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. In addition, 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. In addition, our other product candidates, BT7480 and BT7455, are each 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, and we are conducting IND-enabling studies for BT7455, an EphA2/CD137 Bicycle TICA molecule. Our discovery pipeline in oncology includes next-generation BTC molecules and Bicycle* *radionuclide conjugates, or BRCTM molecules.

Current 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.

Previous wording

remains ongoing. Additionally, in September 2023, we announced our alignment with the FDA on the design of a Phase II/III registrational trial for zelenectide pevedotin, called Duravelo-2, allowing for potential accelerated approval in untreated and previously treated metastatic urothelial cancer. The Duravelo-2 clinical trial is now active and commenced recruiting patients in the first quarter of 2024. In October 2023, we also announced that zelenectide pevedotin has been selected to participate in the Chemistry, Manufacturing and Controls , or CMC, Development and Readiness Pilot Program recently launched by the FDA to facilitate CMC development for therapies with expedited clinical development timeframes based on the anticipated clinical benefits of earlier patient access to the therapy.

Current wording

expedited clinical development timeframes based on the anticipated clinical benefits of earlier patient access to the therapy.

Previous wording

In August 2024, we focused our research and development pipeline on clinical programs and research areas that we believe have the highest potential to maximize value creation. Moving forward, we will prioritize the clinical development of BTC molecules in multiple tumor types; focus near-term research efforts on advancing our BRC pipeline and the discovery of next-generation BTC molecules; and, except for BT7480, explore innovative ways to continue development of our immuno-oncology portfolio, including Bicycle TICA molecules, through collaboration.

Current wording

In August 2024, we focused our research and development pipeline on clinical programs and research areas that we believe have the highest potential to maximize value creation and we consolidated all discovery research activities to our headquarters in Cambridge, U.K. Moving forward, we will prioritize the clinical development of BTC molecules in multiple tumor types; focus near-term research efforts on advancing our BRC pipeline and the discovery of next-generation BTC molecules; and, except for BT7480, explore innovative ways to continue development of our immuno-oncology portfolio, including Bicycle TICA molecules, through collaboration.

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, BT7455 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 with Bayer Consumer Care AG, or Bayer, Novartis Pharma AG, or Novartis, Ionis Pharmaceuticals, Inc, or Ionis, Genentech Inc., or Genentech, the Dementia Discovery Fund, or DDF, AstraZeneca AB, or AstraZeneca and Oxurion NV, or Oxurion; and borrowings pursuant to our loan and security agreement, or Loan Agreement, with Hercules Capital, Inc., or Hercules. From our inception in 2009 through June 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; and $233.2 million of cash payments under our collaboration arrangements, including $45.0 million from Bayer, $50.0 million from Novartis, $47.6 million from Ionis, and $56.0 million from Genentech; and borrowings of $30.0 million pursuant to our Loan Agreement with Hercules. 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 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.

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 $39.8 million and $66.4 million for the three and six months ended June 30, 2024, respectively. As of June 30, 2024, we had an accumulated deficit of $578.1 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 $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.

Previous wording

We anticipate that our expenses and capital requirements will increase substantially in connection with our ongoing activities, particularly as we advance our product candidates into later-stage clinical trials and continue preclinical activities and clinical trials for our pipeline programs and, if any product candidates are approved, pursue the commercialization of such product candidates by building internal sales and marketing capabilities. We expect that our expenses and capital requirements will increase substantially if and as we:

Current wording

We anticipate that our expenses and capital requirements will increase substantially in connection with our ongoing activities, particularly as we advance our product candidates into later-stage clinical trials and continue preclinical activities and clinical trials for our pipeline programs and, if any product candidates are approved, pursue the

Previous wording

As of June 30, 2024, we had cash and cash equivalents of $961.4 million. We believe that our existing cash 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. 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

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.”

Previous wording

U.K. research and development tax credits and government grant funding are recorded as an offset to research and development expenses. See “—Provision for (Benefit from) Income Taxes.”

Current wording

U.K. research and development tax credits and government grant funding are recorded as an offset to research and development expenses. See “—(Benefit from) Provision for Income Taxes.”

Previous 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, contractors and contract manufacturing organizations, or CMOs, in connection

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, contractors 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

Previous wording

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 development programs because these costs are deployed across multiple product development programs and, as such, are not separately classified.

Current 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.

Previous wording

In December 2016, we entered into a Clinical Trial and License Agreement with Cancer Research Technology Limited, or CRTL and Cancer Research UK, pursuant to which the Cancer Research UK Centre for Drug Development is sponsoring and funding a Phase I/IIa clinical trial for our product candidate, BT1718, in patients with advanced solid tumors. The costs incurred by Cancer Research UK are recorded as a liability in accordance with ASC 730,Research and Development as the payments are not based solely on the results of the research and development having future economic benefit. The accrual of the liability is recorded as incremental research and development expense in our condensed consolidated statements of operations and comprehensive loss.

Current wording

In December 2016, we entered into a Clinical Trial and License Agreement with Cancer Research Technology Limited, or CRTL and Cancer Research UK, pursuant to which the Cancer Research UK Centre for Drug Development is sponsoring and funding a Phase I/IIa clinical trial for our product candidate, BT1718, in patients with advanced solid tumors. The costs incurred by Cancer Research UK are recorded as a liability in accordance with ASC 730,Research and Development as the payments are not based solely on the results of the research and development having future economic benefit. The accrual of the liability is recorded as incremental research and development expenses in our condensed consolidated statements of operations and comprehensive loss.

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, including BT7455; 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, 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.

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 expense 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 Disclosures 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 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.

Previous wording

Interest income consists primarily of interest earned on our cash held in operating accounts and our cash equivalents.

Current wording

Interest and other income consists primarily of interest earned on our cash held in operating accounts and our cash equivalents.

Previous wording

Interest expense consists primarily of interest expense for financing arrangements. As of June 30, 2024, we have borrowings of $30.0 million outstanding pursuant to our Loan Agreement with Hercules. Our Loan Agreement with Hercules was repaid in its entirety on July 9, 2024. See Note 15. “Subsequent events” of our condensed consolidated financial statements included elsewhere in this Quarterly Report.

Current wording

Interest expense consists primarily of interest expense for financing arrangements.

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 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) 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.

Previous wording

Research and development expenses increased by $0.3 million in the three months ended June 30, 2024 compared to the three months ended June 30, 2023, due to an increase of $5.5 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 registrational trial which commenced recruiting patients in the first quarter of 2024 and an increase of $2.4 million in employee and contractor related expenses attributable to increased headcount. These increases were offset by decreases of $4.1 million in Bicycle TICA program development expenses due to the timing of clinical program activities, $2.0 million in discovery, platform and other expenses and $1.3 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.

Current 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.

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 June 30, 2024, we have incurred approximately $107.3 million, $43.8 million, and $15.6 million of direct external expenses for the development of zelenectide pevedotin, BT5528, and BT1718, respectively, since their candidate nominations, and an aggregate of $46.1 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 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.

Previous wording

General and administrative expenses increased by $1.2 million in the three months ended June 30, 2024 compared to the three months ended June 30, 2023. This increase is primarily due to an increase of $1.2 million in personnel-related costs as a result of increased headcount.

Current wording

General and administrative expenses increased by $2.0 million in the three months ended September 30, 2024 compared to the three months ended September 30, 2023. This increase is primarily due to increases of $0.7 million in personnel-related costs as a result of increased headcount, $0.7 million of incremental share-based compensation

Previous wording

Other income (expense), net increased by $7.0 million in the three months ended June 30, 2024 compared to the three months ended June 30, 2023, which was due to an increase in interest income related to higher interest rates as well as higher average interest-bearing cash and cash equivalents balances period over period.

Current 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.

Previous wording

Collaboration revenues increased by $12.6 million in the six months ended June 30, 2024, compared to the six months ended June 30, 2023, due to increases of $5.0 million from our collaboration with Novartis entered into in March 2023, $3.6 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 six months ended June 30, 2024 and the resulting expiration of options that are material rights, $3.5 million from our collaboration with Ionis primarily due to a change in the estimated expected external costs used to measure proportional performance, and $1.7 million from our collaboration with Bayer entered into in May 2023. These increases were offset by a decrease in revenue recognized of $1.2 million from our collaboration with AstraZeneca due to the termination of collaboration activities related to the fourth target and recognition of remaining deferred revenue during the six months ended June 30, 2023.

Current 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

Previous wording

Research and development expenses increased by $3.0 million in the six months ended June 30, 2024 compared to the six months ended June 30, 2023, due to an increase of $17.9 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 registrational trial which commenced recruiting patients in the first quarter of 2024 and an increase of $5.4 million in employee and contractor related expenses attributable to increased headcount. These increases were offset by decreases of $6.4 million in Bicycle TICA program development expenses due to the timing of clinical program activities, $2.4 million in discovery, platform and other expenses, $1.3 million in BT5528 clinical program expenses, $1.1 million in facility expenses and $9.5 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.

Current 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.

Previous wording

Other income (expense), net increased by $9.6 million in the six months ended June 30, 2024 compared to the six months ended June 30, 2023, which was due to an increase in interest income related to higher interest rates as well as higher average interest-bearing cash and cash equivalents balances period over period.

Current wording

Other income, net increased by $16.1 million in the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023, which was primarily due to an increase in interest income of $16.2 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.

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 our 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 a Loan Agreement with Hercules.

Previous wording

Net cash used in operating activities for the six months ended June 30, 2024 was $115.5 million as compared to $12.3 million for the six months ended June 30, 2023. The increase in cash used in operations of $103.2 million is primarily due to the timing of cash receipts in the prior year, including the $50.0 million upfront payment received pursuant to our collaboration agreement with Novartis as well as the receipt of the research and development incentive receivable of $19.2 million during the six months ended June 30, 2023. In addition, during the six months ended June 30, 2024, we have incurred higher cash payments associated with ongoing development activities, including the initiation of our Phase II/III Duravelo-2 registrational trial for zelenectide pevedotin.

Current wording

Net cash used in operating activities for the nine months ended September 30, 2024 was $155.3 million as compared to $13.3 million for the nine months ended September 30, 2023. The increase in cash used in operations of $142.0 million is primarily due to the timing of cash receipts in the prior year, including $95.0 million in upfront payments received pursuant to our collaboration agreements with Novartis and Bayer as well as the receipt of the

Previous wording

During the six months ended June 30, 2024 and 2023, we used $0.4 million and $2.4 million, respectively, of cash in investing activities for purchases of property and equipment, consisting primarily of laboratory equipment.

Current 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.

Previous wording

During the six months ended June 30, 2024, net cash provided by financing activities was $551.5 million, primarily consisting of net proceeds of $545.1 million from the Private Placement and $6.4 million from the exercise of share options.

Current wording

During the nine months ended September 30, 2024, net cash provided by financing activities was $519.5 million, primarily consisting of net proceeds of $544.1 million from the private placement completed in May 2024 and $7.3 million from the exercise of share options, offset by payments on debt of $31.9 million associated with the repayment and voluntary termination of the Loan Agreement.

Previous wording

During the six months ended June 30, 2023, net cash provided by financing activities was $15.0 million, primarily consisting of net proceeds from our ATM program.

Current 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.

Previous wording

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 its ATM program pursuant to which the Company may offer and sell through the Sales Agents, from time to time at the Company’s sole discretion, ADSs. No ADSs were issued or sold pursuant to the Sales Agreement during the three and six months ended June 30, 2024. During the three and six months ended June 30, 2023, the Company issued and sold 520,000 and 620,000 ADSs, respectively, under the Sales Agreement for gross proceeds of $12.5 million and $15.3 million, respectively, resulting in net proceeds of $12.1 million and $14.8 million, respectively, after deducting sales commissions and offering expenses of $0.4 million and $0.5 million, respectively.

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 and nine months ended September 30, 2024.

Previous wording

As of June 30, 2024, our Loan Agreement, as amended from time to time, with Hercules as agent, consisted of (i) outstanding term loans of $30.0 million and (ii) subject customary conditions, additional term loans of up to an aggregate of $45.0 million, which had not yet been drawn. Borrowings under the Loan Agreement bear interest at an annual rate equal to the prime rate as reported in the Wall Street Journal plus 4.55%, with a minimum annual rate of at least 8.05%, capped at a rate no greater than 9.05%. On July 9, 2024, we repaid in its entirety and voluntarily terminated the Loan Agreement. We elected to repay all amounts outstanding, including accrued and unpaid interest, an end-of-term charge of $1.5 million and a prepayment charge of $0.3 million, for a total aggregate payment of $31.9 million. In connection with the Loan Agreement, we granted Hercules a security interest in substantially all of our personal property and other assets, other than our intellectual property and, upon the termination of the Loan Agreement, all security interests granted to the secured parties thereunder were terminated and released. The Loan Agreement also included customary affirmative and restrictive covenants and representations and warranties and events of default, as more fully set forth in the Loan Agreement. For additional information on the Loan Agreement, see Note 6. “Debt” and Note 15. “Subsequent events” of our condensed consolidated financial statements included elsewhere in this Quarterly Report.

Current wording

On July 9, 2024, we repaid all amounts outstanding, including $30.0 million in outstanding borrowings, $0.1 million in accrued and unpaid interest, an end-of-term charge of $1.5 million and a prepayment charge of $0.3 million, for a total aggregate payment of $31.9 million, and terminated the Loan Agreement. Upon the termination of the Loan Agreement, all security interests granted to the secured parties thereunder were terminated and released. For additional information on the Loan Agreement, see Note 6. “Debt” of our condensed consolidated financial statements included elsewhere in this Quarterly Report.

Previous wording

The following table summarizes our material contractual obligations as of June 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 6. “Debt,” Note 11. “Commitments and contingencies” and Note 15. “Subsequent events” of our condensed consolidated financial statements included elsewhere in this Quarterly Report.

Current 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.

Previous wording

As of June 30, 2024, we had cash and cash equivalents of $961.4 million. We expect that our existing cash 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 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.

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 terms that may not be favorable to us or grant rights to develop and market products or product candidates that we would

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

Previous wording

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.

Current wording

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.