Bicycle Therapeutics (BCYC) 10-Q 2 Nov 23 2023 Q3 Quarterly report Financial data

Document and Entity Information

Document and Entity Information - shares	9 Months Ended
	Sep. 30, 2023	Oct. 30, 2023
Document Information [Line Items]
Document Type	10-Q
Document Quarterly Report	true
Document Period End Date	Sep. 30, 2023
Document Transition Report	false
Entity File Number	001-38916
Entity Registrant Name	Bicycle Therapeutics plc
Entity Incorporation, State or Country Code	X0
Entity Tax Identification Number	00-0000000
Entity Address, Address Line One	Blocks A & B, Portway Building, Granta Park
Entity Address, City or Town	Great Abington, Cambridge,
Entity Address, Country	GB
Entity Address, Postal Zip Code	CB21 6GS
City Area Code	+44
Local Phone Number	1223 261503
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Filer Category	Non-accelerated Filer
Entity Small Business	true
Entity Emerging Growth Company	false
Entity Shell Company	false
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2023
Document Fiscal Period Focus	Q3
Entity Central Index Key	0001761612
Amendment Flag	false
Ordinary Shares
Document Information [Line Items]
Title of 12(b) Security	Ordinary shares, nominal value £0.01 per share*
No Trading Symbol Flag	true
Security Exchange Name	NASDAQ
Entity Common Stock, Shares Outstanding		37,715,666
American Depositary Shares
Document Information [Line Items]
Title of 12(b) Security	American Depositary Shares, each representing one ordinary share, nominal value £0.01 per share
Trading Symbol	BCYC
Security Exchange Name	NASDAQ
Non-voting ordinary shares
Document Information [Line Items]
Entity Common Stock, Shares Outstanding		4,705,882

Condensed Consolidated Balance

Condensed Consolidated Balance Sheets - USD ($)	Sep. 30, 2023	Dec. 31, 2022
Current assets:
Cash and cash equivalents	$ 572,086,000	$ 339,154,000
Accounts receivable	0	2,045,000
Prepaid expenses and other current assets	13,673,000	9,022,000
Research and development incentives receivable	17,277,000	19,162,000
Total current assets	603,036,000	369,383,000
Property and equipment, net	15,599,000	19,110,000
Operating lease right-of-use assets	14,597,000	13,658,000
Other assets	5,451,000	8,458,000
Total assets	638,683,000	410,609,000
Current liabilities:
Accounts payable	8,493,000	6,472,000
Accrued expenses and other current liabilities	34,053,000	26,452,000
Deferred revenue, current portion	27,190,000	20,418,000
Total current liabilities	69,736,000	53,342,000
Long-term debt, net of discount	30,604,000	30,315,000
Operating lease liabilities, net of current portion	10,423,000	10,885,000
Deferred revenue, net of current portion	107,582,000	41,455,000
Other longterm liabilities	4,316,000	3,829,000
Total liabilities	222,661,000	139,826,000
Commitments and contingencies (Note 11)
Shareholders' equity:
Ordinary shares including non-voting shares, £0.01 nominal value; 59,612,613 and 57,820,181 shares authorized at September 30, 2023 and December 31, 2022, respectively; 42,384,799 and 29,873,893 shares issued and outstanding at September 30, 2023 and December 31, 2022, respectively	550,000	387,000
Additional paid-in capital	875,248,000	601,105,000
Accumulated other comprehensive income	2,885,000	387,000
Accumulated deficit	(462,661,000)	(331,096,000)
Total shareholders' equity	416,022,000	270,783,000
Total liabilities and shareholders' equity	$ 638,683,000	$ 410,609,000

Condensed Consolidated Balanc_2

Condensed Consolidated Balance Sheets (Parenthetical) - £ / shares	Sep. 30, 2023	Dec. 31, 2022
Condensed Consolidated Balance Sheets
Ordinary shares, nominal value	£ 0.01	£ 0.01
Ordinary shares, shares authorized	59,612,613	57,820,181
Ordinary shares, shares issued	42,384,799	29,873,893
Ordinary shares, shares outstanding	42,384,799	29,873,893

Condensed Consolidated Statemen

Condensed Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Consolidated Statements of Operations and Comprehensive Loss
Collaboration revenues	$ 5,352	$ 3,040	$ 21,645	$ 11,278
Operating expenses:
Research and development	39,868	22,752	111,799	56,890
General and administrative	16,281	10,047	45,557	38,830
Total operating expenses	56,149	32,799	157,356	95,720
Loss from operations	(50,797)	(29,759)	(135,711)	(84,442)
Other income (expense):
Interest income	3,985	1,991	7,726	3,117
Interest expense	(814)	(817)	(2,443)	(2,518)
Total other income (expense), net	3,171	1,174	5,283	599
Net loss before income tax provision	(47,626)	(28,585)	(130,428)	(83,843)
Provision for (benefit from) income taxes	2,272	(238)	1,137	(1,104)
Net loss	$ (49,898)	$ (28,347)	$ (131,565)	$ (82,739)
Net loss per share, basic	$ (1.26)	$ (0.96)	$ (3.95)	$ (2.79)
Net loss per share, diluted	$ (1.26)	$ (0.96)	$ (3.95)	$ (2.79)
Weighted average ordinary shares outstanding, basic	39,576,467	29,676,021	33,291,701	29,643,502
Weighted average ordinary shares outstanding, diluted	39,576,467	29,676,021	33,291,701	29,643,502
Comprehensives loss:
Net loss	$ (49,898)	$ (28,347)	$ (131,565)	$ (82,739)
Other comprehensive income:
Foreign currency translation adjustment	3,762	902	2,498	3,916
Total comprehensive loss	$ (46,136)	$ (27,445)	$ (129,067)	$ (78,823)

Condensed Consolidated Statem_2

Condensed Consolidated Statements of Shareholders' Equity - USD ($) $ in Thousands	Ordinary Shares	Additional Paid-in Capital	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit	Total
Beginning balance at Dec. 31, 2021	$ 384	$ 567,637	$ (3,388)	$ (218,379)	$ 346,254
Beginning balance (in shares) at Dec. 31, 2021	29,579,364
Increase (decrease) in shareholders' equity (deficit)
Issuance of ADSs upon exercise of share options	$ 1	449			450
Issuance of ADSs upon exercise of share options (in shares)	30,074
Issuance of ADSs upon vesting of restricted share units (in shares)	35,000
Share-based compensation expense		10,198			10,198
Foreign currency translation adjustment			920		920
Net loss				(27,564)	(27,564)
Ending balance at Mar. 31, 2022	$ 385	578,284	(2,468)	(245,943)	330,258
Ending balance (in shares) at Mar. 31, 2022	29,644,438
Beginning balance at Dec. 31, 2021	$ 384	567,637	(3,388)	(218,379)	346,254
Beginning balance (in shares) at Dec. 31, 2021	29,579,364
Increase (decrease) in shareholders' equity (deficit)
Foreign currency translation adjustment					3,916
Net loss					(82,739)
Ending balance at Sep. 30, 2022	$ 385	589,679	528	(301,118)	289,474
Ending balance (in shares) at Sep. 30, 2022	29,678,431
Beginning balance at Mar. 31, 2022	$ 385	578,284	(2,468)	(245,943)	330,258
Beginning balance (in shares) at Mar. 31, 2022	29,644,438
Increase (decrease) in shareholders' equity (deficit)
Issuance of ADSs upon exercise of share options		195			195
Issuance of ADSs upon exercise of share options (in shares)	21,879
Share-based compensation expense		5,673			5,673
Foreign currency translation adjustment			2,094		2,094
Net loss				(26,828)	(26,828)
Ending balance at Jun. 30, 2022	$ 385	584,152	(374)	(272,771)	311,392
Ending balance (in shares) at Jun. 30, 2022	29,666,317
Increase (decrease) in shareholders' equity (deficit)
Issuance of ADSs upon exercise of share options		159			159
Issuance of ADSs upon exercise of share options (in shares)	12,114
Share-based compensation expense		5,368			5,368
Foreign currency translation adjustment			902		902
Net loss				(28,347)	(28,347)
Ending balance at Sep. 30, 2022	$ 385	589,679	528	(301,118)	289,474
Ending balance (in shares) at Sep. 30, 2022	29,678,431
Beginning balance at Dec. 31, 2022	$ 387	601,105	387	(331,096)	$ 270,783
Beginning balance (in shares) at Dec. 31, 2022	29,873,893				29,873,893
Increase (decrease) in shareholders' equity (deficit)
Issuance of ADSs upon exercise of share options		1			$ 1
Issuance of ADSs upon exercise of share options (in shares)	877
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses	$ 1	2,715			2,716
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses (in shares)	100,000
Issuance of ADSs upon vesting of restricted share units	$ 1				1
Issuance of ADSs upon vesting of restricted share units (in shares)	56,988
Share-based compensation expense		9,042			9,042
Foreign currency translation adjustment			(316)		(316)
Net loss				(39,064)	(39,064)
Ending balance at Mar. 31, 2023	$ 389	612,863	71	(370,160)	243,163
Ending balance (in shares) at Mar. 31, 2023	30,031,758
Beginning balance at Dec. 31, 2022	$ 387	601,105	387	(331,096)	$ 270,783
Beginning balance (in shares) at Dec. 31, 2022	29,873,893				29,873,893
Increase (decrease) in shareholders' equity (deficit)
Foreign currency translation adjustment					$ 2,498
Net loss					(131,565)
Ending balance at Sep. 30, 2023	$ 550	875,248	2,885	(462,661)	$ 416,022
Ending balance (in shares) at Sep. 30, 2023	42,384,799				42,384,799
Beginning balance at Mar. 31, 2023	$ 389	612,863	71	(370,160)	$ 243,163
Beginning balance (in shares) at Mar. 31, 2023	30,031,758
Increase (decrease) in shareholders' equity (deficit)
Issuance of ADSs upon exercise of share options		165			165
Issuance of ADSs upon exercise of share options (in shares)	12,389
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses	$ 7	12,120			12,127
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses (in shares)	520,000
Issuance of ADSs upon vesting of restricted share units (in shares)	21,793
Share-based compensation expense		8,193			8,193
Foreign currency translation adjustment			(948)		(948)
Net loss				(42,603)	(42,603)
Ending balance at Jun. 30, 2023	$ 396	633,341	(877)	(412,763)	220,097
Ending balance (in shares) at Jun. 30, 2023	30,585,940
Increase (decrease) in shareholders' equity (deficit)
Issuance of ADSs upon exercise of share options		139			139
Issuance of ADSs upon exercise of share options (in shares)	13,296
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses	$ 154	234,338			234,492
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses (in shares)	11,764,706
Issuance of ADSs upon vesting of restricted share units (in shares)	20,857
Share-based compensation expense		7,430			7,430
Foreign currency translation adjustment			3,762		3,762
Net loss				(49,898)	(49,898)
Ending balance at Sep. 30, 2023	$ 550	$ 875,248	$ 2,885	$ (462,661)	$ 416,022
Ending balance (in shares) at Sep. 30, 2023	42,384,799				42,384,799

Condensed Consolidated Statem_3

Condensed Consolidated Statements of Shareholders' Equity (Parenthetical) - USD ($) $ in Millions	3 Months Ended
	Sep. 30, 2023	Jun. 30, 2023	Mar. 31, 2023
Condensed Consolidated Statements of Shareholders' Equity
Offering expenses	$ 15.5	$ 0.4	$ 0.1

Condensed Consolidated Statem_4

Condensed Consolidated Statements of Cash Flows $ in Thousands	9 Months Ended
	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)
Cash flows from operating activities:
Net loss	$ (131,565)	$ (82,739)
Adjustments to reconcile net loss to net cash used in operating activities:
Share-based compensation expense	24,665	21,239
Depreciation and amortization	4,892	2,303
Non-cash interest	289	359
Deferred income tax provision (benefit)	3,588	(2,640)
Changes in operating assets and liabilities:
Accounts receivable	2,482	348
Research and development incentives receivable	2,192	(3,064)
Prepaid expenses and other assets	(4,615)	(2,137)
Operating lease rightofuse assets	3,116	2,015
Accounts payable	3,835	4,931
Accrued expenses and other current liabilities	6,084	5,495
Operating lease liabilities	(2,983)	(1,446)
Deferred revenue	74,238	(969)
Other long-term liabilities	442	503
Net cash used in operating activities	(13,340)	(55,802)
Cash flows from investing activities:
Purchases of property and equipment	(2,878)	(17,539)
Net cash used in investing activities	(2,878)	(17,539)
Cash flows from financing activities:
Proceeds from the issuance of ADSs, and non-voting ordinary shares, net of issuance costs	249,335
Proceeds from the exercise of share options and sale of ordinary shares	306	804
Net cash provided by financing activities	249,641	804
Effect of exchange rate changes on cash, cash equivalents and restricted cash	57	(4,674)
Net increase (decrease) in cash, cash equivalents and restricted cash	233,480	(77,211)
Cash, cash equivalents and restricted cash at beginning of period	339,154	438,680
Cash, cash equivalents and restricted cash at end of period	572,634	361,469
Reconciliation of cash, cash equivalents and restricted cash
Cash and cash equivalents	572,086	361,469
Restricted cash included in other assets	548
Total cash, cash equivalents and restricted cash	572,634	361,469
Supplemental disclosure of cash flow information
Cash paid for interest	2,059	2,099
Cash paid for income taxes	664	1,203
Cash paid for amounts included in the measurement of operating lease liabilities	4,188	2,245
Changes in purchases of property and equipment in accounts payable and accrued expenses	(1,689)	318
Non-cash impact right-of-use asset and operating lease liabilities	$ 3,898	$ 3,120

Nature of the business and basi

Nature of the business and basis of presentation	9 Months Ended
	Sep. 30, 2023
Nature of the business and basis of presentation
Nature of the business and basis of presentation	Bicycle Therapeutics plc Notes to Condensed Consolidated Financial Statements (Unaudited) 1. Nature of the business and basis of presentation Bicycle Therapeutics plc (collectively with its subsidiaries, the “Company”) is a clinical-stage biopharmaceutical company developing a novel class of medicines, which the Company refers to as Bicycles Bicycles Bicycle ® TM Bicycle ® Bicycle TM Bicycle Bicycle The accompanying condensed consolidated financial statements include the accounts of Bicycle Therapeutics plc and its wholly owned subsidiaries, BicycleTx Limited, BicycleRD Limited and Bicycle Therapeutics Inc. All intercompany balances and transactions have been eliminated on consolidation. The accompanying condensed consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“GAAP”). The Company has reclassified the deferred income tax benefit within its condensed consolidated statements of cash flows in prior periods to conform to current period presentation. Liquidity As of September 30, 2023, the Company had cash and cash equivalents of $572.1 million. The accompanying condensed consolidated financial statements have been prepared on the basis of continuity of operations, realization of assets and the satisfaction of liabilities and commitments in the ordinary course of business. Since inception, the Company has devoted substantially all of its efforts to business planning, research and development, recruiting management and technical staff, and raising capital. The Company has funded its operations primarily with proceeds from the sale of its ordinary shares, non-voting ordinary shares, convertible preferred shares and American Depositary Shares (“ADSs”), including offerings pursuant to its at-the-market offering program (“ATM”), proceeds received from its collaboration arrangements (Note 9) and borrowings from the Loan Agreement with Hercules Capital, Inc. (“Hercules”) (Note 6). On July 17, 2023, the Company completed an underwritten public offering of its securities, pursuant to which it issued and sold ​ On June 5, 2020, the Company entered into a Sales Agreement (the “Sales Agreement”) with Cantor Fitzgerald & Co. and Oppenheimer & Co. Inc. (the “Sales Agents”) with respect to an ATM program pursuant to which the Company may offer and sell through the Sales Agents, from time to time at the Company’s sole discretion, ADSs, each ADS representing one ordinary share. During the three and nine months ended September 30, 2023, the Company issued and sold 941,176 and 1,561,176 ADSs, respectively, representing the same number of ordinary shares, for gross proceeds of $20.0 million and $35.3 million, respectively, resulting in net proceeds of $19.4 million and $34.2 million, respectively, after deducting sales commissions and offering expenses of $0.6 million and $1.1 million, respectively. No ADSs were issued or sold pursuant to the Sales Agreement during the three or nine months ended September 30, 2022. ​ The Company has incurred recurring losses since inception, including net losses of $49.9 million and $131.6 million for the three and nine months ended September 30, 2023, respectively, and $28.3 million and $82.7 million for the three and nine months ended September 30, 2022, respectively. As of September 30, 2023, the Company had an accumulated deficit of $462.7 million. The Company expects to continue to generate operating losses in the foreseeable future. The Company expects that its cash will be sufficient to fund its operating expenses and capital expenditure requirements through at least twelve months from the issuance date of these interim condensed consolidated financial statements. The Company expects its expenses to increase substantially in connection with ongoing activities, particularly as the Company advances its preclinical activities and clinical trials for its product candidates in development. Accordingly, the Company will need to obtain additional funding in connection with continuing operations. If the Company is unable to raise funding when needed, or on attractive terms, it could be forced to delay, reduce or eliminate its research or drug development programs or any future commercialization efforts. 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. The Company is subject to risks common to companies in the biotechnology industry, including but not limited to, risks of delays in initiating or continuing research programs and clinical trials, risks of failure of preclinical studies and clinical trials, the need to obtain marketing approval for any drug product candidate that it may identify and develop, the need to successfully commercialize and gain market acceptance of its product candidates, if approved, dependence on key personnel and collaboration partners, protection of proprietary technology, compliance with government regulations, development by competitors of technological innovations, and the ability to secure additional capital to fund operations. Product candidates currently under development will require significant additional research and development efforts, including preclinical and clinical testing and regulatory approval prior to commercialization. Even if the Company’s research and development efforts are successful, it is uncertain when, if ever, the Company will realize significant revenue from product sales.

Summary of significant accounti

Summary of significant accounting policies	9 Months Ended
	Sep. 30, 2023
Summary of significant accounting policies
Summary of significant accounting policies	2. Summary of significant accounting policies The Company’s significant accounting policies are disclosed in the audited consolidated financial statements for the year ended December 31, 2022 included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, which was filed with the Securities and Exchange Commission (the “SEC”), on February 28, 2023 (the “2022 Annual Report”). Since the date of such consolidated financial statements, there have been no changes to the Company’s significant accounting policies, other than those disclosed below. Use of estimates The preparation of condensed consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of the condensed consolidated financial statements and the reported amounts of expenses during the reporting periods. Significant estimates and assumptions reflected in these condensed consolidated financial statements include, but are not limited to, the accrual for research and development expenses, revenue recognition, share-based compensation expense, valuation of right-of-use assets and liabilities, and income taxes, including the valuation allowance for deferred tax assets. The Company bases its estimates on historical experience, known trends and other market-specific or other relevant factors that it believes to be reasonable under the circumstances. Estimates are periodically reviewed in light of reasonable changes in circumstances, facts and experience. Changes in estimates are recorded in the period in which they become known. Actual results could differ from those estimates or assumptions. Significant risks and uncertainties The Company currently operates in a period of economic uncertainty which has been significantly impacted by the global health crises, domestic and global monetary and fiscal policy, bank failures, geopolitical conflicts such as the ongoing wars in Ukraine and Israel, rising inflation and interest rates, and fluctuations in monetary exchange rates. While the Company has experienced limited financial impacts at this time, the Company continues to monitor these factors and events and the potential effects each may have on the Company’s business, financial condition, results of operations and growth prospects. Unaudited interim financial information Certain information in the footnote disclosures of these financial statements has been condensed or omitted pursuant to the rules and regulations of the SEC. These unaudited condensed consolidated financial statements should be read in conjunction with the Company’s audited consolidated financial statements and notes thereto for the year ended December 31, 2022 included in the Company’s 2022 Annual Report. The accompanying condensed consolidated balance sheet as of September 30, 2023, condensed consolidated statements of operations and comprehensive loss and condensed consolidated statements of shareholders’ equity for the three and nine months ended September 30, 2023 and 2022, and condensed consolidated statements of cash flows for the nine months ended September 30, 2023 and 2022, and the related financial information disclosed in these notes are unaudited. The unaudited interim financial statements have been prepared on the same basis as the audited annual financial statements for the year ended December 31, 2022, and, in the opinion of management, reflect all adjustments, consisting of normal recurring adjustments, necessary for the fair statement of the Company’s financial position as of September 30, 2023, the results of its operations for the three and nine months ended September 30, 2023 and 2022, and its cash flows for the nine months ended September 30, 2023 and 2022. The results for the three and nine months ended September 30, 2023 are not necessarily indicative of the results to be expected for the year ending December 31, 2023, any other interim periods, or any future year or period. Accounts receivable Recently adopted accounting pronouncements There have been no recent accounting pronouncements, changes in accounting pronouncements or recently adopted accounting guidance during the three and nine months ended September 30, 2023, that are of significance or potential significance to the Company. ​

Fair value of financial assets

Fair value of financial assets and liabilities	9 Months Ended
	Sep. 30, 2023
Fair value of financial assets and liabilities
Fair value of financial assets and liabilities	3. Fair value of financial assets and liabilities 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, Quoted prices in active markets for identical assets or liabilities; Level 2, Observable inputs (other than Level 1 quoted prices), such as quoted prices in active markets for similar assets or liabilities, quoted prices in markets that are not active for identical or similar assets or liabilities, or other inputs that are observable or can be corroborated by observable market data; Level 3, unobservable inputs that are supported by little or no market activity that are significant to determining the fair value of the assets or liabilities, including pricing models, discounted cash flow methodologies and similar techniques. The carrying values of cash and cash equivalents, accounts receivable, research and development incentives receivable, prepaid expenses other current assets, accounts payable and accrued expenses and other current liabilities approximate their fair values due to the short-term nature of these assets and liabilities. As of September 30, 2023, and December 31, 2022, the carrying value of the long-term debt approximates its fair value, which was determined using unobservable Level 3 inputs, including quoted interest rates from a lender for borrowings with similar terms. As of September 30, 2023, and December 31, 2022, there were no assets or liabilities measured at fair value on a recurring basis. Cash, cash equivalents and restricted cash The Company considers all highly liquid investments that are readily convertible to known amounts of cash with original maturities of three months or less at the date of purchase to be cash equivalents. As of September 30, 2023 and December 31, 2022, the Company’s cash equivalents included interest-bearing money market funds and 30-day term deposits, which are considered Level 1 assets. The Company had $63.4 million and $276.1 million of cash equivalents as of September 30, 2023 and December 31, 2022, respectively. As of September 30, 2023, the Company had $0.5 million of restricted cash related to a collateralized letter of credit in connection with the Company’s lease for office and laboratory space in Cambridge, Massachusetts, which is included within other assets in the Company’s condensed consolidated balance sheet.

Property and equipment, net

Property and equipment, net	9 Months Ended
	Sep. 30, 2023
Property and equipment, net
Property and equipment, net	4. Property and equipment, net Property and equipment, net consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ December 31, ​ 2023 2022 Laboratory equipment ​ $ 15,087 ​ $ 14,872 Leasehold improvements ​ 10,547 ​ 10,736 Computer equipment and software ​ 537 ​ 441 Furniture and office equipment ​ 823 ​ 924 ​ ​ 26,994 ​ 26,973 Less: Accumulated depreciation and amortization ​ (11,395) ​ (7,863) ​ ​ $ 15,599 ​ $ 19,110 ​ As of September 30, 2023, property and equipment not yet placed in service was immaterial. As of December 31, 2022, approximately $2.3 million of laboratory equipment was not yet placed in service. Depreciation expense was $1.7 million and $4.9 million for the three and nine months ended September 30, 2023, respectively, and $1.3 million and $2.2 million for the three and nine months ended September 30, 2022, respectively.

Accrued expenses and other curr

Accrued expenses and other current liabilities	9 Months Ended
	Sep. 30, 2023
Accrued expenses and other current liabilities
Accrued expenses and other current liabilities	5. Accrued expenses and other current liabilities Accrued expenses and other current liabilities consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ December 31, ​ 2023 2022 Accrued employee compensation and benefits ​ $ 9,760 ​ $ 9,928 Accrued external research and development expenses ​ 18,010 ​ 10,859 Accrued professional fees ​ 1,319 ​ 1,068 Current portion of operating lease liabilities ​ 4,661 ​ 3,125 Other ​ 303 ​ 1,472 ​ ​ $ 34,053 ​ $ 26,452 ​

Long-term debt

Long-term debt	9 Months Ended
	Sep. 30, 2023
Long-term debt
Long-term debt	6. Long-term debt On September 30, 2020 (the “Closing Date”), Bicycle Therapeutics plc and its subsidiaries (the “Borrowers”) entered into a loan and security agreement (the “Loan Agreement”) with Hercules, which provided for aggregate maximum borrowings of up to $40.0 million, consisting of (i) a term loan of $15.0 million, which was funded on the Closing Date, (ii) subject to customary conditions, an additional term loan of up to $15.0 million available from the Closing Date through March 15, 2021, and (iii) subject to the Borrowers achieving certain performance milestones and satisfying customary conditions and available until March 15, 2022, an additional term loan of $10.0 million. ​ On March 10, 2021 (“the Amendment Closing Date”), the Borrowers entered into the First Amendment to the Loan and Security Agreement (the “First Amendment to LSA”) with Hercules, in its capacity as administrative agent and collateral agent, and the lenders named in the First Amendment to LSA. Pursuant to the First Amendment to LSA, payments on borrowings under the Company’s debt facility with Hercules were interest-only until the first payment was due on August 1, 2023, which date was extended from November 1, 2022, followed by equal monthly payments of principal and interest through the scheduled maturity date on October 1, 2024 (the “Maturity Date”). If the Company achieved certain performance milestones, the interest-only period could be extended, with the first principal payment due on February 1, 2024, which date was extended from May 1, 2023. On the Amendment Closing Date and pursuant to the terms of the First Amendment to LSA, the Company borrowed the additional term loan of $15.0 million that had been available from September 30, 2020 to March 15, 2021. In November 2021, the performance milestones were achieved, and the interest only period was extended until February 1, 2024. On March 15, 2022, the additional term loan of $10.0 million expired unexercised. ​ On July 15, 2022, the Borrowers entered into the Second Amendment to the Loan and Security Agreement (the “Second Amendment to LSA”) with Hercules. Pursuant to the Second Amendment to LSA, the rate at which the borrowings under the Loan Agreement bear interest was decreased and capped. Under the Second Amendment to LSA, interest is paid at an annual rate of the Wall Street Journal prime rate plus 4.55% , with a minimum annual rate of at least 8.05% , capped at a rate no greater than 9.05% . In addition, among other amendments, the Second Amendment to LSA extended the interest-only period to April 1, 2025, extended the Maturity Date to July 1, 2025, and provided the Borrowers, at their request, the potential for additional term loans, subject to satisfaction of customary conditions, in an aggregate principal amount of up to $45.0 million, and as such the aggregate maximum borrowings under the Loan Agreement increased to $75.0 million. ​ At the Borrowers’ option, the Borrowers may prepay all or any portion greater than $5.0 million of the outstanding borrowings, subject to a prepayment premium equal to (i) 1.5% of the principal amount outstanding if the prepayment occurs after the first anniversary of the Closing Date but on or prior to December 31, 2023, and (ii) 1.0% of the principal amount outstanding if the prepayment occurs thereafter but prior to the Maturity Date. The Loan Agreement also provides for an end of term charge (the “End of Term Charge”), payable upon maturity or the repayment of obligations under the Loan Agreement, equal to 5.0% of the principal amount repaid. Borrowings under the Loan Agreement are collateralized by substantially all of the Borrower’s personal property and other assets, other than their intellectual property. Hercules has a perfected first-priority security interest in certain cash accounts. The Loan Agreement contains customary affirmative and restrictive covenants and representations and warranties, including a covenant against the occurrence of a change in control, as defined in the agreement. There are no financial covenants. The Loan Agreement also includes customary events of default, including payment defaults, breaches of covenants following any applicable cure period, cross acceleration to third-party indebtedness, certain events relating to bankruptcy or insolvency, and the occurrence of certain events that could reasonably be expected to have a material adverse effect. Upon the occurrence of an event of default, a default interest rate of an additional ​ The Company incurred fees and transaction costs totaling $0.6 million associated with the initial term loan, which are recorded as a reduction to the carrying value of the long-term debt in the condensed consolidated balance sheets. The fees, transaction costs, and the End of Term Charge are amortized to interest expense through the Maturity Date using the effective interest method. The Company evaluated the First Amendment to LSA and the Second Amendment to LSA and concluded that these amendments represent modifications to the Loan Agreement, and as such, the fees and transaction costs associated with term loan will continue to be amortized to interest expense through the Maturity Date. The effective interest rate of the Hercules borrowings was 10.8% at September 30, 2023. ​ The Company assessed all terms and features of the Loan Agreement in order to identify any potential embedded features that would require bifurcation. As part of this analysis, the Company assessed the economic characteristics and risks of the debt. The Company determined that all features of the Loan Agreement are clearly and closely associated with a debt host and, as such, do not require separate accounting as a derivative liability. Interest expense associated with the Loan Agreement for the three and nine months ended September 30, 2023 was $0.8 million and $2.3 million, respectively, and for the three and nine months ended September 30, 2022, was $0.8 million and $2.5 million, respectively. ​ Long-term debt consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ December 31, ​ 2023 2022 Term loan payable ​ $ 30,000 ​ $ 30,000 End of term charge ​ ​ 881 ​ ​ 682 Unamortized debt issuance costs ​ ​ (277) ​ ​ (367) Carrying value of term loan ​ $ 30,604 ​ $ 30,315 ​ ​ Future principal payments, including the End of Term Charge, are as follows (in thousands): ​ ​ ​ ​ ​ Year Ending December 31, ​ ​ 2023 ​ $ — 2024 ​ ​ — 2025 ​ ​ 31,500 Total ​ $ 31,500 ​

Ordinary shares

Ordinary shares	9 Months Ended
	Sep. 30, 2023
Ordinary shares.
Ordinary shares	​ The Company’s ordinary shares are divided into two classes: (i) ordinary shares and (ii) non-voting ordinary shares. Each holder of ordinary shares 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. Holders of ADSs are not treated as holders of the Company’s ordinary shares, unless they withdraw the ordinary shares underlying their ADSs in accordance with the deposit agreement and applicable laws and regulations. The depositary is the holder of the ordinary shares underlying the ADSs. Holders of ADSs therefore do not have any rights as holders of the Company’s ordinary shares, other than the rights that they have pursuant to the deposit agreement with the depositary. The non-voting ordinary shares have the same rights and restrictions as the ordinary shares and otherwise rank pari passu ● a holder of non-voting ordinary shares shall, in relation to the non-voting ordinary shares held, have no right to receive notice of, or to attend or vote at, any general meeting of shareholders save in relation to a variation of class rights of the non-voting ordinary shares; ● the non-voting ordinary shares shall be re-designated as ordinary shares by the Company’s board of directors, or a duly authorized committee or representative thereof, upon receipt of a re-designation notice and otherwise subject to the terms and conditions set out in the terms of issue. A holder of non-voting ordinary shares shall not be entitled to have any non-voting ordinary shares re-designated as ordinary shares where such re-designation would result in such holder thereof beneficially owning (for purposes of section 13(d) of the Exchange Act), when aggregated with “affiliates” and “group” members with whom such holder is required to aggregate beneficial ownership for the purposes of section 13(d) of the Exchange Act, in excess of 9.99% of any class of the Company’s securities registered under the Exchange Act (which percentage may be increased or decreased on a holder-by-holder basis subject to the provisions set out in the terms of issue); and ● the non-voting ordinary shares shall be re-designated as ordinary shares automatically upon transfer of a non-voting ordinary share by its holder to any person that is not an “affiliate” or “group” member with whom such holder is required to aggregate beneficial ownership for purposes of section 13(d) of the Exchange Act. This automatic re-designation shall only be in respect of the non-voting ordinary shares that are subject to such transfer. As of September 30, 2023, and December 31, 2022, the Company had not declared any dividends. As of September 30, 2023, and December 31, 2022, the Company’s authorized share capital consisted of 59,612,613 and 57,820,181 ordinary shares, respectively, including ordinary shares and non-voting ordinary shares, with a nominal value of £0.01 per share. Authorized share capital, or shares authorized, comprises (i) the currently issued and outstanding ordinary shares and non-voting ordinary shares, (ii) the remaining ordinary shares available for allotment under the existing authority granted to the Board at the annual general meeting held on June 28, 2021, (iii) ordinary shares issuable on the exercise of outstanding options and (iv) ordinary shares reserved for issuance under the Bicycle Therapeutics plc 2020 Equity Incentive Plan and/or the Bicycle Therapeutics plc 2019 Employee Share Purchase Plan. ​ As of September 30, 2023, there were 37,678,917 ordinary shares issued outstanding ​

Share-based compensation

Share-based compensation	9 Months Ended
	Sep. 30, 2023
Share-based compensation
Share-based compensation	8. Share-based compensation Employee incentive pool 2020 Equity Incentive Plan In June 2020, the Company’s shareholders first approved the Bicycle Therapeutics plc 2020 Equity Incentive Plan with Non-Employee Sub-Plan (the “2020 Plan”), under which the Company may grant market value options, market value stock appreciation rights or restricted shares, restricted share units (“RSUs”), performance RSUs and other share-based awards to the Company’s employees. The Company’s non-employee directors and consultants are eligible to receive awards under the 2020 Non-Employee Sub-Plan to the 2020 Plan. All awards under the 2020 Plan, including the 2020 Non-Employee Sub-Plan, will be set forth in award agreements, which will detail the terms and conditions of awards, including any applicable vesting and payment terms, change of control provisions and post-termination exercise limitations. In the event of a change of control of the Company, as defined in the 2020 Plan, any outstanding awards under the 2020 Plan will vest in full immediately prior to such change of control. The Company initially reserved up to 4,773,557 ordinary shares for future issuance under the 2020 Plan, representing 574,679 new shares, 544,866 shares that remained available for future issuance under the Company’s 2019 Share Option Plan (the “2019 Plan”) immediately prior to the effectiveness of the 2020 Plan and up to 3,654,012 shares subject to options that were granted under the 2019 Plan and that were granted pursuant to option contracts granted prior to the Company’s IPO, in each case that expire, terminate, are forfeited or otherwise not issued from time to time, if any. On June 27, 2022, the Company’s shareholders approved an amendment to the 2020 Plan (the “Amendment”) which increased the number of ordinary shares reserved for future issuance by 750,000 shares. Additionally, the number of ordinary shares reserved for issuance pursuant to the 2020 Plan will automatically increase on the first day of January of each year, initially commencing on January 1, 2021, in an amount equal to 5% of the total number of the Company’s ordinary shares outstanding on the last day of the preceding year, or a lesser number of shares determined by the Company’s board of directors. Pursuant to this “evergreen” provision, on January 1, 2023, the number of shares reserved for issuance under the 2020 Plan was increased by 1,493,694 shares. The Amendment extended the final date upon which an “evergreen” increase may occur under this provision from January 1, 2030, to January 1, 2032. As of September 30, 2023, there were 889,257 shares available for issuance. Share options issued under the 2020 Plan have a 10-year The Company grants RSUs to non-employee directors and certain employees under the 2020 Plan. Each RSU represents the right to receive one of the Company’s ordinary shares upon vesting. RSUs granted to employees vest over a four-year service period with 25% of the award vesting on the first anniversary of the vesting commencement date and the remaining RSUs vest in 12 equal quarterly installments. Certain RSUs granted to the Company’s non-employee directors either vest immediately upon grant or over a one-year service period in four equal quarterly installments. As of September 30, 2023, there were options to purchase 4,620,330 shares and RSUs for 335,104 shares outstanding under the 2020 Plan. 2019 Share Option Plan In May 2019, the Company adopted the 2019 Plan, which became effective in conjunction with the IPO. As of September 30, 2023, there were Share options previously issued under the 2019 Plan have a 10-year Employee Share Purchase Plan In May 2019, the Company adopted the 2019 Employee Stock Purchase Plan (the “ESPP”), which became effective in conjunction with the IPO. The Company initially reserved 215,000 ordinary shares for future issuance under this plan. The ESPP provides that the number of shares reserved and available for issuance will automatically increase each January 1, beginning on January 1, 2020 and each January 1 thereafter through January 1, 2029, by the lower of: (i) 1% of the outstanding number of ordinary shares on the immediately preceding December 31; (ii) 430,000 ordinary shares or (iii) such lesser number of shares as determined by the Compensation Committee. The number of shares reserved under the ESPP is subject to adjustment in the event of a split-up, share dividend or other change in the Company’s capitalization. The number of shares reserved for issuance under the ESPP was increased by 298,738 shares effective January 1, 2023. As of September 30, 2023, the total number of shares available for issuance under the ESPP was 1,200,413 ordinary shares. As of September 30, 2023, there have been no offering periods to employees under ESPP. Share-based compensation The Company recorded share-based compensation expense in the following expense categories of its condensed consolidated statements of operations and comprehensive loss (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ Nine Months Ended ​ ​ September 30, ​ September 30, ​ 2023 2022 2023 2022 Research and development expenses ​ $ 3,357 ​ $ 2,637 ​ $ 11,941 ​ $ 7,643 General and administrative expenses ​ 4,073 ​ 2,731 ​ 12,724 ​ 13,596 ​ ​ $ 7,430 ​ $ 5,368 ​ $ 24,665 ​ $ 21,239 ​ Share options The following table summarizes the Company’s option activity since December 31, 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Number of ​ ​ ​ ​ Weighted ​ ​ ​ ​ ​ Shares ​ Weighted ​ Average ​ Aggregate ​ ​ Underlying ​ Average ​ Contractual ​ Intrinsic ​ Share Options Exercise Price Term Value ​ ​ ​ ​ ​ ​ ​ (in years) ​ (in thousands) Outstanding as of December 31, 2022 5,898,888 ​ $ 22.45 7.64 ​ $ 71,002 Granted 1,859,315 ​ 27.57 — ​ — Exercised (26,562) ​ 11.42 — ​ — Forfeited (419,621) ​ 30.69 — ​ — Outstanding as of September 30, 2023 7,312,020 ​ $ 23.32 6.99 ​ $ 29,629 Vested and expected to vest as of September 30, 2023 7,312,020 ​ $ 23.32 ​ 6.99 ​ $ 29,629 Options exercisable as of September 30, 2023 4,334,755 ​ $ 18.39 5.75 ​ $ 28,069 ​ The weighted average grant-date fair value of share options granted during the nine months ended September 30, 2023 and 2022 was $20.16 per share and $32.91 per share, respectively. The aggregate intrinsic value of share options is calculated as the difference between the exercise price of the share options and the fair value of the Company’s ordinary shares. The aggregate intrinsic value of share options exercised was $0.1 million and $0.3 million for the three and nine months ended September 30, 2023, respectively and was $0.1 million and $1.3 million for the three and nine months ended September 30, 2022, respectively. Total share-based compensation expense for share options granted was $6.3 million and $20.5 million for the three and nine months ended September 30, 2023, respectively, and was $4.7 million and $17.1 million for the three and nine months ended September 30, 2022, respectively. Expense for non-employee consultants for the three and nine months ended September 30, 2023 and 2022 was immaterial. The following table presents, on a weighted average basis, the assumptions used in the Black-Scholes option-pricing model to determine the fair value of share options granted to employees and directors: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ Nine Months Ended ​ ​ September 30, ​ ​ September 30, ​ 2023 2022 ​ 2023 2022 Risk-free interest rate 4.1 % 3.0 % ​ 3.9 % 2.0 % Expected volatility 83.3 % 84.1 % ​ 83.5 % 82.2 % Expected dividend yield — — ​ — — ​ Expected term (in years) 6.1 6.1 ​ 6.1 6.0 ​ ​ As of September 30, 2023, total unrecognized compensation expense related to the unvested employee and director share options was $58.6 million, which is expected to be recognized over a weighted average period of 2.7 years. Restricted share units The following table summarizes the Company’s RSU activity under the 2020 Plan since December 31, 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ Number of Shares ​ Weighted-Average ​ ​ Underlying RSUs ​ Grant Date Fair Value Unvested at December 31, 2022 ​ 187,725 ​ $ 60.86 Granted ​ 321,839 ​ ​ 29.59 Vested ​ (99,638) ​ ​ 51.39 Forfeited ​ (74,822) ​ ​ 39.55 Unvested at September 30, 2023 ​ 335,104 ​ $ 38.40 ​ The fair value of RSUs that vested during the three and nine months ended September 30, 2023, was $0.5 million and $2.6 million, respectively, and for the three and nine months ended September 30, 2022, was zero and $2.1 million, respectively. Total share-based compensation expense for RSUs granted was $1.2 million and $4.2 million for the three and nine months ended September 30, 2023, respectively, and was $0.7 million and $4.1 million for the three and nine months ended September 30, 2022, respectively. As of September 30, 2023, the total unrecognized compensation expense related to unvested RSUs was $11.0 million, which is expected to be recognized over a weighted-average period of 2.7 years.

Significant agreements

Significant agreements	9 Months Ended
	Sep. 30, 2023
Significant agreements
Significant agreements	9. Significant agreements For the three and nine months ended September 30, 2023 and 2022, the Company recognized revenue for its collaborations with Bayer Consumer Care AG (“Bayer”), Novartis Pharma AG (“Novartis”), Ionis Pharmaceuticals, Inc. (“Ionis”), Genentech, Inc. (“Genentech”), the Dementia Discovery Fund (“DDF”), and AstraZeneca AB (“AstraZeneca”). The following table summarizes the revenue recognized in the Company’s condensed consolidated statements of operations and comprehensive loss from these arrangements (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months ​ Nine Months ​ ​ Ended ​ Ended ​ ​ September 30, ​ September 30, ​ 2023 2022 2023 2022 Collaboration revenues ​ ​ ​ ​ Bayer ​ $ 434 ​ $ — ​ $ 434 ​ $ — Novartis ​ ​ 772 ​ ​ — ​ ​ 772 ​ ​ — Ionis ​ ​ 2,782 ​ ​ 2,195 ​ ​ 8,123 ​ ​ 6,764 Genentech ​ ​ 1,364 ​ ​ 798 ​ ​ 11,112 ​ ​ 3,144 Dementia Discovery Fund ​ — ​ 47 ​ — ​ 205 AstraZeneca ​ ​ — ​ ​ — ​ ​ 1,204 ​ ​ 1,165 Total collaboration revenues ​ $ 5,352 ​ $ 3,040 ​ $ 21,645 ​ $ 11,278 ​ Bayer Collaboration Agreement On May 4, 2023, the Company and Bayer entered into a collaboration and license agreement (the “Bayer Collaboration Agreement”), pursuant to which the parties will perform research and discovery activities under a mutually agreed upon research plan during a research term up to a specified number of years per target program to generate radiopharmaceutical compounds incorporating optimized Bicycle under the oversight of a joint research committee. In addition, Bayer has a one-time right to expand the collaboration to include a third target program, and with respect to each of the up to three target programs, Bayer has an option, exercisable within a specified period of time following the effective date of the Bayer Collaboration Agreement, to generate, develop and commercialize non-radiopharmaceutical compounds directed to the applicable target, either itself or in collaboration with the Company. Bayer also has certain limited target substitution rights, in certain cases subject to specified additional payments. For each collaboration program, Bayer may elect, at its sole discretion, to progress compounds arising from activities under the research programs into further preclinical development of potential products directed to the target of such collaboration program. On a target-by-target basis, if Bayer elects to progress development candidates directed to such target into further clinical development, Bayer will be required to use commercially reasonable efforts to develop and seek regulatory approval in certain major markets for products directed to the applicable target. Bayer agreed to pay an upfront payment to the Company of $45.0 million, which was received in July 2023. All other payments under the Bayer Collaboration Agreement will be made in British Pound Sterling. If Bayer elects to expand the collaboration to include an additional target program, it will be required to make a one-time payment to the Company in connection with the selection of such target in the high single digit millions. In addition, on a target-by-target basis, if Bayer elects to exercise its option to expand its rights with respect to such target to develop and commercialize non-radiopharmaceutical compounds directed to such target, Bayer will be required to pay to the Company, for each such target program for which it exercises such option, either a one-time option fee payment or quarterly payments of specified installment amounts for a specified maximum time period during which the Company is performing research activities, with the aggregate amounts receivable by the Company ranging from the high single digit millions in the case of the one-time option fee payment, to the low single digit millions in the case of the quarterly installments, in each case where the Company is performing specified research activities following the exercise of the option. Additionally, for each collaboration program, Bayer will reimburse the Company for certain expenses incurred in connection with specified research and discovery activities performed by a contract research organization (“CRO”). On a target-by-target basis for the up to three targets, if Bayer elects to progress one or more candidate compounds into further development, Bayer will be required to pay a candidate selection fee for the first such compound progressed by Bayer directed to such target that incorporates a radionuclide, and for the first such compound directed to such target that does not incorporate a radionuclide (and for which Bayer has not paid the one-time option fee payment for non-radiopharmaceutical compounds), ranging from high single-digit millions to the mid single-digit millions. On a target-by-target basis, if Bayer successfully conducts clinical development and achieves regulatory approval for compounds arising from the collaboration directed to such target in two indications, Bayer will be required to pay to the Company development and regulatory/first commercial sale milestones of up to £178.3 million for the first product directed to the applicable target to achieve such milestones (whether radiopharmaceutical or non-radiopharmaceutical), or £534.9 million across all three potential target programs. In addition, if Bayer successfully commercializes products arising from the collaboration, Bayer will be required to pay to the Company, on a product-by-product basis, tiered royalties on net sales of products by Bayer, its affiliates or sublicensees at percentages ranging from the mid-single digits to the very low double digits, subject to standard reductions and offsets in certain circumstances, and a royalty floor. If Bayer commercializes diagnostic products directed to a target, royalties will be payable on such diagnostic products at a specified reduced percentage of the rates for therapeutic products. Royalties will be payable under the Bayer Collaboration Agreement on a product-by-product and country-by-country basis, commencing on the first commercial sale of each product, until the latest of (a) the expiration of the last valid claim of certain patents licensed by the Company to Bayer, (b) a specified number of years following first commercial sale of such product, and (c) expiration of all data and regulatory exclusivity for such product in the applicable country. On a target-by-target basis, Bayer will also owe the Company tiered sales milestones based on the achievement of specified levels of net sales of therapeutic products directed to such target totaling up to £194.5 million in the aggregate per target, or £583.5 million across all three potential target programs, and on diagnostic products directed to such target at a low double digit percentage of the therapeutic product milestones. The Bayer Collaboration Agreement will remain in force on a product-by-product and country-by-country basis, unless earlier terminated by either party, until the expiration of the obligation for Bayer to make royalty payments to the Company for such product in such country, and will terminate in its entirety on the expiration of all such royalty terms in all countries. Either party may terminate the agreement upon 90 days’ written notice for the other party’s uncured material breach (or 20 business days in the case of non-payment by Bayer), subject to extension of such cure period in certain circumstances, or upon the other party’s insolvency. In addition, the Company has the right to terminate in the case of a patent challenge by or on behalf of Bayer (or any of its affiliates or sublicensees). In addition, Bayer may terminate the Bayer Collaboration Agreement (i) in its entirety or with respect to any product, collaboration program or target for any reason upon 60 or 90 days’ written notice to the Company (depending on whether such termination is prior to or following first commercial sale of a licensed product). The closing of the Bayer Collaboration Agreement was subject to the clearance of the transaction under the U.K. National Security and Investment Act 2021, which occurred on June 22, 2023 (the “Effective Date”). Accounting Analysis (i) Two combined performance obligations comprised of the license and the related research and development services during the research term associated with radiopharmaceutical compounds for the first and second targets; (ii) A material right associated with certain limited substitution rights with respect to either the first or second target; (iii) Two material rights associated with the option to progress radiopharmaceutical candidates directed to the first and second targets into further development; (iv) Two material rights associated with the options to generate, develop, and commercialize non-radiopharmaceutical compounds for each of the first and second targets, for which each option includes an underlying option for research and development services and an option to progress non-radiopharmaceutical candidates directed to the first and second targets into further development; and (v) A material right related to the option to expand the collaboration to include a third target, which upon exercise includes research and development services during the research term associated with radiopharmaceutical compounds directed to the third target, as well as underlying options for: certain limited substitution rights; an option to progress a radiopharmaceutical candidate directed to the third target into further development; and an option to generate, develop, and commercialize non-radiopharmaceutical compounds directed to the third target, inclusive of an underlying option for research and development services and an option to progress a non-radiopharmaceutical candidate into further development. The Company’s participation in the joint research committee was assessed as immaterial in the context of the contract. The Company concluded that the license granted at contract inception is not distinct from the research and development services as Bayer cannot obtain the benefit of the license without the Company performing the research and development services. The services incorporate proprietary technology and unique skills and specialized expertise, particularly as they relate to constrained peptide technology that is not available in the marketplace. As a result, for each target, the license has been combined with the research and development services into a single performance obligation which is the combined performance obligation comprised of the license and related research and development services. In assessing whether the various options under the Bayer Collaboration Agreement represent material rights, the Company considered the additional consideration the Company would be entitled to upon option exercise and the standalone selling price of the underlying goods and services. For the material rights identified above, the Company concluded that each of the options provided Bayer with a discount that it otherwise would not have received. The transaction price was initially determined to be $47.5 million, consisting of the $45.0 million upfront fee and an estimated $2.5 million for the reimbursement of certain external CRO costs. The Company utilized the expected value method to determine the amount of variable consideration to be received. Additional payments to the Company upon Bayer’s exercise of options are excluded from the transaction price as they relate to option fees and milestones that can only be achieved subsequent to the exercise of an option. The estimated $2.5 million in variable consideration was first allocated entirely to the first and second target combined performance obligations as the terms of the variable consideration relate specifically to the Company’s efforts in satisfying the performance obligations and allocating the variable consideration entirely to those performance obligations is consistent with the allocation objective in Accounting Standards Codification (“ASC”) Topic 606, Revenue from Contracts with Customers, ​ ​ ​ ​ ​ ​ ​ Allocation of Performance Obligations ​ Transaction Price Two combined performance obligations related to the licenses and research and development services associated with radiopharmaceutical compounds directed to the first and second targets ​ $ 14,976 Material right associated with limited substitution rights for either the first or second target ​ ​ 1,527 Two material rights associated with the option to progress radiopharmaceutical candidates directed to the first and second targets into further development ​ ​ 14,691 Two material rights associated with the option to progress a non-radiopharmaceutical compound directed to the first and second targets ​ ​ 8,703 Material right for the option to expand the collaboration to include a third target and the underlying additional option rights ​ ​ 7,603 ​ ​ $ 47,500 ​ ​ Novartis Collaboration Agreement On March 27, 2023, the Company and Novartis entered into a collaboration and license agreement (the “Novartis Collaboration Agreement”), pursuant to which the parties will perform research and discovery activities under a mutually agreed upon research plan during a research term of up to a specified number of years per target program to generate compounds incorporating optimized Bicycle (subject to certain restrictions) license under the Company’s intellectual property solely for Novartis to perform its research activities under each collaboration program during the research term (the “Novartis Research License”). For each collaboration program, Novartis may elect to progress compounds arising from activities under the research programs (“Licensed Compounds”) into further preclinical development of potential products directed to the target of such collaboration program. At a specified point, the Company will grant Novartis an exclusive, royalty-bearing, sublicensable, license under certain of the Company’s intellectual property to develop, manufacture, and commercialize such Licensed Compound, subject to certain limitations. Novartis also has certain limited substitution rights for each target, and Novartis may extend the initial research term by one year by electing to make an additional payment. On a target-by-target basis, if Novartis elects to progress development candidates directed to such target into further clinical development, Novartis will be required to use commercially reasonable efforts to develop and seek regulatory approval in certain major markets for products containing Licensed Compounds directed to the applicable target. Novartis agreed to pay a nonrefundable upfront payment to the Company of $50.0 million, which was received in April 2023. During the research term, upon achievement of a specified discovery milestone for the first target program, Novartis will make a one-time payment to the Company in the low single digit millions. On a target-by-target basis, if Novartis elects to progress one or more candidate compounds into further development and obtain an exclusive license for commercialization, Novartis will be required to pay a candidate selection fee for the first such Licensed Compound progressed by Novartis that incorporates a radionuclide, and for the first such Licensed Compound that does not incorporate a radionuclide, in each case in the mid-teen millions. Upon declaring a candidate, Novartis will be responsible for all future development, manufacturing, and commercialization activities. On a target-by-target basis, Novartis will be required to pay to the Company additional development and regulatory/first commercial sale milestones of up to $210.0 million for each of the first radionuclide product and non-radionuclide product directed to the applicable target upon the achievement of specified milestones, or $840.0 million in the aggregate if Novartis successfully achieves all such milestone events for both a radionuclide and a non-radionuclide product in each of the targets. In addition, the Company is eligible to receive tiered sales milestones based on the achievement of specified levels of net sales of such products totaling up to $200.0 million in the aggregate per product, or $800.0 million in the aggregate if Novartis successfully commercializes both a radionuclide and a non-radionuclide product in each of the target programs. In addition, (i) the Company is eligible to receive, on a therapeutic product-by-therapeutic product basis, tiered royalties on net sales of products by Novartis, its affiliates or sublicensees at percentages ranging from the high single digits to the very low double digits, subject to standard reductions and offsets in certain circumstances, and a royalty floor, and (ii) the Company is eligible to receive low single digit royalties on net sales of diagnostic products on a diagnostic product-by-diagnostic product basis and a low single digit percentage of sublicensing income on diagnostic products. Royalties will be payable under the Novartis Collaboration Agreement on a product-by-product and country-by-country basis, commencing on the first commercial sale of each product in a country, until the latest of (a) the expiration of the last valid claim of certain patents licensed by Company to Novartis, (b) a specified number of years following first commercial sale of such product, and (c) expiration of all data and regulatory exclusivity for such product in the applicable country. The Novartis Collaboration Agreement will remain in force on a product-by-product and country-by-country basis, unless earlier terminated by either party, until the expiration of the obligation for Novartis to make royalty payments to Company for such product in such country, and will terminate in its entirety on the expiration of all such royalty payment obligations in all countries. Either party may terminate the agreement upon 60 90 30 30 ​ ​ ​ ​ Accounting Analysis ​ ​ (i) Two combined performance obligations comprised of the Novartis Research License and the related research and development services during the research term for the first and second targets; ​ (ii) Two material rights associated with certain limited substitution rights with respect to the first and second targets; ​ (iii) Two material rights associated with the option to progress development candidates that incorporate a radionuclide with respect to the first and second target; and ​ (iv) Two material rights associated with the option to progress development candidates that do not incorporate a radionuclide with respect to the first and second target. ​ The Company concluded that certain rights that require the payment of additional consideration, which approximates the standalone selling of the underlying services to be provided, do not provide the customer with a material right and therefore, are not considered as performance obligations at the inception of the arrangement. The Company’s participation in the joint steering committee was assessed as immaterial in the context of the contract. ​ The Company has concluded that the Novartis Research License is not distinct from the research and development services as Novartis cannot obtain the benefit of the research license without the Company performing the research and development services. The services incorporate proprietary technology and unique skills and specialized expertise, particularly as they relate to constrained peptide technology that is not available in the marketplace. As a result, for each target, the research license has been combined with the research and development services into a single performance obligation. ​ In assessing whether the various options under the Novartis Collaboration Agreement represent material rights, the Company considered the additional consideration the Company would be entitled to upon option exercise and the standalone selling price of the underlying goods and services. For the material rights identified above the Company concluded that each of the options provided Novartis with a discount that it otherwise would not have received. ​ The total transaction price was initially determined to be $50.0 million, consisting of the $50.0 million upfront fee. The Company utilizes the most likely amount method to determine the amount of variable consideration to be received. Variable consideration for development milestones not subject to option exercises was fully constrained as a result of the uncertainty regarding whether any of the milestones will be achieved. Additional consideration to be paid to the Company upon the exercise of options by Novartis is excluded from the transaction price as they relate to option fees and milestones that can only be achieved subsequent to the exercise of an option. ​ The transaction price was allocated to the performance obligations based on the relative estimated standalone selling prices of each performance obligation. The estimated standalone selling prices for the combined performance obligations for each of the targets were based on the nature of the services to be performed and estimates of the associated effort and costs of the services, adjusted for a reasonable profit margin for what would be expected to be realized under similar contracts. The estimated standalone selling prices for the material rights were determined based on the fees Novartis would pay to exercise the options, the estimated value of the underlying goods and services, and the probability that Novartis would exercise the options. Based on the relative standalone selling prices, the allocation of the transaction price to the separate performance obligations is as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ Allocation of Performance Obligations Transaction Price Two combined performance obligations for the first and second targets ​ $ 18,008 Two material rights associated with limited substitution rights ​ 2,466 Two material rights associated with options to progress development candidates incorporating radionuclides ​ 19,684 Two material rights associated with options to progress development candidates not incorporating radionuclides ​ ​ 9,842 ​ ​ $ 50,000 ​ The Company will recognize revenue related to amounts allocated to the first and second target combined performance obligations as the underlying services are performed using a proportional performance model over the period of service using input-based measurements of total full-time equivalent efforts and external costs incurred to date as a percentage of total full-time equivalent efforts and expected external costs, which best reflects the progress towards satisfaction of the performance obligations. The amounts allocated to the material rights are recorded as deferred revenue and the Company will commence revenue recognition upon exercise of or upon expiry of the respective option. The first and second target combined performance obligations are expected to be satisfied over a period of approximately three years and the remaining material rights are expected to be exercised or expire within approximately six years from contract execution. ​ During the three and nine months ended September 30, 2023, the Company recognized revenue of $0.8 million and $0.8 million, respectively, in connection with the Novartis Collaboration Agreement. The Company did not recognize revenue during the three and nine months ended September 30, 2022 in connection with the Novartis Collaboration Agreement. As of September 30, 2023 and December 31, 2022, the Company recorded deferred revenue of $49.1 million and zero, respectively, in connection with the Novartis Collaboration Agreement. ​ Ionis Agreements Ionis Evaluation and Option Agreement ​ On December 31, 2020 (the “Effective Date”), the Company entered into an Evaluation and Option Agreement (the “Evaluation and Option Agreement”) with Ionis. Under the terms of the Evaluation and Option Agreement, the Company agreed to transfer Bicycles ​ At any point during the term of the agreement and continuing through 30 days after the expiration of the Evaluation Period, Ionis had the option (the “Ionis Option”) to obtain an exclusive license to the Company’s intellectual property for the purpose of continued research, development, manufacture and commercialization of products within a particular application of the Company’s platform technology. The upfront payment of ​ The Company concluded that the only performance obligation was a material right for the option to obtain an exclusive license. All other promises under the Evaluation and Option Agreement were immaterial in the context of the contract. The Company accounted for the 9, 2021, the Ionis Option was exercised upon the parties’ entry into a collaboration and license agreement as contemplated by the Evaluation and Option Agreement. The Company determined that the Ionis Option exercise constituted a continuation of the existing arrangement. Therefore, the million in deferred revenue under the Evaluation and Option Agreement was included in the transaction price of the collaboration and license agreement. ​ Ionis Collaboration Agreement ​ Following the exercise by Ionis of the Ionis Option granted pursuant to the Evaluation and Option Agreement, on July 9, 2021, the Company and Ionis entered into a collaboration and license agreement (the “Ionis Collaboration Agreement”). Pursuant to the Ionis Collaboration Agreement, the Company granted to Ionis a worldwide exclusive license under the Company’s relevant technology to research, develop, manufacture and commercialize products incorporating Bicycle Bicycles ”) intended for the delivery of oligonucleotide compounds directed to targets selected by Ionis for diagnostic, therapeutic, prophylactic and preventative uses in humans. Ionis will maintain exclusivity to all available targets unless it fails to achieve specified development diligence milestone deadlines. If Ionis fails to achieve one or more development diligence milestone deadlines, the Company has the right to limit exclusivity to certain specific collaboration targets, subject to the payment by Ionis of a low-single-digit million dollar amount per target as specified in the Ionis Collaboration Agreement. Each party will be responsible for optimization of such TfR1 Bicycles Bicycles , as specified by a research plan, and thereafter Ionis will be responsible for all future research, development, manufacture and commercialization activities. The Company will perform research and discovery activities including a baseline level of effort for a period of for no additional consideration. The parties will negotiate a commercially reasonable rate if additional research activities are agreed to be performed. For certain research and discovery activities that the Company is responsible for performing, the Company may use the assistance of a contract research organization (“CRO”). The Company has retained certain rights, including the right to use TfR1 Bicycles ​ The activities under the Ionis Collaboration Agreement are governed by a joint steering committee (“JSC”) with an equal number of representatives from the Company and Ionis. The JSC will oversee the performance of the research and development activities. Upon first commercial sales of a licensed product, the JSC will have no further responsibilities or authority under the Ionis Collaboration Agreement. ​ Under the Ionis Collaboration Agreement, Ionis made a non-refundable upfront payment of $31.0 million in addition to the $3.0 million already paid under the Option and Evaluation Agreement. Additionally, Ionis is obligated to reimburse the Company on a pass-through basis for expenses incurred in connection with research and discovery activities performed by a CRO. If Ionis is at risk of failing to achieve a specified development diligence milestone deadline, it can make up to three separate payments of a mid-single-digit million dollar amount to extend the development diligence milestone deadlines. On a collaboration target-by-collaboration target basis, Ionis will be required to make a low-single-digit million dollar payment upon acceptance of an investigational new drug application (“IND”) for the first product directed to such collaboration target (provided that Ionis will have a high single-digit million dollar credit to be applied towards the IND acceptance fee for ​ In December 2021, the Company and Ionis entered into an amendment to the Ionis Collaboration Agreement (the “Ionis Amendment”). Ionis paid the Company Ionis exercised an option it had for the Company to perform additional research services for an additional six months in exchange for the remaining consideration of $0.8 million. In April 2023, the Company and Ionis entered into the third amendment to the Ionis Collaboration Agreement (the “Third Ionis Amendment”). Ionis paid the Company $0.8 million and the Company agreed to perform additional research services to continue to evaluate and optimize the new product candidates that target the TfR1 receptor. The Company will perform the additional research services for a period of one year in exchange for consideration of $0.8 million. ​ Either party may terminate the Ionis Collaboration Agreement for the uncured material breach of the other party or in the case of insolvency. Ionis may terminate the Ionis Collaboration Agreement for convenience on specified notice periods depending on the development stage of the applicable target, either in its entirety or on a target-by-target basis. ​ Ionis Share Purchase Agreement ​ Concurrently with the execution of the Ionis Collaboration Agreement on July 9, 2021, the Company entered into a share purchase agreement (the “Ionis Share Purchase Agreement”) with Ionis, pursuant to which Ionis purchased 282,485 of the Company’s ordinary shares (the “Ionis Shares”) at a price per share of $38.94, for an aggregate purchase price of approximately $11.0 million. ​ The Share Purchase Agreement also provided that, subject to limited exceptions, Ionis could not sell any of the Ionis Shares until July 2022. ​ The Company determined the fair value of the Ionis Shares to be $7.6 million, based on the closing price of the Company’s ADSs of $31.11 per ADS on the date of the Ionis Share Purchase Agreement, less a discount for lack of marketability associated with resale restrictions applicable to the Ionis Shares, which was recorded as a component of shareholders’ equity. The Company concluded that the premium paid by Ionis under the Ionis Share Purchase Agreement represents additional consideration for the goods and services to be provided under the Ionis Collaboration Agreement. As such, the total premium of ​ Accounting analysis Upon execution of the Ionis Collaboration Agreement, the Company identified the following promises in the arrangement: i) a worldwide exclusive license to research, develop, manufacture and commercialize products incorporating TfR1 Bicycles Bicycles collaboration targets. ​ The Company’s participation in the JSC was deemed immaterial in the context of the contract. Bicycles Bicycles that are not available in the marketplace. low-single-digit million dollar payments upon acceptance of an IND (and payment to extend the exclusive license to research, develop, manufacture and commercialize a product candidate for certain specific collaboration targets if Ionis fails to achieve specified development diligence milestone deadlines) is a customer option, as Ionis has the contractual right to choose to make the payment in exchange for the continued exclusive right to research, develop, manufacture and commercialize the product candidate, and the Company is not presently obligated to provide, and does not have a right to consideration, for the additional goods or services prior to Ionis’s exercise of the option. In assessing whether the options under the Ionis Collaboration Agreement represent material rights, the Company considered the additional consideration the Company would be entitled to upon the option exercise and the standalone selling price of the underlying goods and services. For the material rights identified above, the Company concluded that each of the options to obtain credits provided Ionis with a discount that it otherwise would not have received without entering into the Ionis Collaboration Agreement. The total transaction price was initially determined to be $38.0 million, consisting of the $31.0 million up front payment, the $3.0 million payment under the Option and Evaluation Agreement that was credited against the total upfront payment payable pursuant to the Ionis Collaboration Agreement, the $3.4 million premium paid under the Ionis Share Pur

Income taxes

Income taxes	9 Months Ended
	Sep. 30, 2023
Income taxes
Income taxes	10. Income taxes During the three and nine months ended September 30, 2023 the Company recorded an income tax provision of $2.3 million and $1.1 million, respectively, and during the three and nine months ended September 30, 2022, the Company recorded an income tax benefit of $0.2 million and $1.1 million, respectively. The Company is subject to United Kingdom corporate taxation. Due to the nature of its business, the Company has generated losses since inception and has therefore not paid United Kingdom corporation tax. The provision for (benefit from) income taxes included in the condensed consolidated statements of operations and comprehensive loss represents the tax impact from operating activities in the United States, which has generated taxable income based on intercompany service arrangements. Deferred tax assets benefitted in the United States do not have a valuation allowance against them because of profits that will be generated by an intercompany service agreement. ​ Starting in 2022, amendments to Section 174 of the Internal Revenue Code of 1986, as amended (“IRC”), eliminated the option to immediately deduct research and development expenditures in the tax year that such costs are incurred. In accordance with the amendments, beginning on January 1, 2022, and continuing until the end of the second quarter of 2023, these research and development costs were capitalized by the Company and amortized over either a five- or 15-year period, depending on the location of the activities performed. In the third quarter of 2023, the Company completed an assessment, inclusive of an external tax analysis, and concluded that it is not required to capitalize certain research and development expenses incurred by its U.S. subsidiary associated with contractual research services performed on behalf of its U.K. subsidiary pursuant to an intercompany service arrangement because its U.S. subsidiary does not retain any ownership or rights in the underlying intellectual property resulting from the research services. The change in estimate upon the completion of this analysis resulted in an income tax provision of $2.4 million during the three months ended September 30, 2023. The Company's income tax benefit recognized during the three and nine months ended September 30, 2022 is mainly the result of deferred tax assets benefitted in the U.S. that do not have a valuation allowance against them because of profits that will be generated by an intercompany service agreement. ​ The Company regularly assesses its ability to realize its deferred tax assets. Assessing the realization of deferred tax assets requires significant judgment. In determining whether its deferred tax assets are more likely than not realizable, the Company evaluated all available positive and negative evidence, and weighed the evidence based on its objectivity. After consideration of the evidence, including the Company’s history of cumulative net losses in the U.K., the Company 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 accordingly the Company has provided a valuation allowance for the full amount of the net deferred tax assets in the U.K. The Company has considered the Company’s history of cumulative net profits in the U.S., estimated future taxable income and concluded that it is more likely than not that the Company will realize the benefits of its U.S. deferred tax assets and has not provided a valuation allowance against the net deferred tax assets in the U.S. The Company recorded a valuation allowance against all of its U.K. deferred tax assets as of September 30, 2023 and December 31, 2022. ​ The Company intends to continue to maintain a full valuation allowance on its U.K. deferred tax assets until there is sufficient evidence to support the reversal of all or some portion of these allowances. The release of the valuation allowance would result in the recognition of certain deferred tax assets and an increase to the benefit from income taxes for the period the release is recorded. However, the exact timing and amount of the valuation allowance release are subject to change on the basis of the level of profitability that the Company is able to actually achieve. ​ The provision for (benefit from) income taxes recorded in the condensed consolidated statements of operations differs from amounts that would result from applying the statutory tax rates to income before taxes primarily because of certain permanent expenses that were not deductible, U.K., federal and state research and development credits, as well as the application of valuation allowances against the U.K. deferred tax assets.

Commitments and contingencies

Commitments and contingencies	9 Months Ended
	Sep. 30, 2023
Commitments and contingencies
Commitments and contingencies	11. Commitments and contingencies Leases In January 2023, the Company entered into a lease agreement for office and laboratory space in Cambridge, Massachusetts. The lease has a contractual period of approximately three years, which, subject to certain conditions, may be extended for an additional two years at the Company’s option. The Company concluded that the lease term is three years, representing the non-cancelable lease period, as it is not reasonably certain that the lease will be extended. The annual rent is approximately $2.1 million in the first year of the lease and increases annually with the last year of the lease having annual rent of approximately $2.3 million. The annual rent is payable monthly in advance following a two-month rent-free period. In connection with the lease agreement, the Company has delivered to the landlord a security deposit in the form of a letter of credit of approximately $0.5 million. The Company initially recorded a right of use asset On December 6, 2021, the Company entered into a lease of new office and laboratory space in Cambridge, United Kingdom. The lease has a contractual period of 10 years, but may be cancelled by the Company on the fifth anniversary of the lease commencement date. The lease term is five years, representing the non-cancelable lease period, as it is not reasonably certain that the lease will not be cancelled. The Company has a contractual right to renew the lease for a further ten-year period, which also may be cancelled after five years. The annual rent is approximately $3.0 million, payable quarterly in advance beginning in June 2022, following a six-month period of free rent. There was no deposit paid in conjunction with the lease. The Company recorded a right of use asset of approximately $11.6 million and a lease liability of approximately $11.1 million at the lease commencement date, based on the present value of future lease payments, discounted at 6.9%, the Company’s estimated incremental borrowing rate at the commencement of the lease, over the lease term. Rent expense is recognized on a straight-line basis over the five year lease term, including the six month rent-free period. In October 2017, the Company entered into a lease agreement for office and laboratory space in Building 900, Babraham Research Campus, Cambridge, U.K., which was renewed in December 2021 for five years through December 2026. The annual rent for the lease was approximately $0.6 million. Service charges were also payable based on floor area and are estimated to be approximately $0.2 million per year. In April 2023, the Company entered into a deed of surrender related to the lease, pursuant to which the lease was terminated effective immediately. As a result of the deed, the Company derecognized the lease liability and right of use asset associated with the lease. The Company also paid termination-related fees of $0.3 million in connection with the deed, which were recorded as a loss on lease termination and are included in operating expenses in the condensed consolidated statements of operations and comprehensive loss for the nine months ended September 30, 2023. In September 2017, Bicycle Therapeutics Inc. entered into a lease agreement for office and laboratory space in Lexington, Massachusetts, which commenced on January 1, 2018. In March 2022, Bicycle Therapeutics Inc. notified the landlord of its intent to exercise its option to extend the lease, originally set to expire on December 31, 2022, for a successive period through December 31, 2027. The successive period was not included in the original lease term as it was not reasonably certain that the option would be exercised. In March 2022, the Company accounted for the lease extension as a modification of the existing lease and remeasured the right of use asset and lease liability by calculating the present value of lease payments, discounted at 7.0%, the Company’s incremental borrowing rate, over the new lease term. In May 2022, the lease was extended. The payments for the extended lease are approximately $0.2 million remaining through December 31, 2022, $0.7 million in 2023, and increases annually pursuant to an escalation clause with the last year of the lease term having a per annum fixed rent obligation of $0.8 million. In conjunction with the lease agreement, Bicycle Therapeutics Inc. paid a security deposit of $0.2 million as well as prepaid rent of $0.1 million for the first month of the third, fourth, and fifth year of the lease. ​ The components of the Company’s lease expense, which are recorded as a component of research and development expenses and general and administrative expenses in the condensed consolidated statement of operations and comprehensive loss are as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ Nine Months Ended ​ September 30, ​ September 30, ​ 2023 2022 ​ 2023 2022 Operating lease cost $ 1,364 ​ $ 924 ​ $ 4,057 ​ $ 2,866 Variable lease cost ​ 566 ​ 410 ​ ​ 2,017 ​ 1,005 Total lease cost $ 1,930 ​ $ 1,334 ​ $ 6,074 ​ $ 3,871 ​ The weighted average remaining operating lease term was 3.2 years and 4.5 years as of September 30, 2023 and 2022, respectively, and the weighted average discount rate was 7.94% and 7.03% as of September 30, 2023 and 2022, respectively. ​ ​ ​ ​ ​ ​ ​ The following table summarizes the maturities of the Company’s operating lease liabilities as of September 30, 2023 (in thousands): ​ ​ ​ ​ ​ Year Ending December 31, ​ ​ 2023 ​ ​ 1,394 2024 ​ 5,654 2025 ​ 5,740 2026 ​ 3,271 2027 ​ ​ 821 Present value adjustment ​ (1,796) Total lease liabilities ​ ​ 15,084 Less: current lease liabilities ​ (4,661) Long term lease liabilities ​ $ 10,423 ​ The Company has entered into various agreements with contract research organizations to provide clinical trial services, contract manufacturing organizations to provide clinical trial materials and with vendors for preclinical research studies, synthetic chemistry and other services for operating purposes. These payments are not included in the table of operating lease payments above since the contracts are generally cancelable at any time upon less than 90 days’ prior written notice. The Company is not contractually able to terminate for convenience and avoid any and all future obligations to these vendors. In some cases, we are contractually obligated to make certain minimum payments to the vendors, based on the timing of the termination notification and the exact terms of the agreement. The Company’s arrangements with CRUK provide for additional future milestone payments upon the achievement of development, regulatory and commercial milestones, payable in cash and shares, with an aggregate total value of $111.2 million, as well as royalty payments based on a single digit percentage on net sales of products developed. In addition, the Company has a separate agreement with a third party that provides for additional future milestone payments by the Company upon the achievement of specified development, regulatory and commercial milestones, with an aggregate total value of $92.4 million. The Company also has a separate agreement with a third party that provides for future milestone payments by the Company upon the achievement of specified regulatory, development, commercial, and sales-based milestones, with an aggregate total, on a product-by-product basis, of $1.3 million. These additional milestone payments are contingent upon future events. As of September 30, 2023, the Company was unable to estimate the timing or likelihood of achieving any of these milestones. Legal proceedings From time to time, the Company or its subsidiaries may become involved in various legal proceedings and claims, either asserted or unasserted, which arise in the ordinary course of business. The Company is currently not subject to any material legal proceedings. At each reporting date, the Company evaluates whether or not a potential loss amount or a potential range of loss is probable and reasonably estimable under the provisions of ASC 450, Contingencies Founder royalty arrangements At the time BicycleRD Limited was organized, BicycleRD Limited entered into a royalty agreement with its founders and initial investors (the “Founder Royalty Agreement”). Pursuant to the Founder Royalty Agreement, as amended, the Company will pay a royalty rate in the low single digit percentages on net product sales under the collaborations with Oxurion and AstraZeneca to its founders and initial investors, for a period of 10 years from the first commercial sale on a country-by-country basis. No royalties have been earned or paid Indemnification obligations 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 indemnification obligations towards members of its board of directors and officers 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 arrangements is, in many cases, unlimited. To date, the Company has not incurred any material costs as a result of such indemnification obligations. The Company is not aware of any claims under indemnification arrangements, and therefore it has not accrued any liabilities related to such obligations in its condensed consolidated financial statements as of September 30, 2023, and December 31, 2022.

Net loss per share

Net loss per share	9 Months Ended
	Sep. 30, 2023
Net loss per share
Net loss per share	12. Net loss per share Basic and diluted net loss per share was calculated as follows (in thousands, except share and per share amounts): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ Nine Months Ended ​ ​ September 30, ​ September 30, ​ 2023 2022 2023 2022 Numerator: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Net loss ​ $ (49,898) ​ $ (28,347) ​ $ (131,565) ​ $ (82,739) Denominator: ​ ​ ​ ​ Weighted average ordinary shares outstanding, basic and diluted ​ 39,576,467 ​ 29,676,021 ​ 33,291,701 ​ 29,643,502 Net loss per share, basic and diluted ​ $ (1.26) ​ $ (0.96) ​ $ (3.95) ​ $ (2.79) ​ The Company’s potentially dilutive securities, which are options to purchase ordinary shares and restricted share units for ordinary shares, have been excluded from the computation of diluted net loss per share as the effect would be to reduce the net loss per share. Therefore, the weighted average number of ordinary shares outstanding, which includes both ordinary shares and non-voting ordinary shares, used to calculate both basic and diluted net loss per share is the same. The Company excluded the following potentially dilutive ordinary shares, presented based on amounts outstanding at each period end, from the computation of diluted net loss per share for the periods indicated because including them would have had an anti-dilutive effect: ​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ 2023 2022 Restricted ordinary shares 335,104 187,725 Options to purchase ordinary shares 7,312,020 5,784,581 ​ 7,647,124 5,972,306

Related party transactions

Related party transactions	9 Months Ended
	Sep. 30, 2023
Related party transactions
Related party transactions	13. Related party transactions The Company has entered into the Founder Royalty Agreement, as amended, with its founders and initial investors (Note 11). No royalties have been earned or paid The Chairman of the Company’s board of directors is associated with Stone Sunny Isles Inc. and Stone Atlanta Estates LLC, the successor-in-interest to Stone Sunny Isles Inc., which provided consultancy services to the Company totaling $49,000 and $0.2 million during the three and nine months ended September 30, 2023, respectively, and $43,000 and $0.2 million during the three and nine months ended September 30, 2022, respectively.

Geographic information

Geographic information	9 Months Ended
	Sep. 30, 2023
Geographic information
Geographic information	14. Geographic information The Company operates in two geographic regions: the United States and the United Kingdom. Information about the Company’s long-lived assets, including operating lease right-of-use assets, held in different geographic regions is presented in the table below (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ December 31, ​ 2023 2022 United States ​ $ 8,817 ​ $ 4,466 United Kingdom ​ 21,379 ​ 28,302 ​ ​ $ 30,196 ​ $ 32,768 ​ The Company’s collaboration revenues are attributed to the operations of the Company in the United Kingdom.

Subsequent events

Subsequent events	9 Months Ended
	Sep. 30, 2023
Subsequent events.
Subsequent events	​ ​

Summary of significant accoun_2

Summary of significant accounting policies (Policies)	9 Months Ended
	Sep. 30, 2023
Summary of significant accounting policies
Use of estimates	Use of estimates The preparation of condensed consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of the condensed consolidated financial statements and the reported amounts of expenses during the reporting periods. Significant estimates and assumptions reflected in these condensed consolidated financial statements include, but are not limited to, the accrual for research and development expenses, revenue recognition, share-based compensation expense, valuation of right-of-use assets and liabilities, and income taxes, including the valuation allowance for deferred tax assets. The Company bases its estimates on historical experience, known trends and other market-specific or other relevant factors that it believes to be reasonable under the circumstances. Estimates are periodically reviewed in light of reasonable changes in circumstances, facts and experience. Changes in estimates are recorded in the period in which they become known. Actual results could differ from those estimates or assumptions.
Significant risks and uncertainties	Significant risks and uncertainties The Company currently operates in a period of economic uncertainty which has been significantly impacted by the global health crises, domestic and global monetary and fiscal policy, bank failures, geopolitical conflicts such as the ongoing wars in Ukraine and Israel, rising inflation and interest rates, and fluctuations in monetary exchange rates. While the Company has experienced limited financial impacts at this time, the Company continues to monitor these factors and events and the potential effects each may have on the Company’s business, financial condition, results of operations and growth prospects.
Unaudited interim financial information	Unaudited interim financial information Certain information in the footnote disclosures of these financial statements has been condensed or omitted pursuant to the rules and regulations of the SEC. These unaudited condensed consolidated financial statements should be read in conjunction with the Company’s audited consolidated financial statements and notes thereto for the year ended December 31, 2022 included in the Company’s 2022 Annual Report. The accompanying condensed consolidated balance sheet as of September 30, 2023, condensed consolidated statements of operations and comprehensive loss and condensed consolidated statements of shareholders’ equity for the three and nine months ended September 30, 2023 and 2022, and condensed consolidated statements of cash flows for the nine months ended September 30, 2023 and 2022, and the related financial information disclosed in these notes are unaudited. The unaudited interim financial statements have been prepared on the same basis as the audited annual financial statements for the year ended December 31, 2022, and, in the opinion of management, reflect all adjustments, consisting of normal recurring adjustments, necessary for the fair statement of the Company’s financial position as of September 30, 2023, the results of its operations for the three and nine months ended September 30, 2023 and 2022, and its cash flows for the nine months ended September 30, 2023 and 2022. The results for the three and nine months ended September 30, 2023 are not necessarily indicative of the results to be expected for the year ending December 31, 2023, any other interim periods, or any future year or period.
Accounts receivable	Accounts receivable
Recently adopted accounting pronouncements	Recently adopted accounting pronouncements There have been no recent accounting pronouncements, changes in accounting pronouncements or recently adopted accounting guidance during the three and nine months ended September 30, 2023, that are of significance or potential significance to the Company.

Property and equipment, net (Ta

Property and equipment, net (Tables)	9 Months Ended
	Sep. 30, 2023
Property and equipment, net
Schedule of property and equipment, net	Property and equipment, net consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ December 31, ​ 2023 2022 Laboratory equipment ​ $ 15,087 ​ $ 14,872 Leasehold improvements ​ 10,547 ​ 10,736 Computer equipment and software ​ 537 ​ 441 Furniture and office equipment ​ 823 ​ 924 ​ ​ 26,994 ​ 26,973 Less: Accumulated depreciation and amortization ​ (11,395) ​ (7,863) ​ ​ $ 15,599 ​ $ 19,110

Accrued expenses and other cu_2

Accrued expenses and other current liabilities (Tables)	9 Months Ended
	Sep. 30, 2023
Accrued expenses and other current liabilities
Schedule of accrued expenses and other current liabilities	Accrued expenses and other current liabilities consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ December 31, ​ 2023 2022 Accrued employee compensation and benefits ​ $ 9,760 ​ $ 9,928 Accrued external research and development expenses ​ 18,010 ​ 10,859 Accrued professional fees ​ 1,319 ​ 1,068 Current portion of operating lease liabilities ​ 4,661 ​ 3,125 Other ​ 303 ​ 1,472 ​ ​ $ 34,053 ​ $ 26,452 ​

Long-term debt (Tables)

Long-term debt (Tables)	9 Months Ended
	Sep. 30, 2023
Long-term debt
Schedule of long term debt instruments	​ Long-term debt consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ December 31, ​ 2023 2022 Term loan payable ​ $ 30,000 ​ $ 30,000 End of term charge ​ ​ 881 ​ ​ 682 Unamortized debt issuance costs ​ ​ (277) ​ ​ (367) Carrying value of term loan ​ $ 30,604 ​ $ 30,315
Schedule of maturities of long term debt	Future principal payments, including the End of Term Charge, are as follows (in thousands): ​ ​ ​ ​ ​ Year Ending December 31, ​ ​ 2023 ​ $ — 2024 ​ ​ — 2025 ​ ​ 31,500 Total ​ $ 31,500 ​

Share-based compensation (Table

Share-based compensation (Tables)	9 Months Ended
	Sep. 30, 2023
Share-based compensation
Schedule of share based compensation expense	The Company recorded share-based compensation expense in the following expense categories of its condensed consolidated statements of operations and comprehensive loss (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ Nine Months Ended ​ ​ September 30, ​ September 30, ​ 2023 2022 2023 2022 Research and development expenses ​ $ 3,357 ​ $ 2,637 ​ $ 11,941 ​ $ 7,643 General and administrative expenses ​ 4,073 ​ 2,731 ​ 12,724 ​ 13,596 ​ ​ $ 7,430 ​ $ 5,368 ​ $ 24,665 ​ $ 21,239
Schedule of share option activity	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Number of ​ ​ ​ ​ Weighted ​ ​ ​ ​ ​ Shares ​ Weighted ​ Average ​ Aggregate ​ ​ Underlying ​ Average ​ Contractual ​ Intrinsic ​ Share Options Exercise Price Term Value ​ ​ ​ ​ ​ ​ ​ (in years) ​ (in thousands) Outstanding as of December 31, 2022 5,898,888 ​ $ 22.45 7.64 ​ $ 71,002 Granted 1,859,315 ​ 27.57 — ​ — Exercised (26,562) ​ 11.42 — ​ — Forfeited (419,621) ​ 30.69 — ​ — Outstanding as of September 30, 2023 7,312,020 ​ $ 23.32 6.99 ​ $ 29,629 Vested and expected to vest as of September 30, 2023 7,312,020 ​ $ 23.32 ​ 6.99 ​ $ 29,629 Options exercisable as of September 30, 2023 4,334,755 ​ $ 18.39 5.75 ​ $ 28,069
Schedule of assumptions used to determine the fair value of share options granted	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ Nine Months Ended ​ ​ September 30, ​ ​ September 30, ​ 2023 2022 ​ 2023 2022 Risk-free interest rate 4.1 % 3.0 % ​ 3.9 % 2.0 % Expected volatility 83.3 % 84.1 % ​ 83.5 % 82.2 % Expected dividend yield — — ​ — — ​ Expected term (in years) 6.1 6.1 ​ 6.1 6.0 ​
Summarizes activity for RSUs under the 2020 Plan	​ ​ ​ ​ ​ ​ ​ ​ ​ Number of Shares ​ Weighted-Average ​ ​ Underlying RSUs ​ Grant Date Fair Value Unvested at December 31, 2022 ​ 187,725 ​ $ 60.86 Granted ​ 321,839 ​ ​ 29.59 Vested ​ (99,638) ​ ​ 51.39 Forfeited ​ (74,822) ​ ​ 39.55 Unvested at September 30, 2023 ​ 335,104 ​ $ 38.40

Significant agreements (Tables)

Significant agreements (Tables)	9 Months Ended
	Sep. 30, 2023
Significant agreements.
Summary of revenue recognized from collaboration arrangements	The following table summarizes the revenue recognized in the Company’s condensed consolidated statements of operations and comprehensive loss from these arrangements (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months ​ Nine Months ​ ​ Ended ​ Ended ​ ​ September 30, ​ September 30, ​ 2023 2022 2023 2022 Collaboration revenues ​ ​ ​ ​ Bayer ​ $ 434 ​ $ — ​ $ 434 ​ $ — Novartis ​ ​ 772 ​ ​ — ​ ​ 772 ​ ​ — Ionis ​ ​ 2,782 ​ ​ 2,195 ​ ​ 8,123 ​ ​ 6,764 Genentech ​ ​ 1,364 ​ ​ 798 ​ ​ 11,112 ​ ​ 3,144 Dementia Discovery Fund ​ — ​ 47 ​ — ​ 205 AstraZeneca ​ ​ — ​ ​ — ​ ​ 1,204 ​ ​ 1,165 Total collaboration revenues ​ $ 5,352 ​ $ 3,040 ​ $ 21,645 ​ $ 11,278
Summary of changes in the balances of the Company's contract assets and liabilities	The following table presents changes in the balances of the Company’s contract assets and liabilities (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Beginning Balance ​ ​ ​ ​ ​ Impact of ​ Ending Balance ​ ​ January 1, ​ ​ ​ ​ ​ Exchange ​ September 30, ​ 2023 Additions Deductions Rates 2023 Contract liabilities: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Deferred revenue ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Bayer collaboration deferred revenue ​ $ — ​ $ 45,000 ​ $ (434) ​ $ (2,045) ​ $ 42,521 Novartis collaboration deferred revenue ​ ​ — ​ ​ 50,000 ​ ​ (772) ​ ​ (178) ​ ​ 49,050 Ionis collaboration deferred revenue ​ ​ 21,489 ​ ​ 870 ​ ​ (8,123) ​ ​ 227 ​ ​ 14,463 Genentech collaboration deferred revenue ​ ​ 39,308 ​ ​ — ​ ​ (11,112) ​ ​ 542 ​ ​ 28,738 AstraZeneca collaboration deferred revenue ​ 1,076 ​ — ​ (1,204) ​ ​ 128 ​ — Total deferred revenue ​ $ 61,873 ​ $ 95,870 ​ $ (21,645) ​ $ (1,326) ​ $ 134,772 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Beginning Balance ​ ​ ​ ​ Impact of ​ Ending Balance ​ ​ January 1, ​ ​ ​ ​ ​ Exchange ​ December 31, ​ 2022 Additions Deductions Rates 2022 Contract liabilities: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Deferred revenue ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Ionis collaboration deferred revenue ​ $ 34,115 ​ $ 99 ​ $ (9,347) ​ $ (3,378) ​ $ 21,489 Genentech collaboration deferred revenue ​ ​ 34,436 ​ ​ 12,000 ​ ​ (3,565) ​ ​ (3,563) ​ ​ 39,308 DDF collaboration deferred revenue ​ 428 ​ — ​ (386) ​ (42) ​ — AstraZeneca collaboration deferred revenue ​ 2,361 ​ — ​ (1,165) ​ (120) ​ 1,076 Total deferred revenue ​ $ 71,340 ​ $ 12,099 ​ $ (14,463) ​ $ (7,103) ​ $ 61,873
Summary of recognition of revenues as a result of changes in contract asset and contract liability balances	During the three and nine months ended September 30, 2023 and 2022, the Company recognized the following revenues as a result of changes in the contract asset and the contract liability balances in the respective periods (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ Nine Months Ended ​ September 30, ​ September 30, ​ 2023 2022 ​ 2023 2022 Revenue recognized in the period from: ​ ​ ​ ​ ​ ​ ​ Revenue recognized based on proportional performance $ 5,006 ​ $ 3,040 ​ $ 13,829 ​ $ 10,072 Revenue recognized based on expiration of material rights ​ 346 ​ — ​ ​ 7,816 ​ 1,206 Total $ 5,352 ​ $ 3,040 ​ $ 21,645 ​ $ 11,278
Bayer Collaboration Agreement
Significant agreements.
Summary of allocation of transaction price to separate performance obligations	Based on the relative standalone selling prices, the allocation of the transaction price to the separate performance obligations is as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ Allocation of Performance Obligations ​ Transaction Price Two combined performance obligations related to the licenses and research and development services associated with radiopharmaceutical compounds directed to the first and second targets ​ $ 14,976 Material right associated with limited substitution rights for either the first or second target ​ ​ 1,527 Two material rights associated with the option to progress radiopharmaceutical candidates directed to the first and second targets into further development ​ ​ 14,691 Two material rights associated with the option to progress a non-radiopharmaceutical compound directed to the first and second targets ​ ​ 8,703 Material right for the option to expand the collaboration to include a third target and the underlying additional option rights ​ ​ 7,603 ​ ​ $ 47,500
Novartis
Significant agreements.
Summary of allocation of transaction price to separate performance obligations	Based on the relative standalone selling prices, the allocation of the transaction price to the separate performance obligations is as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ Allocation of Performance Obligations Transaction Price Two combined performance obligations for the first and second targets ​ $ 18,008 Two material rights associated with limited substitution rights ​ 2,466 Two material rights associated with options to progress development candidates incorporating radionuclides ​ 19,684 Two material rights associated with options to progress development candidates not incorporating radionuclides ​ ​ 9,842 ​ ​ $ 50,000
Ionis
Significant agreements.
Summary of allocation of transaction price to separate performance obligations	Based on the relative standalone selling price, the allocation of the transaction price to the separate performance obligations is as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ Allocation of Performance Obligations Transaction Price Combined licenses and research and discovery performance obligation ​ $ 34,100 Four material rights associated with credits for IND Acceptance fees ​ 3,900 ​ ​ $ 38,000
Genentech
Significant agreements.
Summary of allocation of transaction price to separate performance obligations	Based on the relative standalone selling price, the initial allocation of the transaction price to the separate performance obligations is as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ Allocation of Performance Obligations Transaction Price Genentech Collaboration Program #1 Performance Obligation ​ $ 4,019 Genentech Collaboration Program #2 Performance Obligation ​ 8,037 Specified Targeting Arm Material Right Arm for Genentech Collaboration Program #1 ​ 352 Two material rights associated with the LSR Go Option for Collaboration Programs #1 and #2 ​ 12,400 Material rights associated with limited substitution rights ​ ​ 1,187 Two material rights for Expansion Options ​ ​ 7,005 ​ ​ $ 33,000

Commitments and contingencies (

Commitments and contingencies (Tables)	9 Months Ended
	Sep. 30, 2023
Commitments and contingencies
Schedule of components of lease expense	The components of the Company’s lease expense, which are recorded as a component of research and development expenses and general and administrative expenses in the condensed consolidated statement of operations and comprehensive loss are as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ Nine Months Ended ​ September 30, ​ September 30, ​ 2023 2022 ​ 2023 2022 Operating lease cost $ 1,364 ​ $ 924 ​ $ 4,057 ​ $ 2,866 Variable lease cost ​ 566 ​ 410 ​ ​ 2,017 ​ 1,005 Total lease cost $ 1,930 ​ $ 1,334 ​ $ 6,074 ​ $ 3,871
Schedule of maturities of operating leases	​ ​ ​ ​ ​ The following table summarizes the maturities of the Company’s operating lease liabilities as of September 30, 2023 (in thousands): ​ ​ ​ ​ ​ Year Ending December 31, ​ ​ 2023 ​ ​ 1,394 2024 ​ 5,654 2025 ​ 5,740 2026 ​ 3,271 2027 ​ ​ 821 Present value adjustment ​ (1,796) Total lease liabilities ​ ​ 15,084 Less: current lease liabilities ​ (4,661) Long term lease liabilities ​ $ 10,423

Net loss per share (Tables)

Net loss per share (Tables)	9 Months Ended
	Sep. 30, 2023
Net loss per share
Schedule of basic and diluted net loss attributable to ordinary shareholders	Basic and diluted net loss per share was calculated as follows (in thousands, except share and per share amounts): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ Nine Months Ended ​ ​ September 30, ​ September 30, ​ 2023 2022 2023 2022 Numerator: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Net loss ​ $ (49,898) ​ $ (28,347) ​ $ (131,565) ​ $ (82,739) Denominator: ​ ​ ​ ​ Weighted average ordinary shares outstanding, basic and diluted ​ 39,576,467 ​ 29,676,021 ​ 33,291,701 ​ 29,643,502 Net loss per share, basic and diluted ​ $ (1.26) ​ $ (0.96) ​ $ (3.95) ​ $ (2.79) ​
Schedule of antidilutive securities excluded from computation of diluted net loss per share	​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ 2023 2022 Restricted ordinary shares 335,104 187,725 Options to purchase ordinary shares 7,312,020 5,784,581 ​ 7,647,124 5,972,306

Geographic information (Tables)

Geographic information (Tables)	9 Months Ended
	Sep. 30, 2023
Geographic information
Schedule of long-lived assets, including operating lease right-of-use assets, held in different geographic regions	Information about the Company’s long-lived assets, including operating lease right-of-use assets, held in different geographic regions is presented in the table below (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ September 30, ​ December 31, ​ 2023 2022 United States ​ $ 8,817 ​ $ 4,466 United Kingdom ​ 21,379 ​ 28,302 ​ ​ $ 30,196 ​ $ 32,768

Nature of the business and ba_2

Nature of the business and basis of presentation - Liquidity (Details) $ / shares in Units, $ in Thousands		3 Months Ended						9 Months Ended
	Jul. 17, 2023 USD ($) shares	Sep. 30, 2023 USD ($) shares	Jun. 30, 2023 USD ($)	Mar. 31, 2023 USD ($)	Sep. 30, 2022 USD ($) shares	Jun. 30, 2022 USD ($)	Mar. 31, 2022 USD ($)	Sep. 30, 2023 USD ($) shares	Sep. 30, 2022 USD ($) shares	Sep. 30, 2023 £ / shares	Jul. 17, 2023 £ / shares	Jul. 17, 2023 $ / shares	Dec. 31, 2022 USD ($)	Dec. 31, 2022 £ / shares
Cash and cash equivalents		$ 572,086			$ 361,469			$ 572,086	$ 361,469				$ 339,154
Par value per share | £ / shares										£ 0.01				£ 0.01
Gross proceeds before discounts and commissions		234,492	$ 12,127	$ 2,716
Offering expenses		15,500	400	100
Net proceeds								249,335
Net loss		49,898	$ 42,603	$ 39,064	$ 28,347	$ 26,828	$ 27,564	131,565	$ 82,739
Accumulated deficit		$ (462,661)						$ (462,661)					$ (331,096)
At the market offering | American Depositary Shares
Shares issued (in shares) | shares		941,176			0			1,561,176	0
Gross proceeds before discounts and commissions		$ 20,000						$ 35,300
Offering expenses		600						1,100
Net proceeds		$ 19,400						$ 34,200
Underwritten Public Offering
Gross proceeds before discounts and commissions	$ 230,000
Offering expenses	14,900
Net proceeds	$ 215,100
Underwritten Public Offering | American Depositary Shares
Shares issued (in shares) | shares	6,117,648
Par value per share | £ / shares											£ 0.01
Public offering price per ADS | $ / shares												$ 21.25
Underwritten Public Offering | American Depositary Shares | Option on securities
Shares issued (in shares) | shares	1,411,764
Underwritten Public Offering | Non voting ordinary shares
Shares issued (in shares) | shares	4,705,882
Par value per share | £ / shares											£ 0.01

Summary of significant accoun_3

Summary of significant accounting policies - (Details) - USD ($)	Sep. 30, 2023	Dec. 31, 2022
Summary of significant accounting policies
Accounts receivable	$ 0	$ 2,045,000

Fair value of financial asset_2

Fair value of financial assets and liabilities - Financial assets and liabilities measured at fair value (Details) - USD ($) $ in Thousands	9 Months Ended	12 Months Ended
	Sep. 30, 2023	Dec. 31, 2022
Fair value of financial assets and liabilities
Cash equivalents	$ 63,400	$ 276,100
Restricted cash included in other assets	548
Recurring
Fair value of financial assets and liabilities
Liabilities at fair value	0	0
Assets at fair value	$ 0	$ 0
Level 1 | Recurring
Fair value of financial assets and liabilities
Term deposit maturity period	30 days	30 days

Property and equipment, net (De

Property and equipment, net (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022	Dec. 31, 2022
Property and equipment, net
Property and equipment, gross	$ 26,994		$ 26,994		$ 26,973
Less: Accumulated depreciation and amortization	(11,395)		(11,395)		(7,863)
Property and equipment, net	15,599		15,599		19,110
Depreciation expense	1,700	$ 1,300	4,900	$ 2,200
Laboratory equipment
Property and equipment, net
Property and equipment, gross	15,087		15,087		14,872
Laboratory equipment was not yet placed in service					2,300
Leasehold improvements
Property and equipment, net
Property and equipment, gross	10,547		10,547		10,736
Computer equipment and software
Property and equipment, net
Property and equipment, gross	537		537		441
Furniture and office equipment
Property and equipment, net
Property and equipment, gross	$ 823		$ 823		$ 924

Accrued expenses and other cu_3

Accrued expenses and other current liabilities (Details) - USD ($) $ in Thousands	Sep. 30, 2023	Dec. 31, 2022
Accrued expenses and other current liabilities
Accrued employee compensation and benefits	$ 9,760	$ 9,928
Accrued external research and development expenses	18,010	10,859
Accrued professional fees	1,319	1,068
Current portion of operating lease liabilities	$ 4,661	$ 3,125
Operating Lease, Liability, Current, Statement of Financial Position [Extensible List]	Accrued expenses and other current liabilities	Accrued expenses and other current liabilities
Other	$ 303	$ 1,472
Accrued expenses and other current liabilities	$ 34,053	$ 26,452

Long-term debt (Details)

Long-term debt (Details) - USD ($) $ in Millions			3 Months Ended		9 Months Ended
	Jul. 15, 2022	Mar. 15, 2022	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022	Mar. 10, 2021	Sep. 30, 2020
Debt Instrument [Line Items]
Borrowing option to prepay subject to minimum debt outstanding			$ 5		$ 5
End term charge rate			5%		5%
Additional interest rate event of default			5%		5%
Prepayment occurs in second year
Debt Instrument [Line Items]
Prepayment rate			1.50%		1.50%
Prepayment occurs after year two
Debt Instrument [Line Items]
Prepayment rate			1%		1%
Second Amendment to LSA
Debt Instrument [Line Items]
Debt instrument stated percentage	8.05%
Basis spread variable rate	4.55%
Second Amendment to LSA | Maximum
Debt Instrument [Line Items]
Term loan	$ 45
Debt instrument stated percentage	9.05%
Term Loan
Debt Instrument [Line Items]
Maximum borrowing	$ 75
Initial Term Loan
Debt Instrument [Line Items]
Fees and transaction costs			$ 0.6		$ 0.6
Debt instrument effective percentage			10.80%		10.80%
Interest expense			$ 0.8	$ 0.8	$ 2.3	$ 2.5
Additional Term Loan One
Debt Instrument [Line Items]
Additional term loan expired unexercised.		$ 10
Loan and Security Agreement | Term Loan
Debt Instrument [Line Items]
Maximum borrowing								$ 40
Loan and Security Agreement | Initial Term Loan
Debt Instrument [Line Items]
Term loan								15
Loan and Security Agreement | Additional Term Loan One
Debt Instrument [Line Items]
Term loan							$ 15	15
Loan and Security Agreement | Additional Term Loan Two
Debt Instrument [Line Items]
Term loan								$ 10

Long-term debt - Debt (Details)

Long-term debt - Debt (Details) - USD ($) $ in Thousands	Sep. 30, 2023	Dec. 31, 2022
Long-term debt
Term loan payable	$ 30,000	$ 30,000
End of term charge	881	682
Unamortized debt issuance costs	(277)	(367)
Carrying value of term loan	$ 30,604	$ 30,315

Long-term debt - Future Princip

Long-term debt - Future Principal Payments (Details) $ in Thousands	Sep. 30, 2023 USD ($)
Long-term debt
2023	$ 0
2024	0
2025	31,500
Total	$ 31,500

Ordinary shares (Details)

Ordinary shares (Details)	9 Months Ended	12 Months Ended
	Sep. 30, 2023 Vote $ / shares £ / shares shares	Dec. 31, 2022 £ / shares $ / shares shares
Ordinary shares.
Vote per ordinary share | Vote	1
Dividends declared | $ / shares	$ 0	$ 0
Ordinary shares, shares authorized | shares	59,612,613	57,820,181
Ordinary shares, nominal value | £ / shares	$ 0.01	$ 0.01

Ordinary shares - Share Purchas

Ordinary shares - Share Purchase Agreement (Details) - shares	Sep. 30, 2023	Jun. 30, 2023	Mar. 31, 2023	Dec. 31, 2022	Sep. 30, 2022	Jun. 30, 2022	Mar. 31, 2022	Dec. 31, 2021
Class of Stock [Line Items]
Ordinary shares, shares issued	42,384,799			29,873,893
Ordinary shares, shares outstanding	42,384,799			29,873,893
Ordinary Shares
Class of Stock [Line Items]
Ordinary shares, shares outstanding	42,384,799	30,585,940	30,031,758	29,873,893	29,678,431	29,666,317	29,644,438	29,579,364
Non voting ordinary shares | Ordinary Shares
Class of Stock [Line Items]
Ordinary shares, shares issued	4,705,882
Ordinary shares, shares outstanding	4,705,882
Voting ordinary shares | Ordinary Shares
Class of Stock [Line Items]
Ordinary shares, shares issued	37,678,917
Ordinary shares, shares outstanding	37,678,917

Share-based compensation (Detai

Share-based compensation (Details)	1 Months Ended		9 Months Ended
	Jun. 30, 2020 installment shares	May 31, 2019 shares	Sep. 30, 2023 installment shares	Jan. 01, 2023 shares	Dec. 31, 2022 shares	Jun. 27, 2022 shares	Jan. 01, 2022 shares
Stock option
Share-based compensation.
Shares outstanding			7,312,020		5,898,888
Employee Share Purchase Plan
Share-based compensation.
Number of shares reserved for issuance							298,738
Percentage of annual increase in reserves on total number of ordinary shares outstanding		1%
Number of ordinary shares reserved for issuance		215,000	1,200,413
Number of shares available for issuance		430,000
2020 Plan
Share-based compensation.
Number of shares reserved for issuance	4,773,557		889,257	1,493,694		750,000
Shares issued (in shares)	574,679
Percentage of annual increase in reserves on total number of ordinary shares outstanding	5%
2020 Plan | Stock option
Share-based compensation.
Shares outstanding			4,620,330
Contractual life	10 years
2020 Plan | Stock option | Non-employee Director
Share-based compensation.
Vesting period	3 years
Number of equal quarterly installments for vesting remaining awards | installment			4
Service period			1 year
2020 Plan | Stock option | First anniversary
Share-based compensation.
Vesting Percentage	25%
2020 Plan | Stock option | Employee
Share-based compensation.
Vesting period	4 years
2020 Plan | Stock option | Employee | Remaining equal installments
Share-based compensation.
Number of equal monthly installments for vesting remaining awards | installment	36
2020 Plan | Restricted ordinary shares
Share-based compensation.
Vesting period			4 years
Right to receive upon vesting			1
Service period			1 year
Number of quarterly installments | installment			4
RSUs outstanding under the 2020 Plan.			335,104		187,725
2020 Plan | Restricted ordinary shares | First anniversary
Share-based compensation.
Vesting Percentage			25%
2020 Plan | Restricted ordinary shares | Remaining equal installments
Share-based compensation.
Number of equal quarterly installments for vesting remaining awards | installment			12
2019 Plan
Share-based compensation.
Number of shares reserved for issuance	544,866
2019 Plan | Stock option
Share-based compensation.
Shares outstanding	3,654,012		2,103,250
Contractual life			10 years
2019 Plan | Minimum | Stock option
Share-based compensation.
Vesting period			3 years
2019 Plan | Maximum | Stock option
Share-based compensation.
Vesting period			4 years
Pre-IPO Share Options and restricted shares | Stock option | First anniversary
Share-based compensation.
Vesting Percentage			25%
Pre-IPO Share Options and restricted shares | Stock option | Remaining equal installments
Share-based compensation.
Number of equal monthly installments for vesting remaining awards | installment			36

Share-based compensation - Shar

Share-based compensation - Share based compensation expense (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Share based compensation expense
Total share-based compensation expense	$ 7,430	$ 5,368	$ 24,665	$ 21,239
Research and development expenses
Share based compensation expense
Total share-based compensation expense	3,357	2,637	11,941	7,643
General and administrative expenses
Share based compensation expense
Total share-based compensation expense	$ 4,073	$ 2,731	$ 12,724	$ 13,596

Share-based compensation - Sh_2

Share-based compensation - Share Options (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended		12 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022	Dec. 31, 2022
Additional Information
Total share-based compensation expense	$ 7,430	$ 5,368	$ 24,665	$ 21,239
Stock option
Number of Shares
Outstanding number of shares at beginning			5,898,888
Granted			1,859,315
Exercised			(26,562)
Forfeited			(419,621)
Outstanding number of shares at end	7,312,020		7,312,020		5,898,888
Number of shares, vested and expected to vest	7,312,020		7,312,020
Number of shares, options exercisable	4,334,755		4,334,755
Weighted Average Exercise Price
Weighted average exercise price at beginning			$ 22.45
Granted			27.57
Exercised			11.42
Forfeited			30.69
Weighted average exercise price at ending	$ 23.32		23.32		$ 22.45
Weighted average exercise price, vested and expected to vest	23.32		23.32
Weighted average exercise price, options exercisable	$ 18.39		$ 18.39
Weighted Average Contractual Term
Weighted average contractual term, outstanding			6 years 11 months 26 days		7 years 7 months 20 days
Weighted average contractual term, vested and expected to vest			6 years 11 months 26 days
Weighted average contractual term ,options exercisable			5 years 9 months
Aggregate Intrinsic Value
Aggregate intrinsic value outstanding	$ 29,629		$ 29,629		$ 71,002
Aggregate intrinsic value, vested and expected to vest	29,629		29,629
Aggregate intrinsic value, options exercisable	28,069		$ 28,069
Additional Information
Granted			$ 20.16	$ 32.91
Exercised	100	100	$ 300	$ 1,300
Total share-based compensation expense	$ 6,300	$ 4,700	$ 20,500	$ 17,100

Share-based compensation - Assu

Share-based compensation - Assumptions used in the Black Scholes option pricing model to determine the fair value of share options (Details) - Stock option - Employees and directors - USD ($) $ in Millions	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Share-based compensation.
Risk-free interest rate	4.10%	3%	3.90%	2%
Expected volatility	83.30%	84.10%	83.50%	82.20%
Expected term (in years)	6 years 1 month 6 days	6 years 1 month 6 days	6 years 1 month 6 days	6 years
Unrecognized compensation expense
Total unrecognized compensation expense related to the unvested employee and director	$ 58.6		$ 58.6
Unrecognized compensation cost expected to be recognized over a weighted average period			2 years 8 months 12 days

Share-based compensation - Rest

Share-based compensation - Restricted Share Units (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Restricted shares
Total share-based compensation expense	$ 7,430	$ 5,368	$ 24,665	$ 21,239
Restricted ordinary shares | 2020 Plan
Number of Shares Underlying RSUs
Unvested restricted ordinary shares at beginning			187,725
Granted			321,839
Vested			(99,638)
Forfeited			(74,822)
Unvested restricted ordinary shares at ending	335,104		335,104
Weighted Average Grant Date Fair Value
Weighted average grant date fair value unvested, Beginning Balance			$ 60.86
Granted			29.59
Vested			51.39
Forfeited			39.55
Weighted average grant date fair value unvested, Ending Balance	$ 38.40		$ 38.40
Restricted shares
Fair value of employee restricted share awards vested	$ 500	0	$ 2,600	2,100
Total share-based compensation expense	1,200	$ 700	4,200	$ 4,100
Unrecognized compensation cost	$ 11,000		$ 11,000
Weighted average Period			2 years 8 months 12 days

Significant agreements - Collab

Significant agreements - Collaboration revenues (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Significant agreements.
Collaboration revenues	$ 5,352	$ 3,040	$ 21,645	$ 11,278
Bayer
Significant agreements.
Collaboration revenues	434	0	434	0
Novartis
Significant agreements.
Collaboration revenues	772	0	772	0
Ionis
Significant agreements.
Collaboration revenues	2,782	2,195	8,123	6,764
Genentech
Significant agreements.
Collaboration revenues	1,364	798	11,112	3,144
Dementia Discovery Fund
Significant agreements.
Collaboration revenues		47		205
AstraZeneca
Significant agreements.
Collaboration revenues	$ 0	$ 0	$ 1,204	$ 1,165

Significant agreements - Bayer

Significant agreements - Bayer Collaboration Agreement (Details) $ in Thousands, £ in Millions		3 Months Ended		9 Months Ended
	May 04, 2023 USD ($) item	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	May 04, 2023 GBP (£) item	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Significant agreements.
Revenue from collaborative arrangement		$ 5,352	$ 3,040	$ 21,645	$ 11,278
Deferred revenue		134,772		134,772			$ 61,873	$ 71,340
Bayer Collaboration Agreement
Significant agreements.
Number of collaboration targets | item	2					2
Upfront cash payment	$ 45,000
Milestone payments, receivable | £						£ 583.5
Period to terminate agreement upon written notice for uncured material breach	90 days
Number of business days to terminate agreement upon non payment by Bayer	20 days
Transaction price	$ 47,500
Estimated amount payable to CROs	$ 2,500
Expected period for satisfaction of performance obligations	4 years
Material rights exercise period	7 years
Revenue from collaborative arrangement		434	$ 0	434	$ 0
Deferred revenue		$ 42,521		$ 42,521			$ 0
Bayer Collaboration Agreement | Minimum
Significant agreements.
Number of candidate compounds into further development | item	1					1
Threshold period to terminate agreement upon written notice by Bayer	60 days
Bayer Collaboration Agreement | Maximum
Significant agreements.
Number of collaboration targets | item	3					3
Milestone payments receivable | £						£ 194.5
Threshold period to terminate agreement upon written notice by Bayer	90 days
Bayer Collaboration Agreement | Development and regulatory milestones | Maximum
Significant agreements.
Milestone payments receivable | £						178.3
Bayer Collaboration Agreement | Across all three potential target programs
Significant agreements.
Milestone payments receivable | £						£ 534.9

Significant agreements - Baye_2

Significant agreements - Bayer Collaboration Agreement - Accounting Analysis (Details) - Bayer Collaboration Agreement $ in Thousands	May 04, 2023 USD ($) item
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Transaction price	$ 47,500
Two combined performance obligations related to the licenses and research and development services associated with radiopharmaceutical compounds directed to the first and second targets [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Combined performance obligations | item	2
Transaction price	$ 14,976
Material right associated with limited substitution rights for either the first or second target [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Transaction price	$ 1,527
Two material rights associated with the option to progress radiopharmaceutical candidates directed to the first and second targets into further development [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of material rights | item	2
Transaction price	$ 14,691
Two material rights associated with the option to progress a non-radiopharmaceutical compound directed to the first and second targets [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of material rights | item	2
Transaction price	$ 8,703
Material right for the option to expand the collaboration to include a third target and the underlying additional option rights [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Transaction price	$ 7,603

Significant agreements - Novart

Significant agreements - Novartis Collaboration Agreement (Details) $ in Thousands		3 Months Ended		9 Months Ended
	Mar. 27, 2023 USD ($) item	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Maximum days allowed for cancellation of contracts prior written notice				90 days
Revenue from collaborative arrangement		$ 5,352	$ 3,040	$ 21,645	$ 11,278
Termination In Entirety Or Product By Product Or Target By Target Basis [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Threshold period of notice required for termination of agreement	90 days
Completion of All Milestones For Targets [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Milestone payments receivable	$ 800,000
Novartis
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of collaboration targets | item	2
Additional research term	1 year
Upfront cash payment	$ 50,000
Milestone payments receivable	210,000
Milestone payments, receivable	$ 840,000
Maximum days allowed for cancellation of contracts prior written notice	30 days
Total transaction price initially determined	$ 50,000
Expected period for satisfaction of performance obligations	3 years
Material rights exercise period	6 years
Revenue from collaborative arrangement		$ 772	$ 0	$ 772	$ 0
Novartis | Termination Based On Other Party's Uncured Material Breach Or Insolvency [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Threshold period of notice required for termination of agreement	60 days
Novartis | Termination If Safety Or Regulatory Issue Exists [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Threshold period of notice required for termination of agreement	30 days
Novartis | Achievement of Specified Levels of Net Sales [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Milestone payments receivable	$ 200,000

Significant agreements - Nova_2

Significant agreements - Novartis Collaboration Agreement - Accounting Analysis (Details) $ in Thousands		3 Months Ended		9 Months Ended
	Mar. 27, 2023 USD ($) item	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Collaboration revenues		$ 5,352	$ 3,040	$ 21,645	$ 11,278
Deferred revenue		134,772		134,772		$ 61,873	$ 71,340
Novartis
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Transaction price	$ 50,000
Collaboration revenues		772	$ 0	772	$ 0
Deferred revenue		$ 49,050		$ 49,050		$ 0
Novartis | Two Combined Performance Obligations For First And Second Targets [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Combined performance obligations | item	2
Transaction price	$ 18,008
Novartis | Two Material Rights Associated With Limited Substitution Rights [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of material rights | item	2
Transaction price	$ 2,466
Novartis | Two Material Rights Associated With Options To Progress Development Candidates Incorporating Radionuclides [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of material rights | item	2
Transaction price	$ 19,684
Novartis | Two Material Rights Associated With Options To Progress Development Candidates Not Incorporating Radionuclides [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of material rights | item	2
Transaction price	$ 9,842

Significant agreements - Ionis

Significant agreements - Ionis Evaluation and Option Agreement (Details) - USD ($) $ in Thousands		1 Months Ended	9 Months Ended	12 Months Ended
	Jul. 09, 2021	Jan. 31, 2021	Sep. 30, 2023	Dec. 31, 2020	Dec. 31, 2022	Dec. 31, 2021
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Deferred revenue			$ 134,772		$ 61,873	$ 71,340
Ionis Evaluation and Option Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Term of the Evaluation Period (in months)				4 months
Upfront cash payment	$ 3,000	$ 3,000	$ 3,000	$ 3,000
Threshold period of notice required for termination of agreement			30 days
Deferred revenue				$ 3,000	$ 21,500

Significant agreements - Ioni_2

Significant agreements - Ionis Collaboration Agreement (Details) $ in Millions		1 Months Ended					9 Months Ended	12 Months Ended
	Jul. 09, 2021 USD ($) item	Apr. 30, 2023 USD ($)	Oct. 31, 2022 USD ($)	Aug. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Jan. 31, 2021 USD ($)	Sep. 30, 2023 USD ($)	Dec. 31, 2020 USD ($)
Ionis
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Period for which research and discovery activities will be performed with no additional consideration	3 years
Upfront cash payment	$ 31
Number of payments of a mid-single-digit million dollar, failing to achieve the specified development diligence | item	3
Number of collaboration targets | item	4
Number of years over which royalty is payable	10 years
Ionis Evaluation and Option Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront cash payment	$ 3					$ 3	$ 3	$ 3
Amended Ionis
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront cash payment					$ 1.6
Amended Ionis | Service for initial six month
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront cash payment				$ 0.8
Amended Ionis | Service for additional six month
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront cash payment			$ 0.8
Third Ionis Amendment
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront cash payment		$ 0.8
Third Ionis Amendment | Additional research service for a year
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront cash payment		$ 0.8

Significant agreements - Ioni_3

Significant agreements - Ionis Share Purchase Agreement (Details) - USD ($) $ / shares in Units, $ in Thousands		3 Months Ended
	Jul. 09, 2021	Sep. 30, 2023	Jun. 30, 2023	Mar. 31, 2023
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Aggregate purchase price		$ 234,492	$ 12,127	$ 2,716
Ionis
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Transaction price	$ 38,000	$ 38,000
Ionis | Ionis Share Purchase Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Shares issued (in shares)	282,485
Purchase price per share	$ 38.94
Aggregate purchase price	$ 11,000
Fair value of shares held	7,600
Transaction price	$ 3,400
Ionis | Ionis Share Purchase Agreement | American Depositary Shares
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Purchase price per share	$ 31.11

Significant agreements - Ioni_4

Significant agreements - Ionis Accounting analysis (Details) $ in Thousands		1 Months Ended			3 Months Ended		9 Months Ended		12 Months Ended
	Jul. 09, 2021 USD ($) item	Oct. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Jan. 31, 2021 USD ($)	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Sep. 30, 2023 USD ($) item	Sep. 30, 2022 USD ($)	Dec. 31, 2020 USD ($)	Dec. 31, 2022 USD ($)
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Collaboration revenues					$ 5,352	$ 3,040	$ 21,645	$ 11,278
Deferred revenue			$ 71,340		134,772		$ 134,772			$ 61,873
Ionis
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of material rights associated with future payments | item							4
Number of collaboration targets | item	4
Total transaction price initially determined	$ 38,000				38,000		$ 38,000
Upfront cash payment	31,000
Estimated amount payable to CROs	600
Period over which performance obligations will be performed							3 years
Material rights exercise period							4 years
Collaboration revenues					2,782	$ 2,195	$ 8,123	$ 6,764
Deferred revenue			34,115		14,463		14,463			21,489
Ionis | Combined licenses and research and discovery performance obligation
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Total transaction price initially determined					34,100		34,100
Ionis | Four material rights associated with credits for IND Acceptance fees
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Total transaction price initially determined					$ 3,900		3,900
Ionis | Ionis Share Purchase Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Total transaction price initially determined	3,400
Ionis Evaluation and Option Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront cash payment	$ 3,000			$ 3,000			3,000		$ 3,000
Deferred revenue									$ 3,000	$ 21,500
Amended Ionis
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront cash payment			1,600
Collaboration revenues		$ 800	$ 800
Third Amended Ionis
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Collaboration revenues							$ 800

Significant agreements - Genent

Significant agreements - Genentech Collaboration Agreement (Details) $ in Thousands		1 Months Ended		3 Months Ended		9 Months Ended		12 Months Ended
	Feb. 21, 2020 USD ($) item	Dec. 31, 2022 USD ($)	Nov. 30, 2021 USD ($)	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Sep. 30, 2023 USD ($) item	Sep. 30, 2022 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Oct. 31, 2021 USD ($)	Mar. 31, 2021 USD ($)
Significant agreements.
Deferred revenue		$ 61,873		$ 134,772		$ 134,772		$ 61,873	$ 71,340
Collaboration revenues				5,352	$ 3,040	21,645	$ 11,278
Genentech
Significant agreements.
Number of potential development candidates | item	4
Upfront cash payment	$ 30,000
Number of immuno oncology targets | item	2
Additional number of immuno oncology targets | item	2
Expansion Fee	$ 10,000
Milestone payments, receivable											$ 2,000
Transaction price	31,000			33,000		33,000					$ 33,000
Deferred revenue		39,308		28,738		28,738		39,308	$ 34,436
Collaboration revenues				1,364	$ 798	$ 11,112	$ 3,144
Genentech | Royalty
Significant agreements.
Number of years over which royalty is payable						10 years
Genentech | Maximum
Significant agreements.
Milestone payments, receivable	200,000
Genentech | Development milestone | Maximum
Significant agreements.
Milestone payments, receivable	65,000
Genentech | Regulatory milestone | Maximum
Significant agreements.
Milestone payments, receivable	$ 135,000
Genentech | Collaboration Program 1 Performance Obligation
Significant agreements.
Transaction price				4,019		$ 4,019
Genentech | Collaboration Program 2 Performance Obligation
Significant agreements.
Transaction price				8,037		8,037
Genentech | Collaboration Program 3 Performance Obligation
Significant agreements.
Expansion Fee			$ 10,000
Milestone payments, receivable										$ 1,000
Transaction price										11,000
Material rights										$ 3,500
Amount of estimate of variable consideration		2,000
Collaboration revenues		$ 8,400
Genentech | Collaboration Program 3 Performance Obligation | Maximum
Significant agreements.
Period over which performance obligations will be performed		3 years
Genentech | Collaboration Program 3 Performance Obligation | Minimum
Significant agreements.
Period over which performance obligations will be performed		2 years
Genentech | Collaboration Program 4 Performance Obligation
Significant agreements.
Transaction price		$ 10,000						10,000
Deferred revenue		100						100
Material rights		3,500						3,500
Collaboration revenues								5,300
Genentech | Specified Targeting Arm Material Right Arm Program One
Significant agreements.
Number of initial collaboration programs exercised | item	1
Option fee for development and exploitation rights	$ 1,000
Milestone payments, receivable	$ 1,000
Transaction price				352		352
Genentech | Material rights for associated and limited substitution rights
Significant agreements.
Transaction price				1,187		$ 1,187
Deferred revenue		700						700
Genentech | Two material rights associated with the LSR Go Option for Collaboration Programs One And Two
Significant agreements.
Number of collaboration programs | item	2					2
Number of expansion option collaboration programs | item						2
Transaction price				12,400		$ 12,400
Genentech | Material rights associated with the LSR Go Option for Collaboration Programs One
Significant agreements.
Deferred revenue				6,000		6,000
Genentech | Material rights associated with the LSR Go Option for Collaboration Programs Three
Significant agreements.
Deferred revenue		$ 7,400						$ 7,400
Genentech | Two material rights for Expansion Options
Significant agreements.
Number of expansion option collaboration programs | item	2
Transaction price				$ 7,005		$ 7,005
Genentech | Collaboration Program One and Two Performance Obligation
Significant agreements.
Material rights exercise period						4 years
Genentech | Collaboration Program One and Two Performance Obligation | Maximum
Significant agreements.
Regulatory, and initial commercialization milestones, payments receivable	$ 200,000
Period over which performance obligations will be performed						3 years
Genentech | Collaboration Program One and Two Performance Obligation | Minimum
Significant agreements.
Period over which performance obligations will be performed						2 years

Significant agreements - AstraZ

Significant agreements - AstraZeneca Collaboration Agreement (Details) $ in Thousands

1 Months Ended

3 Months Ended

9 Months Ended

May 31, 2018 USD ($)

Nov. 30, 2016 item

Sep. 30, 2023 USD ($)

Sep. 30, 2022 USD ($)

Sep. 30, 2023 USD ($)

Sep. 30, 2022 USD ($)

Dec. 31, 2022 USD ($)

Jun. 30, 2022 USD ($)

Dec. 31, 2021 USD ($)

Aug. 31, 2021 USD ($)

Oct. 31, 2020 USD ($)

Jun. 30, 2019 USD ($)

Significant agreements.

Collaboration revenues

$ 5,352

$ 3,040

$ 21,645

$ 11,278

Deferred revenue

134,772

134,772

$ 61,873

$ 71,340

AstraZeneca

Significant agreements.

Option fee for development and exploitation rights

$ 5,000

Transaction price

5,700

Collaboration revenues

0

$ 0

1,204

$ 1,165

Deferred revenue

$ 0

0

$ 1,076

$ 2,361

Deferred revenue recognized

$ 1,200

AstraZeneca | Target 3 Material Right

Significant agreements.

Deferred revenue related to the associated material rights

$ 1,500

AstraZeneca | Target 5 Material Right

Significant agreements.

Deferred revenue related to the associated material rights

$ 1,100

AstraZeneca | Target 6 Material Right

Significant agreements.

Deferred revenue related to the associated material rights

$ 1,200

AstraZeneca | Development Milestone

Significant agreements.

Transaction price

700

AstraZeneca | 2016 Collaboration Agreement

Significant agreements.

Biological Targets | item

2

AstraZeneca | May 2018 Option Exercise

Significant agreements.

Option fee for development and exploitation rights

$ 5,000

Transaction price

$ 6,300

Significant agreements - Summar

Significant agreements - Summary of Contract Assets and Liabilities (Details) - USD ($)	9 Months Ended	12 Months Ended
	Sep. 30, 2023	Dec. 31, 2022
Contract liabilities:
Beginning Balance	$ 61,873,000	$ 71,340,000
Additions	95,870,000	12,099,000
Deductions	(21,645,000)	(14,463,000)
Impact of Exchange Rates	(1,326,000)	(7,103,000)
Ending Balance	134,772,000	61,873,000
Contract assets
Contract assets	0	0
Bayer Collaboration Agreement
Contract liabilities:
Beginning Balance	0
Additions	45,000,000
Deductions	(434,000)
Impact of Exchange Rates	(2,045,000)
Ending Balance	42,521,000	0
Bayer Collaboration Agreement | Deferred revenue material rights option
Contract liabilities:
Ending Balance	31,000,000
Novartis
Contract liabilities:
Beginning Balance	0
Additions	50,000,000
Deductions	(772,000)
Impact of Exchange Rates	(178,000)
Ending Balance	49,050,000	0
Novartis | Deferred revenue material rights option
Contract liabilities:
Ending Balance	31,900,000
Ionis
Contract liabilities:
Beginning Balance	21,489,000	34,115,000
Additions	870,000	99,000
Deductions	(8,123,000)	(9,347,000)
Impact of Exchange Rates	227,000	(3,378,000)
Ending Balance	14,463,000	21,489,000
Ionis | Deferred revenue material rights option
Contract liabilities:
Ending Balance	3,500,000
Genentech
Contract liabilities:
Beginning Balance	39,308,000	34,436,000
Additions	0	12,000,000
Deductions	(11,112,000)	(3,565,000)
Impact of Exchange Rates	542,000	(3,563,000)
Ending Balance	28,738,000	39,308,000
Genentech | Deferred revenue material rights option
Contract liabilities:
Ending Balance	20,900,000
Dementia Discovery Fund
Contract liabilities:
Beginning Balance		428,000
Additions		0
Deductions		(386,000)
Impact of Exchange Rates		(42,000)
AstraZeneca
Contract liabilities:
Beginning Balance	1,076,000	2,361,000
Additions	0	0
Deductions	(1,204,000)	(1,165,000)
Impact of Exchange Rates	128,000	(120,000)
Ending Balance	$ 0	$ 1,076,000

Significant agreements - Revenu

Significant agreements - Revenue recognition due to changes in contract assets and liabilities (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Significant agreements
Revenue recognized based on proportional performance	$ 5,006	$ 3,040	$ 13,829	$ 10,072
Revenue recognized based on expiration of material rights	346		7,816	1,206
Total	$ 5,352	$ 3,040	$ 21,645	$ 11,278

Significant agreements - Cancer

Significant agreements - Cancer Research UK (Details) - USD ($) $ in Millions		1 Months Ended
	Dec. 13, 2016	Dec. 31, 2019	Sep. 30, 2023	Dec. 31, 2022
Research and development arrangement obligation to repay other parties
Contingent future milestones payments under research and development arrangement	$ 50.9	$ 60.3
Other long term liabilities
Research and development arrangement obligation to repay other parties
Liability from research and development			$ 4.1	$ 3.6
BT1718 | Minimum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)	70%
BT1718 | Maximum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)	90%
BT7401 | Minimum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)		55%
BT7401 | Maximum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)		80%

Income taxes (Details)

Income taxes (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Income taxes
Provision for (benefit from) income taxes	$ 2,272	$ (238)	$ 1,137	$ (1,104)
Increase (decrease) in income taxes	$ 2,400

Commitments and contingencies -

Commitments and contingencies - Leases, Office and laboratory space Cambridge (Details) - USD ($) $ in Thousands			3 Months Ended	9 Months Ended
	Jan. 26, 2023	Dec. 06, 2021	Sep. 30, 2023	Sep. 30, 2023	Jan. 31, 2023	Dec. 31, 2022	Mar. 31, 2022	Dec. 31, 2021	Sep. 30, 2017
Leases
Operating lease right-of-use assets			$ 14,597	$ 14,597		$ 13,658
Lease liabilities			15,084	15,084
Payments for the extended lease due remainder of fiscal year			1,394	1,394
Office and laboratory space in Cambridge Massachusetts
Leases
Lease total contractual Term	3 years
Renewal term					2 years
Leases, term of contract	3 years
Annual rent	$ 2,100
Rental payment	$ 2,300
Rent free period	2 months
Security deposit	$ 500
Operating lease right-of-use assets	5,800
Lease liabilities	$ 5,800
Discounted percentage for present value of lease payments	9%
New Office and laboratory space in Cambridge, United Kingdom
Leases
Lease total contractual Term		10 years
Renewal term		10 years
Leases, term of contract		5 years
Annual rent		$ 3,000
Rent free period		6 months
Security deposit		$ 0
Operating lease right-of-use assets		11,600
Lease liabilities		$ 11,100
Discounted percentage for present value of lease payments		6.90%
Office and laboratory space in Building 900, Babraham Research Campus, Cambridge
Leases
Renewal term								5 years
Annual rent								$ 600
Estimated service charges payable								$ 200
Office and laboratory space in Building 900, Babraham Research Campus, Cambridge | General and administrative expenses
Leases
Loss on lease termination			300	300
Office and laboratory space in Lexington, Massachusetts
Leases
Annual rent			800	800
Security deposit									$ 200
Discounted percentage for present value of lease payments							7%
Payments for the extended lease remaining through December						$ 200
Payments for the extended lease due remainder of fiscal year			$ 700	$ 700
Prepaid rent									$ 100

Commitments and contingencies_2

Commitments and contingencies - Components of lease expense (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Commitments and contingencies
Operating lease cost	$ 1,364	$ 924	$ 4,057	$ 2,866
Variable lease cost	566	410	2,017	1,005
Total lease cost	$ 1,930	$ 1,334	$ 6,074	$ 3,871
Weighted-average remaining operating lease term (years)	3 years 2 months 12 days	4 years 6 months	3 years 2 months 12 days	4 years 6 months
Weighted-average discount rate	7.94%	7.03%	7.94%	7.03%

Commitments and contingencies_3

Commitments and contingencies - Leases, Maturities of operating leases (Details) - USD ($) $ in Thousands	9 Months Ended
	Sep. 30, 2023	Dec. 31, 2022
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
2023	$ 1,394
2024	5,654
2025	5,740
2026	3,271
2027	821
Present value adjustment	(1,796)
Total lease liabilities	15,084
Less: current lease liabilities	$ (4,661)	$ (3,125)
Operating Lease, Liability, Current, Statement of Financial Position [Extensible List]	Accrued Liabilities and Other Liabilities, Current	Accrued Liabilities and Other Liabilities, Current
Long term lease liabilities	$ 10,423	$ 10,885
Maximum days allowed for cancellation of contracts prior written notice	90 days
Agreement With Third Party
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Milestone payments	$ 92,400
Future milestone payment payable	1,300
Agreement With CRUK
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Future milestone payment receivable	$ 111,200

Commitments and contingencies_4

Commitments and contingencies - Founder Royalty arrangements (Details)	9 Months Ended
	Sep. 30, 2023 USD ($)
Founder Royalty arrangements
Period of royalty payments agreed under arrangement	10 years
Royalties earned	$ 0
Royalties paid	0
Founders and initial investors | Royalty Agreements
Founder Royalty arrangements
Royalties earned	0
Royalties paid	$ 0

Net loss per share - Basic and

Net loss per share - Basic and diluted net loss per share (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Numerator:
Net loss	$ (49,898)	$ (28,347)	$ (131,565)	$ (82,739)
Denominator:
Weighted average ordinary shares outstanding, basic	39,576,467	29,676,021	33,291,701	29,643,502
Weighted average ordinary shares outstanding, diluted	39,576,467	29,676,021	33,291,701	29,643,502
Net loss per share, basic	$ (1.26)	$ (0.96)	$ (3.95)	$ (2.79)
Net loss per share, diluted	$ (1.26)	$ (0.96)	$ (3.95)	$ (2.79)

Net loss per share - Securities

Net loss per share - Securities excluded from the diluted per share calculation (Details) - shares	9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022
Antidilutive securities
Antidilutive securities (in shares)	7,647,124	5,972,306
Restricted ordinary shares
Antidilutive securities
Antidilutive securities (in shares)	335,104	187,725
Options to purchase ordinary shares
Antidilutive securities
Antidilutive securities (in shares)	7,312,020	5,784,581

Related party transactions (Det

Related party transactions (Details) - USD ($)	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Related party transactions
Royalties earned			$ 0
Royalties paid			0
General and administrative	$ 16,281,000	$ 10,047,000	45,557,000	$ 38,830,000
Affiliated Entity | Consultancy services with Stone Sunny Isles Inc.
Related party transactions
General and administrative	$ 49,000	$ 43,000	$ 200,000	$ 200,000

Geographic information (Details

Geographic information (Details) $ in Thousands	9 Months Ended
	Sep. 30, 2023 USD ($) segment	Dec. 31, 2022 USD ($)
Geographic information
Number of geographic regions | segment	2
Long lived assets, including operating lease right of use assets	$ 30,196	$ 32,768
United States
Geographic information
Long lived assets, including operating lease right of use assets	8,817	4,466
United Kingdom
Geographic information
Long lived assets, including operating lease right of use assets	$ 21,379	$ 28,302