6,517		$	(2,246	)	$	4,271
2024		6,972			(2,313	)		4,659
2025		6,035			(2,382	)		3,653
2026		4,809			(2,454	)		2,355
2027		3,774			(2,527	)		1,247
Thereafter		12,266			(6,432	)		5,834
Total future minimum lease payments	$	40,373		$	(18,354	)	$	22,019
Less: imputed interest		(14,703	)
Total operating lease payments	$	25,670

Notes Payable

12 Months Ended

Dec. 31, 2022

Debt Disclosure [Abstract]

Notes Payable

11. 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.

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.

In January 2023, the Company again amended and restated the credit facility to change from LIBOR to SOFR. The newly amended facility bears a variable interest rate of 5.95% above SOFR plus 0.10% per annum, plus a final payment equal to 3.5% of the principal borrowed under the Amended Credit Facility.

Notes payable consisted of the following (in thousands):


	December 31,
	2022			2021
Notes payable, net of issuance costs	$	31,970		$	32,669
Less: current portion		(9,429	)		(786	)
Notes payable, net of current portion		22,541			31,883
Accretion related to final payment		450			203
Notes payable, long term	$	22,991		$	32,086

As of December 31, 2022, the future principal payments and final payment that are due are as follows (in thousands):


	Aggregate Minimum Payments
2023	$	9,429
2024		9,429
2025		9,429
2026		5,084
Total		33,371
Less current portion		(9,429	)
Less unamortized portion of final payment		(705	)
Less unamortized debt issuance costs		(246	)
Notes payable, long term	$	22,991

During the years ended December 31, 2022 and 2021, the Company recognized $3.0 million and $2.5 million of interest expense related to the term loan, respectively. The effective annual interest rate as of December 31, 2022 and 2021, on the outstanding debt under the Term Loan was approximately 9.2% and 8.4%, respectively.

- 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.

+ References

Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-URI https://asc.fasb.org/topic&trid=2208564

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1B
-Subparagraph (h)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1C
-Subparagraph (c)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495334-112611

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1I
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1I
-Subparagraph (d)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 235
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SX 210.4-08(c))
-URI https://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1B
-Subparagraph (g)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1C
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495334-112611

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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-SubTopic 20
-Section 50
-Paragraph 1C
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495334-112611

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
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-Section 50
-Paragraph 1E
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495348-112611

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1B
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611

Reference 12: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1I
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611

Reference 13: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1B
-Subparagraph (i)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611

+ Details

Share-based Compensation

12 Months Ended

Dec. 31, 2022

Share-Based Payment Arrangement [Abstract]

Share-based Compensation

12. 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 board of directors has determined not to make any further awards under the 2016 plan. As of December 31, 2022, there were 5,341,768 shares available for grant under the 2018 Plan, 721,500 available for grant under the Inducement Plan, and 627,677 shares available for grant under the ESPP.

The numbers of options and restricted stock units, the weighted average grant date fair values per stock option and per share, and the weighted average exercise prices are all shown below on a per ordinary share basis. Effective March 10, 2023, The Company’s ADSs that are listed on the NASDAQ Capital Market each represent ten ordinary shares.

On October 4, 2022, the Company’s Compensation Committee approved a one-time stock option repricing for certain previously granted and still outstanding options held by the Company’s employees and certain independent contractors which had an exercise price above $1.25. As a result of the repricing, the exercise price for 7,946,139 vested and unvested options outstanding was lowered to $0.58. No other terms of the repriced options were modified and the repriced stock will continue to vest according to their original vesting schedules and will retain their original expiration dates. The repricing resulted in one-time stock-based compensation expense of $0.9 million related to vested options and incremental stock option expense of $0.8 million related to unvested options which will be amortized on a straight-line basis over the remaining vesting period of those options.

Share options

The fair value of each stock option award is estimated on the date of grant using the Black-Scholes option-pricing model using the range of assumptions for the years ended December 31, 2022 and 2021, as noted in the following table:


	Year Ended December 31,
	2022	2021
Risk-free interest rate	1.5% - 4.4%	0.5% - 1.3%
Expected term (in years)	2.0 - 6.1	5.3 - 6.1
Expected volatility	74.4% - 79.5%	74.2% - 78.7%
Expected dividend rate	0.0%	0.0%

The following table summarizes option activity under the plans for the year ended December 31, 2022:


	Shares			Weighted Average Exercise Price per Share		Weighted Average Remaining Contractual Life (Years)		Aggregate Intrinsic Value (in thousands)
Outstanding at December 31, 2021		17,300,740		$	6.57
Granted		4,600,154			0.56
Exercised		(699,234	)		-
Forfeited		(4,777,493	)		6.81
Outstanding at December 31, 2022		16,424,167		$	1.56		7.38	$	-
Vested and expected to vest at December 31, 2022		16,424,167		$	1.56		7.38	$	-
Exercisable at of December 31, 2022		9,212,552		$	2.28		6.26	$	-

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, 2022 and 2021, the total intrinsic value of share options exercised was $0.4 million and $7.4 million, respectively. The weighted average grant date fair value per share of options granted during the years ended December 31, 2022 and 2021, was $0.32 and $3.10, respectively.

Restricted share units

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 the 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, 2022.

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, 2022:


	Performance-based RSUs		Time-based RSUs			Total RSUs			Weighted Average Grant Date Fair Value per Share
Unvested at December 31, 2021		195,000		123,333			318,333		$	6.41
Granted		—		2,192,988			2,192,988			0.46
Vested		—		(55,001	)		(55,001	)		5.58
Forfeited		—		(392,444	)		(392,444	)		0.60
Unvested at December 31, 2022		195,000		1,868,876			2,063,876		$	0.55

During the years ended December 31, 2022 and 2021, the total fair value of time-based RSU’s that vested was $0.3 million and $0.3 million, respectively.

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 (in thousands):


	Year Ended December 31,
	2022		2021
Research and development	$	6,791	$	9,214
Selling, general and administrative		9,219		13,322
Total	$	16,010	$	22,536

Total share-based compensation by award type was as follows (in thousands):


	Year Ended December 31,
	2022		2021
Restricted share units	$	838	$	550
Share options		15,172		21,986
Total	$	16,010	$	22,536

As of December 31, 2022, total unrecognized compensation cost related to options was $14.0 million. This amount is expected to be recognized over a weighted average period of 2.34 years. As of December 31, 2022, total unrecognized compensation cost related to time-based RSUs was $0.8 million. This amount is expected to be recognized over a weighted average period of 1.96 years. As of December 31, 2022, 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 Arrangements

12 Months Ended

Dec. 31, 2022

License And Research Arrangements [Abstract]

License and Research Agreements

13. 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 pre-clinical 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, 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, resulting in total consideration of $133.6 million, which was recorded in the second quarter of 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. As part of the GSK Agreement the Company is also 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.

The Company will pay GSK non-refundable royalties and milestone payments in relation to the gene therapy programs acquired. The Company will pay a flat mid-single digit percentage royalty on the annual net sales of 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 or through December 31, 2022, and are not included as part of consideration.

Telethon-OSR research and development collaboration and license agreements

In connection with the Company’s entering into the GSK Agreement in April 2018, 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 and TDT.

As consideration for the licenses, the Company will be required to make payments to Telethon-OSR upon achievement of certain product development milestones, up to an aggregate of approximately €31.0 million ($33.4 million at December 31, 2022). 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.

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, including the Hurler variant (“MPS-IH”). Under the terms of the agreement, Telethon-OSR received €15.0 million ($16.1 million at December 31, 2022) in upfront and milestone payments from the Company upon entering into the agreement, resulting in $17.2 million in in-process research and development expense. The Company is also required to pay up to €28.0 million ($30.1 million at December 31, 2022) related to milestone payments contingent upon achievement of certain development, regulatory and commercial milestones. 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 expenses based on the fair value of the ordinary shares as of the time the agreement was executed or modified.

Under the UCLB/UCLA License Agreement, the Company may become obligated to make payments to the parties of up to an aggregate of £19.9 million ($24.1 million at December 31, 2022) 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.

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 25th anniversary of the agreement.

Oxford BioMedica license, development and supply agreement

In November 2016, and amended in June 2017, May 2018, July 2018, September 2018, May 2019 and April 2020, the Company entered into an arrangement with Oxford BioMedica plc whereby Oxford BioMedica granted an exclusive intellectual property license to the Company for the purposes of research, development, and commercialization of collaboration products, and whereby Oxford BioMedica will provide process development services (“Oxford BioMedica Development Agreement”). As part of the consideration to rights and licenses granted under the Oxford BioMedica Development 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 another 75,413 ordinary shares to Oxford BioMedica with a total value of $0.8 million which was recorded to research and development expense. No milestones were met during the year ended December 31, 2022. The Company may also pay low single-digit percentage royalties on net sales of collaborated products generated under the Oxford BioMedica Agreement.

Income Taxes

12 Months Ended

Dec. 31, 2022

Income Tax Disclosure [Abstract]

Income Taxes

14. Income taxes

The components of net loss before income taxes for the years ended December 31, 2022 and 2021 are as follows (in thousands):


	December 31,
	2022			2021
U.K.	$	(156,000	)	$	(147,337	)
Non-U.K.		2,966			3,581
Net loss before taxes	$	(153,034	)	$	(143,756	)

The provision for (benefit from) income taxes for the years ended December 31, 2022 and 2021 are as follows (in thousands):


	December 31,
	2022			2021
Current (benefit) provision
Federal—United States	$	618		$	(1,025	)
State—United States		144			334
Other foreign		147			388
United Kingdom		—			—
Total current (benefit) provision		909			(303	)
Deferred provision (benefit)
Federal—United States		(3,066	)		1,099
State—United States		(204	)		(312	)
United Kingdom		(13	)		—
Other foreign		—			344
Total deferred provision (benefit)		(3,283	)		1,131
Total provision (benefit) for income taxes	$	(2,374	)	$	828

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 (in thousands):


	December 31,
	2022			2021
Income taxes at United Kingdom statutory rate	$	(29,072	)	$	(27,313	)
Change in valuation allowance		34,333			59,691
Reduction in research expense for credits granted		1,805			6,674
Change in tax rates		(8,240	)		(38,785	)
Tax credits		(2,049	)		(2,232	)
U.S. Deduction for foreign derived intangible income		(1,489	)		(196	)
Permanent differences, including share-based compensation deduction shortfalls		2,387			2,863
U.S. state income taxes		(45	)		17
Foreign rate differential		(4	)		109
Total provision (benefit) for income taxes	$	(2,374	)	$	828

The Company’s income tax expense for the year ended December 31, 2022, compared to the year ended December 31, 2021, decreased primarily related to an increase of the U.S. deduction for foreign derived intangible income (“FDII”), a decrease to the amount of shortfalls related to share-based compensation that is not deductible for tax purposes, and a decrease in the non-U.K. profit before tax.

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 of $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, 2022 and 2021 (in thousands):


	December 31,
	2022			2021
Deferred tax assets
Net operating loss carryforwards	$	158,344		$	126,563
Amortization		11,215			25,206
Research and development credits		2,525			2,449
Capitalized research and development costs		2,285			—
Share-based compensation		9,282			9,353
Accruals		946			798
Lease liability		6,126			6,444
Property and equipment		—			1,022
Total deferred tax assets		190,723			171,835
Valuation allowance		(177,630	)		(161,573	)
Fixed assets and right-of-use asset		(5,724	)		(6,176	)
Other non-current assets (net deferred tax assets and liabilities)	$	7,369		$	4,086

For the years ended December 31, 2022 and 2021, the Company had cumulative U.K. net operating loss carryforwards of approximately $633.4 million and $506.2 million, respectively. U.K. 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, 2022 and 2021, the Company also had U.S. federal orphan drug tax credits of $0.7 million and $0.6 million, respectively, and U.S. state research and development tax credits of $2.2 million and $2.4 million. The U.S. federal orphan drug tax credits expire in 2042, 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 the future realization of our deferred tax assets. Management has considered the Company’s history of cumulative net losses in the U.K., 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 U.K. 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, 2022 and 2021, respectively.

Changes in the valuation allowance for deferred tax assets during the years ended December 31, 2022 and 2021 related primarily to the increase in UK net operating loss carryforwards as follows (in thousands):


	December 31,
	2022			2021
Valuation allowance as of beginning of year	$	(161,573	)	$	(103,890	)
Increases recorded to income tax provision		(34,248	)		(59,691	)
Effect of foreign currency translation		18,191			2,008
Valuation allowance as of end of year	$	(177,630	)	$	(161,573	)

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, 2022 and 2021.

The Company will recognize interest and penalties related to uncertain tax positions in income tax expense. As of December 31, 2022, and 2021, 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 2018 through 2022 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

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

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
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Reference 4: http://www.xbrl.org/2003/role/disclosureRef
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Reference 5: http://www.xbrl.org/2003/role/disclosureRef
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Reference 6: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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Reference 7: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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-URI https://asc.fasb.org/topic&trid=2144680

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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-SubTopic 30
-Section 50
-Paragraph 2
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=6424122&loc=d3e41874-109331

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 235
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SX 210.4-08(h)(2))
-URI https://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

+ Details

Product Revenue, Net

12 Months Ended

Dec. 31, 2022

Revenue from Contract with Customer [Abstract]

Product Revenue, Net

15. Product revenue, net

The following table presents the Company's net revenue by product (in thousands):


	Year Ended December 31,
	2022		2021
Libmeldy	$	18,796	$	—
Strimvelis		1,814		700
Total	$	20,610	$	700

Net product revenue of Libmeldy by geography consisted of the following and is attributable to individual countries based on the location of the customer as of December 31, 2022 (in thousands):


	Year ended December 31, 2022
United Kingdom	$	6,322
Italy		5,544
France		3,883
Germany		3,047
Total Libmeldy revenue, net	$	18,796

As of December 31, 2022 and 2021, all Strimvelis revenue was generated in Italy.

Activity in each of the product revenue allowance and reserve categories for Libmeldy is summarized as follows (in thousands):


	Trade Discounts and Allowances			Government rebates		Total
Balance as of December 31, 2021	$	—		$	—	$	—
Provision Related to sales in the current year		4,573			2,300		6,873
Credits and payments made during the period		(183	)		—		(183	)
Balance as of December 31, 2022	$	4,390		$	2,300	$	6,690

The total reserves described above are summarized as components of the Company's consolidated balance sheets as follows (in thousands):


	December 31, 2022
Reduction of accounts receivable, net	$	4,390
Component of accrued expenses and other current liabilities		2,300
Balance as of December 31, 2022	$	6,690

There were no Libmeldy reserves or revenue allowances as of December 31, 2021. Strimvelis had no trade discounts and allowances or government rebates in the years ended December 31, 2022 and 2021.

- 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 https://asc.fasb.org/topic&trid=49130388

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
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Reference 4: http://www.xbrl.org/2003/role/disclosureRef
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Reference 5: http://www.xbrl.org/2003/role/disclosureRef
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Reference 6: http://www.xbrl.org/2003/role/disclosureRef
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Reference 8: http://www.xbrl.org/2003/role/disclosureRef
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Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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-Paragraph 12
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-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130554-203045

+ Details

Collaboration Revenue

12 Months Ended

Dec. 31, 2022

Collaborative Arrangement [Abstract]

Collaboration Revenue

16. Collaboration revenue

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 pre-clinical 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.

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.

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 $13.4 million attributed to the Collaboration Agreement 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. The Company re-evaluates the transaction price as of the end of each reporting period.

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. Reimbursement for research, development, and manufacturing services are recognized as the costs are incurred consistent with the cost-to-cost method. The estimated costs associated with the remaining efforts required to complete the performance obligations may change which may materially impact revenue recognition and the Company regularly evaluates and, when necessary, updates the costs associated with the remaining efforts. 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 (in thousands):


	Year Ended December 31,
	2022		2021
Reimbursement revenue	$	1,776	$	843
Upfront and milestone payment revenue		269		132
Total	$	2,045	$	975

The Company had $0.5 million and $0.8 due from Pharming included in accounts receivable as of December 31, 2022 and 2021, respectively.

As of December 31, 2022, the Company had contract liabilities of $11.3 million, of which $1.0 million was classified as current and $10.3 million was classified as long-term in the consolidated balance sheets. 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, 2022.

Commitments and Contingencies

12 Months Ended

Dec. 31, 2022

Commitments and Contingencies Disclosure [Abstract]

Commitments and Contingencies

17. Commitments and contingencies

Lease commitments

The Company leases office and laboratory space and has an embedded lease with AGC. Refer to Note 10 for further information on the terms of our 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, 2022 (in thousands):


Due in:	Product manufacturing commitments (1)		Dedicated manufacturing and development resources (2)		Exclusive transduction suites (3)		Total AGC Commitment
2023	$	1,933	$	5,655	$	2,147	$	9,735
2024		1,933		5,655		2,147		9,735
2025		966		2,827		1,074		4,867
Total manufacturing commitments	$	4,832	$	14,137	$	5,368	$	24,337

The tabular disclosure above has been translated from Euros to U.S. Dollars using an exchange rate of €1.00 to $1.07.

(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 10 for further information on the embedded operating lease agreement

The Company incurred $13.7 million and $16.4 million in expenses related to the AGC Agreement in the years ended December 31, 2022 and 2021, respectively. 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 13). 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.

Legal proceedings

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

Indemnification agreements

In the ordinary course of business, the Company may provide indemnification of varying scope and terms to vendors, lessors, business partners, and other parties with respect to certain matters including, but not limited to, losses arising out of breach of such agreements or from intellectual property infringement claims made by third parties. In addition, the Company has entered into indemnification agreements with members of its board of directors and senior management that will require the Company, among other things, to indemnify them against certain liabilities that may arise by reason of their status or service as directors or officers. The maximum potential amount of future payments the Company could be required to make under these indemnification agreements is, in many cases, unlimited. To date, the Company has not incurred any material costs as a result of such indemnifications. The Company is not aware of any claims under indemnification arrangements, and it has not accrued any liabilities related to such obligations in its consolidated financial statements as of December 31, 2022 or 2021.

Benefit Plans

12 Months Ended

Dec. 31, 2022

Retirement Benefits [Abstract]

Benefit Plans

18. 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 in which the employees are located. The Company paid $1.6 million and $1.7 million, in matching contributions for the years ended December 31, 2022 and 2021, respectively.

- Definition

The entire disclosure for retirement benefits.

+ References

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

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section S99
-Paragraph 2
-URI https://asc.fasb.org/extlink&oid=21916913&loc=d3e273930-122802

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 50
-Paragraph 1
-Subparagraph (d)(i)
-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
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-Paragraph 1
-Subparagraph (o)
-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 50
-Paragraph 1
-Subparagraph (p)
-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 70
-Section 50
-Paragraph 1
-URI https://asc.fasb.org/extlink&oid=49170846&loc=d3e28014-114942

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-URI https://asc.fasb.org/topic&trid=2235017

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 60
-Section 50
-Paragraph 3
-Subparagraph (c)
-URI https://asc.fasb.org/extlink&oid=6414203&loc=d3e39689-114964

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 50
-Paragraph 1
-Subparagraph (d)(iv)(03)
-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 50
-Paragraph 1
-Subparagraph (q)
-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 50
-Paragraph 1
-Subparagraph (r)(1)
-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

Reference 12: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 50
-Paragraph 1
-Subparagraph (d)(iii)
-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

Reference 13: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 50
-Paragraph 1
-Subparagraph (l)
-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

Reference 14: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 50
-Paragraph 1
-Subparagraph (r)(2)
-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

+ Details

Subsequent Events

12 Months Ended

Dec. 31, 2022

Subsequent Events [Abstract]

Subsequent Events

19. Subsequent events

Ratio change

On February 10, 2023, the Company announced that the Company's Board of Directors approved a change to the ratio of the Company's ADSs to ordinary shares (the "ADS Ratio") from the previous ADS Ratio of one ADS to one ordinary share to a new ADS Ratio of one ADS to ten ordinary shares. The ratio change became effective on March 10, 2023. The change in the ADS Ratio had the same effect as a one-for-ten reverse ADS split and is intended to enable the Company to regain compliance with the Nasdaq minimum bid price requirement. As all financial statement and disclosure information is presented in ordinary share amounts, not ADSs, there was no impact to the consolidated financial statements and footnote disclosures.

Issuance of shares through 2023 Private Placement

On March 6, 2023, the Company entered into a Securities Purchase Agreement (the “Purchase Agreement”) pursuant to which the Company agreed to sell, in an unregistered offering, up to an aggregate of (i) 99,166,900 shares, consisting of a combination of Ordinary Shares, nominal value £0.10 per share (“Ordinary Shares”) and Non-Voting Ordinary Shares, nominal value £0.10 per share (“Non-Voting Ordinary Shares” and together with the Ordinary Shares, “Shares”) and (ii) warrants to purchase an aggregate of 109,083,590 Ordinary Shares or Non-Voting Ordinary Shares (the “Warrants”).

The 2023 Private Placement consists of two closings. The Company agreed to sell and issue in the initial closing of the 2023 Private Placement (i) 56,666,900 Shares and (ii) Warrants to purchase an aggregate of 62,333,590 Shares, at a purchase price of $6.00 per unit, where each unit consists of ten (10) Shares and an accompanying Warrant to purchase eleven (11) Shares. The initial closing of the 2023 Private Placement occurred on March 10, 2023. The Company received gross proceeds of approximately $34.0 million from the initial closing of the 2023 Private Placement, before deducting fees to the placement agent and other offering expenses payable by the Company.

In addition, the Company agreed to sell and issue in the second closing of the 2023 Private Placement (i) 42,500,000 Shares and (ii) Warrants to purchase an aggregate of 46,750,000 Shares, at a purchase price of $8.00 per unit, where each unit consists of ten (10) Shares and an accompanying Warrant to purchase eleven (11) Shares. The second closing is conditioned upon (x) the Company’s announcement of its intention to file a biologics license application (“BLA”) submission following receipt of the minutes from the U.S. Food and Drug Administration (“FDA”) in connection with the Company’s pre-BLA (Type B) meeting for OTL-200, provided such minutes do not expressly advise the Company not to proceed with a BLA submission, and (y) receipt of Shareholder Approval (as defined below) (collectively, the “Second Closing Trigger”).

In connection with the Private Placement, the Company has agreed to hold a meeting of its shareholders no later than 120 days following the initial closing of the Private Placement to seek approval to give the Company’s directors authority under s551 Companies Act 2006 to issue the securities to be issued and sold in the second closing of the Private Placement and the Shares issuable upon exercise of the Warrants to be issued and sold in the Private Placement, and to disapply pre-emption rights in respect of such authority under s570 of the Companies Act 2006 (collectively, “Shareholder Approval”).

The second closing is expected to occur on the fifth trading day after the Company notifies the purchasing parties that the Second Closing Trigger has occurred and is subject to additional, customary closing conditions. If the Second Closing Trigger occurs, the Company anticipates receiving gross proceeds of approximately $34.0 million from the second closing of

the 2023 Private Placement, before deducting fees to the placement agent and other offering expenses payable by the Company.

Each Warrant will have an exercise price equal to $1.10 per Share in the event the Vesting Event (as defined below) occurs on or prior to December 31, 2024, and $0.95 per Share in the event the Vesting Event occurs after December 31, 2024. The Warrants will be exercisable during the 30 days following the Company’s announcement of receipt of marketing approval of its BLA with respect to OTL-200 (the “Vesting Event”); provided that exercise of any Warrant is conditioned upon the receipt of Shareholder Approval. Commencement of the 30-day exercise period may be delayed as set forth in the Warrants in the event the Vesting Event occurs prior to Shareholder Approval. The Warrants will expire at the conclusion of the 30-day exercise period or, if the Vesting Event does not occur, March 10, 2026.

Summary of Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Basis of presentation

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.

Principles of consolidation

Use of estimates

Concentration of credit risk and of significant suppliers

Company believes that its relationship with this manufacturer is satisfactory and has contingency plans in place to mitigate any adverse effects around the loss of this contract manufacturer.

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

Accounts receivable

Fair Value Measurements

Level 1—Valuations based on quoted prices in active markets for identical assets or liabilities that the Company has the ability to access at the measurement date.

Level 3—Valuations that require inputs that reflect the Company’s own assumptions that are both significant to the fair value measurement and unobservable.

Restricted cash and construction deposits


	As of December 31,
	2022		2021
Cash and cash equivalents	$	68,424	$	55,912
Restricted cash		4,215		4,266
Total cash, cash equivalents and restricted cash shown in the statement of cash flows	$	72,639	$	60,178

Inventory

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.


Asset Type:		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

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.

Research and development costs

Accrued external research and development expenses

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, 2022 and 2021 (in thousands):


	Year Ended December 31,
	2022			2021
Balance at beginning of period	$	3,419		$	4,482
Amortization of loss provision		(274	)		(1,037	)
Foreign currency translation		(326	)		(26	)
Balance at end of period	$	2,819		$	3,419

United Kingdom Research and development income tax credits


	Year Ended December 31,
	2022			2021
Balance at beginning of period	$	30,723		$	17,344
Recognition of credit claims as offset to research and development expense		8,243			13,920
Receipt of credit claims		(30,811	)		-
Foreign currency translation		(2,213	)		(541	)
Balance at end of period	$	5,942		$	30,723

As of December 31, 2022 and 2021, the Company’s tax credit receivable was classified as current with receipt of the credit expected within twelve months of the balance sheet date.

Income taxes

Product revenue, net

Libmeldy

Product returns: Based on the timing of revenue recognition upon treatment with the patient, the Company does not expect any returns of the Company’s products.

Strimvelis

Collaboration revenue

Net loss per share


	As of December 31,
	2022		2021
Share options		13,076,959		14,042,781
Unvested restricted incentive shares		2,253,199		512,908
		15,330,158		14,555,689

Recent accounting pronouncements

Summary of Significant Accounting Policies (Tables)

12 Months Ended

Dec. 31, 2022

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 (in thousands):


	As of December 31,
	2022		2021
Cash and cash equivalents	$	68,424	$	55,912
Restricted cash		4,215		4,266
Total cash, cash equivalents and restricted cash shown in the statement of cash flows	$	72,639	$	60,178

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.


Asset Type:		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

The following table below outlines the changes to the Strimvelis loss provision for the periods ended December 31, 2022 and 2021 (in thousands):


	Year Ended December 31,
	2022			2021
Balance at beginning of period	$	3,419		$	4,482
Amortization of loss provision		(274	)		(1,037	)
Foreign currency translation		(326	)		(26	)
Balance at end of period	$	2,819		$	3,419

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, 2022 and 2021 (in thousands):


	Year Ended December 31,
	2022			2021
Balance at beginning of period	$	30,723		$	17,344
Recognition of credit claims as offset to research and development expense		8,243			13,920
Receipt of credit claims		(30,811	)		-
Foreign currency translation		(2,213	)		(541	)
Balance at end of period	$	5,942		$	30,723

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


	As of December 31,
	2022		2021
Share options		13,076,959		14,042,781
Unvested restricted incentive shares		2,253,199		512,908
		15,330,158		14,555,689

Fair Value Measurements and Marketable Securities (Tables)

12 Months Ended

Dec. 31, 2022

Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Abstract]

Schedule of Cash Equivalents and Marketable Securities


	Fair Value Measurements as of December 31, 2022
	Level 1		Level 2		Level 3		Total
Cash equivalents
Money market funds	$	1,239	$	—	$	—	$	1,239
U.S. treasuries		—		6,600		—		6,600
U.S. government securities		—		5,200		—		5,200
Commercial paper		—		14,122		—		14,122
Total cash equivalents	$	1,239	$	25,922	$	—	$	27,161
Marketable securities
U.S. government securities	$	—	$	1,984	$	—	$	1,984
Corporate bonds		—		25,475		—		25,475
Commercial paper		—		47,867		—		47,867
Total marketable securities	$	—	$	75,326	$	—	$	75,326
Total Assets	$	1,239	$	101,248	$	—	$	102,487


	Fair Value Measurements as of December 31, 2021
	Level 1		Level 2		Level 3		Total
Cash equivalents
Money market funds	$	21,085	$	—	$	—	$	21,085
U.S. government securities		—		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

Schedule of Amortized Cost and Fair Value of Available-for-Sale Marketable Debt Securities

The following tables summarize the amortized cost and fair value of the Company's available-for-sale marketable debt securities (in thousands):


	December 31, 2022
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Credit Losses		Fair Value
U.S. government securities	$	7,188	$	1	$	(6	)	$	—	$	7,183
U.S. treasuries		6,599		1		—			—		6,600
Corporate bonds		25,656		—		(180	)		—		25,476
Commercial paper		62,038		3		(52	)		—		61,989
Total	$	101,481	$	5	$	(238	)	$	—	$	101,248


	December 31, 2021
	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

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, 2022 and 2021 (in thousands):


	2022		2021
Maturities in one year or less	$	98,277	$	172,575
Maturities between one and three years		2,971		12,139
Total	$	101,248	$	184,714

Prepaid Expenses and Other Current Assets (Tables)

12 Months Ended

Dec. 31, 2022

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 (in thousands):


	December 31,
	2022		2021
Prepaid external research and development expenses	$	881	$	2,438
Inventories		3,400		2,016
Other prepayments		1,817		6,128
VAT receivable		1,077		1,169
Construction deposit - current		—		7,909
Non-trade receivables		1,851		3,351
Rent deposits		960		—
Total prepaid expenses and other current assets	$	9,986	$	23,011

Property and Equipment (Tables)

12 Months Ended

Dec. 31, 2022

Property, Plant and Equipment [Abstract]

Schedule of Property and Equipment

Property and equipment consist of the following (in thousands):


	December 31,
	2022			2021
Property and equipment:
Lab equipment	$	6,722		$	5,937
Leasehold improvements		5,069			2,450
Furniture and fixtures		226			303
Office and computer equipment		2,153			2,023
Construction-in-progress		759			211
Property and equipment		14,929			10,924
Less: accumulated depreciation		(6,791	)		(6,157	)
Property and equipment, net	$	8,138		$	4,767

Intangible Assets, Net (Tables)

12 Months Ended

Dec. 31, 2022

Goodwill and Intangible Assets Disclosure [Abstract]

Schedule of Intangible Assets Net of Accumulated Amortization

Intangible assets, net of accumulated amortization, consisted of the following (in thousands):


	As of December 31, 2022
	Cost		Accumulated Amortization			Net
License milestones	$	4,069	$	(509	)	$	3,560
Total	$	4,069	$	(509	)	$	3,560

	As of December 31, 2021
	Cost		Accumulated Amortization			Net
License milestones	$	4,329	$	(180	)		4,149
Total	$	4,329	$	(180	)	$	4,149

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 (in thousands):


2023	$	343
2024		343
2025		343
2026		343
2027		343
Thereafter		1,845
Total	$	3,560

Other Assets (Tables)

12 Months Ended

Dec. 31, 2022

Other Assets, Noncurrent Disclosure [Abstract]

Schedule of Other Assets

Other assets consist of the following (in thousands):


	December 31,
	2022		2021
Deferred tax assets	$	7,369	$	4,086
Deposits		1,048		1,404
Deferred financing costs		462		693
Other non-current assets		3,196		3,407
Total other assets	$	12,075	$	9,590

Accrued Expenses and Other Liabilities (Tables)

12 Months Ended

Dec. 31, 2022

Accrued Liabilities and Other Liabilities [Abstract]

Schedule of Accrued Expenses and Other Liabilities

Accrued expenses and other current liabilities consisted of the following (in thousands):


	December 31,
	2022		2021
Accrued external research and development expenses	$	11,230	$	9,273
Accrued payroll and related expenses		12,312		8,521
Accrued milestone payments		85		2,058
Accrued professional fees		2,263		854
Accrued other		2,562		2,941
Accrued governmental rebates		2,300		—
Strimvelis liability - current portion		3,685		671
Total accrued expenses and other current liabilities	$	34,437	$	24,318

Restructuring Charges (Tables)

12 Months Ended

Dec. 31, 2022

Restructuring and Related Activities [Abstract]

Summary of Restructuring Charges

Activity during the year ended December 31, 2022, was as follows (in thousands):


	Year Ended December 31,
	2022
Balance at beginning of period	$	6
Charged to expense		2,481
Non-cash adjustments and foreign currency translation		(760	)
Payments made		(1,727	)
Balance at end of period	$	-

Leases (Tables)

12 Months Ended

Dec. 31, 2022

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, 2022 and 2021 (in thousands, where applicable):


	2022			2021
Fixed lease cost	$	7,693		$	7,701
Variable lease cost		1,602			1,696
Sublease income		(2,820	)		(2,746	)
Total lease cost	$	6,475		$	6,651

Other information
Operating cash flows used for operating leases	$	7,442		$	7,989
Weighted-average remaining lease term (years)		6.5			6.0
Weighted-average discount rate		8.5	%		8.7	%

Schedule of Future Minimum Base Rent Commitments Under Operating Leases

As of December 31, 2022, future minimum base rent commitments under ASC 842 under the Company’s property leases were as follows (in thousands):


Due in:	Gross lease payments			Gross sublease receipts			Net lease payments
2023	$	6,517		$	(2,246	)	$	4,271
2024		6,972			(2,313	)		4,659
2025		6,035			(2,382	)		3,653
2026		4,809			(2,454	)		2,355
2027		3,774			(2,527	)		1,247
Thereafter		12,266			(6,432	)		5,834
Total future minimum lease payments	$	40,373		$	(18,354	)	$	22,019
Less: imputed interest		(14,703	)
Total operating lease payments	$	25,670

Notes Payable (Tables)

12 Months Ended

Dec. 31, 2022

Debt Disclosure [Abstract]

Summary of Notes Payable

Notes payable consisted of the following (in thousands):


	December 31,
	2022			2021
Notes payable, net of issuance costs	$	31,970		$	32,669
Less: current portion		(9,429	)		(786	)
Notes payable, net of current portion		22,541			31,883
Accretion related to final payment		450			203
Notes payable, long term	$	22,991		$	32,086

Summary of Future Principal Payments and Final Payment Due

As of December 31, 2022, the future principal payments and final payment that are due are as follows (in thousands):


	Aggregate Minimum Payments
2023	$	9,429
2024		9,429
2025		9,429
2026		5,084
Total		33,371
Less current portion		(9,429	)
Less unamortized portion of final payment		(705	)
Less unamortized debt issuance costs		(246	)
Notes payable, long term	$	22,991

Share-based Compensation (Tables)

12 Months Ended

Dec. 31, 2022

Share-Based Payment Arrangement [Abstract]

Assumptions Used in Black-Scholes Option Pricing Model


	Year Ended December 31,
	2022	2021
Risk-free interest rate	1.5% - 4.4%	0.5% - 1.3%
Expected term (in years)	2.0 - 6.1	5.3 - 6.1
Expected volatility	74.4% - 79.5%	74.2% - 78.7%
Expected dividend rate	0.0%	0.0%

Summary of Option Activity

The following table summarizes option activity under the plans for the year ended December 31, 2022:


	Shares			Weighted Average Exercise Price per Share		Weighted Average Remaining Contractual Life (Years)		Aggregate Intrinsic Value (in thousands)
Outstanding at December 31, 2021		17,300,740		$	6.57
Granted		4,600,154			0.56
Exercised		(699,234	)		-
Forfeited		(4,777,493	)		6.81
Outstanding at December 31, 2022		16,424,167		$	1.56		7.38	$	-
Vested and expected to vest at December 31, 2022		16,424,167		$	1.56		7.38	$	-
Exercisable at of December 31, 2022		9,212,552		$	2.28		6.26	$	-

Summary of Award Activity

The following table summarizes restricted share unit award activity for the year-end December 31, 2022:


	Performance-based RSUs		Time-based RSUs			Total RSUs			Weighted Average Grant Date Fair Value per Share
Unvested at December 31, 2021		195,000		123,333			318,333		$	6.41
Granted		—		2,192,988			2,192,988			0.46
Vested		—		(55,001	)		(55,001	)		5.58
Forfeited		—		(392,444	)		(392,444	)		0.60
Unvested at December 31, 2022		195,000		1,868,876			2,063,876		$	0.55

During the years ended December 31, 2022 and 2021, the total fair value of time-based RSU’s that vested was $0.3 million and $0.3 million, respectively.

Share-based Compensation Expense


	Year Ended December 31,
	2022		2021
Research and development	$	6,791	$	9,214
Selling, general and administrative		9,219		13,322
Total	$	16,010	$	22,536

Total share-based compensation by award type was as follows (in thousands):


	Year Ended December 31,
	2022		2021
Restricted share units	$	838	$	550
Share options		15,172		21,986
Total	$	16,010	$	22,536

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2022

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, 2022 and 2021 are as follows (in thousands):


	December 31,
	2022			2021
U.K.	$	(156,000	)	$	(147,337	)
Non-U.K.		2,966			3,581
Net loss before taxes	$	(153,034	)	$	(143,756	)

Schedule of Provision for (Benefit from) Income Taxes

The provision for (benefit from) income taxes for the years ended December 31, 2022 and 2021 are as follows (in thousands):


	December 31,
	2022			2021
Current (benefit) provision
Federal—United States	$	618		$	(1,025	)
State—United States		144			334
Other foreign		147			388
United Kingdom		—			—
Total current (benefit) provision		909			(303	)
Deferred provision (benefit)
Federal—United States		(3,066	)		1,099
State—United States		(204	)		(312	)
United Kingdom		(13	)		—
Other foreign		—			344
Total deferred provision (benefit)		(3,283	)		1,131
Total provision (benefit) for income taxes	$	(2,374	)	$	828

Schedule of Reconciliation of Income Tax Expense (Benefit)


	December 31,
	2022			2021
Income taxes at United Kingdom statutory rate	$	(29,072	)	$	(27,313	)
Change in valuation allowance		34,333			59,691
Reduction in research expense for credits granted		1,805			6,674
Change in tax rates		(8,240	)		(38,785	)
Tax credits		(2,049	)		(2,232	)
U.S. Deduction for foreign derived intangible income		(1,489	)		(196	)
Permanent differences, including share-based compensation deduction shortfalls		2,387			2,863
U.S. state income taxes		(45	)		17
Foreign rate differential		(4	)		109
Total provision (benefit) for income taxes	$	(2,374	)	$	828

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, 2022 and 2021 (in thousands):


	December 31,
	2022			2021
Deferred tax assets
Net operating loss carryforwards	$	158,344		$	126,563
Amortization		11,215			25,206
Research and development credits		2,525			2,449
Capitalized research and development costs		2,285			—
Share-based compensation		9,282			9,353
Accruals		946			798
Lease liability		6,126			6,444
Property and equipment		—			1,022
Total deferred tax assets		190,723			171,835
Valuation allowance		(177,630	)		(161,573	)
Fixed assets and right-of-use asset		(5,724	)		(6,176	)
Other non-current assets (net deferred tax assets and liabilities)	$	7,369		$	4,086

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


	December 31,
	2022			2021
Valuation allowance as of beginning of year	$	(161,573	)	$	(103,890	)
Increases recorded to income tax provision		(34,248	)		(59,691	)
Effect of foreign currency translation		18,191			2,008
Valuation allowance as of end of year	$	(177,630	)	$	(161,573	)

Product Revenue, Net (Tables)

12 Months Ended

Dec. 31, 2022

Revenue from Contract with Customer [Abstract]

Disaggregated Product Revenue

The following table presents the Company's net revenue by product (in thousands):


	Year Ended December 31,
	2022		2021
Libmeldy	$	18,796	$	—
Strimvelis		1,814		700
Total	$	20,610	$	700

Summary of Net Product Revenue of Libmeldy by Geography

Net product revenue of Libmeldy by geography consisted of the following and is attributable to individual countries based on the location of the customer as of December 31, 2022 (in thousands):


	Year ended December 31, 2022
United Kingdom	$	6,322
Italy		5,544
France		3,883
Germany		3,047
Total Libmeldy revenue, net	$	18,796

Summary of Activity of Product Revenue Allowance and Reserve Categories

Activity in each of the product revenue allowance and reserve categories for Libmeldy is summarized as follows (in thousands):


	Trade Discounts and Allowances			Government rebates		Total
Balance as of December 31, 2021	$	—		$	—	$	—
Provision Related to sales in the current year		4,573			2,300		6,873
Credits and payments made during the period		(183	)		—		(183	)
Balance as of December 31, 2022	$	4,390		$	2,300	$	6,690

Summary as Components of Balance Sheets

The total reserves described above are summarized as components of the Company's consolidated balance sheets as follows (in thousands):


	December 31, 2022
Reduction of accounts receivable, net	$	4,390
Component of accrued expenses and other current liabilities		2,300
Balance as of December 31, 2022	$	6,690

Collaboration Revenue (Tables)

12 Months Ended

Dec. 31, 2022

Collaborative Arrangement [Abstract]

Summary of Research and Development Costs Incurred and Collaboration Revenue Recognized


	Year Ended December 31,
	2022		2021
Reimbursement revenue	$	1,776	$	843
Upfront and milestone payment revenue		269		132
Total	$	2,045	$	975

Commitments and Contingencies (Tables)

12 Months Ended

Dec. 31, 2022

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, 2022 (in thousands):


Due in:	Product manufacturing commitments (1)		Dedicated manufacturing and development resources (2)		Exclusive transduction suites (3)		Total AGC Commitment
2023	$	1,933	$	5,655	$	2,147	$	9,735
2024		1,933		5,655		2,147		9,735
2025		966		2,827		1,074		4,867
Total manufacturing commitments	$	4,832	$	14,137	$	5,368	$	24,337

The tabular disclosure above has been translated from Euros to U.S. Dollars using an exchange rate of €1.00 to $1.07.

(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 10 for further information on the embedded operating lease agreement

Nature of the Business and Liquidity - Additional Information (Details)				12 Months Ended
	Mar. 10, 2023 USD ($) shares	Mar. 06, 2023 £ / shares shares	Feb. 09, 2021 USD ($) shares	Dec. 31, 2022 USD ($) VotingRight	Dec. 31, 2021 USD ($)	Mar. 10, 2023 £ / shares shares	Mar. 10, 2023 $ / shares shares	Dec. 31, 2022 £ / shares	Dec. 31, 2022 USD ($)	Dec. 31, 2021 £ / shares	Feb. 09, 2021 £ / shares	Feb. 09, 2021 $ / shares
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Ordinary shares voting rights description				As of December 31, 2022, each holder of ordinary shares and ADSs is entitled to one vote per ordinary share
Number of ordinary voting rights \| VotingRight				1
Ordinary shares dividends declared				$ 0	$ 0
Nominal value of shares issued and sold \| £ / shares								£ 0.10		£ 0.10
Placement agent fees				$ 100,000	$ 6,355,000
Cash, cash equivalents and marketable securities									$ 143,800,000
Subsequent Event
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Number of ordinary shares issued and sold \| shares	56,666,900
Nominal value of shares issued and sold \| £ / shares						£ 0.10
Warrants to purchase ordinary shares \| shares						62,333,590	62,333,590
Warrants to purchase price per share \| $ / shares							$ 6.00
2023 Private Placement \| Subsequent Event
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Gross proceeds of offering	$ 34,000,000.0
Securities Purchase Agreement \| Private Placement
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Number of ordinary shares issued and sold \| shares			20,900,321
Nominal value of shares issued and sold \| £ / shares											£ 0.10
Purchase price per share \| $ / shares												$ 6.22
Closing price of share date			Feb. 04, 2021
Securities Purchase Agreement \| Private Placement \| Non-voting Ordinary Shares
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Number of ordinary shares issued and sold \| shares			3,215,434
Nominal value of shares issued and sold \| £ / shares											£ 0.10
Securities Purchase Agreement \| 2021 Private Placement
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Placement agent fees			$ 6,000,000.0
Other issuance costs			400,000
Net proceeds from private placement			$ 143,600,000
Securities Purchase Agreement \| 2023 Private Placement \| Subsequent Event
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Number of ordinary shares issued and sold \| shares		99,166,900
Nominal value of shares issued and sold \| £ / shares		£ 0.10
Warrants to purchase ordinary shares \| shares		109,083,590
Securities Purchase Agreement \| 2023 Private Placement \| Non-voting Ordinary Shares \| Subsequent Event
Organization Consolidation And Presentation Of Financial Statements [Line Items]
Nominal value of shares issued and sold \| £ / shares		£ 0.10

Summary of Significant Accounting Policies - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2018
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)	$ (24,300,000)	$ (1,200,000)
Outstanding letter of credit associated with a lease	3,000,000.0	3,000,000.0
Cash collateral associated with corporate credit cards and other leases	1,300,000	1,300,000
Credit losses related to outstanding accounts receivable	$ 0	0
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. 2021-10
Change in accounting principle, accounting standards update, immaterial effect	true
Property and equipment	$ 8,138,000	4,767,000
Right-of-use assets	$ 22,774,000	24,316,000
Minimum
Summary Of Significant Accounting Policies [Line Items]
General payment terms	30 days
Maximum
Summary Of Significant Accounting Policies [Line Items]
General payment terms	90 days
Strimvelis
Summary Of Significant Accounting Policies [Line Items]
Liability associated with the loss contract			$ 18,400,000
Strimvelis loss provision current		700,000
Strimvelis loss provision non current		2,700,000
Libmeldy \| Minimum
Summary Of Significant Accounting Policies [Line Items]
General payment terms	30 days
Libmeldy \| Maximum
Summary Of Significant Accounting Policies [Line Items]
General payment terms	1 year
United Kingdom
Summary Of Significant Accounting Policies [Line Items]
Property and equipment	$ 7,500,000	3,600,000
Right-of-use assets	11,600,000
US
Summary Of Significant Accounting Policies [Line Items]
Property and equipment	600,000	1,200,000
Right-of-use assets	$ 11,200,000	12,500,000
United Kingdom and European Union
Summary Of Significant Accounting Policies [Line Items]
Right-of-use assets		$ 11,800,000

Summary of Significant Accounting Policies - Schedule of Reconciliation of Cash, Cash Equivalents and Restricted Cash (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Summary Of Significant Accounting Policies [Abstract]
Cash and cash equivalents	$ 68,424	$ 55,912
Restricted cash	4,215	4,266
Total cash, cash equivalents and restricted cash shown in the statement of cash flows	$ 72,639	$ 60,178	$ 59,401

Summary of Significant Accounting Policies - Schedule of Estimated Useful Lives of Property and Equipment (Details)	12 Months Ended
	Dec. 31, 2022
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) - Strimvelis - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Asset Acquisition [Line Items]
Balance at beginning of period	$ 3,419	$ 4,482
Amortization of loss provision	(274)	(1,037)
Foreign currency translation	(326)	(26)
Balance at end of period	$ 2,819	$ 3,419

Summary of Significant Accounting Policies - Summary of Amounts recognized to Offset Research and Development Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Summary Of Significant Accounting Policies [Line Items]
Receipt of credit claims	$ (2,049)	$ (2,232)
Foreign currency translation	(24,300)	(1,200)
United Kingdom \| Research and Development Expense
Summary Of Significant Accounting Policies [Line Items]
Balance at beginning of period	30,723	17,344
Recognition of credit claims as offset to research and development expense	8,243	13,920
Receipt of credit claims	(30,811)
Foreign currency translation	(2,213)	(541)
Balance at end of period	$ 5,942	$ 30,723

Summary of Significant Accounting Policies - Securities Excluded in the Computation of Diluted Net Loss Per Ordinary Share (Details) - shares	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common shares attributable to anti-dilutive shares	15,330,158	14,555,689
Share options
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common shares attributable to anti-dilutive shares	13,076,959	14,042,781
Unvested Restricted Incentive Shares
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common shares attributable to anti-dilutive shares	2,253,199	512,908

Fair Value Measurements and Marketable Securities - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Fair Value Disclosures [Abstract]
Fair value of assets transfers between level 1 and level 2	$ 0	$ 0
Realized gains or losses recognized on investments	$ 0	$ 0

Fair Value Measurements and Marketable Securities - Schedule of Cash Equivalents and Marketable Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Cash equivalents
Total cash equivalents	$ 27,161	$ 41,604
Marketable securities
Total marketable securities	75,326	164,195
Total	102,487	205,799
Level 1
Cash equivalents
Total cash equivalents	1,239	21,085
Marketable securities
Total	1,239	21,085
Level 2
Cash equivalents
Total cash equivalents	25,922	20,519
Marketable securities
Total marketable securities	75,326	164,195
Total	101,248	184,714
Money Market Funds
Cash equivalents
Total cash equivalents	1,239	21,085
Money Market Funds \| Level 1
Cash equivalents
Total cash equivalents	1,239	21,085
Corporate Bonds
Marketable securities
Total marketable securities	25,475	94,794
Corporate Bonds \| Level 2
Marketable securities
Total marketable securities	25,475	94,794
Commercial Paper
Cash equivalents
Total cash equivalents	14,122	13,198
Marketable securities
Total marketable securities	47,867	69,401
Commercial Paper \| Level 2
Cash equivalents
Total cash equivalents	14,122	13,198
Marketable securities
Total marketable securities	47,867	69,401
U.S. Treasuries
Cash equivalents
Total cash equivalents	6,600
U.S. Treasuries \| Level 2
Cash equivalents
Total cash equivalents	6,600
U.S. Government Securities
Cash equivalents
Total cash equivalents	5,200	7,321
Marketable securities
Total marketable securities	1,984
U.S. Government Securities \| Level 2
Cash equivalents
Total cash equivalents	5,200	$ 7,321
Marketable securities
Total marketable securities	$ 1,984

Fair Value Measurements and Marketable Securities - Schedule of Amortized Cost and Fair Value of Available-for-Sale Marketable Debt Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	$ 101,481	$ 184,881
Gross Unrealized Gains	5
Gross Unrealized Losses	(238)	(167)
Fair Value	101,248	184,714
U.S. Government Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	7,188
Gross Unrealized Gains	1
Gross Unrealized Losses	(6)
Fair Value	7,183
U.S. Treasuries
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	6,599
Gross Unrealized Gains	1
Fair Value	6,600
Corporate Bonds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	25,656	102,224
Gross Unrealized Losses	(180)	(109)
Fair Value	25,476	102,115
Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	62,038	82,657
Gross Unrealized Gains	3
Gross Unrealized Losses	(52)	(58)
Fair Value	$ 61,989	$ 82,599

Fair Value Measurements and Marketable Securities - Schedule of Available-for-Sale Marketable Debt Securities by contractual Maturity (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Fair Value Disclosures [Abstract]
Maturities in one year or less	$ 98,277	$ 172,575
Maturities between one and three years	2,971	12,139
Total	$ 101,248	$ 184,714

Prepaid Expenses and Other Current Assets - Schedule of Prepaid Expenses and Other Current Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Prepaid Expense and Other Assets, Current [Abstract]
Prepaid external research and development expenses	$ 881	$ 2,438
Inventories	3,400	2,016
Other prepayments	1,817	6,128
VAT receivable	1,077	1,169
Construction deposit - current		7,909
Non-trade receivables	1,851	3,351
Rent deposits	960
Total prepaid expenses and other current assets	$ 9,986	$ 23,011

Property and Equipment - Schedule of Property and Equipment (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Property Plant And Equipment [Line Items]
Property and equipment	$ 14,929	$ 10,924
Less: accumulated depreciation	(6,791)	(6,157)
Property and equipment, net	8,138	4,767
Lab Equipment
Property Plant And Equipment [Line Items]
Property and equipment	6,722	5,937
Leasehold Improvements
Property Plant And Equipment [Line Items]
Property and equipment	5,069	2,450
Furniture and Fixtures
Property Plant And Equipment [Line Items]
Property and equipment	226	303
Office and Computer Equipment
Property Plant And Equipment [Line Items]
Property and equipment	2,153	2,023
Construction-In-Progress
Property Plant And Equipment [Line Items]
Property and equipment	$ 759	$ 211

Property and Equipment - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Property, Plant and Equipment [Abstract]
Depreciation expense	$ 2.4	$ 2.2

Intangible Assets, Net - Schedule of Intangible Assets Net of Accumulated Amortization (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Finite Lived Intangible Assets [Line Items]
Intangible Assets, Cost	$ 4,069	$ 4,329
Intangible Assets, Accumulated Amortized	(509)	(180)
Intangible Assets, Net	3,560	4,149
License Milestones
Finite Lived Intangible Assets [Line Items]
Intangible Assets, Cost	4,069	4,329
Intangible Assets, Accumulated Amortized	(509)	(180)
Intangible Assets, Net	$ 3,560	$ 4,149

Intangible Assets, Net - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Goodwill and Intangible Assets Disclosure [Abstract]
Intangible asset, useful life	12 years
Amortization of intangible assets	$ 0.3	$ 0.2
Effect of foreign currency translation on the net carrying value of intangible assets	$ 0.2

Intangible Assets, Net - Schedule of Estimated Future Amortization For Intangible Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Goodwill and Intangible Assets Disclosure [Abstract]
2023	$ 343
2024	343
2025	343
2026	343
2027	343
Thereafter	1,845
Intangible Assets, Net	$ 3,560	$ 4,149

Other Assets - Schedule of Other Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Other Assets, Noncurrent Disclosure [Abstract]
Deferred tax assets	$ 7,369	$ 4,086
Deposits	1,048	1,404
Deferred financing costs	462	693
Other non-current assets	3,196	3,407
Total other assets	$ 12,075	$ 9,590

Accrued Expenses and Other Liabilities - Schedule of Accrued Expenses and Other Current Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Accrued Liabilities and Other Liabilities [Abstract]
Accrued external research and development expenses	$ 11,230	$ 9,273
Accrued payroll and related expenses	12,312	8,521
Accrued milestone payments	85	2,058
Accrued professional fees	2,263	854
Accrued other	2,562	2,941
Accrued governmental rebates	2,300
Strimvelis liability - current portion	3,685	671
Total accrued expenses and other current liabilities	$ 34,437	$ 24,318

Restructuring Charges - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Restructuring Cost And Reserve [Line Items]
Research and development	$ 93,847,000	$ 86,977,000
Selling, general and administrative	49,125,000	54,905,000
Restructuring costs	2,481,000	$ 0
Neurometabolic Diseases and Early Research Programs
Restructuring Cost And Reserve [Line Items]
Research and development	1,400,000
Selling, general and administrative	300,000
Neurometabolic Diseases and Early Research Programs \| Employee-Related Termination Costs
Restructuring Cost And Reserve [Line Items]
One-time charge	$ 1,700,000

Restructuring Charges - Summary of Restructuring Charges (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Restructuring and Related Activities [Abstract]
Balance at beginning of period	$ 6,000
Charged to expense	2,481,000	$ 0
Non cash adjustments and foreign currency translation	(760,000)
Payments made	$ (1,727,000)
Balance at end of period		$ 6,000

Leases - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended						12 Months Ended
	Mar. 31, 2022	Jul. 31, 2021	Jul. 31, 2019	Dec. 31, 2018	Mar. 31, 2018	Jan. 31, 2018	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Operating Leases [Line Items]
Operating leases expiration term							Jul. 02, 2025
Sublease income							$ 2,820	$ 2,746
Operating lease right-of-use-assets							22,774	24,316
Operating lease liabilities							25,670
Outstanding letter of credit associated with a lease							3,000	3,000
Operating lease, liability, noncurrent							19,246	19,278
Operating lease, right-of-use asset obtained in exchange for lease liabilities							6,100	600
Rental Lab Space [Member]
Operating Leases [Line Items]
Annual rental payment							200	200
Ten Years Lease Term Expires In February 2032 [Member] \| Office Space London United Kingdom Lease Agreement [Member]
Operating Leases [Line Items]
Operating leases expiration term	Feb. 28, 2032
Lessee, operating Lease, existence of option to extend [true false]	false
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							1,700	1,800
Lessee, operating Lease, existence of option to extend [true false]				false		false
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							300	400
Sublease income							200	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							1,200	1,100
Operating leases Commenced term			Jan. 31, 2020
Lessee, operating Lease, existence of option to extend [true false]		false
Boston and London Office Space Lease Agreements [Member]
Operating Leases [Line Items]
Operating lease right-of-use-assets							8,100	4,100
Operating lease liabilities							8,700	4,300
Fremont Lease Agreement [Member]
Operating Leases [Line Items]
Operating leases expiration term				May 31, 2030
Annual rental payment							3,200	3,100
Operating lease duration for free rent				8 months
Operating lease right-of-use-assets							8,800
Reduction of standby letter of credit amount percentage				25.00%
Outstanding letter of credit associated with a lease				$ 3,000
Operating lease, liability, noncurrent							12,000
Fremont Lease Agreement [Member] \| Maximum [Member]
Operating Leases [Line Items]
Tenant improvements allowance							5,300
Fremont Sublease Agreement
Operating Leases [Line Items]
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]
Annual rental payment							2,500	3,100
Operating lease right-of-use-assets							5,800	10,700
Operating lease, liability, noncurrent							$ 5,300	$ 9,300
Operating lease term							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

Leases - Summary of Lease Cost Under Operating Leases (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Leases [Abstract]
Fixed lease cost	$ 7,693	$ 7,701
Variable lease cost	1,602	1,696
Sublease income	(2,820)	(2,746)
Total lease cost	6,475	6,651
Operating cash flows used for operating leases	$ 7,442	$ 7,989
Weighted-average remaining lease term (years)	6 years 6 months	6 years
Weighted-average discount rate	8.50%	8.70%

Leases - Schedule of Future Minimum Base Rent Commitments Under Operating Leases (Details) $ in Thousands	Dec. 31, 2022 USD ($)
Gross lease payments
2023	$ 6,517
2024	6,972
2025	6,035
2026	4,809
2027	3,774
Thereafter	12,266
Total future minimum lease payments	40,373
Less: imputed interest	(14,703)
Total operating lease payments	25,670
Gross sublease receipts
2023	(2,246)
2024	(2,313)
2025	(2,382)
2026	(2,454)
2027	(2,527)
Thereafter	(6,432)
Total future minimum lease payments	(18,354)
Net lease payments
2023	4,271
2024	4,659
2025	3,653
2026	2,355
2027	1,247
Thereafter	5,834
Total future minimum lease payments	$ 22,019

Notes Payable - Additional Information (Details) - USD ($)	1 Months Ended			12 Months Ended
	Jan. 31, 2023	May 31, 2021	May 31, 2019	Dec. 31, 2022	Dec. 31, 2021
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
Credit facility, remaining borrowings		$ 67,000,000.0
Line of credit facility interest payments term		18 months
Line of credit facility, frequency of payments				monthly payments
Line of credit facility, percentage of final payment		3.50%
Final payment amount		$ 1,200,000
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				$ 3,000,000.0	$ 2,500,000
Debt instrument, effective annual interest rate				9.20%	8.40%
LIBOR
Debt Instrument [Line Items]
Debt instrument, annual interest rate		5.95%
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
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
Subsequent Event [Member] \| Amended Credit Facility \| SOFR
Debt Instrument [Line Items]
Debt instrument, annual interest rate	5.95%
Line of credit facility, percentage of final payment	3.50%
Debt instrument, effective annual interest rate	0.10%

Notes Payable - Summary of Notes Payable (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Notes and Loans, Noncurrent [Abstract]
Notes payable, net of issuance costs	$ 31,970	$ 32,669
Less: current portion	(9,429)	(786)
Notes payable, net of current portion	22,541	31,883
Accretion related to final payment	450	203
Notes payable, long term	$ 22,991	$ 32,086

Notes Payable - Summary of Future Principal Payments and Final Payment Due (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Long-Term Debt, Fiscal Year Maturity [Abstract]
2023	$ 9,429
2024	9,429
2025	9,429
2026	5,084
Total	33,371
Less current portion	(9,429)
Less unamortized portion of final payment	(705)
Less unamortized debt issuance costs	(246)
Notes payable, long term	$ 22,991	$ 32,086

Share-based Compensation - Additional Information (Details) - USD ($) $ / shares in Units, $ in Thousands			1 Months Ended	12 Months Ended
	Oct. 04, 2022	Oct. 03, 2022	Apr. 30, 2020	Dec. 31, 2022	Dec. 31, 2021
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total intrinsic value of share options exercised				$ 400	$ 7,400
Exercise of share options, Shares				699,234
Weighted average grant date fair value of share options granted				$ 0.32	$ 3.10
Number of shares vested				55,001
Compensation cost recognized				$ 16,010	$ 22,536
Number of shares granted				2,192,988
Total unrecognized compensation cost of stock option and time-based RSUs				$ 14,000
Compensation cost expected to be recognized weighted average period				2 years 4 months 2 days
Total unrecognized compensation cost of performance-based RSUs				$ 1,400
Employees and Certain Independent Contractors
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Exercise of share options, Shares	7,946,139
Exercise price, lower limit	$ 0.58
Compensation cost recognized	$ 900
Incremental stock option expense related to unvested options	$ 800
Employees and Certain Independent Contractors \| Minimum
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Exercise price, upper limit		$ 1.25
Performance-based Restricted Share Units ("RSUs") \| Chief Executive Officer
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Number of shares vested				0
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
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				55,001
Number of shares granted				2,192,988
Total unrecognized compensation cost of stock option and time-based RSUs				$ 800
Compensation cost expected to be recognized weighted average period				1 year 11 months 15 days
Vested in period, total fair value				$ 300	$ 300
2018 Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Remaining shares available for issuance				5,341,768
2018 ESPP
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Remaining shares available for issuance				627,677
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, 2022	Dec. 31, 2021
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Risk-free interest rate, minimum	1.50%	0.50%
Risk-free interest rate, maximum	4.40%	1.30%
Expected volatility, minimum	74.40%	74.20%
Expected volatility, maximum	79.50%	78.70%
Expected dividend rate	0.00%	0.00%
Minimum
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expected term (in years)	2 years	5 years 3 months 18 days
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)	12 Months Ended
	Dec. 31, 2022 $ / shares shares
Share-Based Payment Arrangement [Abstract]
Number of Options, Outstanding at December 31, 2021	17,300,740
Number of Options, Granted	4,600,154
Number of Options, Exercised	(699,234)
Number of Options, Forfeited	(4,777,493)
Number of Options, Outstanding at December 31, 2022	16,424,167
Number of Options, Vested and expected to vest at December 31, 2022	16,424,167
Number of Options, Exercisable at of December 31, 2022	9,212,552
Weighted Average Exercise Price per Share, Outstanding at December 31, 2021 \| $ / shares	$ 6.57
Weighted Average Exercise Price per Share, Granted \| $ / shares	0.56
Weighted Average Exercise Price per Share, Forfeited \| $ / shares	6.81
Weighted Average Exercise Price per Share, Outstanding at December 31,2022 \| $ / shares	1.56
Weighted Average Exercise Price per Share, Vested and expected to vest at December 31, 2022 \| $ / shares	1.56
Weighted Average Exercise Price per Share, Exercisable at of December 31, 2022 \| $ / shares	$ 2.28
Weighted Average Remaining Contractual Life, Outstanding at December 31, 2022	7 years 4 months 17 days
Weighted Average Remaining Contractual Life, Vested and expected to vest at December 31, 2022	7 years 4 months 17 days
Weighted Average Remaining Contractual Life, Exercisable at of December 31, 2022	6 years 3 months 3 days

Share-based Compensation - Summary of Award Activity (Details)	12 Months Ended
	Dec. 31, 2022 $ / shares shares
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
RSUs, Unvested at December 31, 2021	318,333
RSUs, Granted	2,192,988
RSUs, Vested	(55,001)
RSUs, Forfeited	(392,444)
RSUs, Unvested at December 31, 2022	2,063,876
Weighted Average Grant Date Fair Value per share, Unvested at December 31, 2021 \| $ / shares	$ 6.41
Weighted Average Grant Date Fair Value per Share, Granted \| $ / shares	0.46
Weighted Average Grant Date Fair Value per share, Vested \| $ / shares	5.58
Weighted Average Grant Date Fair Value per share, Forfeited \| $ / shares	0.60
Weighted Average Grant Date Fair Value per Share, Unvested at December 31, 2022 \| $ / shares	$ 0.55
Performance-based RSUs
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
RSUs, Unvested at December 31, 2021	195,000
RSUs, Unvested at December 31, 2022	195,000
Time-based Restricted Share Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
RSUs, Unvested at December 31, 2021	123,333
RSUs, Granted	2,192,988
RSUs, Vested	(55,001)
RSUs, Forfeited	(392,444)
RSUs, Unvested at December 31, 2022	1,868,876

Share-based Compensation - Share-based Compensation Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Total share-based compensation	$ 16,010	$ 22,536
Restricted Share Units
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Total share-based compensation	838	550
Share options
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Total share-based compensation	15,172	21,986
Research and Development
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Total share-based compensation	6,791	9,214
Selling General and Administrative
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Total share-based compensation	$ 9,219	$ 13,322

License and Research Arrangements - Additional Information (Details) € in Millions	1 Months Ended				3 Months Ended	12 Months Ended
	Apr. 30, 2020 USD ($) shares	May 31, 2019 EUR (€)	May 31, 2019 USD ($)	Apr. 30, 2018 Program	Jun. 30, 2018 USD ($)	Dec. 31, 2022 GBP (£) Milestone	Dec. 31, 2022 USD ($) Milestone	Dec. 31, 2016 USD ($) shares	Dec. 31, 2022 EUR (€) shares	Dec. 31, 2022 GBP (£) shares	Dec. 31, 2022 USD ($) shares	Dec. 31, 2021 shares	Dec. 31, 2018 shares	Nov. 30, 2018 shares	Sep. 30, 2018 shares	Dec. 31, 2017 shares
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Ordinary shares issued \| shares									126,947,225	126,947,225	126,947,225	125,674,095
GSK Asset Purchase and License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Number of additional programs in preclinical development \| Program				3
Number of late-stage clinical gene therapy programs \| Program				2
Number of earlier stage clinical gene therapy program \| Program				1
Number of additional earlier-stage development programs \| Program				3
Total consideration					$ 133,600,000
Payment of tiered royalty, maximum percentage									20.00%	20.00%	20.00%
Milestone payments payable upon achievement of certain sales milestones \| £										£ 90,000,000.0
Telethon-OSR License Agreements
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments payable upon achievement of certain sales milestones									€ 31.0		$ 33,400,000
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, including the Hurler variant (“MPS-IH”). Under the terms of the agreement, Telethon-OSR received €15.0 million ($16.1 million at December 31, 2022) in upfront and milestone payments from the Company upon entering into the agreement, resulting in $17.2 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, including the Hurler variant (“MPS-IH”). Under the terms of the agreement, Telethon-OSR received €15.0 million ($16.1 million at December 31, 2022) in upfront and milestone payments from the Company upon entering into the agreement, resulting in $17.2 million in in-process research and development expense.
Upfront and milestone payments		€ 15.0					$ 16,100,000
In-process research and development expense for upfront and milestone payments			$ 17,200,000
Milestone payments payable upon achievement of certain development regulatory and commercial milestones									€ 28.0		$ 30,100,000
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								3,441,290					4,665,384			1,224,094
UCLB/UCLA License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Payments upon achievement of specified regulatory milestones						£ 19,900,000	$ 24,100,000
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			150,826	150,826
Number of milestones met \| Milestone						0	0
Oxford BioMedica License, Development and Supply Agreement \| Research and Development Expense
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payment	$ 800,000

Income Taxes - Schedule of Components of Net Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
U.K.	$ (156,000)	$ (147,337)
Non-U.K.	2,966	3,581
Net loss before income tax	$ (153,034)	$ (143,756)

- Definition

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

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
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Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 30
-Subparagraph (b)
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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-Section 50
-Paragraph 32
-Subparagraph (f)
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Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef
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-Section 25
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Reference 5: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
-Topic 280
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Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 220
-SubTopic 10
-Section S99
-Paragraph 2
-Subparagraph (SX 210.5-03(10))
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Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef
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-Subparagraph (SX 210.7-04(8))
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Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 942
-SubTopic 235
-Section S99
-Paragraph 1
-Subparagraph (SX 210.9-05(b)(2))
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Reference 9: http://www.xbrl.org/2003/role/exampleRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
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Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 942
-SubTopic 220
-Section S99
-Paragraph 1
-Subparagraph (SX 210.9-04(15))
-URI https://asc.fasb.org/extlink&oid=120399700&loc=SL114874048-224260

+ Details

Income Taxes - Schedule of Provision for (Benefit from) Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Current (benefit) provision
Federal—United States	$ 618	$ (1,025)
State—United States	144	334
Other foreign	147	388
Total current (benefit) provision	909	(303)
Deferred provision (benefit)
Federal—United States	(3,066)	1,099
State—United States	(204)	(312)
United Kingdom	(13)
Other foreign		344
Total deferred provision (benefit)	(3,283)	1,131
Total provision (benefit) for income taxes	$ (2,374)	$ 828

Income Taxes - Schedule of Reconciliation of Income Tax Expense (Benefit) (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Income taxes at United Kingdom statutory rate	$ (29,072)	$ (27,313)
Change in valuation allowance	34,333	59,691
Reduction in research expense for credits granted	1,805	6,674
Change in tax rates	(8,240)	(38,785)
Tax credits	(2,049)	(2,232)
U.S. Deduction for foreign derived intangible income	(1,489)	(196)
Permanent differences, including share-based compensation deduction shortfalls	2,387	2,863
U.S. state income taxes	(45)	17
Foreign rate differential	(4)	109
Total provision (benefit) for income taxes	$ (2,374)	$ 828

Income Taxes - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
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	2018
Latest Tax Year
Operating Loss Carryforwards [Line Items]
Income tax year open to examination	2022
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	$ 633,400,000	506,200,000
US \| Federal \| Orphan Drug
Operating Loss Carryforwards [Line Items]
Tax credits carryforward, amount	700,000	600,000
US \| State \| Research and Development
Operating Loss Carryforwards [Line Items]
Tax credits carryforward, amount	$ 2,200,000	$ 2,400,000
Tax credit carryforward expiration year	2042

Income Taxes - Schedule of Deferred Tax Assets and Liabilities Taxes (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Deferred tax assets
Net operating loss carryforwards	$ 158,344	$ 126,563
Amortization	11,215	25,206
Research and development credits	2,525	2,449
Capitalized research and development costs	2,285
Share-based compensation	9,282	9,353
Accruals	946	798
Lease liability	6,126	6,444
Property and equipment		1,022
Total deferred tax assets	190,723	171,835
Valuation allowance	(177,630)	(161,573)	$ (103,890)
Fixed assets and right-of-use asset	(5,724)	(6,176)
Other non-current assets (net deferred tax assets and liabilities)	$ 7,369	$ 4,086

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, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Valuation allowance as of beginning of year	$ (161,573)	$ (103,890)
Increases recorded to income tax provision	(34,248)	(59,691)
Effect of foreign currency translation	18,191	2,008
Valuation allowance as of end of year	$ (177,630)	$ (161,573)

Product Revenue, Net - Schedule of Net Revenue by Product (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Disaggregation of Revenue [Line Items]
Total revenues	$ 22,655	$ 1,675
Libmeldy
Disaggregation of Revenue [Line Items]
Total revenues	18,796
Strimvelis
Disaggregation of Revenue [Line Items]
Total revenues	1,814	700
Product
Disaggregation of Revenue [Line Items]
Total revenues	$ 20,610	$ 700

- 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.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 30
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8906-108599

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 40
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e9031-108599

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 41
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e9038-108599

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8933-108599

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8933-108599

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 4
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130543-203045

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 22
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8736-108599

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 22
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8736-108599

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 42
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e9054-108599

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 5
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130545-203045

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 924
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SAB Topic 11.L)
-URI https://asc.fasb.org/extlink&oid=6472922&loc=d3e499488-122856

+ Details

Product Revenue, Net - Summary of Net Product Revenue of Libmeldy by Geography (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Disaggregation of Revenue [Line Items]
Total revenues	$ 22,655	$ 1,675
Libmeldy
Disaggregation of Revenue [Line Items]
Total revenues	18,796
United Kingdom \| Libmeldy
Disaggregation of Revenue [Line Items]
Total revenues	6,322
Italy \| Libmeldy
Disaggregation of Revenue [Line Items]
Total revenues	5,544
France \| Libmeldy
Disaggregation of Revenue [Line Items]
Total revenues	3,883
Germany \| Libmeldy
Disaggregation of Revenue [Line Items]
Total revenues	$ 3,047

- Definition

+ References

+ Details

Product Revenue, Net - Summary of Activity of Product Revenue Allowance and Reserve Categories (Details)	12 Months Ended
	Dec. 31, 2022 USD ($)
SEC Schedule, 12-09, Valuation and Qualifying Accounts Disclosure [Line Items]
Balance as of December 31, 2021	$ 0
Provision Related to sales in the current year	6,873,000
Credits and payments made during the period	(183,000)
Balance as of December 31, 2022	6,690,000
Trade Discounts and Allowances
SEC Schedule, 12-09, Valuation and Qualifying Accounts Disclosure [Line Items]
Provision Related to sales in the current year	4,573,000
Credits and payments made during the period	(183,000)
Balance as of December 31, 2022	4,390,000
Government Rebates
SEC Schedule, 12-09, Valuation and Qualifying Accounts Disclosure [Line Items]
Provision Related to sales in the current year	2,300,000
Balance as of December 31, 2022	$ 2,300,000

Product Revenue, Net - Summary as Components of Balance Sheets (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2022 USD ($)
SEC Schedule, 12-09, Valuation and Qualifying Accounts [Abstract]
Reduction of accounts receivable, net	$ 4,390
Component of accrued expenses and other current liabilities	2,300
Balance as of December 31, 2022	$ 6,690

Product Revenue, Net - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Revenue from Contract with Customer [Abstract]
Reserves or revenue allowances	$ 6,690,000	$ 0
Trade discount and allowance	$ 0	$ 0

Collaboration Revenue - Additional Information (Details) - USD ($) $ in Thousands		12 Months Ended
	Jul. 01, 2021	Dec. 31, 2021	Dec. 31, 2022
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total consideration		$ 143,645
Strategic Collaboration Agreement with Pharming
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Cash upfront payment received	$ 10,000
Strategic Collaboration Agreement with Pharming \| Maximum
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments receivable	189,500
Share Purchase Agreement with Pharming
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total consideration	$ 7,500
Issuance of ordinary shares	1,227,738
Common stock consideration	$ 4,100
Premium consideration	3,400
Pharming Agreements
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total upfront payments	17,500
Upfront payments attributed to equity sold	4,100
Upfront payments attributed to research activities	13,400
Estimated reimbursement payments	$ 13,400
Collaborative Arrangement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Contract liabilities			$ 11,300
Contract liabilities current			1,000
Contract liabilities non current			10,300
Collaborative Arrangement \| Accounts Receivable
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Accounts receivable		$ 800	$ 500

Collaboration Revenue - Summary of Research and Development Costs Incurred and Collaboration Revenue Recognized (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total revenues	$ 22,655	$ 1,675
Collaborative Arrangement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total revenues	2,045	975
Collaborative Arrangement \| Reimbursement Revenue
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total revenues	1,776	843
Collaborative Arrangement \| Upfront and Milestone Payment Revenue
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Total revenues	$ 269	$ 132

- Definition

+ References

+ Details

Commitments and Contingencies - Schedule of Annual Commitments Associated with the Contract (Details) $ in Thousands	Dec. 31, 2022 USD ($)
Other Commitments [Line Items]
2023	$ 9,735
2024	9,735
2025	4,867
Total manufacturing commitments	24,337
Product Manufacturing Commitments
Other Commitments [Line Items]
2023	1,933
2024	1,933
2025	966
Total manufacturing commitments	4,832
Dedicated Manufacturing and Development Resources
Other Commitments [Line Items]
2023	5,655
2024	5,655
2025	2,827
Total manufacturing commitments	14,137
Exclusive Transduction Suites
Other Commitments [Line Items]
2023	2,147
2024	2,147
2025	1,074
Total manufacturing commitments	$ 5,368

Commitments and Contingencies - Schedule of Annual Commitments Associated with the Contract (Parenthetical) (Details)	Dec. 31, 2022
Commitments and Contingencies Disclosure [Abstract]
Exchange rate, Euro to U.S. Dollar	1.07

Commitments and Contingencies - Additional Information (Details) - Agreement - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Other Commitments [Line Items]
Initial term of agreement	5 years
Agreement maturity date	Jul. 02, 2025
Agreement extension term	2 years
Master agreement	$ 13.7	$ 16.4

Benefit Plans - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Retirement Benefits [Abstract]
Maximum annual contribution employer matches per employee, percent	6.00%
Contribution expenses	$ 1.6	$ 1.7

Subsequent Events - Additional Information (Details) $ / shares in Units, $ in Millions				12 Months Ended
	Mar. 10, 2023 USD ($) shares	Mar. 06, 2023 USD ($) shares	Feb. 09, 2021 £ / shares shares	Dec. 31, 2022 £ / shares	Jan. 01, 2025 $ / shares	Dec. 31, 2024 $ / shares	Mar. 10, 2023 £ / shares shares	Mar. 10, 2023 $ / shares shares	Mar. 06, 2023 £ / shares shares	Mar. 06, 2023 $ / shares shares	Dec. 31, 2021 £ / shares
Subsequent Event [Line Items]
Ordinary shares, nominal value \| £ / shares				£ 0.10							£ 0.10
Private Placement \| Securities Purchase Agreement
Subsequent Event [Line Items]
Sale of voting and non-voting ordinary shares, net of issuance costs, Shares			20,900,321
Ordinary shares, nominal value \| £ / shares			£ 0.10
Private Placement \| Securities Purchase Agreement \| Non-voting Ordinary Shares
Subsequent Event [Line Items]
Sale of voting and non-voting ordinary shares, net of issuance costs, Shares			3,215,434
Ordinary shares, nominal value \| £ / shares			£ 0.10
Scenario Forecast \| 2023 Private Placement
Subsequent Event [Line Items]
Warrants to purchase price per share \| $ / shares					$ 0.95	$ 1.10
Warrants exercisable term						30 days
Subsequent Event
Subsequent Event [Line Items]
Ratio change, reverse stock split description	On February 10, 2023, the Company announced that the Company's Board of Directors approved a change to the ratio of the Company's ADSs to ordinary shares (the "ADS Ratio") from the previous ADS Ratio of one ADS to one ordinary share to a new ADS Ratio of one ADS to ten ordinary shares. The ratio change became effective on March 10, 2023. The change in the ADS Ratio had the same effect as a one-for-ten reverse ADS split and is intended to enable the Company to regain compliance with the Nasdaq minimum bid price requirement. As all financial statement and disclosure information is presented in ordinary share amounts, not ADSs, there was no impact to the consolidated financial statements and footnote disclosures.
Sale of voting and non-voting ordinary shares, net of issuance costs, Shares	56,666,900
Ordinary shares, nominal value \| £ / shares							£ 0.10
Warrants to purchase ordinary shares							62,333,590	62,333,590
Warrants to purchase price per share \| $ / shares								$ 6.00
Subsequent Event \| 2023 Private Placement
Subsequent Event [Line Items]
Gross proceeds of offering \| $	$ 34.0
Shares sold in fixed combinaton of warrants as units		The 2023 Private Placement consists of two closings. The Company agreed to sell and issue in the initial closing of the 2023 Private Placement (i) 56,666,900 Shares and (ii) Warrants to purchase an aggregate of 62,333,590 Shares, at a purchase price of $6.00 per unit, where each unit consists of ten (10) Shares and an accompanying Warrant to purchase eleven (11) Shares. The initial closing of the 2023 Private Placement occurred on March 10, 2023. The Company received gross proceeds of approximately $34.0 million from the initial closing of the 2023 Private Placement, before deducting fees to the placement agent and other offering expenses payable by the Company.
Warrants expiration, description		The Warrants will expire at the conclusion of the 30-day exercise period or, if the Vesting Event does not occur, March 10, 2026.
Subsequent Event \| 2023 Private Placement \| Securities Purchase Agreement
Subsequent Event [Line Items]
Sale of voting and non-voting ordinary shares, net of issuance costs, Shares		99,166,900
Ordinary shares, nominal value \| £ / shares									£ 0.10
Warrants to purchase ordinary shares									109,083,590	109,083,590
Subsequent Event \| 2023 Private Placement \| Securities Purchase Agreement \| Non-voting Ordinary Shares
Subsequent Event [Line Items]
Ordinary shares, nominal value \| £ / shares									£ 0.10
Subsequent Event \| Initial Closing \| 2023 Private Placement \| Securities Purchase Agreement
Subsequent Event [Line Items]
Sale of voting and non-voting ordinary shares, net of issuance costs, Shares	56,666,900
Warrants to purchase ordinary shares							62,333,590	62,333,590
Warrants to purchase price per share \| $ / shares								$ 6.00
Gross proceeds of offering \| $	$ 34.0
Subsequent Event \| Second Closing \| 2023 Private Placement \| Securities Purchase Agreement
Subsequent Event [Line Items]
Sale of voting and non-voting ordinary shares, net of issuance costs, Shares		42,500,000
Warrants to purchase ordinary shares									46,750,000	46,750,000
Warrants to purchase price per share \| $ / shares										$ 8.00
Gross proceeds of offering \| $		$ 34.0
ADS
Subsequent Event [Line Items]
Current ADS ratio				1
ADS \| Subsequent Event
Subsequent Event [Line Items]
Current ADS ratio	0.1