BICYCLE THERAPEUTICS PLC

Previous wording

Our product candidates zelenectide pevedotin, previously called BT8009, BT5528, and BT1718, are each a Bicycle Toxin Conjugate, or BTC®molecule. These Bicycle molecules are chemically attached to a toxin that when administered is cleaved from the Bicycle molecule and kills the tumor cells. We are evaluating zelenectide pevedotin, a BTC molecule targeting Nectin-4, in both an ongoing company-sponsored Phase I/II clinical trial and an ongoing Phase II/III registrational trial called Duravelo-2, and BT5528, a BTC molecule targeting Ephrin type A receptor 2, or EphA2, in a company-sponsored Phase I/II clinical trial. Enrollment in the Phase I/II clinical trial of zelenectide pevedotin, in Duravelo-2, and in the Phase I/II clinical trial of BT5528 remains ongoing. BT1718 is being developed to target tumors that express Membrane Type 1 matrix metalloproteinase, or MT1 MMP, and is being investigated for safety, tolerability and efficacy in a Phase I/IIa clinical trial sponsored and fully funded by the Cancer Research UK Centre for Drug Development, or Cancer Research UK. Additionally, our other product candidate, BT7480, is a Bicycle Tumor-Targeted Immune Cell Agonist®, or Bicycle TICA®molecule. A Bicycle TICA molecule links immune cell receptor binding Bicycle molecules to tumor antigen binding Bicycle molecules. We are evaluating BT7480, a Bicycle TICA molecule targeting Nectin-4 and agonizing CD137, in a company-sponsored Phase I/II clinical trial. Enrollment in the company-sponsored Phase I/II clinical trial of BT7480 remains ongoing. Our discovery pipeline in oncology includes next-generation BTC molecules and Bicycle* *radionuclide conjugates, or BRC® molecules.

Current wording

Our product candidates zelenectide pevedotin, formerly BT8009, and BT5528 are each a Bicycle Drug Conjugate, or BDCTM molecule. These Bicycle molecules are chemically attached to a toxin that when administered is cleaved from the Bicycle molecule and kills the tumor cells. We are evaluating zelenectide pevedotin, a BDC molecule targeting Nectin-4, in an ongoing company-sponsored Phase I/II clinical trial to assess the safety, pharmacokinetics and clinical activity in patients with Nectin-4 expressing advanced malignancies and an ongoing Phase II/III registrational trial called Duravelo-2, allowing for potential accelerated approval in untreated and previously treated metastatic urothelial cancer. We are also evaluating zelenectide pevedotin in an ongoing company-sponsored Phase I/II clinical trial to assess the efficacy and safety of zelenectide pevedotin in patients with NECTIN4 amplified advanced breast cancer, which commenced recruiting patients in the first quarter of 2025. Enrollment in these trials is ongoing. In addition, we are evaluating BT5528, a BDC molecule targeting Ephrin type A receptor 2, or EphA2, in a company-sponsored Phase I/II clinical trial, for which enrollment is ongoing. Additionally, our other product candidate, BT7480, is a Bicycle Tumor-Targeted Immune Cell Agonist®, or Bicycle TICA®molecule. A Bicycle TICA molecule links immune cell receptor binding Bicycle molecules to tumor antigen binding Bicycle molecules. We are evaluating BT7480, a Bicycle TICA molecule targeting Nectin-4 and agonizing CD137, in a company-sponsored Phase I/II clinical trial. Our discovery pipeline in oncology includes next-generation BDC molecules and Bicycle* *Radioconjugates, or BRC® molecules.

Previous wording

Zelenectide pevedotin has been granted Fast Track Designation, or FTD, by the FDA as a monotherapy for the treatment of adult patients with previously treated locally advanced or metastatic urothelial cancer, and BT5528 has been granted FTD for the treatment of adult patients with previously treated, locally advanced or metastatic urothelial cancer. Zelenectide pevedotin has also been selected to participate in the Chemistry, Manufacturing and Controls, or CMC, Development and Readiness Pilot Program launched by the FDA to facilitate CMC development for therapies with

Current wording

Zelenectide pevedotin has been granted Fast Track Designation, or FTD, by the FDA as a monotherapy for the treatment of adult patients with previously treated locally advanced or metastatic urothelial cancer as well as for the treatment of adult patients with previously treated, NECTIN4 gene-amplified, advanced or metastatic triple-negative breast cancer and non-small cell lung cancer. BT5528 has been granted FTD for the treatment of adult patients with previously treated, locally advanced or metastatic urothelial cancer. Zelenectide pevedotin has also been selected to

Previous wording

In September 2024, we announced updated Phase I/II clinical results for zelenectide pevedotin used as a monotherapy in metastatic urothelial cancer at the European Society for Medical Oncology, or ESMO, Congress 2024. In addition, at the ESMO Congress 2024, we announced updated Phase I/II clinical results for BT5528 in advanced solid tumors, such as metastatic urothelial cancer and ovarian cancer, and updated Phase I/II clinical results for BT7480 in advanced solid tumors. In October 2024, first human imaging data for a BRC molecule targeting MT1-MMP was presented by the German Cancer Consortium, or DKTK, and we presented preclinical data about BRC molecules for radioisotope delivery to solid tumors at the European Association of Nuclear Medicine, or EANM, 2024 Congress. In addition, in October 2024, Cancer Research UK released preliminary results of the Phase I/IIa clinical trial of BT1718 on the International Standard Randomized Controlled Trial Number, or ISRCTN, registry.

Current wording

In addition, at the ESMO Congress 2024, we announced updated Phase I/II clinical results for BT5528 in advanced solid tumors, including metastatic urothelial cancer and ovarian cancer, and updated Phase I/II clinical results for BT7480 in advanced solid tumors. In October 2024, first human imaging data for a BRC molecule targeting MT1-MMP was presented by the German Cancer Consortium, or DKTK, and we presented preclinical data about BRC molecules for radioisotope delivery to solid tumors at the European Association of Nuclear Medicine, or EANM, 2024 Congress.

Previous wording

Since our inception, we have devoted substantially all of our resources to developing our Bicycle platform and our product candidates zelenectide pevedotin, BT5528, BT1718, BT7480 and BT7401, conducting research and development of our product candidates and preclinical programs, raising capital and providing general and administrative support for our operations. To date, we have financed our operations primarily with proceeds from the sale of our ordinary shares, American Depositary Shares representing ordinary shares, or ADSs, non-voting ordinary shares and convertible preferred shares; proceeds received from upfront payments, research and development payments, and development milestone payments from our collaboration agreements; and borrowings pursuant to a loan and security agreement, or the Loan Agreement, with Hercules Capital, Inc., or Hercules. From our inception in 2009 through September 30, 2024, we have received gross proceeds of $1.4 billion from the sale of ordinary shares, ADSs, non-voting ordinary shares, and convertible preferred shares; $233.6 million of cash payments under our collaboration arrangements, including $45.2 million from Bayer, $50.0 million from Novartis, $47.7 million from Ionis, and $56.0 million from Genentech; and proceeds of $30.0 million pursuant to the Loan Agreement. We do not have any products approved for sale and have not generated any revenue from product sales.

Current wording

Since our inception, we have devoted substantially all of our resources to developing our Bicycle platform and our product candidates, conducting research and development of our product candidates and preclinical programs, raising capital and providing general and administrative support for our operations. To date, we have financed our operations primarily with proceeds from the sale of our equity securities; proceeds received from upfront payments, research and development payments, and development milestone payments from our collaboration agreements; and borrowings pursuant to a loan and security agreement, or the Loan Agreement, with Hercules Capital, Inc., or Hercules. From our inception in 2009 through March 31, 2025, we have received gross proceeds of $1.4 billion from the sale of our equity securities; and $236.6 million of cash payments under our collaboration arrangements, including $45.3 million from Bayer, $53.0 million from Novartis, $47.7 million from Ionis, and $56.0 million from Genentech. We do not have any products approved for sale and have not generated any revenue from product sales.

Previous wording

Since our inception, we have incurred significant operating losses. Our ability to generate product revenue sufficient to achieve profitability will depend on the successful development and eventual commercialization of one or more of our product candidates. Our net losses were $50.8 million and $117.2 million for the three and nine months ended September 30, 2024, respectively. As of September 30, 2024, we had an accumulated deficit of $628.9 million. These losses have resulted primarily from costs incurred in connection with research and development activities and general and administrative costs associated with our operations. We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future.

Current wording

Since our inception, we have incurred significant operating losses. Our ability to generate product revenue sufficient to achieve profitability will depend on the successful development and eventual commercialization of one or more of our product candidates. Our net losses were $60.8 million and $26.6 million for the three months ended March 31, 2025 and 2024, respectively. As of March 31, 2025, we had an accumulated deficit of $741.5 million. These losses have resulted primarily from costs incurred in connection with research and development activities and general and administrative costs associated with our operations. We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future.

Previous wording

expenses and capital expenditure requirements for at least 12 months from the date of filing of this Quarterly Report. We have based this estimate on assumptions that may prove to be wrong, and we could deplete our available capital resources sooner than we expect. See “— Liquidity and Capital Resources” and “Capital Resources and Funding Requirements.”

Current wording

be wrong, and we could deplete our available capital resources sooner than we expect. See “—Liquidity and Capital Resources” and “—Capital Resources and Funding Requirements.”

Previous wording

Research and development costs are expensed as incurred. Costs for certain activities are recognized based on an evaluation of the progress to completion of specific tasks. Payments for these activities are based on the terms of the individual agreements, which may differ from the pattern of costs incurred, and are reflected in our consolidated financial statements as a prepaid expense or accrued research and development expenses. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are capitalized. The capitalized amounts are expensed as the related goods are delivered or the services are performed.

Current wording

Research and development costs are expensed as incurred. Costs for certain activities are recognized based on an evaluation of the progress to completion of specific tasks. Payments for these activities are based on the terms of the individual agreements, which may differ from the pattern of costs incurred, and are reflected in our condensed consolidated financial statements as a prepaid expense or accrued research and development expenses. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are capitalized. The capitalized amounts are expensed as the related goods are delivered or the services are performed.

Previous wording

that are directly related to the product candidate are included in direct research and development expenses for that program. Costs incurred prior to designating a product candidate are included in discovery, platform and other expenses. We do not allocate employee costs, costs associated with our discovery efforts, laboratory supplies, and facilities, including depreciation or other indirect costs, to specific product development programs because these costs are deployed across multiple product development programs and, as such, are not separately classified.

Current wording

Our direct external research and development expenses are tracked on a program-by-program basis and consist of costs, such as fees paid to consultants, contract research organizations, or CROs, and contract manufacturing organizations, or CMOs, in connection with our preclinical and clinical development activities. Costs incurred after a product candidate has been designated and that are directly related to the product candidate are included in direct research and development expenses for that program. Costs incurred prior to designating a product candidate are included in discovery, platform and other expenses. We do not allocate employee costs, costs associated with our discovery efforts, laboratory supplies, and facilities, including depreciation or other indirect costs, to specific product

Previous wording

Further amendments to the U.K. R&D tax credit regime included in Finance Act 2024 introduce restrictions (unless limited exceptions apply) on the tax relief that can be claimed for expenditures incurred on sub-contracted R&D activities or externally provided workers, where such sub-contracted activities are not carried out in the United Kingdom or such workers are not subject to U.K. payroll taxes. These amendments take effect for accounting periods beginning on or after April 1, 2024, which may limit our ability to claim R&D tax credits for sub-contracted R&D in the future. In addition, the Finance Act 2024 includes amendments which merge the SME Program and the RDEC Program into a single scheme with effect for accounting periods beginning on or after April 1, 2024, with a single 20% gross rate applying to all claims with an exception for SMEs qualifying as R&D intensive, whose cash rebate that may be claimed will be 26.97% of qualifying expenditures.

Current wording

For 2025 and beyond, the Finance Act 2024 also introduces restrictions (unless limited exceptions apply) on the tax relief that can be claimed for expenditures incurred on sub-contracted R&D activities or externally provided workers, where such sub-contracted activities are not carried out in the U.K. or such workers are not subject to U.K. payroll taxes. These restrictions may limit our ability to claim R&D tax credits for sub-contracted R&D in the future.

Previous wording

The research and development tax credit received in the United Kingdom is recorded as a reduction to research and development expenses. The U.K. research and development tax credit, as described below, is fully refundable to us after surrendering tax losses and is not dependent on current or future taxable income. As a result, we have recorded the entire benefit from the U.K. research and development tax credit as a reduction to research and development expenses and is not reflected as part of the income tax provision. If, in the future, any U.K. research and development tax credits generated are needed to offset a corporate income tax liability in the United Kingdom, that portion would be recorded as a benefit within the income tax provision and any refundable portion not dependent on taxable income would continue to be recorded as a reduction to research and development expenses.

Current wording

The U.K. research and development tax credit is fully refundable to us after surrendering tax losses and is not dependent on current or future taxable income. As a result, we have recorded the entire benefit from the U.K. research and development tax credit as a reduction to research and development expenses and is not reflected as part of the income tax provision. If, in the future, any U.K. research and development tax credits generated are needed to offset a corporate income tax liability in the U.K., that portion would be recorded as a benefit within the income tax provision and any refundable portion not dependent on taxable income would continue to be recorded as a reduction to research and development expenses.

Previous wording

Research and development activities are central to our business model. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We expect that our research and development expenses will continue to increase for the foreseeable future as a result of our expanded portfolio of product candidates and as we: (i) continue the clinical development and seek to obtain marketing approval for our product candidates, including zelenectide pevedotin, BT5528, BT7480 and BT1718; (ii) initiate clinical trials for our product candidates; and (iii) build our in-house process development and analytical capabilities and continue to discover and develop additional product candidates.

Current wording

Research and development activities are central to our business model. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We expect that our research and development expenses will continue to increase for the foreseeable future as a result of our expanded portfolio of product candidates and as we: (i) continue the clinical development and seek to obtain marketing approval for our product candidates; (ii) initiate clinical trials for our product candidates; and (iii) build our in-house process development and analytical capabilities and continue to discover and develop additional product candidates.

Previous wording

A change in the outcome of any of these variables with respect to the development of a product candidate could mean a significant change in the costs and timing associated with the development of that product candidate. For example, the FDA, the European Medicines Agency, or EMA, or another regulatory authority may require us to conduct clinical trials beyond those that we anticipate will be required for the completion of clinical development of a product candidate, or we may experience significant trial delays due to patient enrollment or other reasons in which case we would be required to expend significant additional financial resources and time on the completion of clinical development. In addition, we may obtain unexpected results from our clinical trials and we may elect to discontinue, delay or modify clinical trials of some product candidates or focus on others. Identifying potential product candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to obtain marketing approval and achieve product sales. In addition, our product candidates, if approved, may not achieve commercial success. In addition, on April 26, 2023, the European Commission adopted a proposal for a new Directive and Regulation to revise the current EU pharmaceutical legislation. If adopted in the form proposed, the European Commission proposals may result in a decrease in data and market exclusivity opportunities for our product candidates in the EU and make them open to generic or biosimilar competition earlier than is currently the case with a related reduction in reimbursement status.

Current wording

A change in the outcome of any of these variables with respect to the development of a product candidate could mean a significant change in the costs and timing associated with the development of that product candidate. For example, the FDA, the European Medicines Agency, or EMA, or another regulatory authority may require us to conduct clinical trials beyond those that we anticipate will be required for the completion of clinical development of a product candidate, or we may experience significant trial delays due to patient enrollment or other reasons in which case we would be required to expend significant additional financial resources and time on the completion of clinical development. In addition, we may obtain unexpected results from our clinical trials and we may elect to discontinue, delay or modify clinical trials of some product candidates or focus on others. Identifying potential product candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to obtain marketing approval and achieve product sales. In addition, our product candidates, if approved, may not achieve commercial success. In addition, on April 26, 2023, the European Commission adopted a proposal for a new Directive and Regulation to revise the current EU pharmaceutical legislation. The proposed revisions remain to be agreed and adopted by the European Council. Moreover, on December 1, 2024, a new European Commission took office. The proposal could, therefore, still be subject to revisions. If adopted in the form proposed, the European Commission proposals may result in a decrease in data and market exclusivity opportunities for our product candidates in the EU and make them open to generic or biosimilar competition earlier than is currently the case with a related reduction in reimbursement status.

Previous wording

Foreign currency transactions in currencies different from the applicable functional currency are translated into the functional currency using the exchange rates prevailing at the dates of the transactions. Foreign exchange differences resulting from the settlement of such transactions and from the remeasurement at period-end exchange rates in foreign currencies are recorded in general and administrative expenses in the condensed consolidated statement of operations and comprehensive loss. As such, our operating expenses may be impacted by future changes in exchange rates. See “Quantitative and Qualitative Disclosure About Market Risks” for further discussion.

Current wording

Foreign currency transactions in currencies different from the applicable functional currency are translated into the functional currency using the exchange rates prevailing at the dates of the transactions. Foreign exchange differences resulting from the settlement of such transactions and from the remeasurement at period-end exchange rates in foreign currencies are recorded in general and administrative expenses in the condensed consolidated statements of operations and comprehensive loss. As such, our operating expenses may be impacted by future changes in exchange rates. See “Quantitative and Qualitative Disclosure About Market Risks” for further discussion.

Previous wording

We are subject to corporate taxation in the United States and the United Kingdom. We have generated losses since inception and have therefore not paid U.K. corporation tax. The (benefit from) provision for income taxes included in the condensed consolidated statements of operations and comprehensive loss represents the tax impact from operating activities in the United States, which has generated taxable income based on intercompany service arrangements.

Current wording

We are subject to corporate taxation in the United States and the United Kingdom. We have generated losses since inception and have therefore not paid U.K. corporation tax. The benefit from income taxes included in the condensed consolidated statements of operations and comprehensive loss represents the tax impact from operating activities in the United States, which has generated taxable income based on intercompany service arrangements.

Previous wording

Collaboration revenues increased by $9.9 million in the nine months ended September 30, 2024, compared to the nine months ended September 30, 2023, due to increases of $5.5 million from our collaboration with Novartis entered into in March 2023, $2.8 million from our collaboration with Genentech which was primarily due to revenue recognized upon the Genentech joint research committee’s decision to discontinue research activities for Collaboration Program #3 during the nine months ended September 30, 2024 and the resulting expiration of options that are material

Current wording

Collaboration revenue decreased by $9.6 million in the three months ended March 31, 2025, compared to the three months ended March 31, 2024, due to decreases of $5.9 million from our collaboration with Ionis due to the completion of the combined licenses and research and discovery performance obligation in the second quarter of 2024, as well as $3.9 million from our collaboration with Genentech which was primarily due to the timing of revenue recognized upon the Genentech joint research committee’s decision to discontinue research activities for Collaboration Program #3 in the first quarter of 2024 and the notice of termination for Genentech Collaboration Program #4 in the first quarter of 2025.

Previous wording

Research and development expenses increased by $8.4 million in the three months ended September 30, 2024 compared to the three months ended September 30, 2023, due to increases of $10.2 million in clinical program expenses for zelenectide pevedotin due to the ongoing Phase II expansion portion of the Phase I/II clinical trial as well as the ongoing Phase II/III Duravelo-2 registrational trial which commenced recruiting patients in the first quarter of 2024, $3.6 million in employee and contractor related expenses primarily attributable to one-time severance-related costs of $1.9 million as well as increased headcount, $1.1 million of incremental share-based compensation expense primarily associated with equity grants issued since the same period in the prior year and $0.9 million in facility expenses. These increases were offset by decreases of $3.3 million of incremental U.K. research and development tax incentives primarily associated with the impact of U.K. R&D tax credit reimbursement rate changes enacted in February 2024, $3.2 million in Bicycle TICA program development expenses due to the timing of clinical program activities, and $1.5 million in discovery, platform and other expenses.

Current wording

Research and development expenses increased by $24.2 million in the three months ended March 31, 2025 compared to the three months ended March 31, 2024, due to increases of $14.6 million in clinical program expenses for zelenectide pevedotin primarily due to the ongoing Phase II/III Duravelo-2 registrational trial as well as the ongoing

Previous wording

Research and development expenses increased by $11.4 million in the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023, due to increases of $28.1 million in clinical program expenses for zelenectide pevedotin due to the ongoing Phase II expansion portion of the Phase I/II clinical trial as well as the ongoing Phase II/III Duravelo-2 registrational trial which commenced recruiting patients in the first quarter of 2024, $9.0 million in employee and contractor related expenses primarily attributable to increased headcount and $1.6 million of incremental share-based compensation expense primarily associated with equity grants issued since the same period in the prior year. These increases were offset by decreases of $12.7 million of incremental U.K. research and development tax incentives primarily associated with the impact of U.K. R&D tax credit reimbursement rate changes enacted in February 2024, retroactively applied to April 1, 2023, $9.6 million in Bicycle TICA program development expenses due to the timing of clinical program activities, $3.9 million in discovery, platform and other expenses, and $0.7 million in BT5528 clinical program expenses.

Current wording

Phase I/II clinical trial assessing zelenectide pevedotin in patients with NECTIN4 amplified advanced breast cancer, which commenced recruiting patients in the first quarter of 2025, $6.0 million resulting from a decrease in research and development incentives due to the impact of U.K. R&D tax credit reimbursement rate changes which were enacted in the first quarter of 2024, retroactively applied to April 1, 2023, $3.8 million in employee and contractor related expenses primarily attributable to increased headcount, $0.8 million in discovery, platform and other expense and $0.7 million in BT5528 clinical program expenses. These increases were primarily offset by a decrease of $1.5 million in Bicycle TICA program development expenses due to the timing of clinical program activities.

Previous wording

We begin to separately track program expenses at candidate nomination, at which point we accumulate all direct external program costs to support that program to date. Through September 30, 2024, we have incurred approximately $129.3 million, $46.6 million, and $15.7 million of direct external expenses for the development of zelenectide pevedotin, BT5528, and BT1718, respectively, since their candidate nominations, and an aggregate of $47.6 million of direct external expenses for the development of the two named Bicycle TICA candidates since their nominations.

Current wording

We begin to separately track program expenses at candidate nomination, at which point we accumulate all direct external program costs to support that program to date. Through March 31, 2025, we have incurred approximately $189.0 million and $51.3 million of direct external expenses for the development of zelenectide pevedotin and BT5528, respectively, since their candidate nominations, and an aggregate of $50.4 million of direct external expenses for the development of two named Bicycle TICA candidates since their nominations.

Previous wording

General and administrative expenses increased by $5.0 million in the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023. This increase is primarily due to increases of $3.4 million in personnel-related costs as a result of increased headcount, $1.5 million of incremental share-based compensation expense primarily associated with equity grants issued since the same period in the prior year and $1.3 million in professional and consulting fees that was primarily related to increased legal and consulting fees.

Current wording

General and administrative expenses increased by $4.7 million in the three months ended March 31, 2025 compared to the three months ended March 31, 2024. This increase is primarily due to increases of $2.5 million in professional and consulting fees primarily associated with increased legal and consulting fees to support our growth, $1.3 million in personnel-related costs as a result of increased headcount, and $0.5 million of incremental share-based compensation expense primarily associated with equity grants issued since the same period in the prior year.

Previous wording

Other income, net increased by $6.4 million in the three months ended September 30, 2024 compared to the three months ended September 30, 2023, which was primarily due to an increase in interest income of $6.5 million related to higher interest rates as well as higher average interest-bearing cash and cash equivalents balances period over period and a decrease in interest expense of $0.8 million due to the repayment and voluntary termination of the Loan Agreement in July 2024, offset by the loss on extinguishment of debt of $1.0 million recognized in the third quarter of 2024.

Current wording

Other income, net increased by $3.6 million in the three months ended March 31, 2025 compared to the three months ended March 31, 2024, which was primarily due to an increase in interest income of $2.8 million primarily related to higher average interest-bearing cash and cash equivalents balances period over period and a decrease in interest expense of $0.8 million due to the repayment and termination of the Loan Agreement in July 2024.

Previous wording

The benefit from income taxes of $3.7 million for the nine months ended September 30, 2024, is mainly the result of deferred tax assets 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, including incremental income tax benefits of approximately $3.5 million recognized during the three months ended September 30, 2024 related to the completion of a U.S. research and development tax credit study. The provision for income taxes of $1.1 million for the nine months ended September 30, 2023 is primarily associated with a change in estimate that certain research and development expenses incurred by our U.S. subsidiary pursuant to an intercompany service arrangement are not required to be capitalized under IRC Section 174 because our U.S. subsidiary does not retain any ownership or rights in the underlying intellectual property resulting from the research activities, offset by the impact of deferred tax assets benefited 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.

Current wording

The benefit from income taxes of $1.1 million and $0.4 million for the three months ended March 31, 2025 and 2024, respectively, is mainly the result of deferred tax assets in the United States that do not have a valuation allowance against them because of profits that will be generated by an intercompany service agreement.

Previous wording

To date, we have financed our operations primarily with proceeds from the sale of our ordinary shares, ADSs, non-voting ordinary shares and convertible preferred shares; proceeds received from upfront payments, payments for research and development services, and development milestone payments pursuant to collaboration agreements; and borrowings pursuant to a Loan Agreement with Hercules.

Current wording

To date, we have financed our operations primarily with proceeds from the sale of our ordinary shares, ADSs, non-voting ordinary shares and convertible preferred shares; proceeds received from upfront payments, payments for research and development services, and development milestone payments pursuant to collaboration agreements; and borrowings pursuant to our Loan Agreement with Hercules.

Previous wording

During the nine months ended September 30, 2024 and 2023, we used $0.9 million and $2.9 million, respectively, of cash in investing activities for purchases of property and equipment, consisting primarily of laboratory equipment.

Current wording

During the three months ended March 31, 2025 and 2024, we used $0.6 million and $12,000, respectively, of cash in investing activities for purchases of property and equipment, consisting primarily of laboratory equipment.

Previous wording

During the nine months ended September 30, 2023, net cash provided by financing activities was $249.6 million, primarily consisting of net proceeds of $215.1 million from the underwritten public offering in July 2023 and $34.2 million from our ATM program.

Current wording

During the three months ended March 31, 2024, net cash provided by financing activities was $1.9 million, primarily consisting of net proceeds of from the exercise of share options.

Previous wording

On June 5, 2020, we entered into a Sales Agreement, or the Sales Agreement, with Cantor Fitzgerald & Co. and Oppenheimer & Co. Inc., or the Sales Agents, with respect to an ATM program pursuant to which we may offer and sell through the Sales Agents, from time to time at our sole discretion, ADSs, each ADS representing one ordinary share. No ADSs were issued or sold pursuant to the Sales Agreement during the three and nine months ended September 30, 2024.

Current wording

On June 5, 2020, we entered into a Sales Agreement, or the Sales Agreement, with Cantor Fitzgerald & Co. and Oppenheimer & Co. Inc., or the Sales Agents, with respect to an ATM program pursuant to which we may offer and sell through the Sales Agents, from time to time at our sole discretion, ADSs, each ADS representing one ordinary share. No ADSs were issued or sold pursuant to the Sales Agreement during the three months ended March 31, 2025.

Previous wording

The following table summarizes our material contractual obligations as of September 30, 2024, and the effects that such obligations are expected to have on our liquidity and cash flows in future periods. For additional information, see Note 11. “Commitments and contingencies” of our condensed consolidated financial statements included elsewhere in this Quarterly Report.

Current wording

The following table summarizes our contractual obligations as of March 31, 2025, and the effects that such obligations are expected to have on our liquidity and cash flows in future periods. For additional information, see Note 11 to our condensed consolidated financial statements included in this Quarterly Report.

Previous wording

In the ordinary course of business, we enter into various agreements with contract research organizations to provide clinical trial services, with contract manufacturing organizations to provide clinical trial materials, and with vendors for preclinical research studies, synthetic chemistry and other services for operating purposes. These payments are not included in the table above since the contracts are generally cancelable with advanced written notice, generally with a notice period of 90 days or less. From the time of notice until termination, we are contractually obligated to make certain minimum payments to the vendors, based on the timing of the notification and the exact terms of the agreement.

Current wording

are not included in the table above since the contracts are generally cancelable with advanced written notice, generally with a notice period of 90 days or less. From the time of notice until termination, we are contractually obligated to make certain minimum payments to the vendors, based on the timing of the notification and the exact terms of the agreement.

Previous wording

Our arrangements with Cancer Research UK provide for additional future milestone payments by us 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, we have entered into separate agreements with other third parties which provide for various future milestone payments by us upon the achievement of specified development, regulatory, commercial and sales-based milestones with an aggregate total value of $105.1 million. We have not included future payments under these agreements in the table of contractual obligations above since these obligations are contingent upon future events. As of September 30, 2024, we were unable to estimate the timing or likelihood of achieving these milestones.

Current wording

We have also 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 $166.2 million, as well as potential future royalty and other payments at percentages ranging from very low to low single digits. These additional milestone payments are contingent upon future events that are not considered probable of achievement as of March 31, 2025. As of March 31, 2025, we were unable to estimate the timing or likelihood of achieving these milestones.

Previous wording

As of September 30, 2024, we had cash and cash equivalents of $890.9 million. In October 2024, we received $31.7 million of research and development incentives related to relevant expenditures incurred in the year ended December 31, 2023. We expect that our existing cash and cash equivalents will enable us to fund our operating expenses and capital expenditure requirements for at least 12 months from the date of filing of this Quarterly Report.

Current wording

As of March 31, 2025, we had cash and cash equivalents of $793.0 million. We expect that our existing cash and cash equivalents will enable us to fund our operating expenses and capital expenditure requirements for at least 12 months from the date of filing of this Quarterly Report.

Previous wording

Until such time, if ever, that we can generate product revenue sufficient to achieve profitability, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, monetization transactions, government contracts or other strategic transactions. To the extent that we raise additional capital through the sale of equity, ownership interests of existing holders of our ADSs and ordinary shares will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of holders of our ADSs or ordinary shares. If we raise additional funds through collaboration agreements, strategic alliances, licensing arrangements, monetization transactions, or marketing and distribution arrangements, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on

Current wording

Until such time, if ever, that we can generate product revenue sufficient to achieve profitability, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, monetization transactions, government contracts or other strategic transactions. To the extent that we raise additional capital through the sale of equity, ownership interests of existing holders of our ADSs and ordinary shares will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of holders of our ADSs or ordinary shares. If we raise additional funds through collaboration agreements, strategic alliances, licensing arrangements, monetization transactions, or marketing and distribution arrangements, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us or grant rights to develop and market products or product candidates that we would otherwise prefer to develop and market ourselves. Future debt financing, if available, may involve covenants restricting our operations or our ability to incur additional debt. Any debt or equity financing that we raise may contain terms that are not favorable to us or our shareholders.

Previous wording

There have been significant disruptions to global financial markets that have contributed to a general global economic slowdown. The resulting high inflation rates may materially affect our business and corresponding financial position and cash flows. Inflationary factors, such as increases in the cost of our clinical trial materials and supplies, interest rates and overhead costs may adversely affect our operating results. Rising interest rates also present a recent challenge impacting the U.S. economy and could make it more difficult for us to obtain traditional financing on acceptable terms, if at all, in the future. Additionally, the general consensus among economists suggests that we should expect a higher recession risk to continue over the next year, which, together with the foregoing, could result in further economic uncertainty and volatility in the capital markets in the near term, and could negatively affect our operations. Furthermore, such economic conditions have produced downward pressure on share prices. Although we do not believe that inflation has had a material impact on our financial position or results of operations to date, we may experience increases in the near future (especially if inflation rates remain high or begin to rise again) on our operating costs, including our labor costs and research and development costs, due to supply chain constraints, consequences associated with geopolitical conflicts such as the ongoing wars involving Ukraine and Israel, worsening global macroeconomic conditions, and employee availability and wage increases, which may result in additional stress on our working capital resources. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce, or eliminate our research and development programs or future commercialization efforts.

Current wording

Recent global trade disruption, volatility in the capital markets and continued uncertainty may contribute to a general global economic slowdown or recession. The resulting high inflation rates may materially affect our business and corresponding financial position and cash flows. Inflationary factors, such as increases in the cost of our clinical trial materials and supplies, interest rates and overhead costs may adversely affect our operating results. High interest rates also present a recent challenge impacting the U.S. economy and could make it more difficult for us to obtain traditional financing on acceptable terms, if at all, in the future. Additionally, the general consensus among economists suggests that we should expect a higher recession risk to continue over the next year, which, together with the foregoing, could result in further economic uncertainty and volatility in the capital markets in the near term, and could negatively affect our operations. Furthermore, such economic conditions have produced downward pressure on share prices. Although we do not believe that inflation has had a material impact on our financial position or results of operations to date, we may experience increases in the near future (especially if inflation rates remain high or begin to rise again) on our operating costs, including our labor costs and research and development costs, due to supply chain constraints, consequences associated with geopolitical conflicts such as the ongoing wars involving Ukraine and Israel, worsening global macroeconomic conditions, including those resulting from changes in global trade policies, which may result in additional stress on our working capital resources. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce, or eliminate our research and development programs or future commercialization efforts.