0001558370-24-001324 | 10-K | XBRL Viewer

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Significant agreements - Genentech Collaboration Agreement (Details) $ in Thousands		1 Months Ended			12 Months Ended
	Feb. 21, 2020 USD ($) item	Dec. 31, 2022 USD ($)	Jun. 30, 2022 USD ($)	Oct. 31, 2021 USD ($)	Dec. 31, 2023 USD ($) item	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Mar. 31, 2021 USD ($)
Significant agreements.
Deferred revenue		$ 61,873			$ 135,194	$ 61,873	$ 71,340
Collaboration revenues					26,976	14,463	11,697
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
Deferred revenue		39,308			29,104	39,308	34,436
Collaboration revenues					$ 11,969	3,565	$ 5,660
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
Genentech \| Collaboration Program 2 Performance Obligation
Significant agreements.
Transaction price					8,037
Genentech \| Collaboration Program 3 Performance Obligation
Significant agreements.
Expansion Fee			$ 10,000	$ 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.
Expansion Fee			10,000
Deferred revenue		$ 100				100
Material rights			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
Genentech \| Material rights for associated and limited substitution rights
Significant agreements.
Transaction price					$ 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
Genentech \| Material rights associated with the LSR Go Option for Collaboration Programs One
Significant agreements.
Deferred revenue					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
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

Long-term debt (Tables)

12 Months Ended

Dec. 31, 2023

Long-term debt

Schedule of long term debt instruments

Long-term debt consisted of the following (in thousands):


	December 31,		December 31,
	2023		2022
Term loan payable	$	30,000	$	30,000
End of term charge		946		682
Unamortized debt issuance costs		(248)		(367)
Carrying value of term loan	$	30,698	$	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,
2024		—
2025		31,500
Total	$	31,500

- Definition

Tabular disclosure of long-debt instruments or arrangements, including identification, terms, features, collateral requirements and other information necessary to a fair presentation. These are debt arrangements that originally required repayment more than twelve months after issuance or greater than the normal operating cycle of the entity, if longer.

+ References

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+ Details

Property and equipment, net

12 Months Ended

Dec. 31, 2023

Property and equipment, net

Property and equipment, net

4. Property and equipment, net

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


	December 31,		December 31,
	2023		2022
Laboratory equipment	$	15,554	$	14,872
Leasehold improvements		11,000		10,736
Computer equipment and software		532		441
Furniture and office equipment		822		924
		27,908		26,973
Less: Accumulated depreciation and amortization		(13,393)		(7,863)
	$	14,515	$	19,110

As of December 31, 2023, there was no property and equipment that was not yet placed in service. As of December 31, 2022, approximately $2.3 million of laboratory equipment was not yet placed in service. Depreciation expense was $6.5 million, $3.7 million and $1.4 million for the years ended December 31, 2023, 2022 and 2021, respectively.

Significant agreements - Novartis Collaboration Agreement - Accounting Analysis (Details) $ in Thousands		12 Months Ended
	Mar. 27, 2023 USD ($) item	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Collaboration revenues		$ 26,976	$ 14,463	$ 11,697
Deferred revenue		135,194	61,873	$ 71,340
Novartis
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Transaction price	$ 50,000
Collaboration revenues		1,909
Deferred revenue		$ 50,008	$ 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

Document and Entity Information - USD ($)	12 Months Ended
Document and Entity Information - USD ($)	Dec. 31, 2023	Feb. 15, 2024	Jun. 30, 2023
Document Information [Line Items]
Document Type	10-K
Document Annual Report	true
Document Period End Date	Dec. 31, 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 Well Known Seasoned Issuer	Yes
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Filer Category	Large Accelerated Filer
Entity Small Business	true
Entity Emerging Growth Company	false
ICFR Auditor Attestation Flag	true
Document Financial Statement Error Correction [Flag]	false
Entity Shell Company	false
Entity Public Float			$ 767,088,071
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2023
Document Fiscal Period Focus	FY
Entity Central Index Key	0001761612
Amendment Flag	false
Auditor Name	PricewaterhouseCoopers LLP
Auditor Location	Cambridge, United Kingdom
Auditor Firm ID	876
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		37,880,303
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

Summary of significant accounting policies - Share based compensation (Details)	12 Months Ended
	Dec. 31, 2023
Summary of significant accounting policies
Expected dividend yield	0.00%

Significant agreements - Novartis Collaboration Agreement (Details) $ in Thousands		12 Months Ended
	Mar. 27, 2023 USD ($) item	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
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		$ 26,976	$ 14,463	$ 11,697
Termination in entirety or product by product or target by target basis
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
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		$ 1,909
Novartis \| Termination based on other party's uncured material breach or insolvency
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
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
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Milestone payments receivable	$ 200,000

Subsequent events (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended	12 Months Ended
Subsequent events (Details) - USD ($) $ in Thousands	Jun. 30, 2022	Mar. 31, 2024	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Subsequent Event [Line Items]
Collaboration revenues			$ 26,976	$ 14,463	$ 11,697
Genentech
Subsequent Event [Line Items]
Collaboration revenues			$ 11,969	$ 3,565	$ 5,660
Genentech \| Collaboration Program 3 Performance Obligation
Subsequent Event [Line Items]
Collaboration revenues	$ 8,400
Subsequent events \| Forecast \| Genentech \| Collaboration Program 3 Performance Obligation
Subsequent Event [Line Items]
Collaboration revenues		$ 10,400
Revenue recognized		$ 7,400

- Definition

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

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 924
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Reference 4: http://www.xbrl.org/2003/role/disclosureRef
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-URI https://asc.fasb.org//1943274/2147482810/280-10-50-42

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Reference 9: http://www.xbrl.org/2003/role/disclosureRef
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+ Details

Significant agreements - Dementia Discovery Fund Agreement (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2019
Significant agreements.
Collaboration revenues		$ 26,976	$ 14,463	$ 11,697
Deferred revenue		135,194	61,873	71,340
Dementia Discovery Fund
Significant agreements.
Upfront cash payment					$ 1,100
Collaboration revenues		0	386	391
Deferred revenue		$ 0	$ 0	$ 428
Dementia Discovery Fund \| Specific scientific criteria milestone
Significant agreements.
Milestone payment received	$ 500

- Definition

+ References

+ Details

Summary of significant accounting policies - Research and development incentives and receivable (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Research and development incentives and receivable
Reduction of research and development	$ 23.5	$ 19.3	$ 10.8
Certain research and development expenditures incurred prior to April 1, 2023
Research and development incentives and receivable
Percentage of surrenderable losses	14.50%
Certain research and development expenditures incurred thereafter April 1, 2023
Research and development incentives and receivable
Percentage of surrenderable losses	10.00%

Significant agreements - Oxurion Collaboration Agreement (Details) € in Millions, £ in Millions	12 Months Ended
	Dec. 31, 2023 USD ($)	Dec. 31, 2023 EUR (€)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2023 GBP (£)	Dec. 31, 2023 EUR (€)
Significant agreements.
Deferred revenue	$ 135,194,000		$ 61,873,000	$ 71,340,000
Oxurion
Significant agreements.
Revenue recognized	0		$ 0	$ 0
Deferred revenue	$ 0
Oxurion \| Development milestone
Significant agreements.
Potential milestone payments \| €						€ 8.3
Revenue under contracts with customer from milestone payment \| €		€ 3.8
Oxurion \| Regulatory milestone
Significant agreements.
Potential milestone payments \| £					£ 16.5
Oxurion \| Granting first regulatory approval or first indication
Significant agreements.
Potential milestone payments \| £					£ 5.0

Long-term debt

12 Months Ended

Dec. 31, 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.

During 2021, borrowings under the Loan Agreement bore interest at an annual rate equal to the greater of (i) 8.85% or (ii) 5.60% plus The Wall Street Journal prime rate. 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, 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 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 1.0% of the principal amount outstanding. 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 5.0% may be applied to the outstanding principal and interest payments due, and Hercules may declare all outstanding obligations immediately due and payable and take such other actions as set forth in the Loan Agreement. The Company has determined that the risk of subjective acceleration under the material adverse events clause is not probable and therefore has classified the outstanding principal in long-term liabilities based on scheduled principal payments.

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 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 the 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 December 31, 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 years ended December 31, 2023, 2022 and 2021 was $3.1 million, $3.2 million and $2.9 million, respectively.

Long-term debt consisted of the following (in thousands):


	December 31,		December 31,
	2023		2022
Term loan payable	$	30,000	$	30,000
End of term charge		946		682
Unamortized debt issuance costs		(248)		(367)
Carrying value of term loan	$	30,698	$	30,315

Future principal payments, including the End of Term Charge, are as follows (in thousands):


Year Ending December 31,
2024		—
2025		31,500
Total	$	31,500

- Definition

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

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 470
-SubTopic 20
-Name Accounting Standards Codification
-Section 50
-Paragraph 1B
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+ Details

Income taxes - Reconciliation of benefit for income taxes (Details)	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Income taxes
Provision for (benefit from) income taxes at statutory rate	23.50%	19.00%	19.00%
(Decreases) increases resulting from:
Federal tax credits	0.30%	0.30%	0.60%
Change in valuation allowance	(14.80%)	(16.80%)	(27.00%)
Net losses surrendered for research credit	(11.10%)	(6.50%)	(5.90%)
Impact of statutory rate change	2.70%	11.30%	12.10%
Impact of foreign exchange rates	(0.10%)	(9.90%)
Other	(1.30%)	3.90%	3.60%
Effective income tax rate	(0.80%)	1.30%	2.40%

Significant agreements

12 Months Ended

Dec. 31, 2023

Significant agreements

Significant agreements

9. Significant agreements

For the years ended December 31, 2023, 2022 and 2021, the Company recognized revenue in connection with its collaborations with Bayer, Novartis, Ionis, Genentech, DDF, and AstraZeneca. The following table summarizes the revenue recognized in the Company’s consolidated statements of operations and comprehensive loss from these arrangements (in thousands):



	Year Ended
	December 31,
	2023		2022		2021
Collaboration revenues
Bayer	$	1,160	$	—	$	—
Novartis		1,909		—		—
Ionis		10,734		9,347		4,242
Genentech		11,969		3,565		5,660
Dementia Discovery Fund		—		386		391
AstraZeneca		1,204		1,165		1,404
Total collaboration revenues	$	26,976	$	14,463	$	11,697

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 constructs directed to two specified targets, 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 paid an upfront payment to the Company of $45.0 million 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. Upon declaring a candidate, Bayer will be responsible for all future development, manufacturing, and commercialization activities. 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

At inception of the Bayer Collaboration Agreement, the Company identified the following performance obligations:

(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 Company exercised judgment in concluding that certain development and commercialization rights associated with progressing product candidates into further development and commercialization represent options that are material rights, as Bayer cannot benefit from the development and commercialization rights until Bayer, in its sole discretion, elects to progress candidates into further development and pays the associated candidate selection fees.

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 ASC 606. The remaining 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 the first and second 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 that Bayer would pay to exercise the options, the estimated value of the underlying goods and services, and the probability that Bayer would exercise the options, inclusive of the probability of technical success. 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

The Company is recognizing 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 full-time equivalent efforts and external costs incurred to date as a percentage of total expected full-time equivalent efforts and 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 four years and the remaining material rights are expected to be exercised or expire within approximately seven years from contract inception.

During the year ended December 31, 2023, the Company recognized revenue of $1.2 million in connection with the Bayer Collaboration Agreement. The Company did not recognize revenue in connection with the Bayer Collaboration Agreement during the years ended December 31, 2022 or 2021. As of December 31, 2023 and 2022, the Company recorded deferred revenue of $43.6 million and zero, respectively, in connection with the Bayer Collaboration Agreement.

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 constructs directed to two specified targets, under the oversight of a joint steering committee. The Company granted Novartis a non-exclusive, worldwide, royalty-free, sublicensable (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 paid a nonrefundable upfront payment to the Company of $50.0 million 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 days’ written notice for the other party’s uncured material breach, or upon the other party’s insolvency. In addition, Novartis may terminate the Collaboration Agreement (i) in its entirety or on a product-by-product or target-by-target basis for any reason upon 90 days’ written notice to Company, and (ii) on a target-by-target basis on 30 days’ written notice if Novartis determines that a safety or regulatory issue exists which would have a material adverse effect on the development, manufacture, or commercialization of any product with respect to a given target. The Company may terminate the Novartis Collaboration Agreement, (a) on a target-by-target basis upon 30 days’ prior written notice if Novartis has not yet declared a development candidate for such target by the sixth anniversary of the commencement of research activities for such target and (b) if Novartis or any of its affiliates or sublicensees challenges the validity or enforceability of any of the patents in the Company’s licensed intellectual property.

Accounting Analysis

Upon the execution of the Novartis Collaboration Agreement, the Company identified the following performance obligations:

(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 price 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. The Company exercised judgment in concluding that Novartis’ rights to obtain certain research and development services associated with compounds that do not incorporate a radionuclide during the research term are not options that are material rights as they do not represent either options for additional goods or services or options for additional services that are at a discount that it would not have otherwise received.

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, inclusive of the probability of technical success. 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 comprised of the Novartis Research License and the related research and development services during the research term 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 is recognizing 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 year ended December 31, 2023, the Company recognized revenue of $1.9 million in connection with the Novartis Collaboration Agreement. The Company did not recognize revenue in connection with the Novartis Collaboration Agreement during the years ended December 31, 2022 or 2021. As of December 31, 2023 and 2022, the Company recorded deferred revenue of $50.0 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, 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. Ionis paid the Company a nonrefundable option fee of $3.0 million in January 2021 that was fully creditable against the upfront payment to be paid upon the execution of a license agreement. On July 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 an existing arrangement. Therefore, the $3.0 million paid 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 peptides directed to the protein coded by the gene TFRC1 (transferrin receptor) (“TfR1 Bicycle” molecules) 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 Bicycle molecules and other research and discovery activities related to TfR1 Bicycle molecules, 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 three years 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 Bicycle molecules for all non-oligonucleotide therapeutic purposes.

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 four collaboration targets, or for exclusivity payments for certain targets if specified development diligence milestones deadlines are not achieved), and Ionis will be required to make milestone payments upon the achievement of specified development and regulatory milestones of up to a low double-digit million dollar amount per collaboration target. In addition, the Company is eligible to receive up to a low double-digit million dollar amount in cumulative sales milestone payments. The Company is also entitled to receive tiered royalty payments on net sales at percentages in the low single digits, subject to certain standard reductions and offsets. Royalties will be payable, on a product-by-product and country-by-country basis, until the latest of the expiration of specified licensed patents covering such product in such country, ten years from first commercial sale of such product in such country, or expiration of marketing exclusivity for such product in such country.

In December 2021, the Company and Ionis entered into an amendment to the Ionis Collaboration Agreement (the “Ionis Amendment”). Ionis paid the Company $1.6 million and the Company agreed to perform additional research services utilizing its proprietary phage screening technology to identify and optimize new product candidates that target the TfR1 receptor. The Company performed the additional research services for an initial six-month period, which was extended in August 2022 for an additional three months, in exchange for consideration of $0.8 million. In October 2022, 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 the Ionis Share Purchase Agreement with Ionis, pursuant to which Ionis purchased 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. 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 $3.4 million was included in the transaction price under the Ionis Collaboration Agreement.

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 Bicycle molecules intended for the delivery of oligonucleotide compounds directed to targets selected by Ionis for diagnostic, therapeutic, prophylactic and preventative uses in humans; ii) research and discovery activities to customize and optimize such TfR1 Bicycle molecules; iii) four material rights associated with options to obtain credits to be applied towards the IND acceptance fee for four collaboration targets.

The Company’s participation in the JSC was deemed immaterial in the context of the contract. The Company has concluded that the exclusive license to research, develop, manufacture and commercialize products is not distinct from the research and discovery services as Ionis cannot obtain the intended benefit of the license without the Company performing the agreed upon research and discovery services, including the optimization of such TfR1 Bicycle molecules. The services incorporate proprietary technology, unique skills and specialized expertise to optimize Bicycle molecules that are not available in the marketplace. As a result, the exclusive license to research, develop, manufacture and commercialize products has been combined with the research and discovery activities into a single performance obligation. The Company concluded that the 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 as performance obligations 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 Purchase Agreement, and an estimated $0.6 million for the reimbursement of CRO costs. Additional variable consideration including development diligence milestone deadline extension payments, development and regulatory milestone payments, sales milestone payments and royalty payments was fully constrained as a result of the uncertainty regarding whether any of the milestones will be achieved.

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 price of the Ionis combined licenses and research and discovery performance obligation was based on the nature of the licenses to be delivered, as well as 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 price for the material rights was determined based on the estimated value of the underlying goods and services, and the probability

that Ionis would exercise the option. 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

The Company is recognizing revenue related to amounts allocated to the combined licenses and research and discovery performance obligation using a proportional performance model over the period of service using input-based measurements including total full-time equivalent effort and CRO costs incurred to date as a percentage of total full-time equivalent effort and CRO costs expected, which best reflects the progress towards satisfaction of the performance obligation. The amount allocated to the material rights is recorded as deferred revenue and the Company commences revenue recognition upon exercise of or upon expiry of the respective option. The Company anticipates that the combined licenses and research and discovery performance obligation will be satisfied over a period of three years and anticipates the material rights may be exercisable or may expire after approximately four years from contract execution.

The Company concluded that the Ionis Amendment will be accounted for as a separate contract, as the services are distinct from the Ionis Collaboration Agreement, and the price of the contract increased by an amount of consideration that reflects the Company’s standalone selling price. The Company concluded that the option does not contain a material right. The Company recognized the $0.8 million associated with the services in the initial six-month period as revenue as the underlying services were 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 expected full time equivalent efforts and expected external costs, which best reflects the progress towards satisfaction of the performance obligation. As the option to perform additional research services for an additional six months does not contain a material right, the Company accounted for Ionis’ exercise of the option in October 2022 as a separate contract. The Company recognized the $0.8 million associated with the services for the additional six-month period as revenue as the underlying services were 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 expected full time equivalent efforts and expected external costs, which best reflects the progress towards satisfaction of the performance obligation.

The Company concluded that the Third Ionis Amendment will be accounted for as a contract modification to the separate contract under the Ionis Amendment, as the services are not distinct from the services provided under the Ionis Amendment. The Company is recognizing the $0.8 million associated with the services for the additional one-year period as revenue 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 expected full time equivalent efforts and expected external costs, which best reflects the progress towards satisfaction of the performance obligation.

For the years ended December 31, 2023, 2022 and 2021, the Company recognized $10.7 million, $9.3 million and $4.2 million in revenue, respectively, and as of December 31, 2023 and 2022, the Company recorded deferred revenue of $12.5 million and $21.5 million, respectively, in connection with the Ionis Collaboration Agreement, Ionis Amendments, and Ionis Evaluation and Option Agreement.

Genentech Collaboration Agreement

On February 21, 2020, the Company entered into a Discovery Collaboration and License Agreement, as amended from time to time (as amended, the “Genentech Collaboration Agreement”), with Genentech. The collaboration is focused on the discovery and development of Bicycle peptides directed to biological targets selected by Genentech and aimed at developing up to four potential development candidates against multiple immuno-oncology targets suitable for Genentech to advance into further development and commercialization.

Under the terms of the Genentech Collaboration Agreement, the Company received a $30.0 million upfront, non-refundable payment. The initial discovery and optimization activities are focused on utilizing the Company’s phage screening technology to identify product candidates aimed at two immuno-oncology targets (“Genentech Collaboration Programs”), which may also include additional discovery and optimization of Bicycle molecules as a targeting element for each Genentech Collaboration Program (each a “Targeting Arm”). Genentech also had the option to nominate up to two additional immuno-oncology targets (each, an “Expansion Option”) as additional Genentech Collaboration Programs, which may also include an additional Targeting Arm for each Expansion Option. Genentech exercised the Expansion Options in October 2021 and June 2022, respectively. Genentech paid to the Company an expansion fee of $10.0 million for each Expansion Option. Genentech also has rights, under certain limited circumstances, to select an alternative target to be the subject of a Genentech Collaboration Program, in some cases subject to payment of an additional target selection fee.

If Genentech elects for the Company to perform discovery and optimization services for certain Targeting Arms, the Company will be entitled to receive an additional advance payment for the additional research services. Genentech exercised its right to select a Targeting Arm for one of the initial Genentech Collaboration Programs at the inception of the arrangement, and for the first Expansion Option in October 2021, which entitled the Company to additional payments of $1.0 million each. If a Targeting Arm achieves specified criteria in accordance with the research plan, Genentech will be required to pay a further specified amount in the low single digit millions for each such Targeting Arm as consideration for the additional services to be provided.

The Company granted to Genentech a non-exclusive research license under the Company’s intellectual property solely to enable Genentech to perform any activities under the agreement. The activities under the Genentech Collaboration Agreement are governed by a joint research committee (“JRC”) with representatives from each of the Company and Genentech. The JRC will oversee, review and recommend direction of each Genentech Collaboration Program, achievement of development criteria, and variations of or modifications to the research plans.

After the Company performs the initial discovery and optimization activities in accordance with an agreed research plan and achieves specified criteria, Genentech will have the option to have the Company perform initial pre-clinical development and optimization activities in exchange for an additional specified milestone payment in the mid-single digit millions for each Genentech Collaboration Program (the “LSR Go Option”). Upon completion of such initial pre-clinical development and optimization activities for each Genentech Collaboration Program, Genentech will have the option to obtain an exclusive license to exploit any compound developed under such Genentech Collaboration Program in exchange for an additional specified payment in the mid to high single digit millions for each of the initial two Genentech Collaboration Programs and each of the two Expansion Option Genentech Collaboration Programs (the “Dev Go Option”).

On a Genentech Collaboration Program by Genentech Collaboration Program basis, if Genentech elects to obtain exclusive development and commercialization rights and pays the applicable LSR Go Option and Dev Go Option fees, Genentech will be required to make milestone payments to the Company upon the achievement of specified development, regulatory, and initial commercialization milestones for products arising from each collaboration program, totaling up to $200.0 million. Specifically, the Company is eligible for additional development milestones totaling up to $65.0 million, as well as regulatory milestones of up to $135.0 million for each collaboration program. In addition, the Company is also eligible to receive up to $200.0 million in sales milestone payments on a Genentech Collaboration Program-by-Genentech Collaboration Program basis. In addition, to the extent any of the product candidates covered by the licenses conveyed to Genentech are commercialized, the Company would be entitled to receive tiered royalty payments on net sales at percentages ranging from the mid-single to low double-digits, subject to certain standard reductions and offsets. Royalties will be payable, on a product by product and country by country basis, until the later of the expiration of specified licensed patents covering such product in such country, or ten years from first commercial sale of such product in such country.

Accounting Analysis

Upon the execution of the Genentech Collaboration Agreement, the Company has identified the following performance obligations:

(i)

Research license, and the related research and development and preclinical services through LSR Go for a first Genentech Collaboration Program (Genentech Collaboration Program #1);

(ii)

Research license, and the related research and development and preclinical services through LSR Go for a second Genentech Collaboration Program with a specified Targeting Arm (Genentech Collaboration Program #2);

(iii)

Material right associated with an option to a specified Targeting Arm for Genentech Collaboration Program #1;

(iv)

Two material rights associated with the LSR Go Option for Genentech Collaboration Program #1 and Genentech Collaboration Program #2, which includes research services to be provided through the Dev Go Option and an option to receive an exclusive license;

(v)

Material rights associated with certain limited substitution rights with respect to a limited number of collaboration targets;

(vi)

Two material rights related to each Genentech Expansion Option, which upon exercise include the services for an additional immuno-oncology target through the LSR Go Option, an LSR Go Option which includes the services to be provided through the Dev Go Option and an option to receive an exclusive license, limited substitution rights, and an option to select a specified Targeting Arm.

The Company concluded that certain substitution rights that require the payment of additional consideration, which approximate the standalone selling price of the underlying services to be provided, do not provide the customer with a material right and therefore, are not considered as performance obligations and are accounted for as separate contracts upon exercise, if ever. The Company’s participation in the JRC was assessed as immaterial in the context of the contract.

The Company has concluded that the research license is not distinct from the research and development services as Genentech 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 it relates to constrained peptide technology that is not available in the marketplace. As a result, for each research program, the research license has been combined with the research and development services into a single performance obligation. In addition, the Company concluded that the Dev Go Option is not distinct or separately exercisable from the LSR Go Option, as the customer cannot benefit from the Dev Go Option unless and until the LSR Go Option is exercised.

In assessing whether the various options under the Genentech Collaboration Agreement represent material rights, the Company considered the additional consideration the Company would be entitled to upon the option exercise, the standalone selling price of the underlying goods, services, and additional options. For the material rights identified above the Company concluded that each of the options provided Genentech with a discount that it otherwise would not have received.

The total transaction price was initially determined to be $31.0 million, consisting of the $30.0 million upfront fee and the additional $1.0 million for Genentech’s selection of a new Targeting Arm at inception. The Company utilizes the most likely amount method to determine the amount of research and development funding to be received. Additional consideration to be paid to the Company upon the exercise of options by Genentech and subsequent milestones 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. In addition, other 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. In March 2021, the Company achieved specified criteria in accordance with the research plan under the Genentech Collaboration Agreement and therefore updated its estimate of the variable consideration to include an additional $2.0 million, that is no longer constrained. The arrangement consideration was increased to $33.0 million.

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 Genentech Collaboration Programs was 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 price for the material rights was determined based on the fees Genentech would pay to exercise the options, the estimated value of the underlying goods and services, and the probability that Genentech would exercise the option and any underlying options. 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
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

The Company recognizes revenue related to amounts allocated to the Genentech Collaboration Program #1 and #2 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 obligation. The amount allocated to the material rights is recorded as deferred revenue and the Company will commence revenue recognition upon exercise of or upon expiry of the respective option. The Company anticipates that the Genentech Collaboration Performance Program #1 and #2 obligations will be performed over a period of approximately two to three years, and the remaining material rights will be exercised or expire within approximately four years from contract execution. In June 2023, Genentech terminated Genentech Collaboration Program #2 and revenue of $6.0 million was recognized during the year ended December 31, 2023 related to the expiration of the material right associated with the LSR Go Option for Collaboration Program #2.

In October 2021 and June 2022, respectively, Genentech exercised the first and second Expansion Options to add additional Genentech Collaboration Programs (Genentech Collaboration Program #3 and Genentech Collaboration Program #4) and paid to the Company an expansion fee of $10.0 million for each option. For the first Expansion Option, Genentech also elected for the Company to perform discovery and optimization services for a Targeting Arm, and the Company received an additional payment of $1.0 million for additional research services. The Company concluded that the exercise of each Expansion Option, including the option to a specified Targeting Arm for the first Expansion Option, is accounted for as a continuation of an existing contract as the customer decided to purchase additional goods and services contemplated in the original contract. For the first Expansion Option, the additional arrangement consideration of $11.0 million received upon the option exercises and the $3.5 million originally allocated to the first Expansion Option material right is allocated to the underlying goods and services associated with the first Expansion Option on the same basis as the initial allocation of the Genentech Collaboration Agreement. In December 2022, the Targeting Arm associated with the first Expansion Option achieved specified criteria in accordance with the research plan under the Genentech Collaboration Agreement and therefore the Company updated its estimate of variable consideration to include an additional $2.0 million, that is no longer constrained. The Company allocated the additional $2.0 million entirely to the Genentech Collaboration Program #3 and Targeting Arm services as the terms of the variable consideration relate specifically to the Company’s efforts in satisfying the performance obligation and allocating the variable consideration entirely to the performance obligation is consistent with the allocation objective in ASC 606. For the second Expansion

Option, the additional arrangement consideration of $10.0 million received pursuant to the option exercise together with the $3.5 million originally allocated to the second Expansion Option material right is allocated to the underlying goods and services associated with the second Expansion option on the same basis as the initial allocation of the Genentech Collaboration Agreement. The Company recognizes the $8.4 million allocated to the Genentech Collaboration Program #3 and Targeting Arm services and $5.3 million allocated to the Genentech Collaboration Program #4 services as the underlying services are performed using a proportional performance model over the period of service of approximately two to three years for each program 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 external costs expected, which best reflects the progress towards satisfaction of the performance obligations. The amount allocated to the material rights associated with an LSR Go Options for Genentech Collaboration Program #3 and Genentech Collaboration Program #4 of $7.4 million and $7.4 million, respectively, limited substitution material rights of $0.7 million and $0.7 million, respectively, and the material right associated with the option to select a Targeting Arm for Genentech Collaboration Program #4 of $0.1 million, are recorded as deferred revenue and the Company will commence revenue recognition upon exercise or expiry of each respective option which is expected to be within approximately four years of the Expansion Option exercise. Other 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.

For the years ended December 31, 2023, 2022 and 2021, the Company recognized revenue of $12.0 million, $3.6 million and $5.7 million, respectively, and as of December 31, 2023 and 2022, the Company recorded deferred revenue of $29.1 million and $39.3 million, respectively, in connection with the Genentech Collaboration Agreement.

Dementia Discovery Fund Agreement

In 2019, the Company entered into a collaboration with the Dementia Discovery Fund (“DDF”) to use Bicycle technology for the discovery and development of novel therapeutics for dementia (the “DDF Collaboration Agreement”) along with Oxford University’s Oxford Drug Discovery Institute (“ODDI”). Under the terms of the DDF Collaboration Agreement, the Company performed certain research activities to identify Bicycle molecules that bind to clinically validated dementia targets (the “DDF Research Plan”). The Company received an upfront payment of $1.1 million, which was allocated to a single performance obligation associated with the performance of research and development services under the DDF Research Plan. The Company recognized revenue as the underlying services were performed using a proportional performance model over the period of service using input-based measurements of total costs, including total full-time equivalent effort incurred to date as a percentage of total costs expected, which best reflects the progress towards satisfaction of the performance obligation. In December 2020, the Company received a payment of $0.5 million upon the achievement of specified scientific criteria, which was allocated to a single performance obligation to perform lead optimization activities, and recognized revenue as the underlying services were performed using a proportional performance model, over the period of service using input based measurements of total costs, including total full time equivalent effort and external costs incurred to date as a percentage of total expected costs, which best reflects the progress towards satisfaction of the performance obligation. In August 2023, the DDF Collaboration Agreement expired.

For the years ended December 31, 2023, 2022 and 2021, the Company recognized revenue of zero, $0.4 million, and $0.4 million, respectively. The Company recorded deferred revenue of zero as of December 31, 2023 and 2022, respectively, related to the DDF Collaboration Agreement.

AstraZeneca Collaboration Agreement

In November 2016, the Company entered into a Research Collaboration Agreement (the “AstraZeneca Collaboration Agreement”) with AstraZeneca. The collaboration activities initially focused on two targets within respiratory, cardiovascular and metabolic disease, for which collaboration activities were terminated by AstraZeneca in October 2020 and March 2021, respectively. In May 2018, AstraZeneca made an irrevocable election to exercise an option to nominate four additional targets (“Additional Four Target Option”). As a result, AstraZeneca was entitled to obtain research and development services from the Company with respect to Bicycle peptides that bind to up to four additional targets, along with license rights to those selected targets, in exchange for an option fee of $5.0 million.

Upon the execution of the Additional Four Target Option, the Company identified the following five performance obligations: (i) Research license and the related research and development services during the Bicycle Research Term for the third target (the “Target Three Research License and Related Services”); (ii) Material right associated with the development and exploitation license option for the third target (“Target Three Material Right”); (iii) Material right associated with the research services option, including the underlying development and exploitation license option for the fourth target (“Target Four Material Right”); (iv) Material right associated with the research services option, including the underlying development and exploitation license option for the fifth target (“Target Five Material Right”); and (v) Material right associated with the research services option, including the underlying development and exploitation license option for the sixth target (“Target Six Material Right”). The total transaction price was initially determined to be $5.7 million, consisting of the $5.0 million option exercise fee and research and development funding of an estimated $0.7 million. The transaction price was allocated to the performance obligations based on the relative estimated standalone selling prices of each performance obligation. In June 2019, the transaction was increased to $6.3 million for additional research and development funding received.

The Company recognized revenue related to amounts allocated to the Target Three Research License and Related Services as the underlying services were performed using a proportional performance model over the period of service using input-based measurements of total full-time equivalent effort incurred to date as a percentage of total full-time equivalent effort expected, which best reflected the progress towards satisfaction of the performance obligation. The amount allocated to the material rights was recorded as deferred revenue and the Company commenced revenue recognition upon exercise of or upon expiry of the option. In October 2020, August 2021, and June 2022, AstraZeneca terminated the collaboration activities related to the third, sixth and fifth targets, respectively, and the deferred revenue related to the associated material rights of $1.5 million, $1.1 million, and $1.2 million, respectively, was recognized in each of the respective years of option exercise. In April 2023, AstraZeneca terminated the collaboration activities related to the fourth target and the deferred revenue related to the associated material right of $1.2 million was recognized during the year ended December 31, 2023. As of December 31, 2023, there are no research programs remaining under the AstraZeneca Collaboration Agreement.

For the years ended December 31, 2023, 2022 and 2021 the Company recognized $1.2 million, $1.2 million, and $1.4 million, respectively, of revenue related to the AstraZeneca Collaboration Agreement. As of December 31, 2023 and 2022, the Company recorded zero and $1.1 million of deferred revenue, respectively, in connection with AstraZeneca Collaboration Agreement.

Oxurion Collaboration Agreement

In August 2013, the Company entered into a Research Collaboration and License Agreement (the “Oxurion Collaboration Agreement”) with Oxurion. Under the Oxurion Collaboration Agreement, the Company was responsible for identifying Bicycle peptides related to the collaboration target, plasma kallikrein, for use in various ophthalmic indications. Oxurion is responsible for further development and product commercialization after the defined research screening is performed by the Company. Under the Oxurion Collaboration Agreement, the Company granted certain worldwide intellectual property rights to Oxurion for the development, manufacture and commercialization of licensed compounds associated with plasma kallikrein. The Company was eligible to receive up to €8.3 million upon the achievement of specified research, development, regulatory and commercial events and research and development milestones, of which €3.8 million has been received as of December 31, 2023. In addition, the Company is eligible to receive up to €16.5 million upon achievement of certain regulatory milestone payments (e.g., €5 million for granting first regulatory approval in either the United States or the European Union for the first indication). In addition, to the extent any of the collaboration products covered by the licenses granted to Oxurion are commercialized, the Company would be entitled to receive tiered royalty payments of mid-single digits based on a percentage of net sales.

Either party may terminate the Oxurion Collaboration Agreement in the event of the commencement of any proceeding in or for bankruptcy, insolvency, dissolution or winding up by or against the other party that is not dismissed or otherwise disposed of within a specified time period. In November 2023, Oxurion announced that it would be filing for bankruptcy after its product candidate, THR-149, did not meet the primary endpoint in its Phase 2, Part B clinical trial. In December 2023, Oxurion announced that it would not be filing for bankruptcy as it had previously announced. As of February 15, 2024, neither party had terminated the Oxurion Collaboration Agreement.

The Company recognized no collaboration revenue during any of the years ended December 31, 2023, 2022, or 2021. As of December 31, 2023 and 2022, the Company recorded no deferred revenue related to its collaboration with Oxurion.

Summary of Contract Assets and Liabilities

The following table presents changes in the balances of the Company’s contract liabilities (in thousands):


	Beginning Balance						Impact of		Ending Balance
	January 1,						Exchange		December 31,
	2023		Additions		Deductions		Rates		2023
Contract liabilities:
Deferred revenue
Bayer collaboration deferred revenue	$	—	$	45,000	$	(1,160)	$	(222)	$	43,618
Novartis collaboration deferred revenue		—		50,000		(1,909)		1,917		50,008
Ionis collaboration deferred revenue		21,489		960		(10,734)		749		12,464
Genentech collaboration deferred revenue		39,308		—		(11,969)		1,765		29,104
AstraZeneca collaboration deferred revenue		1,076		—		(1,204)		128		—
Total deferred revenue	$	61,873	$	95,960	$	(26,976)	$	4,337	$	135,194


	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

Contract assets represent research and development services which have been performed but have not yet been billed, and are reduced when they are subsequently billed. There were no contract assets at December 31, 2023 or 2022.

As of December 31, 2023, the Bayer, Novartis, Ionis, and Genentech deferred revenue balances include $32.4 million, $33.2 million, $3.6 million, and $21.8 million, respectively, allocated to material rights that will commence revenue recognition when the respective option is exercised or when the option expires.

During the years ended December 31, 2023, 2022 and 2021, 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):


	Year Ended
	December 31,
	2023		2022		2021
Revenue recognized in the period from:
Revenue recognized based on proportional performance	$	19,160	$	12,358	$	9,652
Revenue recognized based on expiration of material rights		7,816		1,433		1,876
Revenue recognized based on changes in transaction price		—		672		169
Total	$	26,976	$	14,463	$	11,697

Cancer Research UK

BT1718

On December 13, 2016, the Company entered into a Clinical Trial and License Agreement with Cancer Research Technology Limited (“CRTL”), a wholly owned subsidiary of Cancer Research UK that Cancer Research UK’s commercial activities operate through, and Cancer Research UK (the “Cancer Research UK Agreement”). Pursuant to the Cancer Research UK Agreement, as amended in March 2017 and June 2018, Cancer Research UK’s Centre for Drug Development will sponsor and fund a Phase I/IIa clinical trial for BT1718, a BTC molecule, in patients with advanced solid tumors.

Cancer Research UK is responsible for designing, preparing, carrying out and sponsoring the clinical trial at its cost. The Company is responsible for supplying agreed quantities of GMP materials for the trial, the supply of which has been completed. In the event that additional quantities are needed, the Company will provide Cancer Research UK with all reasonable assistance to complete the arrangements necessary for the generation and supply of such additional GMP materials, but Cancer Research UK will be responsible for supplying and paying for such additional quantities of GMP materials.

The Company granted Cancer Research UK a license to its intellectual property in order to design, prepare for, sponsor, and carry out the clinical trial. The Company retains the right to continue the development of BT1718 during the clinical trial. Upon the completion of the Phase I/IIa clinical trial, the Company has the right to obtain a license to the results of the clinical trial upon the payment of a milestone, in cash and ordinary shares, with a combined value in the mid six-digit dollar amount. If such license is not acquired, or if it is acquired and the license is terminated and the Company decides to abandon development of all products that deliver cytotoxic payloads to the MT1 target antigen, CRTL may elect to receive an assignment and exclusive license to develop and commercialize the product on a revenue sharing basis (in which case the Company will receive tiered royalties of 70% to 90% of the net revenue depending on the stage of development when the license is granted). The Cancer Research UK Agreement contains additional future milestone payments upon the achievement of development and regulatory milestones, payable in cash and shares, with an aggregate total value of $50.9 million, as well as royalty payments based on a single digit percentage on net sales of products developed.

The Cancer Research UK Agreement can be terminated by either party upon an insolvency event, material breach of the terms of the contract, or upon a change in control (and the new controlling entity develops, sells or manufactures tobacco products or generates the majority of its profits from tobacco products or is an affiliate of such party). Cancer Research UK may also terminate the arrangement for safety reasons or if it determines that the objectives of the clinical trial will not be met. The Company was obligated to reimburse Cancer Research UK for certain costs if the Cancer Research UK agreement was terminated by Cancer Research UK prior to the completion of the dose escalation (Phase I) part of the clinical trial for an insolvency event of, or material breach by, the Company or upon termination for safety reasons or if Cancer Research UK determined that the objectives of the clinical trial would not be met, however, these reimbursement obligations expired unexercised upon the completion of the Phase I portion of the clinical trial in 2020. If the Company is subject to a change in control and the new controlling entity develops, sells or manufactures tobacco products or generates the majority of its profits from tobacco products or is an affiliate of such party prior to the last cycle of treatment under the Phase IIa clinical trial, the Company will reimburse Cancer Research UK in full for all costs paid or committed in connection with the clinical trial and no further license payments, where applicable, shall be due. In such case, Cancer Research UK will not be obliged to grant a license to the Company in respect of the results of the clinical trial and the Company will assign or grant to CRTL an exclusive license to develop and commercialize the product without CRTL being required to make any payment to the Company.

The Company concluded that the costs incurred by Cancer Research UK is a liability in accordance with ASC 730, Research and Development, as certain payments are not based solely on the results of the research and development having future economic benefit. As such, as of December 31, 2023 and 2022, the Company recorded a liability of $4.3 million and $3.6 million, respectively, which is recorded in other long-term liabilities in the consolidated balance sheets. The liability is recorded as incremental research and development expense in the consolidated statements of operations and comprehensive loss.

BT7401

In December 2019, the Company entered into a clinical trial and license agreement with Cancer Research Technology Limited and Cancer Research UK. Pursuant to the agreement, Cancer Research UK’s Centre for Drug Development will fund and sponsor development of BT7401, a multivalent Bicycle CD137 agonist, from current preclinical studies through the completion of a Phase IIa trial in patients with advanced solid tumors.

The Company granted to Cancer Research UK a license to the Company’s intellectual property in order to design, prepare for, sponsor, and carry out the clinical trial and all necessary preclinical activities to support the trial. The Company retains the right to continue the development of BT7401 during the clinical trial. Upon the completion of the Phase I/IIa clinical trial, the Company has the right to obtain a license to the results of the clinical trial upon the payment of a milestone, in cash and ordinary shares, with a combined value in the mid six digit dollar amount. If such license is not acquired, or if it is acquired and the license is terminated and the Company decides to abandon development of all products that contain BT7401 or all the pharmaceutically active parts of BT7401, CRTL may elect to receive an exclusive license to develop and commercialize the product on a revenue sharing basis (in which case the Company will receive tiered royalties of 55% to 80% of the net revenue depending on the stage of development when the license is granted) less certain costs, as defined by the agreement. The BT7401 Cancer Research UK agreement contains additional future milestone payments upon the achievement of development, regulatory and commercial milestones, payable in cash, with an aggregate total value of up to $60.3 million for each licensed product, as well as royalty payments based on a single digit percentage on net sales of products developed, and sublicense royalties to the Cancer Research UK in the low double digit percentage of sublicense income depending on the stage of development when the license is granted.

The BT7401 Cancer Research UK agreement can be terminated by either party upon an insolvency event, material breach of the terms of the contract, or upon a change in control (and the new controlling entity develops, sells or manufactures tobacco products or generates the majority of its profits from tobacco products or is an affiliate of such party), or upon written notice by Cancer Research UK prior to the last cycle of treatment has been completed under the clinical trial. If the trial is terminated by the Company prior to the filing of a clinical trial authorization, or by Cancer Research UK for an insolvency event or a material breach by the Company prior to the start of a clinical trial, the Company will reimburse Cancer Research UK for certain costs paid or committed prior to the start of the clinical trial. In such case where the Company is subject to a change of control and the new controlling entity develops, sells or manufactures tobacco products or generates the majority of its profits from tobacco products or is an affiliate of such party, Cancer Research UK will not be obliged to grant a license to the Company in respect of the results of the clinical trial and CRTL may elect to receive an exclusive license to develop and commercialize the product without CRTL being required to make any payment to the Company. The Company concluded that the BT7401 Cancer Research UK arrangement does not represent a liability in accordance with ASC 730, Research and Development, as the payments are based solely on the results of the research and development having future economic benefit and risk of repayment is substantive and genuine, and as such there was no accounting impact as of and for the year ended December 31, 2023.

- Definition

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

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 606
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 9
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479806/606-10-50-9

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Topic 606
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 10
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479806/606-10-50-10

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 606
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 15
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479806/606-10-50-15

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Topic 606
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 12
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479806/606-10-50-12

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Topic 606
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 12
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479806/606-10-50-12

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Topic 606
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 12
-Subparagraph (c)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479806/606-10-50-12

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Topic 606
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 12
-Subparagraph (d)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479806/606-10-50-12

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Topic 606
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 12
-Subparagraph (e)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479806/606-10-50-12

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Topic 606
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 13
-Subparagraph (b)(2)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479806/606-10-50-13

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Name Accounting Standards Codification
-Topic 606
-Publisher FASB
-URI https://asc.fasb.org//606/tableOfContent

+ Details

Fair value of financial assets and liabilities

12 Months Ended

Dec. 31, 2023

Fair value of financial assets and liabilities

Fair value of financial assets and liabilities

3. Fair value of financial assets and liabilities

At December 31, 2023, the Company had cash equivalents of $72.3 million, consisting of $22.1 million of interest-bearing money market funds and $50.2 million of 30-day term deposits, which are considered Level 1 assets. As of December 31, 2022, the Company had cash equivalents of $276.1 million consisting of 30-day term deposits, which

are considered Level 1 assets. As of December 31, 2023 and 2022, there were no other assets or liabilities measured at fair value on a recurring basis.

- Definition

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

+ References + Details

Subsequent events

12 Months Ended

Dec. 31, 2023

Subsequent events.

Subsequent events

16. Subsequent events

In January 2024, the joint research committee under the Genentech Collaboration Agreement reached a decision to discontinue research activities associated with Genentech Collaboration Program #3 and, as a result, the Company expects to recognize revenue of approximately $10.4 million in the first quarter of 2024 associated with the completion of its performance obligations, including $7.4 million related to the expiration of remaining material rights. Genentech Collaboration Programs #1 and #4 remain ongoing.

Insider Trading Arrangements

3 Months Ended

Dec. 31, 2023

Trading Arrangements, by Individual

Material Terms of Trading Arrangement

Insider Trading Arrangements

During our last fiscal quarter, our directors and officers (as defined in Rule 16a-1(f) under the Exchange Act) adopted or terminated the contracts, instructions or written plans for the purchase or sale of our securities set forth in the table below.


			Type of Trading Arrangement
Name and Position	Action	Adoption/Termination Date	Rule 10b5-1*	Non-Rule 10b5-1**	Total Shares of Ordinary Shares to be Sold	Expiration Date
Pierre Legault, Chairman	Adoption	October 11, 2023	X		266,014	October 12, 2026

* Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act.

** “Non-Rule 10b5-1 trading arrangement” as defined in Item 408(c) of Regulation S-K under the Exchange Act.

We adopted insider trading policies and procedures governing the purchase, sale, and/or other dispositions of our ordinary shares by directors, officers, employees and consultants that are reasonably designed to promote compliance with insider trading laws, rules and regulations, and the Nasdaq listing standards.

Rule 10b5-1 Arrangement Adopted

true

Non-Rule 10b5-1 Arrangement Adopted

false

Rule 10b5-1 Arrangement Terminated

false

Non-Rule 10b5-1 Arrangement Terminated

false

Pierre Legault [Member]

Trading Arrangements, by Individual

Pierre Legault

Chairman

October 11, 2023

October 11, 2023

266,014

Trd Arr Expiration Date

October 12, 2026

Share-based compensation - Restricted Share Units (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Restricted shares
Total share-based compensation expense	$ 32,477	$ 26,779	$ 12,083
Restricted ordinary shares \| 2020 Plan
Number of Shares Underlying RSUs
Unvested restricted ordinary shares at beginning	187,725
Granted	333,089
Vested	(119,144)
Forfeited	(74,822)
Unvested restricted ordinary shares at ending	326,848	187,725
Weighted Average Grant Date Fair Value
Weighted average grant date fair value unvested, Beginning Balance	$ 60.86
Granted	29.27
Vested	50.30
Forfeited	39.55
Weighted average grant date fair value unvested, Ending Balance	$ 37.40	$ 60.86
Restricted shares
Fair value of employee restricted share awards vested	$ 3,000	$ 2,100	0
Total share-based compensation expense	5,500	$ 4,900	$ 0
Unrecognized compensation cost	$ 10,000
Weighted average Period	2 years 7 months 6 days

Summary of significant accounting policies - Property and equipment (Details)	Dec. 31, 2023
Computer equipment and software
Property and equipment
Estimated Useful Life	3 years
Minimum \| Laboratory equipment
Property and equipment
Estimated Useful Life	3 years
Minimum \| Furniture and office equipment
Property and equipment
Estimated Useful Life	3 years
Maximum \| Laboratory equipment
Property and equipment
Estimated Useful Life	5 years
Maximum \| Furniture and office equipment
Property and equipment
Estimated Useful Life	5 years

Significant agreements - Ionis Accounting analysis (Details) $ in Thousands		1 Months Ended			12 Months Ended
	Jul. 09, 2021 USD ($) item	Oct. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Jan. 31, 2021 USD ($)	Dec. 31, 2023 USD ($) item	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2020 USD ($)
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Collaboration revenues					$ 26,976	$ 14,463	$ 11,697
Deferred revenue			$ 71,340		$ 135,194	61,873	71,340
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
Upfront cash payment	31,000
Estimated amount payable to CROs	600
Expected period for satisfaction of performance obligations					3 years
Material rights exercise period					4 years
Collaboration revenues					$ 10,734	9,347	4,242
Deferred revenue			34,115		12,464	$ 21,489	$ 34,115
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
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
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
Deferred revenue								$ 3,000
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

Consolidated Statements of Shareholders' Equity - USD ($) $ in Thousands	Ordinary Shares Ionis Share Purchase Agreement	Ordinary Shares	Additional Paid-in Capital Ionis Share Purchase Agreement	Additional Paid-in Capital	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit	Ionis Share Purchase Agreement	Total
Beginning balance at Dec. 31, 2020		$ 266		$ 249,947	$ (3,193)	$ (151,560)		$ 95,460
Beginning balance (in shares) at Dec. 31, 2020		21,094,557
Increase (decrease) in shareholders' equity (deficit)
Issuance of ADSs upon exercise of share options		$ 10		7,173				7,183
Issuance of ADSs upon exercise of share options (in shares)		703,786
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses	$ 4	$ 104	$ 7,554	290,880			$ 7,558	290,984
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses (in shares)	282,485	7,498,536
Share-based compensation expense				12,083				12,083
Foreign currency translation adjustment					(195)			(195)
Net Income (Loss)						(66,819)		(66,819)
Ending balance at Dec. 31, 2021		$ 384		567,637	(3,388)	(218,379)		346,254
Ending 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		988				989
Issuance of ADSs upon exercise of share options (in shares)		78,074
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses		$ 2		5,701				5,703
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses (in shares)		181,455
Issuance of ADSs upon vesting of restricted share units (in shares)		35,000
Share-based compensation expense				26,779				26,779
Foreign currency translation adjustment					3,775			3,775
Net Income (Loss)						(112,717)		(112,717)
Ending balance at Dec. 31, 2022		$ 387		601,105	387	(331,096)		$ 270,783
Ending 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				681				$ 681
Issuance of ADSs upon exercise of share options (in shares)		54,023
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses		$ 162		249,183				249,345
Issuance of ADSs and non-voting ordinary shares, net of commissions and offering expenses (in shares)		12,384,706
Issuance of ADSs upon vesting of restricted share units		$ 1						1
Issuance of ADSs upon vesting of restricted share units (in shares)		119,144
Share-based compensation expense				32,477				32,477
Foreign currency translation adjustment					(1,691)			(1,691)
Net Income (Loss)						(180,664)		(180,664)
Ending balance at Dec. 31, 2023		$ 550		$ 883,446	$ (1,304)	$ (511,760)		$ 370,932
Ending balance (in shares) at Dec. 31, 2023		42,431,766						42,431,766

Commitments and contingencies (Tables)

12 Months Ended

Dec. 31, 2023

Commitments and contingencies

Schedule of components of lease expense

The components of the Company’s lease expense are as follows (in thousands):


	Year Ended
	December 31,
	2023		2022		2021
Operating lease cost	$	5,408	$	3,790	$	1,224
Variable lease cost		2,777		1,643		612
Total lease cost	$	8,185	$	5,433	$	1,836

Schedule of maturities of operating leases

The following table summarizes the maturities of the Company’s operating leases as of December 31, 2023 (in thousands):


Year Ending December 31,
2024		5,772
2025		5,858
2026		3,353
2027		821
Present value adjustment		(1,546)
Total lease liabilities		14,258
Less: current lease liabilities		(4,876)
Long term lease liabilities	$	9,382

Summary of significant accounting policies - Government grants (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Summary of significant accounting policies
Reduction of research and development related to government grant arrangements	$ 1.0	$ 1.5	$ 3.0
Government grant funding remaining for future cost reimbursement	$ 0.1

Commitments and contingencies - Components of lease expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Commitments and contingencies
Operating lease cost	$ 5,408	$ 3,790	$ 1,224
Variable lease cost	2,777	1,643	612
Total lease cost	$ 8,185	$ 5,433	$ 1,836
Weighted-average remaining operating lease term (years)	2 years 10 months 24 days	4 years 2 months 12 days
Weighted-average discount rate	7.90%	7.00%

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

Income taxes - Components of benefit for income taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Current income tax (benefit) provision
Federal	$ (1,180)	$ 2,048	$ (2)
State	(669)	1,404	7
Total current income tax (benefit) provision	(1,849)	3,452	5
Deferred income tax provision (benefit)
Federal	2,513	(4,111)	(1,236)
State	793	(865)	(432)
Total deferred income tax provision (benefit)	3,306	(4,976)	(1,668)
Total provision for (benefit from) income taxes	$ 1,457	$ (1,524)	$ (1,663)

- Definition

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

+ References + Details

Nature of the business and basis of presentation

12 Months Ended

Dec. 31, 2023

Nature of the business and basis of presentation

Nature of the business and basis of presentation

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 Bicycle^® molecules, for diseases that are underserved by existing therapeutics. Bicycle molecules are a unique therapeutic modality combining the pharmacology usually associated with a biologic with the manufacturing and pharmacokinetic properties of a small molecule. The Company’s initial internal programs are focused on oncology indications with high unmet medical need. The Company is evaluating BT8009, a Bicycle Toxin Conjugate (a “BTC^®”molecule) targeting Nectin-4, in both an ongoing Company-sponsored Phase I/II clinical trial and a Phase II/III registrational trial, called Duravelo-2, which was initiated and commenced recruiting patients in the first quarter of 2024, BT5528, a BTC molecule targeting Ephrin type-A receptor 2 (“EphA2”), in a Company-sponsored Phase I/II clinical trial, and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist^® (a “Bicycle TICA^®” molecule) targeting Nectin-4 and agonizing CD137, in a Company-sponsored Phase I/II clinical trial. In addition, BT1718, a BTC molecule that is being developed to target tumors that express Membrane Type 1 matrix metalloproteinase, is being investigated for safety, tolerability and efficacy in a Phase I/IIa clinical trial sponsored and fully funded by the Centre for Drug Development of Cancer Research UK. The Company’s discovery pipeline in oncology includes next-generation BTC molecules, Bicycle radionuclide conjugates (“BRC^TM”molecules), Bicycle based systemic immune cell agonists and Bicycle TICA molecules. Beyond the Company’s wholly owned oncology portfolio, the Company is collaborating with biopharmaceutical companies and organizations in therapeutic areas in which the Company believes its proprietary Bicycle screening platform can identify therapies to treat diseases with significant unmet medical need.

The accompanying 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 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 provision (benefit) within its consolidated statements of cash flows in prior periods to conform to current period presentation.

Liquidity

As of December 31, 2023, the Company had cash and cash equivalents of $526.4 million.

The accompanying consolidated financial statements have been prepared on the basis of continuity of operations, realization of assets and the satisfaction of liabilities and commitments in the ordinary course of business. 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 with proceeds from the sale of its ordinary shares, American Depositary Shares (“ADSs”), including in its offerings pursuant to its at-the-market offering program (“ATM”) program, non-voting ordinary shares and, prior to its IPO, convertible preferred shares, proceeds received from its collaboration arrangements (Note 9) and proceeds from a loan agreement with Hercules Capital, Inc. (“Hercules”) (Note 6). The Company has incurred recurring losses since inception, including net losses of $180.7 million, $112.7 million, and $66.8 million for the years ended December 31, 2023, 2022, and 2021, respectively. As of December 31, 2023, the Company had an accumulated deficit of $511.8 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 annual consolidated financial statements.

The Company expects its expenses to increase substantially in connection with ongoing activities, particularly as the Company advances its clinical trials for its product candidates in development and preclinical activities. 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.

Share-based compensation - Assumptions used in the Black Scholes option pricing model to determine the fair value of share options (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Share-based compensation.
Expected dividend yield	0.00%
Stock option \| Employees and directors
Share-based compensation.
Risk-free interest rate	4.00%	2.20%	0.60%
Expected volatility	82.90%	82.50%	79.80%
Expected term (in years)	6 years 1 month 6 days	6 years	6 years
Unrecognized compensation expense
Total unrecognized compensation expense related to the unvested employee and director	$ 54.0
Unrecognized compensation cost expected to be recognized over a weighted average period	2 years 7 months 6 days

Commitments and contingencies

12 Months Ended

Dec. 31, 2023

Commitments and contingencies

Commitments and contingencies

11. Commitments and contingencies

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 recorded a right of use asset and lease liability of approximately $5.8 million, respectively, at the lease commencement date, based on the present value of future lease payments, discounted at 9.0%, the Company’s estimated incremental borrowing rate at the commencement of the lease, over the lease term.

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 rent-free period. There was no deposit paid in conjunction with the lease. The Company recorded a ROU 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 a 6.9%, the Company’s estimated incremental borrowing rate at the commencement of the lease, over the lease term.

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 consolidated statements of operations and comprehensive loss for the year ended December 31, 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 conjunction with the lease agreement, Bicycle Therapeutics Inc. paid a security deposit of $0.2 million. The deposit is recorded in other assets in the consolidated balance sheets. 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, which successive period was not included in the original lease term. The Company accounted for the change in lease term as a modification of the existing lease and remeasured the ROU asset and lease liability by calculating the present value of lease payments, discounted at 7.0%, the Company’s incremental borrowing rate at the date of the modification of the lease, over the remaining lease term. In May 2022, the lease was extended. The payments for the extended lease are approximately $0.2 million for the remainder of 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.

The components of the Company’s lease expense are as follows (in thousands):


	Year Ended
	December 31,
	2023		2022		2021
Operating lease cost	$	5,408	$	3,790	$	1,224
Variable lease cost		2,777		1,643		612
Total lease cost	$	8,185	$	5,433	$	1,836

The weighted average remaining operating lease term was 2.9 years and 4.2 years as of December 31, 2023 and 2022, respectively, and the weighted average discount rate was 7.9% and 7.0% as of December 31, 2023 and 2022, respectively.

The following table summarizes the maturities of the Company’s operating leases as of December 31, 2023 (in thousands):


Year Ending December 31,
2024		5,772
2025		5,858
2026		3,353
2027		821
Present value adjustment		(1,546)
Total lease liabilities		14,258
Less: current lease liabilities		(4,876)
Long term lease liabilities	$	9,382

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 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, the Company is 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 Cancer Research UK 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 entered into separate agreements with third parties which provide for various future milestone payments upon the achievement of specified development, regulatory, commercial and sales-based milestones with an aggregate total value of $105.1 million. These additional milestone payments are contingent upon future events that are not considered probable of achievement as of December 31, 2023. As of December 31, 2023, the Company was unable to estimate the timing or likelihood of achieving 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 not currently 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.

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 consolidated financial statements as of December 31, 2023 and 2022.

Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Consolidated Statements of Operations and Comprehensive Loss
Collaboration revenues	$ 26,976	$ 14,463	$ 11,697
Operating expenses:
Research and development	156,496	81,609	44,880
General and administrative	60,426	49,507	32,435
Total operating expenses	216,922	131,116	77,315
Loss from operations	(189,946)	(116,653)	(65,618)
Other income (expense):
Interest income	14,002	5,756	120
Interest expense	(3,263)	(3,344)	(2,984)
Total other income (expense), net	10,739	2,412	(2,864)
Net loss before income tax provision	(179,207)	(114,241)	(68,482)
Provision for (benefit from) income taxes	1,457	(1,524)	(1,663)
Net loss	$ (180,664)	$ (112,717)	$ (66,819)
Net loss per share, basic	$ (5.08)	$ (3.80)	$ (2.67)
Net loss per share, diluted	$ (5.08)	$ (3.80)	$ (2.67)
Weighted average ordinary shares outstanding, basic	35,592,362	29,660,659	25,061,734
Weighted average ordinary shares outstanding, diluted	35,592,362	29,660,659	25,061,734
Comprehensives loss:
Net Income (Loss)	$ (180,664)	$ (112,717)	$ (66,819)
Other comprehensive (loss) income:
Foreign currency translation adjustment	(1,691)	3,775	(195)
Total comprehensive loss	$ (182,355)	$ (108,942)	$ (67,014)

Nature of the business and basis of presentation - Liquidity (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Nature of the business and basis of presentation
Cash and cash equivalents	$ 526,423	$ 339,154	$ 438,680
Net loss	180,664	112,717	$ 66,819
Accumulated deficit	$ (511,760)	$ (331,096)

- Definition

The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.

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+ Details

- Definition

Amount of accumulated undistributed earnings (deficit).

+ References + Details

Ordinary shares

12 Months Ended

Dec. 31, 2023

Ordinary shares

Ordinary shares

7. 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 in all respects with the ordinary shares except for the following:

●

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 December 31, 2023 and 2022, the Company had not declared any dividends.

As of December 31, 2023 and 2022, the Company’s authorized capital share 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 December 31, 2023, there were 37,725,884 ordinary shares issued and outstanding and 4,705,882 non-voting ordinary shares issued and outstanding.

On July 17, 2023, the Company completed an underwritten public offering of its securities, pursuant to which the Company issued and sold 6,117,648 ADSs, representing the same number of ordinary shares, nominal value £0.01 per share, which included 1,411,764 ADSs sold upon the underwriters’ full exercise of their option to purchase additional ADSs, and 4,705,882 non-voting ordinary shares, nominal value £0.01 per share, at a public offering price of $21.25 per ADS or non-voting ordinary share, respectively. The transaction resulted in gross proceeds to the Company of $230.0 million, and after deducting underwriting discounts, commissions, and offering expenses of $14.9 million, net proceeds to the Company of $215.1 million.

On October 15, 2021, the Company issued and sold 3,726,852 ADSs, representing the same number of ordinary shares, at a price to the public of $54.00 per ADS, resulting in gross proceeds of $201.3 million before deducting underwriting discounts, commissions and offering expenses, for net proceeds for $188.4 million.

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 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 (Note 9).

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, American Depositary Shares (“ADSs”), each ADS representing one ordinary share. During the year ended December 31, 2023, the Company issued and sold 1,561,176 ADSs, representing the same number of ordinary shares for gross proceeds of $35.3 million, resulting in net proceeds of $34.2 million after deducting sales commissions and offering expenses of $1.1 million. During the year ended December 31, 2022, the Company issued and sold 181,455 ADSs, representing the same number of ordinary shares for gross proceeds of $5.9 million, resulting in net proceeds of $5.7 million after deducting sales commissions and offering expenses of $0.2 million. During the year ended December 31, 2021, the Company issued and sold 3,771,684 ADSs, representing the same number of ordinary shares for gross proceeds of $105.8 million, resulting in net proceeds of $102.6 million after deducting sales commissions and offering expenses of $3.2 million.

- Definition

The entire disclosure for equity.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 13
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-13

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 13
-Subparagraph (h)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-13

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 14
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-14

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Topic 946
-SubTopic 235
-Name Accounting Standards Codification
-Section 50
-Paragraph 2
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481062/946-235-50-2

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Topic 946
-SubTopic 235
-Name Accounting Standards Codification
-Section 50
-Paragraph 2
-Subparagraph (d)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481062/946-235-50-2

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Topic 946
-SubTopic 505
-Name Accounting Standards Codification
-Section 50
-Paragraph 6
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481004/946-505-50-6

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Topic 815
-SubTopic 40
-Name Accounting Standards Codification
-Section 50
-Paragraph 6
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480237/815-40-50-6

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section S99
-Paragraph 1
-Subparagraph (SX 210.3-04)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480008/505-10-S99-1

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Topic 235
-SubTopic 10
-Name Accounting Standards Codification
-Section S99
-Paragraph 1
-Subparagraph (SX 210.4-08(e)(1))
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1

Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef
-Topic 505
-Name Accounting Standards Codification
-Publisher FASB
-URI https://asc.fasb.org//505/tableOfContent

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 13
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-13

Reference 12: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 13
-Subparagraph (g)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-13

Reference 13: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 13
-Subparagraph (i)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-13

Reference 14: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 14
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-14

Reference 15: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 14
-Subparagraph (c)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-14

Reference 16: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 16
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-16

Reference 17: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 18
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-18

Reference 18: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 18
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-18

Reference 19: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 18
-Subparagraph (d)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481112/505-10-50-18

+ Details

Income taxes

12 Months Ended

Dec. 31, 2023

Income taxes

Income taxes

10. Income taxes

The components of net loss before income tax provision are as follows (in thousands):


	Year Ended
	December 31,
	2023		2022		2021
United Kingdom	$	(182,980)	$	(116,275)	$	(69,546)
United States		3,773		2,034		1,064
Total	$	(179,207)	$	(114,241)	$	(68,482)

The components of the provision for (benefit from) income taxes are as follows (in thousands):


	Year Ended
	December 31,
	2023		2022		2021
Current income tax (benefit) provision
Federal	$	(1,180)	$	2,048	$	(2)
State		(669)		1,404		7
Total current income tax (benefit) provision		(1,849)		3,452		5
Deferred income tax provision (benefit)
Federal		2,513		(4,111)		(1,236)
State		793		(865)		(432)
Total deferred income tax provision (benefit)		3,306		(4,976)		(1,668)
Total provision for (benefit from) income taxes	$	1,457	$	(1,524)	$	(1,663)

A reconciliation of the provision for (benefit from) income taxes computed at the statutory income tax rate to the provision for (benefit from) income taxes as reflected in the financial statement is as follows:


	Year Ended
	December 31,
	2023		2022		2021
Provision for (benefit from) income taxes at statutory rate	23.5	%	19.0	%	19.0	%
(Decreases) increases resulting from:
Federal tax credits	0.3	%	0.3	%	0.6	%
Change in valuation allowance	(14.8)	%	(16.8)	%	(27.0)	%
Net losses surrendered for research credit	(11.1)	%	(6.5)	%	(5.9)	%
Impact of statutory rate change	2.7	%	11.3	%	12.1	%
Impact of foreign exchange rates	(0.1)	%	(9.9)	%	—	%
Other	(1.3)	%	3.9	%	3.6	%
Effective income tax rate	(0.8)	%	1.3	%	2.4	%

Significant components of the Company’s current and deferred tax assets are as follows (in thousands):



	December 31,
	2023		2022
Deferred tax assets:
Operating loss carryforwards	$	66,555	$	45,452
Operating lease liability		3,680		3,566
Share-based compensation		15,577		9,842
Capitalized research and development expenses		—		5,168
Accrued expenses and other		2,742		2,318
Total deferred tax assets		88,554		66,346
Deferred tax liabilities:
Operating lease right-of-use asset		(3,389)		(3,474)
Depreciation & amortization		—		(933)
Total deferred tax liabilities		(3,389)		(4,407)
Valuation allowance		(80,274)		(53,743)
Net deferred tax assets	$	4,891	$	8,196

During the year ended December 31, 2023, the Company recorded an income tax provision of $1.5 million, and during the years ended December 31, 2022 and 2021, the Company recorded an income tax benefit of $1.5 million and $1.7 million, respectively. The Company is subject to U.K. corporate taxation. Due to the nature of its business, the Company has generated losses since inception and therefore not paid U.K. corporation tax. The provision for (benefit

from) income taxes included in the 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. During the year ended December 31, 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 the recognition of an income tax provision of $2.4 million during the year ended December 31, 2023. The Company's income tax benefit recognized during the years ended December 31, 2022 and 2021 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 its history of cumulative net profits in the United States and estimated future taxable income and has concluded that it is more likely than not that the Company will realize the benefits of its United States deferred tax assets and has not provided a valuation allowance against the net deferred tax assets in the United States. The valuation allowance increased in the year ended December 31, 2023 by $26.5 million due to the corresponding increase in U.K. deferred tax assets, primarily due to operating loss carryforwards generated during the year that were not surrendered for research credit utilization. The Company recorded a valuation allowance against all of its U.K. deferred tax assets as of December 31, 2023 and 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 for 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 shown on the 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 and U.K., U.S. federal and state research and development credits, as well as the application of valuation allowances against the U.K. deferred tax assets.

As of December 31, 2023, the Company had $266.2 million of U.K. operating loss carryforwards that have an indefinite life.

The Company recognizes, in its consolidated financial statements, the effect of a tax position when it is more likely than not, based on the technical merits, that the position will be sustained upon examination. The Company had no uncertain tax positions during the years ended of December 31, 2023 and 2022. There are no amounts of interest or penalties recognized in the consolidated statement of operations or accrued on the consolidated balance sheet for any period presented. The Company does not expect any material changes in these uncertain tax benefits within the next 12 months.

The Company files income tax returns in the United Kingdom, and in the United States for federal income taxes and in 11 jurisdictions for state income taxes. In the normal course of business, the Company is subject to examination by tax authorities in these jurisdictions. The 2022 and 2021 tax years remains open to examination by the HM Revenue & Customs. The statute of limitations for assessment with the Internal Revenue Service is generally three years from filing the tax return. As such, all years since 2020 in the U.S. remain open to examination. The Company is currently not under examination by jurisdictions for any tax years.

- Definition

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

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 946
-SubTopic 20
-Name Accounting Standards Codification
-Section 50
-Paragraph 13
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480990/946-20-50-13

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Topic 235
-SubTopic 10
-Name Accounting Standards Codification
-Section S99
-Paragraph 1
-Subparagraph (SX 210.4-08(h)(2))
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
-Name Accounting Standards Codification
-Publisher FASB
-URI https://asc.fasb.org//740/tableOfContent

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 14
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482685/740-10-50-14

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 21
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482685/740-10-50-21

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
-SubTopic 270
-Name Accounting Standards Codification
-Section 50
-Paragraph 1
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482526/740-270-50-1

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 17
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482685/740-10-50-17

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
-SubTopic 10
-Name Accounting Standards Codification
-Section S99
-Paragraph 1
-Subparagraph (SAB TOPIC 6.I.5.Q1)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
-SubTopic 10
-Name Accounting Standards Codification
-Section S99
-Paragraph 2
-Subparagraph (SAB Topic 11.C)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479360/740-10-S99-2

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
-SubTopic 30
-Name Accounting Standards Codification
-Section 50
-Paragraph 2
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482603/740-30-50-2

+ Details

Significant agreements (Tables)

12 Months Ended

Dec. 31, 2023

Significant agreements.

Summary of revenue recognized from collaboration arrangements

The following table summarizes the revenue recognized in the Company’s consolidated statements of operations and comprehensive loss from these arrangements (in thousands):



	Year Ended
	December 31,
	2023		2022		2021
Collaboration revenues
Bayer	$	1,160	$	—	$	—
Novartis		1,909		—		—
Ionis		10,734		9,347		4,242
Genentech		11,969		3,565		5,660
Dementia Discovery Fund		—		386		391
AstraZeneca		1,204		1,165		1,404
Total collaboration revenues	$	26,976	$	14,463	$	11,697

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 liabilities (in thousands):


	Beginning Balance						Impact of		Ending Balance
	January 1,						Exchange		December 31,
	2023		Additions		Deductions		Rates		2023
Contract liabilities:
Deferred revenue
Bayer collaboration deferred revenue	$	—	$	45,000	$	(1,160)	$	(222)	$	43,618
Novartis collaboration deferred revenue		—		50,000		(1,909)		1,917		50,008
Ionis collaboration deferred revenue		21,489		960		(10,734)		749		12,464
Genentech collaboration deferred revenue		39,308		—		(11,969)		1,765		29,104
AstraZeneca collaboration deferred revenue		1,076		—		(1,204)		128		—
Total deferred revenue	$	61,873	$	95,960	$	(26,976)	$	4,337	$	135,194


	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


	Year Ended
	December 31,
	2023		2022		2021
Revenue recognized in the period from:
Revenue recognized based on proportional performance	$	19,160	$	12,358	$	9,652
Revenue recognized based on expiration of material rights		7,816		1,433		1,876
Revenue recognized based on changes in transaction price		—		672		169
Total	$	26,976	$	14,463	$	11,697

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 comprised of the Novartis Research License and the related research and development services during the research term 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 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

Net loss per share - Basic and diluted net loss per share (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Numerator:
Net loss	$ (180,664)	$ (112,717)	$ (66,819)
Denominator:
Weighted average ordinary shares outstanding, basic	35,592,362	29,660,659	25,061,734
Weighted average ordinary shares outstanding, diluted	35,592,362	29,660,659	25,061,734
Net loss per share, basic	$ (5.08)	$ (3.80)	$ (2.67)
Net loss per share, diluted	$ (5.08)	$ (3.80)	$ (2.67)

- Definition

The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 250
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 3
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147483443/250-10-50-3

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Topic 260
-SubTopic 10
-Name Accounting Standards Codification
-Section 55
-Paragraph 15
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482635/260-10-55-15

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 815
-SubTopic 40
-Name Accounting Standards Codification
-Section 65
-Paragraph 1
-Subparagraph (e)(4)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480175/815-40-65-1

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Topic 815
-SubTopic 40
-Name Accounting Standards Codification
-Section 65
-Paragraph 1
-Subparagraph (f)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480175/815-40-65-1

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Topic 250
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 11
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147483443/250-10-50-11

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Topic 250
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 11
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147483443/250-10-50-11

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Topic 250
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 7
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147483443/250-10-50-7

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Topic 260
-SubTopic 10
-Name Accounting Standards Codification
-Section 45
-Paragraph 2
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482689/260-10-45-2

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Topic 260
-SubTopic 10
-Name Accounting Standards Codification
-Section 45
-Paragraph 60B
-Subparagraph (d)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482689/260-10-45-60B

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Topic 250
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 4
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147483443/250-10-50-4

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Topic 260
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 1
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482662/260-10-50-1

Reference 12: http://www.xbrl.org/2003/role/disclosureRef
-Topic 260
-SubTopic 10
-Name Accounting Standards Codification
-Section 45
-Paragraph 10
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482689/260-10-45-10

Reference 13: http://www.xbrl.org/2003/role/disclosureRef
-Topic 220
-SubTopic 10
-Name Accounting Standards Codification
-Section S99
-Paragraph 2
-Subparagraph (SX 210.5-03(25))
-Publisher FASB
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+ Details

- Definition

The amount of net income (loss) for the period available to each share of common stock or common unit outstanding during the reporting period and to each share or unit that would have been outstanding assuming the issuance of common shares or units for all dilutive potential common shares or units outstanding during the reporting period.

+ References

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- Definition

Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities; of income (loss) available to common shareholders.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 250
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+ Details

Summary of significant accounting policies (Tables)

12 Months Ended

Dec. 31, 2023

Summary of significant accounting policies

Schedule of estimated useful lives of property and equipment


		Estimated Useful Life
Laboratory equipment		3 to 5 years
Leasehold improvements		Lesser of lease term or useful life
Computer equipment and software		3 years
Furniture and office equipment		3 to 5 years

Insider Trading Policies and Procedures	3 Months Ended
Insider Trading Policies and Procedures	Dec. 31, 2023
Insider Trading Policies and Procedures [Line Items]
Insider Trading Policies and Procedures Adopted	true

Share-based compensation - Share based compensation expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Share based compensation expense
Total share-based compensation expense	$ 32,477	$ 26,779	$ 12,083
Research and development expenses
Share based compensation expense
Total share-based compensation expense	15,581	10,394	4,974
General and administrative expenses
Share based compensation expense
Total share-based compensation expense	$ 16,896	$ 16,385	$ 7,109

Fair value of financial assets and liabilities - Financial assets and liabilities measured at fair value (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Fair value of financial assets and liabilities
Cash equivalents	$ 72.3	$ 276.1
Recurring
Fair value of financial assets and liabilities
Liabilities at fair value	0.0	0.0
Assets at fair value	0.0	0.0
Level 1 \| Recurring
Fair value of financial assets and liabilities
Cash equivalents	72.3	$ 276.1
Market funds	22.1
Term deposits	$ 50.2
Term deposit maturity period	30 days	30 days

Summary of significant accounting policies - Concentrations of credit risk and of significant suppliers (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Summary of significant accounting policies
Accounts receivable	$ 0	$ 2,045

Share-based compensation (Details)		1 Months Ended		12 Months Ended
Share-based compensation (Details)	Jan. 01, 2021	Jun. 30, 2020 installment shares	May 31, 2019 shares	Dec. 31, 2023 installment shares	Jan. 01, 2024 shares	Jan. 01, 2023 shares	Dec. 31, 2022 shares	Jun. 27, 2022 shares
Stock option
Share-based compensation.
Shares outstanding				7,469,527			5,898,888
Employee Share Purchase Plan
Share-based compensation.
Number of shares reserved for issuance						377,258
Percentage of annual increase in reserves on total number of ordinary shares outstanding			1.00%
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		693,039	1,886,294	1,493,694		750,000
Percentage of annual increase in reserves on total number of ordinary shares outstanding	5.00%
2020 Plan \| Stock option
Share-based compensation.
Shares outstanding				4,803,054
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		25.00%
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
RSUs outstanding under the 2020 Plan.				326,848			187,725
Service period				1 year
Number of quarterly installments \| installment				4
2020 Plan \| Restricted ordinary shares \| First anniversary
Share-based compensation.
Vesting Percentage				25.00%
2020 Plan \| Restricted ordinary shares \| Remaining equal installments
Share-based compensation.
Number of equal quarterly installments for vesting remaining awards \| installment				12
2019 Plan \| Stock option
Share-based compensation.
Shares outstanding				2,078,033
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				25.00%
Pre-IPO Share Options and restricted shares \| Stock option \| Employee \| Remaining equal installments
Share-based compensation.
Number of equal monthly installments for vesting remaining awards \| installment				36

Property and equipment, net (Tables)

12 Months Ended

Dec. 31, 2023

Property and equipment, net

Schedule of property and equipment, net

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


	December 31,		December 31,
	2023		2022
Laboratory equipment	$	15,554	$	14,872
Leasehold improvements		11,000		10,736
Computer equipment and software		532		441
Furniture and office equipment		822		924
		27,908		26,973
Less: Accumulated depreciation and amortization		(13,393)		(7,863)
	$	14,515	$	19,110

Net loss per share - Securities excluded from the diluted per share calculation (Details) - shares	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Antidilutive securities
Antidilutive securities (in shares)	7,796,375	6,086,613	4,603,486
Restricted ordinary shares
Antidilutive securities
Antidilutive securities (in shares)	326,848	187,725
Employee Stock Option [Member]
Antidilutive securities
Antidilutive securities (in shares)	7,469,527	5,898,888	4,603,486

Ordinary shares (Details)	12 Months Ended
Ordinary shares (Details)	Dec. 31, 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

Commitments and contingencies - Leases, Maturities of operating leases (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
2024	$ 5,772
2025	5,858
2026	3,353
2027	821
Present value adjustment	(1,546)
Total lease liabilities	14,258
Less: current lease liabilities	$ (4,876)	$ (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	$ 9,382	$ 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	$ 105,100
Agreement With CRUK
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Future milestone payment receivable	$ 111,200

Share-based compensation (Tables)

12 Months Ended

Dec. 31, 2023

Share-based compensation

Schedule of share based compensation expense

The Company recorded share-based compensation expense in the following expense categories of its consolidated statements of operations and comprehensive loss (in thousands):


	Year Ended
	December 31,
	2023		2022		2021
Research and development expenses	$	15,581	$	10,394	$	4,974
General and administrative expenses		16,896		16,385		7,109
	$	32,477	$	26,779	$	12,083

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	2,099,895		26.53	—		—
Exercised	(54,023)		12.57	—		—
Forfeited	(475,233)		30.94	—		—
Outstanding as of December 31, 2023	7,469,527	$	23.13	6.83	$	21,920
Vested and expected to vest as of December 31, 2023	7,469,527	$	23.13	6.83	$	21,920
Options exercisable as of December 31, 2023	4,561,511	$	18.95	5.61	$	21,358

Schedule of assumptions used to determine the fair value of share options granted


	Year Ended
	December 31,
	2023		2022		2021
Risk-free interest rate	4.0	%	2.2	%	0.6	%
Expected volatility	82.9	%	82.5	%	79.8	%
Expected dividend yield	—		—		—
Expected term (in years)	6.1		6.0		6.0

Schedule of restricted ordinary share award activity


	Number of Shares	Weighted-Average
	Underlying RSUs	Grant Date Fair Value
Unvested at December 31, 2022	187,725	$	60.86
Granted	333,089		29.27
Vested	(119,144)		50.30
Forfeited	(74,822)		39.55
Unvested at December 31, 2023	326,848	$	37.40

Significant agreements - Ionis Share Purchase Agreement (Details) - USD ($) $ / shares in Units, $ in Thousands		12 Months Ended
	Jul. 09, 2021	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Aggregate purchase price		$ 249,345	$ 5,703	$ 290,984
Ionis Share Purchase Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Aggregate purchase price				$ 7,558
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]
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

- Definition

Equity impact of the value of new stock issued during the period. Includes shares issued in an initial public offering or a secondary public offering.

+ References + Details

Pay vs Performance Disclosure - USD ($) $ in Thousands	12 Months Ended
Pay vs Performance Disclosure - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Pay vs Performance Disclosure
Net Income (Loss)	$ (180,664)	$ (112,717)	$ (66,819)

- Definition

The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.

+ References

+ Details

Geographic information (Details) $ in Thousands	12 Months Ended
Geographic information (Details) $ in Thousands	Dec. 31, 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	$ 27,684	$ 32,768
United States
Geographic information
Long lived assets, including operating lease right of use assets	7,486	4,466
United Kingdom
Geographic information
Long lived assets, including operating lease right of use assets	$ 20,198	$ 28,302

Net loss per share (Tables)

12 Months Ended

Dec. 31, 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):


	Year Ended
	December 31,
	2023		2022		2021
Numerator:
Net loss	$	(180,664)	$	(112,717)	$	(66,819)
Denominator:
Weighted average ordinary shares outstanding, basic and diluted		35,592,362		29,660,659		25,061,734
Net loss per share, basic and diluted	$	(5.08)	$	(3.80)	$	(2.67)

Schedule of antidilutive securities excluded from computation of diluted net loss per share


	December 31,
	2023	2022	2021
Restricted ordinary shares	326,848	187,725	—
Options to purchase ordinary shares	7,469,527	5,898,888	4,603,486
	7,796,375	6,086,613	4,603,486

Accrued expenses and other current liabilities (Tables)

12 Months Ended

Dec. 31, 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):


	December 31,		December 31,
	2023		2022
Accrued employee compensation and benefits	$	13,394	$	9,928
Accrued external research and development expenses		11,839		10,859
Accrued professional fees		1,143		1,068
Current portion of operating lease liabilities		4,876		3,125
Other		257		1,472
	$	31,509	$	26,452

Geographic information

12 Months Ended

Dec. 31, 2023

Geographic information

Geographic information

15. 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 ROU assets, held in different geographic regions is presented in the table below (in thousands):


	December 31,
	2023		2022
United States	$	7,486	$	4,466
United Kingdom		20,198		28,302
	$	27,684	$	32,768

The Company’s collaboration revenues are attributed to the operations of the Company in the United Kingdom.

- Definition

The entire disclosure for reporting segments including data and tables. Reportable segments include those that meet any of the following quantitative thresholds a) it's reported revenue, including sales to external customers and intersegment sales or transfers is 10 percent or more of the combined revenue, internal and external, of all operating segments b) the absolute amount of its reported profit or loss is 10 percent or more of the greater, in absolute amount of 1) the combined reported profit of all operating segments that did not report a loss or 2) the combined reported loss of all operating segments that did report a loss c) its assets are 10 percent or more of the combined assets of all operating segments.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 280
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 22
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482810/280-10-50-22

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Topic 280
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 15
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482810/280-10-50-15

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 280
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 31
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482810/280-10-50-31

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Topic 280
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-Publisher FASB
-URI https://asc.fasb.org//1943274/2147482810/280-10-50-32

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
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+ Details

Benefit plans (Details) - USD ($) $ in Millions	12 Months Ended
Benefit plans (Details) - USD ($) $ in Millions	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
United States \| 401(k) Plan
Benefit plans
Contributions made	$ 0.8	$ 0.5	$ 0.3
Foreign Plan \| U.K. Plan
Benefit plans
Contributions made	$ 2.2	$ 1.4	$ 0.7

Related party transactions (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Related party transactions
General and administrative	$ 60,426	$ 49,507	$ 32,435
Affiliated Entity \| Consultancy services with Stone Sunny Isles Inc.
Related party transactions
General and administrative	$ 200	$ 200	$ 200

Summary of significant accounting policies (Policies)

12 Months Ended

Dec. 31, 2023

Summary of significant accounting policies

Use of estimates

The preparation of consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the consolidated financial statements and the reported amounts of expenses during the reporting periods. Significant estimates and assumptions reflected in these consolidated financial statements include, but are not limited to, revenue recognition, the accrual for research and development expenses, 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 global health crises, domestic and global monetary and fiscal policy, geopolitical conflicts such as the ongoing wars involving 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.

Foreign currency and currency translation

The reporting currency of the Company is the U.S. Dollar (“USD”). The functional currency of Bicycle Therapeutics plc’s wholly owned non-U.S. subsidiaries, BicycleTx Limited and BicycleRD Limited, is the British Pound Sterling, and the functional currency of its U.S. subsidiary, Bicycle Therapeutics Inc., is the USD. The functional currency of the Company’s subsidiaries is the same as the local currency. Monetary assets and liabilities denominated in foreign currencies are remeasured into the functional currency at rates of exchange prevailing at the balance sheet dates. Non-monetary assets and liabilities denominated in foreign currencies are remeasured into the functional currency at the exchange rates prevailing at the date of the transaction. Exchange gains or losses arising from foreign currency transactions are included in the determination of net loss for the respective periods. Adjustments that arise from exchange rate changes on transactions denominated in a currency other than the local currency are included in general and administrative expense in the consolidated statements of operations and comprehensive loss as incurred. The Company recorded foreign exchange losses of $0.6 million and $0.6 million for the years ended December 31, 2023 and 2022, respectively, and a foreign exchange gain of $0.4 million for the year ended December 31, 2021.

The Company translates the assets and liabilities of its non-U.S. subsidiaries into USD at the exchange rate in effect on the balance sheet date. Revenues and expenses are translated at the average exchange rate in effect during the period. Unrealized translation gains and losses are recorded as a foreign currency translation adjustment, which is included in the consolidated statements of shareholders’ equity as a component of accumulated other comprehensive (loss) income.

Concentrations of credit risk and of significant suppliers

Financial instruments that potentially expose the Company to concentrations of credit risk consist primarily of cash and cash equivalents and accounts receivable. The Company deposits its cash in financial institutions in amounts that may exceed federally insured limits and has not experienced any losses on such accounts. The Company diversifies its cash and cash equivalents in multiple financial institutions and does not believe it is exposed to any unusual credit risk beyond the normal credit risk associated with commercial banking relationships.

As of December 31, 2023, the Company had no accounts receivable. As such December 31, 2022, accounts receivable consists of amounts due under the Company’s collaboration agreements with Ionis Pharmaceuticals, Inc. (“Ionis”) and Genentech, Inc. (“Genentech”) for which the Company does not obtain collateral. For the years ended December 31, 2023, 2022, and 2021, the Company’s revenue has primarily been generated from collaboration agreements with Bayer Consumer Care AG (“Bayer”), Novartis Pharma AG (“Novartis”), Ionis, Genentech, the Dementia Discovery Fund (“DDF”), and AstraZeneca AB (“AstraZeneca”) (Note 9).

The Company relies, and expects to continue to rely, on multiple vendors to manufacture clinical trial materials and raw materials for its development programs. These programs could be adversely affected by a significant interruption in these manufacturing services or the availability of raw materials.

Cash and cash equivalents

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 date of purchase to be cash equivalents. The Company had cash equivalents of $72.3 million and $276.1 million at December 31, 2023 and 2022, respectively.

As of December 31, 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 consolidated balance sheet. The Company had no restricted cash as of December 31, 2022.

Accounts receivable

The Company makes judgments as to its ability to collect outstanding receivables and estimates credit losses at the reporting date resulting from the inability of its customers to make required payments. Provisions are made based upon a specific review of all significant outstanding invoices and the overall quality and age of those invoices. To date, the Company has not had any write-offs of bad debt, and the Company did not have an allowance for credit losses as of December 31, 2023 and 2022.

Deferred offering costs

The Company capitalizes certain legal, professional, accounting and other third-party fees that are directly associated with in-process equity financings as deferred offering costs until such financings are consummated. After consummation of the equity financing, these costs are recorded in shareholders’ equity as a reduction of proceeds generated as a result of the offering. Should an in-process equity financing be abandoned, the deferred offering costs will be expensed immediately as a charge to operating expenses in the consolidated statements of operations and comprehensive loss.

Property and equipment

Property and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation and amortization expense is recognized using the straight-line method over the estimated useful lives of the respective assets as follows:


		Estimated Useful Life
Laboratory equipment		3 to 5 years
Leasehold improvements		Lesser of lease term or useful life
Computer equipment and software		3 years
Furniture and office equipment		3 to 5 years

Costs for property and equipment not yet placed into service are capitalized as construction-in-progress and depreciated in accordance with the above guidelines once placed into service. Upon retirement or sale, the cost of assets disposed of and the related accumulated depreciation are removed from the accounts and any resulting gain or loss is included in loss from operations. To date, there have been no significant asset retirements. Expenditures for repairs and maintenance are charged to expense as incurred.

Impairment of longlived assets

Impairment of long-lived assets

Long-lived assets to be held and used are tested for recoverability whenever events or changes in business circumstances indicate that the carrying amount of the assets may not be fully recoverable. Factors that the Company considers in deciding when to perform an impairment review include significant underperformance of the business in relation to expectations, significant negative industry or economic trends and significant changes or planned changes in the use of the assets. If an impairment review is performed to evaluate a long-lived asset group for recoverability, the Company compares forecasts of undiscounted cash flows expected to result from the use and eventual disposition of the long-lived asset group to its carrying value. An impairment loss may be recognized when estimated undiscounted future cash flows expected to result from the use of an asset group are less than its carrying amount. The impairment loss would be based on the excess of the carrying value of the impaired asset group over its fair value, determined based on discounted cash flows. To date, the Company has not recorded any material impairment losses on long-lived assets.

Fair value measurements

Certain of the Company’s assets and liabilities are carried at fair value under U.S. GAAP. Fair value is defined as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. Valuation techniques used to measure fair value must maximize the use of observable inputs and minimize the use of unobservable inputs. 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, cash equivalents and restricted cash, accounts receivable, research and development incentives receivable, prepaid expenses and 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

December 31, 2023 and 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.

Debt issuance costs

Debt issuance costs consist of certain third-party legal expenses and payments made to secure commitments under certain debt financing arrangements. These amounts are recognized as interest expense over the period of the financing arrangement.

Segment and geographic information

Operating segments are defined as components of a business for which separate discrete financial information is available for evaluation by the chief operating decision maker in deciding how to allocate resources and assess performance. The Company and its chief operating decision maker, the Company’s Chief Executive Officer, view the Company’s operations and manages its business as a single operating segment, which is developing a unique class of chemically synthesized medicines based on its proprietary platform.

The Company operates in two geographic regions: the United Kingdom and the United States.

Leases

Leases are accounted for in accordance with Accounting Standards Codification (“ASC”) Topic 842, Leases (“ASC 842”). The Company determines if an arrangement is a lease at inception. Assets and liabilities related to operating leases are included in operating lease right of use (“ROU”) assets, other current liabilities, and operating lease liabilities in the Company’s consolidated balance sheet. The Company has not entered into any finance leases.

ROU assets represent the Company’s right to use and control an underlying asset for the lease term and lease liabilities represent the Company’s obligation to make lease payments arising from the lease. ROU assets and liabilities are recognized on the lease commencement date based on the present value of lease payments over the lease term. The ROU asset also includes lease payments made before the lease commencement date and excludes any lease incentives. The Company identifies and assesses the following significant assumptions in recognizing the ROU assets and corresponding lease liabilities:

●

Expected lease term – The expected lease term includes both contractual lease periods and, when applicable, periods covered by an option to extend the lease when it is reasonably certain that the Company will exercise the extension option, or cancelable option periods when it is reasonably certain that the Company would not exercise such cancelation option.

●

Incremental borrowing rate – As the Company’s leases do not provide an implicit rate, the Company uses its incremental borrowing rate based on the information available on the commencement date in determining the present value of lease payments. As the Company does not have any external borrowings for comparable terms of its leases, the Company estimates the incremental borrowing rate by comparing interest rates available in the market for similar borrowings and third-party quotations.

●

Lease and non-lease components – The components of a lease shall be split into three categories, if applicable: lease components (e.g., land, building, etc.), non-lease components (e.g., common area maintenance, maintenance, consumables, etc.) and non-components (e.g., property taxes, insurance, etc.). The fixed and in-substance fixed contract consideration (including any related to non-components) must then be allocated based on fair values to the lease components and non-lease components. The Company’s facilities operating leases may have both lease components and non-lease components for which the Company has elected to apply the

practical expedient to account for each lease component and related non-lease component as one single component. The lease component results in a ROU asset being recorded on the balance sheet.

Lease expense for lease payments is considered operating lease cost and is recognized on a straight-line basis over the lease term. Variable payments for other operating costs, which may be billed based on both usage and as a percentage of the Company’s share of total square footage, are considered variable lease cost and are recognized in the period in which the costs are incurred. Operating and variable lease cost are recorded as a component of research and development expenses and general and administrative expenses in the consolidated statements of operations and comprehensive loss.

Revenue recognition

The Company’s revenues are generated primarily through collaborative arrangements and license agreements with pharmaceutical companies. The terms of these arrangements may include (i) performing research and development services using the Company’s bicyclic peptide screening platform with the goal of identifying and/or optimizing compounds for further development and commercialization, (ii) the transfer of intellectual property rights (licenses), or (iii) options to obtain additional research and development services or licenses for additional targets, or to optimize product candidates, upon the payment of option fees.

The terms of these arrangements typically include payment to the Company of one or more of the following: non-refundable, upfront license fees; payments for research and development services; fees upon the exercise of options to obtain additional services or licenses; payments based upon the achievement of defined collaboration objectives; future regulatory and sales-based milestone payments; and royalties on net sales of future products.

The Company recognizes revenue in accordance with ASC Topic 606, Revenue from Contracts with Customers (“ASC 606”). This standard applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases, insurance, and financial instruments.

Under ASC 606, an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the entity expects to receive in exchange for those goods or services.

To determine revenue recognition for arrangements that the Company determines are within the scope of ASC 606, it performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when, or as, the Company satisfies the performance obligations. The Company only applies the five-step model to contracts when it is probable that the entity will collect substantially all of the consideration it is entitled to in exchange for the goods or services it transfers to the customer. As part of the accounting for these arrangements, the Company must make significant judgments, including identifying performance obligations in the contract, estimating the amount of variable consideration to include in the transaction price and allocating the transaction price to each performance obligation based on estimated relative standalone selling prices.

Once a contract is determined to be within the scope of ASC 606, the Company assesses the goods or services promised within the contract and determines those that are performance obligations. Arrangements that include rights to additional goods or services that are exercisable at a customer’s discretion are generally considered options. The Company assesses if these options provide a material right to the customer and if so, they are considered performance obligations.

Performance obligations are promised goods or services in a contract to transfer a distinct good or service to the customer. The promised goods or services in the Company’s contracts with customers primarily consist of license rights to the Company’s intellectual property, research and development services, options to acquire additional research and development services, and options to obtain additional licenses, such as a commercialization license for a potential product candidate. Promised goods or services are considered distinct when: (i) the customer can benefit from the good or service on its own or together with other readily available resources, and (ii) the promised good or service is separately identifiable from other promises in the contract. In assessing whether promised goods or services are distinct,

the Company considers factors such as the stage of development of the underlying intellectual property, the capabilities of the collaboration partner to develop the intellectual property on their own and whether the required expertise is readily available. In addition, the Company considers whether the customer can benefit from a promise for its intended purpose without the receipt of the remaining promises, whether the value of the promise is dependent on the unsatisfied promises, whether there are other vendors that could provide the remaining promises, and whether it is separately identifiable from the remaining promises.

The Company estimates the transaction price based on the amount of consideration the Company expects to receive for transferring the promised goods or services in the contract. The consideration may include both fixed consideration and variable consideration. At the inception of each arrangement that includes variable consideration, the Company evaluates the amount of the potential payments and the likelihood that the payments will be received. The Company utilizes either the most likely amount method or expected value method to estimate variable consideration to include in the transaction price based on which method better predicts the amount of consideration expected to be received. The amount included in the transaction price is constrained to the amount for which it is probable that a significant reversal of cumulative revenue recognized will not occur. At the end of each subsequent reporting period, the Company re-evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis in the period of adjustment. The initial transaction price of a contract does not include amounts associated with customer option payments.

After the transaction price is determined, it is allocated to the identified performance obligations based on the estimated standalone selling price. The Company must develop assumptions that require judgment to determine the standalone selling price for each performance obligation identified in the contract. The Company utilizes key assumptions to determine the standalone selling price, which may include other comparable transactions, pricing considered in negotiating the transaction, probabilities of technical and regulatory success and the estimated costs. Certain variable consideration is allocated specifically to one or more performance obligations in a contract when the terms of the variable consideration relate to the satisfaction of the performance obligation and the resulting amounts allocated to each performance obligation are consistent with the amounts the Company would expect to receive for each performance obligation.

The Company then recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) each performance obligation is satisfied at a point in time or over time, and if over time based on the use of an input method.

Licenses of intellectual property: If a license to the Company’s intellectual property is determined to be distinct from the other promises or performance obligations identified in the contract, the Company recognizes revenue from portion of the transaction price allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are combined with other promises, such as research and development services and a research license, the Company utilizes judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue. The Company evaluates the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition. The measure of progress, and thereby periods over which revenue should be recognized, are subject to estimates by management and may change over the course of the arrangement.

Research and development services: The promises under the Company’s collaboration agreements may include research and development services to be performed by the Company on behalf of the partner. Payments or reimbursements resulting from the Company’s research and development efforts are recognized as the services are performed and presented on a gross basis because the Company is the principal for such efforts.

Customer options: A customer’s rights to choose, at its discretion, to make a payment for additional goods or services is generally considered an option. If the Company is not presently obligated to provide, and does not have a right to consideration for delivering additional goods or services, the item is considered an option. The Company evaluates the customer options for material rights, such as the ability to acquire additional goods or services for free or at

a discount. Optional future goods and services that reflect their standalone selling prices do not provide the customer with a material right and, therefore, are not considered performance obligations and are accounted for as separate contracts. If optional future goods and services include a material right, they are accounted for as performance obligations. The Company determines an estimated standalone selling price of any material rights for the purpose of allocating the transaction price. The Company considers factors such as the identified discount and the probability that the customer will exercise the option. Amounts allocated to a material right are not recognized as revenue until, at the earliest, the option is exercised or expires.

Milestone payments: The Company’s collaboration agreements may include development and regulatory milestones. The Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. The Company evaluates factors such as the scientific, clinical, regulatory, commercial, and other risks that must be overcome to achieve the particular milestone in making this assessment. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the Company’s control or the licensee’s control, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. At the end of each reporting period, the Company re-evaluates the probability of achievement of such milestones and any related constraint, and if necessary, adjusts the estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect collaboration revenue and net loss in the period of adjustment. Milestone payments that may only be achieved after the exercise of a customer option are excluded from the initial determination of the transaction price.

Royalties: For sales-based royalties, including milestone payments based on the level of sales, the Company determines whether the sole or predominant item to which the royalties relate is a license. When the license is the sole or predominant item to which the sales-based royalty relates, the Company recognizes revenue at the later of: (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, the Company has not recognized any sales-based royalty revenue resulting from the Company’s collaboration agreements.

The Company receives payments from customers based on billing schedules established in each contract. Up-front payments and fees are recorded as deferred revenue upon receipt or when due until the Company performs its obligations under these arrangements. Amounts are recorded as accounts receivable when the Company’s right to consideration is unconditional, such as when the Company has a contractual right to payment per the terms of the contract.

For a complete discussion of the Company’s accounting for collaboration revenues, see Note 9, “Significant agreements.”

Government grants

From time to time, the Company may enter into arrangements with governmental entities for the purposes of obtaining funding for research and development activities. The Company is reimbursed for costs incurred that are associated with specified research and development activities included in the grant application approved by the government authority. The Company recognizes government grant funding in the consolidated statements of operations and comprehensive loss as the related expenses being funded are incurred. The Company classifies government grants received under these arrangements as a reduction to the related research and development expense incurred, and accrued but unpaid grant income is included in other current assets. The Company analyzes each arrangement on a case-by-case basis, and income is recognized when the Company concludes that it has reasonable assurance that it will comply with the conditions attached to the grant and the expenses have been incurred. There are no significant performance criteria other than to maintain satisfactory progress on the specified project, and there are no significant acceptance or recapture provisions associated with the government grants for the years ended December 31, 2023, 2022 and 2021, respectively. For the years ended December 31, 2023, 2022 and 2021, the Company recognized $1.0 million, $1.5 million, and $3.0 million, respectively, as a reduction of research and development expense related to government grant arrangements. As of December 31, 2023, the Company has approximately $0.1 million of government grant funding remaining for future cost reimbursement through February of 2024.

Research and development costs

Research and development costs are expensed as incurred. Research and development costs consist of costs incurred in performing research and development activities, including salaries, share-based compensation and benefits, travel, facilities costs, depreciation, materials and laboratory supplies, and external costs of outside vendors engaged to conduct preclinical development and clinical development activities, as well as costs to manufacture clinical trial materials. Facilities costs primarily include the allocation of rent and utilities.

Non-refundable prepayments for goods or services that will be used or rendered for future research and development activities are deferred and capitalized until the related goods are delivered or the related services are performed, or until it is no longer expected that the goods will be delivered, or the services rendered.

Research and manufacturing contract costs and accruals

The Company has entered into various research and development and manufacturing contracts, including contracts with respect to preclinical studies and clinical trials, with companies both inside and outside of the United States. These agreements are generally cancelable with 90 days or less notice, and related costs are recorded as research and development expenses as incurred. The Company records accruals for estimated ongoing costs. When evaluating the adequacy of the accrued liabilities, the Company analyzes progress of the research and development and manufacturing activities, including the phase or completion of events, invoices received and contracted costs. Significant judgments and estimates are made in determining the accrued balances at the end of any reporting period. Actual results could differ from the Company’s estimates. The Company’s historical accrual estimates have not been materially different from the actual costs.

Research and development incentives and receivable

The Company, through its subsidiaries in the United Kingdom, receives reimbursements of certain research and development expenditures as part of a United Kingdom government’s research and development tax reliefs program. Under the program, the Company is able to surrender trading losses that arise from qualifying research and development expenses incurred by the Company’s subsidiaries in the United Kingdom for a tax credit of up to 14.5% of the surrenderable losses related expenditures incurred prior to April 1, 2023 and up to 10.0% of the surrenderable losses related to expenditures incurred thereafter, subject to certain limitations.

Management has assessed the Company’s research and development activities and expenditures to determine which activities and expenditures are likely to be eligible under the research and development incentive program described above. At each period end, management estimates the reimbursement available to the Company based on available information at the time.

The Company recognizes income from the research and development incentives when the relevant expenditure has been incurred, the associated conditions have been satisfied and there is reasonable assurance that the reimbursement will be received. The Company records these research and development incentives as a reduction to research and development expenses in the statements of operations and comprehensive loss, as the research and development tax credits are not dependent on us generating future taxable income, the Company’s ongoing tax status, or tax position. The research and development incentives receivable represent an amount due in connection with the above program. The Company recorded a reduction to research and development expense of $23.5 million, $19.3 million and $10.8 million during the years ended December 31, 2023, 2022 and 2021, respectively.

Patent costs

All patent-related costs incurred in connection with preparing, filing and prosecuting patent applications are expensed as incurred due to the uncertainty about the recovery of the expenditure. Amounts incurred are classified as general and administrative expenses in the consolidated statements of operations and comprehensive loss.

Share-based compensation

The Company measures all equity awards granted to employees and directors based on the fair value on the date of grant. Compensation expense of those awards is recognized over the requisite service period, which is generally the vesting period of the respective award. The Company records the expense for awards with only service-based vesting conditions using the straight-line method. The Company accounts for forfeitures as they occur.

For share-based awards granted to non-employee consultants, the measurement date is the date of grant. The compensation expense is then recognized over the requisite service period, which is the vesting period of the respective award, without subsequent changes in the fair value of the award.

The fair value of each restricted share award is based on the fair value of the Company’s shares, less any applicable purchase price. The fair value of each share option is estimated using the Black-Scholes option-pricing model, which requires inputs based on certain subjective assumptions, including the fair value of shares, the expected share price volatility, the expected term of the award, the risk-free interest rate and expected dividends.

Previously, due to a lack of company-specific historical volatility data, the Company’s expected volatility was calculated based on reported volatility data for a representative group of publicly traded companies for which historical information was available. The historical volatility was calculated based on a period of time commensurate with the assumption used for the expected term. During 2022, the Company began to estimate its volatility by using a blend of its stock price history for the length of time it has market data for its stock and the historical volatility of similar public companies for the expected term of each grant. The Company will continue to apply this process until a sufficient amount of historical information regarding the volatility of its own stock price becomes available. The risk-free interest rate is based on the U.S. Treasury yield curve in effect at the time of grant commensurate with the expected term assumption. The Company uses the simplified method, under which the expected term is presumed to be the midpoint between the vesting date and the end of the contractual term. The Company utilizes this method due to the lack of historical exercise data and the plain nature of its share-based awards. The Company uses the remaining contractual term for the expected life of non-employee awards. The expected dividend yield is assumed to be zero as the Company has never paid dividends and has no current plans to pay any dividends on ordinary shares.

The Company classifies share-based compensation expense in its consolidated statements of operations and comprehensive loss in the same manner in which the award recipient’s payroll or service costs are classified.

Comprehensive loss

Comprehensive loss includes net loss as well as other changes in shareholders’ equity that result from transactions and economic events other than those with shareholders. The Company records unrealized gains and losses related to foreign currency translation as a component of other comprehensive loss in the consolidated statements of operations and comprehensive loss.

Contingencies

Liabilities for loss contingencies arising from claims, assessments, litigation, fines, penalties and other sources are recorded when it is probable that a liability has been incurred and the amount can be reasonably estimated. At each reporting date, the Company evaluates whether or not a potential loss amount or a potential loss range is probable and reasonably estimable under the provisions of ASC Topic 450, Contingencies. The Company expenses costs as incurred in relation to such legal proceedings as general and administrative expense within the consolidated statements of operations and comprehensive loss.

Income taxes

The Company accounts for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in the consolidated financial statements or in the Company’s tax returns. Deferred tax assets and liabilities are determined on

the basis of the differences between the consolidated financial statements and tax basis of assets and liabilities using enacted tax rates in effect for the year in which the differences are expected to reverse. Changes in deferred tax assets and liabilities are recorded in the provision for income taxes. The Company assesses the likelihood that its deferred tax assets will be recovered from future taxable income and, to the extent it believes, based upon the weight of available evidence, that it is more likely than not that all or a portion of the deferred tax assets will not be realized, a valuation allowance is established through a charge to income tax expense. Potential for recovery of deferred tax assets is evaluated by estimating the future taxable profits expected and considering prudent and feasible tax planning strategies.

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

Net loss per share

Basic net loss per share is computed by dividing the net loss by the weighted average number of ordinary shares, including non-voting ordinary shares, outstanding for the period. Diluted net loss is computed by adjusting net loss to reallocate undistributed earnings based on the potential impact of dilutive securities. Diluted net loss per share is computed by dividing the diluted net loss by the weighted average number of ordinary shares, including non-voting ordinary shares, outstanding for the period, including potential dilutive ordinary shares assuming the dilutive effect of ordinary share equivalents. In periods in which the Company reported a net loss, diluted net loss per share is the same as basic net loss per share, since dilutive ordinary shares are not assumed to have been issued if their effect is anti-dilutive.

Recently adopted accounting pronouncements and Recently issued accounting pronouncements not yet adopted

Recently adopted accounting pronouncements

There were no recently adopted accounting pronouncements during the year ended December 31, 2023 that are of significance or potential significance to the Company.

Recently issued accounting pronouncements not yet adopted

In December 2023, the FASB issued ASU No. 2023-09, Income Taxes (Topic 740) Improvements to Income Tax Disclosures, which prescribes standard categories for the components of the effective tax rate reconciliation and requires disclosure of additional information for reconciling items meeting certain quantitative thresholds, requires disclosure of disaggregated income taxes paid, and modifies certain other income tax-related disclosures. ASU No. 2023-09 is effective for annual periods beginning after December 15, 2024 and allows for adoption on a prospective basis, with a retrospective option. The Company is currently evaluating the potential impact of the adoption of ASU 2023-09 on its consolidated financial statements and related disclosures.

In November 2023, the FASB issued ASU No. 2023-07, Segment Reporting (Topic 280) Improvements to Reportable Segment Disclosures, which requires disclosure of incremental segment information on an interim and annual basis. ASU 2023-07 is effective for annual periods beginning after December 15, 2023, and interim periods within annual periods beginning after December 15, 2024, and requires retrospective adoption to all prior periods presented in the consolidated financial statements. The Company is currently evaluating the potential impact of the adoption of ASU 2023-07 on its consolidated financial statements and related disclosures.

Consolidated Statements of Shareholders' Equity (Parenthetical) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Consolidated Statements of Shareholders' Equity
Offering expenses	$ 16.0	$ 0.2	$ 16.1

Significant agreements - Summary of Contract Assets and Liabilities (Details) - USD ($)	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Contract liabilities:
Beginning Balance	$ 61,873,000	$ 71,340,000
Additions	95,960,000	12,099,000
Deductions	(26,976,000)	(14,463,000)
Impact of Exchange Rates	4,337,000	(7,103,000)
Ending Balance	135,194,000	61,873,000
Contract assets
Contract assets	0	0
Bayer collaboration deferred revenue
Contract liabilities:
Beginning Balance	0
Additions	45,000,000
Deductions	(1,160,000)
Impact of Exchange Rates	(222,000)
Ending Balance	43,618,000	0
Bayer collaboration deferred revenue \| Deferred revenue material rights option
Contract liabilities:
Ending Balance	32,400,000
Novartis
Contract liabilities:
Beginning Balance	0
Additions	50,000,000
Deductions	(1,909,000)
Impact of Exchange Rates	1,917,000
Ending Balance	50,008,000	0
Novartis \| Deferred revenue material rights option
Contract liabilities:
Ending Balance	33,200,000
Ionis collaboration deferred revenue
Contract liabilities:
Beginning Balance	21,489,000	34,115,000
Additions	960,000	99,000
Deductions	(10,734,000)	(9,347,000)
Impact of Exchange Rates	749,000	(3,378,000)
Ending Balance	12,464,000	21,489,000
Ionis collaboration deferred revenue \| Deferred revenue material rights option
Contract liabilities:
Ending Balance	3,600,000
Genentech
Contract liabilities:
Beginning Balance	39,308,000	34,436,000
Additions		12,000,000
Deductions	(11,969,000)	(3,565,000)
Impact of Exchange Rates	1,765,000	(3,563,000)
Ending Balance	29,104,000	39,308,000
Genentech \| Deferred revenue material rights option
Contract liabilities:
Ending Balance	21,800,000
Dementia Discovery Fund
Contract liabilities:
Beginning Balance	0	428,000
Deductions		(386,000)
Impact of Exchange Rates		(42,000)
Ending Balance	0	0
AstraZeneca
Contract liabilities:
Beginning Balance	1,076,000	2,361,000
Deductions	(1,204,000)	(1,165,000)
Impact of Exchange Rates	128,000	(120,000)
Ending Balance	$ 0	$ 1,076,000

Consolidated Balance Sheets (Parenthetical) - £ / shares	Dec. 31, 2023	Dec. 31, 2022
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	42,431,766	29,873,893
Ordinary shares, shares outstanding	42,431,766	29,873,893

Net loss per share

12 Months Ended

Dec. 31, 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):


	Year Ended
	December 31,
	2023		2022		2021
Numerator:
Net loss	$	(180,664)	$	(112,717)	$	(66,819)
Denominator:
Weighted average ordinary shares outstanding, basic and diluted		35,592,362		29,660,659		25,061,734
Net loss per share, basic and diluted	$	(5.08)	$	(3.80)	$	(2.67)

The Company’s potentially dilutive securities, which include 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:


	December 31,
	2023	2022	2021
Restricted ordinary shares	326,848	187,725	—
Options to purchase ordinary shares	7,469,527	5,898,888	4,603,486
	7,796,375	6,086,613	4,603,486

Share-based compensation

12 Months Ended

Dec. 31, 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 approved the Bicycle Therapeutics plc 2020 Equity Incentive 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, including shares subject to options that were granted under the Company’s 2019 Share Option Plan (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, 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 December 31, 2023, there were 693,039 shares available for issuance under the 2020 Plan. The number of shares reserved for issuance under the 2020 Plan was increased by 1,886,294 shares effective January 1, 2024.

Share options issued under the 2020 Share Option Plan have a 10-year contractual life, and generally vest over either a three-year service period for non-employee directors, or a four-year service period with 25% of the award vesting on the first anniversary of the commencement date and the balance thereafter in 36 equal monthly installments for employees and consultants. Certain options 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.

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 generally 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 vesting 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. The Company may also, in its sole discretion, provide for deferred settlement of RSUs awarded to the Company’s non-employee directors.

As of December 31, 2023, there were options to purchase 4,803,054 shares and RSUs for 326,848 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 December 31, 2023, there were 2,078,033 options to purchase ordinary shares outstanding under the 2019 Plan. In conjunction with the adoption of the 2020 Plan, all shares available for future issuance under the 2019 Plan as of June 29, 2020 became available for issuance under the 2020 Plan and the Company ceased making awards under the 2019 Plan. The 2020 Plan is the successor of the 2019 Plan.

Share options previously issued under the 2019 Plan have a 10-year contractual life, and generally either vest monthly over a three-year service period, or over a four-year service period with 25% of the award vesting on the first anniversary of the commencement date and the balance thereafter in 36 equal monthly installments. Certain awards granted to the Company’s non-employee directors were fully vested on the date of grant. The exercise price of share options issued under the 2019 Plan is not less than the fair value of ordinary shares as of the date of grant.

Employee Share Purchase Plan (“ESPP”)

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 least 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. As of December 31, 2023, the total number of shares available for issuance under the ESPP was 1,200,413 shares. The number of shares reserved for issuance under the ESPP was increased by 377,258 shares effective January 1, 2024. As of December 31, 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 consolidated statements of operations and comprehensive loss (in thousands):


	Year Ended
	December 31,
	2023		2022		2021
Research and development expenses	$	15,581	$	10,394	$	4,974
General and administrative expenses		16,896		16,385		7,109
	$	32,477	$	26,779	$	12,083

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	2,099,895		26.53	—		—
Exercised	(54,023)		12.57	—		—
Forfeited	(475,233)		30.94	—		—
Outstanding as of December 31, 2023	7,469,527	$	23.13	6.83	$	21,920
Vested and expected to vest as of December 31, 2023	7,469,527	$	23.13	6.83	$	21,920
Options exercisable as of December 31, 2023	4,561,511	$	18.95	5.61	$	21,358

The weighted average grant-date fair value of share options granted during the years ended December 31, 2023, 2022 and 2021 was $19.36 per share, $31.45 per share and $15.66 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 during the years ended December 31, 2023, 2022 and 2021 was $0.5 million, $1.5 million and $22.0 million, respectively.

For the years ended December 31, 2023, 2022 and 2021, the Company recorded share-based compensation expense for share options granted of $27.0 million, $21.9 million and $12.1 million, respectively. Expense for non-employee consultants for each of the years ended December 31, 2022, 2021 and 2020, 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:


	Year Ended
	December 31,
	2023		2022		2021
Risk-free interest rate	4.0	%	2.2	%	0.6	%
Expected volatility	82.9	%	82.5	%	79.8	%
Expected dividend yield	—		—		—
Expected term (in years)	6.1		6.0		6.0

As of December 31, 2023, total unrecognized compensation expense related to the unvested employee and director share options was $54.0 million, which is expected to be recognized over a weighted average period of 2.6 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	333,089		29.27
Vested	(119,144)		50.30
Forfeited	(74,822)		39.55
Unvested at December 31, 2023	326,848	$	37.40

The fair value of RSUs that vested during the years ended December 31, 2023, 2022 and 2021 was $3.0 million, $2.1 million and zero, respectively.

Total share-based compensation expense for RSUs granted for the years ended December 31, 2023, 2022 and 2021 was $5.5 million, $4.9 million and zero, respectively. As of December 31, 2023, the total unrecognized compensation expense related to unvested RSUs was $10.0 million, which is expected to be recognized over a weighted-average period of 2.6 years.

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Current assets:
Cash and cash equivalents	$ 526,423	$ 339,154
Accounts receivable	0	2,045
Prepaid expenses and other current assets	11,406	9,022
Research and development incentives receivable	24,039	19,162
Total current assets	561,868	369,383
Property and equipment, net	14,515	19,110
Operating lease right-of-use assets	13,169	13,658
Other assets	5,792	8,458
Total assets	595,344	410,609
Current liabilities:
Accounts payable	13,050	6,472
Accrued expenses and other current liabilities	31,509	26,452
Deferred revenue, current portion	24,978	20,418
Total current liabilities	69,537	53,342
Long-term debt, net of discount	30,698	30,315
Operating lease liabilities, net of current portion	9,382	10,885
Deferred revenue, net of current portion	110,216	41,455
Other longterm liabilities	4,579	3,829
Total liabilities	224,412	139,826
Commitments and contingencies (Note 11)
Shareholders' equity:
Ordinary shares, including non-voting ordinary shares, £0.01 nominal value; 59,612,613 and 57,820,181 shares authorized at December 31, 2023 and December 31, 2022, respectively; 42,431,766 and 29,873,893 shares issued and outstanding at December 31, 2023 and December 31, 2022, respectively	550	387
Additional paid-in capital	883,446	601,105
Accumulated other comprehensive (loss) income	(1,304)	387
Accumulated deficit	(511,760)	(331,096)
Total shareholders' equity	370,932	270,783
Total liabilities and shareholders' equity	$ 595,344	$ 410,609

Significant agreements - Cancer Research UK (Details) - USD ($) $ in Millions		1 Months Ended
	Dec. 13, 2016	Dec. 31, 2019	Dec. 31, 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			$ 4.3	$ 3.6
BT1718 \| Minimum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)	70.00%
BT1718 \| Maximum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)	90.00%
BT7401 \| Minimum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)		55.00%
BT7401 \| Maximum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)		80.00%

Ordinary shares - Share Purchase Agreement (Details) $ / shares in Units, $ in Thousands				12 Months Ended
	Jul. 17, 2023 USD ($) $ / shares shares	Oct. 15, 2021 USD ($) $ / shares shares	Jul. 09, 2021 USD ($) $ / shares shares	Dec. 31, 2023 USD ($) shares	Dec. 31, 2022 USD ($) shares	Dec. 31, 2021 USD ($) shares	Dec. 31, 2023 £ / shares shares	Jul. 17, 2023 £ / shares	Dec. 31, 2022 £ / shares shares	Dec. 31, 2020 shares
Class of Stock [Line Items]
Ordinary shares, shares issued \| shares							42,431,766		29,873,893
Ordinary shares, shares outstanding \| shares							42,431,766		29,873,893
Gross proceeds before discounts and commissions				$ 249,345	$ 5,703	$ 290,984
Net proceeds				249,345	5,703	290,984
Offering expenses				16,000	200	$ 16,100
Ordinary shares, nominal value \| £ / shares							£ 0.01		£ 0.01
Ordinary Shares
Class of Stock [Line Items]
Ordinary shares, shares outstanding \| shares						29,579,364	42,431,766		29,873,893	21,094,557
Gross proceeds before discounts and commissions				$ 162	$ 2	$ 104
Shares issued (in shares) \| shares				12,384,706	181,455	7,498,536
Non voting ordinary shares \| Ordinary Shares
Class of Stock [Line Items]
Ordinary shares, shares issued \| shares							4,705,882
Ordinary shares, shares outstanding \| shares							4,705,882
Voting ordinary shares \| Ordinary Shares
Class of Stock [Line Items]
Ordinary shares, shares issued \| shares							37,725,884
Ordinary shares, shares outstanding \| shares							37,725,884
Ionis Share Purchase Agreement
Class of Stock [Line Items]
Gross proceeds before discounts and commissions						$ 7,558
Ionis Share Purchase Agreement \| Ordinary Shares
Class of Stock [Line Items]
Gross proceeds before discounts and commissions						$ 4
Shares issued (in shares) \| shares						282,485
At the market offering
Class of Stock [Line Items]
Gross proceeds before discounts and commissions				$ 35,300	$ 5,900	$ 105,800
Shares issued (in shares) \| shares				1,561,176	181,455	3,771,684
Net proceeds				$ 34,200	$ 5,700	$ 102,600
Offering expenses				$ 1,100	$ 200	$ 3,200
Underwritten Public Offering
Class of Stock [Line Items]
Gross proceeds before discounts and commissions	$ 230,000
Net proceeds	215,100
Offering expenses	$ 14,900
Underwritten Public Offering \| American Depositary Shares
Class of Stock [Line Items]
Price per share \| $ / shares	$ 21.25	$ 54.00
Gross proceeds before discounts and commissions		$ 201,300
Shares issued (in shares) \| shares	6,117,648	3,726,852
Net proceeds		$ 188,400
Ordinary shares, nominal value \| £ / shares								£ 0.01
Underwritten Public Offering \| American Depositary Shares \| Option on securities
Class of Stock [Line Items]
Shares issued (in shares) \| shares	1,411,764
Underwritten Public Offering \| Non voting ordinary shares
Class of Stock [Line Items]
Shares issued (in shares) \| shares	4,705,882
Ordinary shares, nominal value \| £ / shares								£ 0.01
Ionis \| Ionis Share Purchase Agreement
Class of Stock [Line Items]
Ordinary shares, shares issued \| shares			282,485
Price per share \| $ / shares			$ 38.94
Gross proceeds before discounts and commissions			$ 11,000
Fair value of shares held			$ 7,600
Ionis \| Ionis Share Purchase Agreement \| American Depositary Shares
Class of Stock [Line Items]
Price per share \| $ / shares			$ 31.11

Significant agreements - Collaboration revenues (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Significant agreements.
Collaboration revenues	$ 26,976	$ 14,463	$ 11,697
Bayer
Significant agreements.
Collaboration revenues	1,160	0	0
Novartis
Significant agreements.
Collaboration revenues	1,909
Ionis
Significant agreements.
Collaboration revenues	10,734	9,347	4,242
Genentech
Significant agreements.
Collaboration revenues	11,969	3,565	5,660
Dementia Discovery Fund
Significant agreements.
Collaboration revenues	0	386	391
AstraZeneca
Significant agreements.
Collaboration revenues	$ 1,204	$ 1,165	$ 1,404

- Definition

+ References

+ Details

Commitments and contingencies - Leases, Office and laboratory space Cambridge (Details) - USD ($)		1 Months Ended	12 Months Ended
	Dec. 06, 2021	Jan. 31, 2023	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Sep. 30, 2017
Leases
Lease liabilities			$ 14,258,000
Operating lease right-of-use assets			13,169,000	$ 13,658,000
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		$ 2,100,000
Rental payment		$ 2,300,000
Rent free period		2 months
Security deposit		$ 500,000
Lease liabilities		$ 5,800,000
Discounted percentage for present value of lease payments		9.00%
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	$ 3,000,000.0
Rent free period	6 months
Security deposit	$ 0
Lease liabilities	$ 11,100,000
Discounted percentage for present value of lease payments	6.90%
Operating lease right-of-use assets	$ 11,600,000
Office and laboratory space in Building 900, Babraham Research Campus, Cambridge
Leases
Renewal term					5 years
Annual rent					$ 600,000
Estimated service charges payable					$ 200,000
Office and laboratory space in Building 900, Babraham Research Campus, Cambridge \| General and administrative expenses
Leases
Loss on lease termination			300,000
Office and laboratory space in Lexington, Massachusetts
Leases
Annual rent			$ 800,000
Security deposit						$ 200,000
Discounted percentage for present value of lease payments			7.00%
Payments for the extended lease remaining			$ 700,000	$ 200,000

Long-term debt (Details) - USD ($) $ in Millions			12 Months Ended
Long-term debt (Details) - USD ($) $ in Millions	Jul. 15, 2022	Mar. 15, 2022	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Mar. 10, 2021	Sep. 30, 2020
Debt Instrument [Line Items]
Borrowing option to prepay subject to minimum debt outstanding			$ 5.0
End term charge rate			5.00%
Additional interest rate event of default			5.00%
Prepayment occurs after year two
Debt Instrument [Line Items]
Prepayment rate			1.00%
Prime Rate
Debt Instrument [Line Items]
Debt instrument stated percentage					8.85%
Basis spread variable rate					5.60%
Second Amendment to LSA
Debt Instrument [Line Items]
Debt instrument stated percentage	8.05%
Second Amendment to LSA \| Prime Rate
Debt Instrument [Line Items]
Basis spread variable rate	4.55%
Second Amendment to LSA \| Maximum
Debt Instrument [Line Items]
Term loan	$ 45.0
Debt instrument stated percentage	9.05%
Term Loan
Debt Instrument [Line Items]
Maximum borrowing	$ 75.0
Initial Term Loan
Debt Instrument [Line Items]
Fees and transaction costs			$ 0.6
Debt instrument effective percentage			10.80%
Interest expense			$ 3.1	$ 3.2	$ 2.9
Additional Term Loan One
Debt Instrument [Line Items]
Additional term loan expired unexercised.		$ 10.0
Loan and Security Agreement \| Term Loan
Debt Instrument [Line Items]
Maximum borrowing							$ 40.0
Loan and Security Agreement \| Initial Term Loan
Debt Instrument [Line Items]
Term loan							15.0
Loan and Security Agreement \| Additional Term Loan One
Debt Instrument [Line Items]
Term loan						$ 15.0	15.0
Loan and Security Agreement \| Additional Term Loan Two
Debt Instrument [Line Items]
Term loan							$ 10.0

Accrued expenses and other current liabilities

12 Months Ended

Dec. 31, 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):


	December 31,		December 31,
	2023		2022
Accrued employee compensation and benefits	$	13,394	$	9,928
Accrued external research and development expenses		11,839		10,859
Accrued professional fees		1,143		1,068
Current portion of operating lease liabilities		4,876		3,125
Other		257		1,472
	$	31,509	$	26,452

Summary of significant accounting policies

12 Months Ended

Dec. 31, 2023

Summary of significant accounting policies

Summary of significant accounting policies

2. Summary of significant accounting policies

Use of estimates

Significant risks and uncertainties

Foreign currency and currency translation

Concentrations of credit risk and of significant suppliers

Cash, cash equivalents and restricted cash

Accounts receivable

Deferred offering costs

Property and equipment


		Estimated Useful Life
Laboratory equipment		3 to 5 years
Leasehold improvements		Lesser of lease term or useful life
Computer equipment and software		3 years
Furniture and office equipment		3 to 5 years

Impairment of long-lived assets

Fair value measurements

●

Level 1 — Quoted prices in active markets for identical assets or liabilities.

●

Debt issuance costs

Segment and geographic information

The Company operates in two geographic regions: the United Kingdom and the United States.

Leases

●

practical expedient to account for each lease component and related non-lease component as one single component. The lease component results in a ROU asset being recorded on the balance sheet.

Revenue recognition

For a complete discussion of the Company’s accounting for collaboration revenues, see Note 9, “Significant agreements.”

Government grants

Research and development costs

Research and manufacturing contract costs and accruals

Research and development incentives and receivable

Patent costs

Share-based compensation

Comprehensive loss

Contingencies

Income taxes

Net loss per share

Recently adopted accounting pronouncements

There were no recently adopted accounting pronouncements during the year ended December 31, 2023 that are of significance or potential significance to the Company.

Recently issued accounting pronouncements not yet adopted

Income taxes (Details)	12 Months Ended
Income taxes (Details)	Dec. 31, 2023 USD ($) jurisdiction	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Income taxes.
Provision for (benefit from) income taxes	$ 1,457,000	$ (1,524,000)	$ (1,663,000)
Increase (decrease) in income taxes	2,400,000
Increases recorded to income tax provision	26,500,000
U.K. operating loss carryforwards	266,200,000
Uncertain tax positions	0	0
Interest and penalties accrued	$ 0	$ 0
State
Income taxes.
Number of jurisdictions \| jurisdiction	11

- Definition

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

+ References + Details

Related party transactions

12 Months Ended

Dec. 31, 2023

Related party transactions

Related party transactions

14. Related party transactions

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 $0.2 million, $0.2 million and $0.2 million during each of the years ended December 31, 2023, 2022 and 2021, respectively.

- Definition

The entire disclosure for related party transactions. Examples of related party transactions include transactions between (a) a parent company and its subsidiary; (b) subsidiaries of a common parent; (c) and entity and its principal owners; and (d) affiliates.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 946
-SubTopic 20
-Name Accounting Standards Codification
-Section 50
-Paragraph 2
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480990/946-20-50-2

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Topic 946
-SubTopic 20
-Name Accounting Standards Codification
-Section 50
-Paragraph 5
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480990/946-20-50-5

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 946
-SubTopic 20
-Name Accounting Standards Codification
-Section 50
-Paragraph 6
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480990/946-20-50-6

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Topic 946
-SubTopic 235
-Name Accounting Standards Codification
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-Paragraph 2
-Subparagraph (c)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481062/946-235-50-2

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
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-Section 50
-Paragraph 2
-Subparagraph (e)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147481062/946-235-50-2

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Topic 850
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-Name Accounting Standards Codification
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-Paragraph 1
-Subparagraph (d)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147483326/850-10-50-1

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
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-SubTopic 220
-Name Accounting Standards Codification
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-Paragraph 1
-Subparagraph (SX 210.6-07(2)(g)(3))
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Reference 8: http://www.xbrl.org/2003/role/disclosureRef
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Reference 9: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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-Paragraph 1
-Subparagraph (SX 210.6-07(2)(e))
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-URI https://asc.fasb.org//1943274/2147483575/946-220-S99-1

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Topic 850
-Name Accounting Standards Codification
-Publisher FASB
-URI https://asc.fasb.org//850/tableOfContent

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Topic 850
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 6
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147483326/850-10-50-6

Reference 12: http://www.xbrl.org/2003/role/disclosureRef
-Topic 850
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 1
-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147483326/850-10-50-1

Reference 13: http://www.xbrl.org/2003/role/disclosureRef
-Topic 850
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-Name Accounting Standards Codification
-Section 50
-Paragraph 1
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147483326/850-10-50-1

+ Details

Property and equipment, net (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Property and equipment, net
Property and equipment, gross	$ 27,908	$ 26,973
Less: Accumulated depreciation and amortization	(13,393)	(7,863)
Property and equipment, net	14,515	19,110
Depreciation expense	6,500	3,700	$ 1,400
Laboratory equipment
Property and equipment, net
Property and equipment, gross	15,554	14,872
Laboratory equipment was not yet placed in service	0	2,300
Leasehold improvements
Property and equipment, net
Property and equipment, gross	11,000	10,736
Computer equipment and software
Property and equipment, net
Property and equipment, gross	532	441
Furniture and office equipment
Property and equipment, net
Property and equipment, gross	$ 822	$ 924

Long-term debt - Debt (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Long-term debt
Term loan payable	$ 30,000	$ 30,000
End of term charge	946	682
Unamortized debt issuance costs	(248)	(367)
Carrying value of term loan	$ 30,698	$ 30,315

- Definition

Amount, after deduction of unamortized premium (discount) and debt issuance cost, of long-term debt. Excludes lease obligation.

+ References + Details

Income taxes - Components of net loss before tax provision from income taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Income taxes
United Kingdom	$ (182,980)	$ (116,275)	$ (69,546)
United States	3,773	2,034	1,064
Net loss before income tax provision	$ (179,207)	$ (114,241)	$ (68,482)

- Definition

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

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 944
-SubTopic 220
-Name Accounting Standards Codification
-Section S99
-Paragraph 1
-Subparagraph (SX 210.7-04(11))
-Publisher FASB
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Reference 2: http://www.xbrl.org/2003/role/disclosureRef
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
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-Subparagraph (b)
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-URI https://asc.fasb.org//1943274/2147482810/280-10-50-30

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
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Reference 5: http://www.xbrl.org/2003/role/exampleRef
-Topic 280
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Reference 6: http://www.xbrl.org/2003/role/disclosureRef
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-Publisher FASB
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Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Topic 942
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-Name Accounting Standards Codification
-Section S99
-Paragraph 1
-Subparagraph (SX 210.9-05(b)(2))
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147479557/942-235-S99-1

Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef
-Name Accounting Standards Codification
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Reference 9: http://fasb.org/us-gaap/role/ref/legacyRef
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-Name Accounting Standards Codification
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Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef
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-URI https://asc.fasb.org//1943274/2147483589/942-220-S99-1

+ Details

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Cash flows from operating activities:
Net loss	$ (180,664)	$ (112,717)	$ (66,819)
Adjustments to reconcile net loss to net cash used in operating activities:
Share-based compensation expense	32,477	26,779	12,083
Depreciation and amortization	6,546	3,689	1,409
Non-cash interest	383	442	468
Deferred income tax provision (benefit)	3,306	(4,976)	(1,668)
Other non-cash charges	661
Changes in operating assets and liabilities:
Accounts receivable	2,482	(1,641)	4,543
Research and development incentives receivable	(3,684)	(9,707)	(1,866)
Prepaid expenses and other assets	(2,072)	(2,020)	(2,974)
Operating lease rightofuse assets	4,186	2,698	404
Accounts payable	8,002	2,561	1,196
Accrued expenses and other current liabilities	2,398	12,362	1,185
Operating lease liabilities	(4,109)	(2,114)	(582)
Deferred revenue	68,951	(2,135)	37,117
Other long-term liabilities	509	668	710
Net cash used in operating activities	(60,628)	(86,111)	(14,794)
Cash used in investing activities:
Purchases of property and equipment	(2,929)	(18,987)	(2,030)
Net cash used in investing activities	(2,929)	(18,987)	(2,030)
Cash flows from financing activities:
Proceeds from the issuance of ADSs and non-voting ordinary shares, net of issuance costs	249,345	5,703	290,984
Issuance of ordinary shares pursuant to the Ionis share purchase agreement			7,558
Proceeds from the exercise of share options and sale of ordinary shares	682	989	7,183
Proceeds from issuance of debt			15,000
Net cash provided by financing activities	250,027	6,692	320,725
Effect of exchange rate changes on cash, cash equivalents and restricted cash	1,346	(1,120)	(1,211)
Net increase (decrease) in cash, cash equivalents and restricted cash	187,816	(99,526)	302,690
Cash, cash equivalents and restricted cash at beginning of period	339,154	438,680	135,990
Cash, cash equivalents and restricted cash at end of period	526,970	339,154	438,680
Reconciliation of cash, cash equivalents and restricted cash
Cash and cash equivalents	526,423	339,154	438,680
Restricted cash included in other assets	547	0
Total cash, cash equivalents and restricted cash	526,970	339,154	438,680
Supplemental disclosure of cash flow information
Cash paid for interest	2,753	2,793	2,515
Cash paid for income taxes	562	2,228	73
Cash paid for amounts included in the measurement of operating lease liabilities	5,595	3,154	911
Changes in purchases of property and equipment in accounts payable and accrued expenses	(1,744)	1,564	324
Non-cash impact to right-of-use asset and operating lease liabilities	$ 3,898	$ 3,120	$ 13,846

Income taxes (Tables)

12 Months Ended

Dec. 31, 2023

Income taxes

Schedule of components of net loss before tax provision from income taxes

The components of net loss before income tax provision are as follows (in thousands):


	Year Ended
	December 31,
	2023		2022		2021
United Kingdom	$	(182,980)	$	(116,275)	$	(69,546)
United States		3,773		2,034		1,064
Total	$	(179,207)	$	(114,241)	$	(68,482)

Schedule of components of the benefit for income taxes

The components of the provision for (benefit from) income taxes are as follows (in thousands):


	Year Ended
	December 31,
	2023		2022		2021
Current income tax (benefit) provision
Federal	$	(1,180)	$	2,048	$	(2)
State		(669)		1,404		7
Total current income tax (benefit) provision		(1,849)		3,452		5
Deferred income tax provision (benefit)
Federal		2,513		(4,111)		(1,236)
State		793		(865)		(432)
Total deferred income tax provision (benefit)		3,306		(4,976)		(1,668)
Total provision for (benefit from) income taxes	$	1,457	$	(1,524)	$	(1,663)

Schedule of reconciliation of the provision (benefit) for income taxes


	Year Ended
	December 31,
	2023		2022		2021
Provision for (benefit from) income taxes at statutory rate	23.5	%	19.0	%	19.0	%
(Decreases) increases resulting from:
Federal tax credits	0.3	%	0.3	%	0.6	%
Change in valuation allowance	(14.8)	%	(16.8)	%	(27.0)	%
Net losses surrendered for research credit	(11.1)	%	(6.5)	%	(5.9)	%
Impact of statutory rate change	2.7	%	11.3	%	12.1	%
Impact of foreign exchange rates	(0.1)	%	(9.9)	%	—	%
Other	(1.3)	%	3.9	%	3.6	%
Effective income tax rate	(0.8)	%	1.3	%	2.4	%

Schedule of significant components of the Company's current and deferred tax assets

Significant components of the Company’s current and deferred tax assets are as follows (in thousands):



	December 31,
	2023		2022
Deferred tax assets:
Operating loss carryforwards	$	66,555	$	45,452
Operating lease liability		3,680		3,566
Share-based compensation		15,577		9,842
Capitalized research and development expenses		—		5,168
Accrued expenses and other		2,742		2,318
Total deferred tax assets		88,554		66,346
Deferred tax liabilities:
Operating lease right-of-use asset		(3,389)		(3,474)
Depreciation & amortization		—		(933)
Total deferred tax liabilities		(3,389)		(4,407)
Valuation allowance		(80,274)		(53,743)
Net deferred tax assets	$	4,891	$	8,196

Significant agreements - Ionis Evaluation and Option Agreement (Details) - USD ($) $ in Thousands		1 Months Ended
	Jul. 09, 2021	Jan. 31, 2021	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Deferred revenue			$ 135,194	$ 61,873	$ 71,340
Ionis Evaluation and Option Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront cash payment	$ 3,000	$ 3,000
Deferred revenue						$ 3,000

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
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

Benefit plans

12 Months Ended

Dec. 31, 2023

Benefit plans

Benefit plans

13. Benefit plans

The Company established a defined-contribution savings plan under Section 401(k) of the Code (the “401(k) Plan”). The 401(k) Plan covers all U.S. employees and allows participants to defer a portion of their annual compensation on a pre-tax basis. Matching contributions to the 401(k) Plan may be made at the discretion of the Company’s board of directors. During the years ended December 31, 2023, 2022 and 2021, the Company made contributions totaling $0.8 million, $0.5 million and $0.3 million, respectively, to the 401(k) Plan.

The Company provides a pension contribution plan for its employees in the United Kingdom, pursuant to which the Company may make contributions each year (“U.K Plan”). During the years ended December 31, 2023, 2022 and 2021, the Company made contributions totaling $2.2 million, $1.4 million and $0.7 million, respectively, to the U.K. Plan.

- Definition

The entire disclosure for retirement benefits.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
-SubTopic 70
-Name Accounting Standards Codification
-Section 50
-Paragraph 1
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480794/715-70-50-1

Reference 2: http://www.xbrl.org/2003/role/exampleRef
-Topic 715
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-Name Accounting Standards Codification
-Section 55
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-URI https://asc.fasb.org//1943274/2147480482/715-20-55-17

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
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-Name Accounting Standards Codification
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-Paragraph 1
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Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
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-Name Accounting Standards Codification
-Section 50
-Paragraph 1
-Subparagraph (d)(i)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480506/715-20-50-1

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
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-SubTopic 20
-Name Accounting Standards Codification
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-Paragraph 1
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-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480506/715-20-50-1

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
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-URI https://asc.fasb.org//1943274/2147480506/715-20-50-1

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
-Name Accounting Standards Codification
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-URI https://asc.fasb.org//715/tableOfContent

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
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-Name Accounting Standards Codification
-Section 50
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Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
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Reference 10: http://www.xbrl.org/2003/role/disclosureRef
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-URI https://asc.fasb.org//1943274/2147480506/715-20-50-1

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
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Reference 12: http://www.xbrl.org/2003/role/disclosureRef
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-Subparagraph (r)(2)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480506/715-20-50-1

Reference 13: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
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-Name Accounting Standards Codification
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-Paragraph 2
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480126/715-20-S99-2

Reference 14: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
-SubTopic 60
-Name Accounting Standards Codification
-Section 50
-Paragraph 3
-Subparagraph (c)
-Publisher FASB
-URI https://asc.fasb.org//1943274/2147480266/715-60-50-3

+ Details

Significant agreements - Bayer Collaboration Agreement (Details) $ in Thousands, £ in Millions		12 Months Ended
	May 04, 2023 USD ($) item	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	May 04, 2023 GBP (£) item
Significant agreements.
Revenue from collaborative arrangement		$ 26,976	$ 14,463	$ 11,697
Deferred revenue		135,194	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		1,160	0	$ 0
Deferred revenue		$ 43,618	$ 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

Summary of significant accounting policies - Cash and cash equivalents (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Summary of significant accounting policies
Cash equivalents	$ 72,300	$ 276,100
Restricted cash included in other assets	$ 547	$ 0

Significant agreements - Ionis Collaboration Agreement (Details) $ in Millions		1 Months Ended
	Jul. 09, 2021 USD ($) item	Apr. 30, 2023 USD ($)	Oct. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Jan. 31, 2021 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	$ 31.0
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	$ 3.0				$ 3.0
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 - AstraZeneca Collaboration Agreement (Details) $ in Thousands	1 Months Ended		12 Months Ended
	May 31, 2018 USD ($)	Nov. 30, 2016 item	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Jun. 30, 2022 USD ($)	Aug. 31, 2021 USD ($)	Oct. 31, 2020 USD ($)	Jun. 30, 2019 USD ($)
Significant agreements.
Collaboration revenues			$ 26,976	$ 14,463	$ 11,697
Deferred revenue			135,194	61,873	71,340
AstraZeneca
Significant agreements.
Option fee for development and exploitation rights	$ 5,000
Transaction price	5,700
Deferred revenue recognized			1,200
Collaboration revenues			1,204	1,165	1,404
Deferred revenue			$ 0	$ 1,076	$ 2,361
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						$ 1,200
AstraZeneca \| Target 6 Material Right
Significant agreements.
Deferred revenue related to the associated material rights							$ 1,100
AstraZeneca \| Research and 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

Summary of significant accounting policies - Foreign currency and currency translation (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Summary of significant accounting policies
Foreign exchange gain (loss)	$ (0.6)	$ (0.6)	$ 0.4

Significant agreements - Revenue recognition due to changes in contract assets and liabilities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Significant agreements
Revenue recognized based on proportional performance	$ 19,160	$ 12,358	$ 9,652
Revenue recognized based on expiration of material rights	7,816	1,433	1,876
Revenue recognized based on changes in transaction price		672	169
Total	$ 26,976	$ 14,463	$ 11,697

Income taxes - Components of the company's current and deferred tax assets (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Deferred tax assets:
Operating loss carryforwards	$ 66,555	$ 45,452
Operating lease liability	3,680	3,566
Share-based compensation	15,577	9,842
Capitalized research and development expenses		5,168
Accrued expenses and other	2,742	2,318
Total deferred tax assets	88,554	66,346
Deferred tax liabilities:
Operating lease right-of-use asset	(3,389)	(3,474)
Depreciation & amortization		(933)
Total deferred tax liabilities	(3,389)	(4,407)
Valuation allowance	(80,274)	(53,743)
Net deferred tax assets	$ 4,891	$ 8,196

Share-based compensation - Share Options (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Additional Information
Total share-based compensation expense	$ 32,477	$ 26,779	$ 12,083
Stock option
Number of Shares
Outstanding number of shares at beginning	5,898,888
Granted	2,099,895
Exercised	(54,023)
Forfeited	(475,233)
Outstanding number of shares at end	7,469,527	5,898,888
Number of shares, vested and expected to vest	7,469,527
Number of shares, options exercisable	4,561,511
Weighted Average Exercise Price
Weighted average exercise price at beginning	$ 22.45
Granted	26.53
Exercised	12.57
Forfeited	30.94
Weighted average exercise price at ending	23.13	$ 22.45
Weighted average exercise price, vested and expected to vest	23.13
Weighted average exercise price, options exercisable	$ 18.95
Weighted Average Contractual Term
Weighted average contractual term, outstanding	6 years 9 months 29 days	7 years 7 months 20 days
Weighted average contractual term, vested and expected to vest	6 years 9 months 29 days
Weighted average contractual term ,options exercisable	5 years 7 months 9 days
Aggregate Intrinsic Value
Aggregate intrinsic value outstanding	$ 21,920	$ 71,002
Aggregate intrinsic value, vested and expected to vest	21,920
Aggregate intrinsic value, options exercisable	$ 21,358
Additional Information
Granted	$ 19.36	$ 31.45	$ 15.66
Exercised	$ 500	$ 1,500	$ 22,000
Total share-based compensation expense	$ 27,000	$ 21,900	$ 12,100

Geographic information (Tables)

12 Months Ended

Dec. 31, 2023

Geographic information

Schedule of long-lived assets, including operating lease right-of-use assets, held in different geographic regions


	December 31,
	2023		2022
United States	$	7,486	$	4,466
United Kingdom		20,198		28,302
	$	27,684	$	32,768

Accrued expenses and other current liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Accrued expenses and other current liabilities
Accrued employee compensation and benefits	$ 13,394	$ 9,928
Accrued external research and development expenses	11,839	10,859
Accrued professional fees	1,143	1,068
Current portion of operating lease liabilities	$ 4,876	$ 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	$ 257	$ 1,472
Accrued expenses and other current liabilities	$ 31,509	$ 26,452