BCYC

MKT CAP $106.7MP/E —DIV YIELD —FCF YIELD -195.28%REV TTM $61.2M +217.4%NET INCOME −$190.4MNET CASH $479.1M52W 3.38 – 8.76SEC XBRL · TTM TO Invalid Date

How BCYC rewrote its risk factors

10-K ITEM 1A · FY2024 → FY2025

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These risks and uncertainties include, among others, the following: ● We have a history of significant operating losses and expect to incur significant and increasing losses for the foreseeable future, and we may never achieve or maintain profitability. ● We may need substantial additional funding, and if we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our product discovery and development programs or commercialization efforts. ● Raising additional capital may cause dilution to our existing shareholders or holders of our ADSs, restrict our operations or cause us to relinquish valuable rights. ● We are substantially dependent on the success of our internal development programs and of our product candidates from our Bicycle ® Drug Conjugate, or BDC ® , and Bicycle Radioconjugate, or BRC ® , programs, which may not successfully complete clinical trials, receive regulatory approval or be successfully commercialized. ● We are at an early stage in our development efforts, and our product candidates and those of our collaborators represent a new category of medicines and may be subject to heightened regulatory scrutiny until they are established as a therapeutic modality. ● We may find it difficult to enroll patients in our clinical trials, which could delay or prevent us from proceeding with clinical trials of our product candidates. ● Results of preclinical studies and early clinical trials may not be predictive of results of future clinical trials. ● Our current or future product candidates may cause undesirable side effects or have other properties when used alone or in combination with other approved products or investigational new drugs, or IND, that could halt their clinical development, prevent their marketing approval, limit their commercial potential or result in significant negative consequences. ● We may be delayed or not be successful in our efforts to identify or discover additional product candidates. ● We may expend our limited resources to pursue a particular development strategy, product candidate or indication and fail to capitalize on strategies, product candidates or indications that may be more profitable or for which there is a greater likelihood of success. ● We may seek designations for our product candidates with the U.S.
Our (and third parties with whom we work) actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions, litigation, fines and penalties, disruptions of our business operations, reputational harm, loss of revenue or profits, and other adverse business consequences. ● We rely on third parties, including independent clinical investigators and CROs to conduct and sponsor some of the clinical trials of our product candidates.
Any failure by a third party to meet its obligations with respect to the clinical development of our product candidates may delay or impair our ability to obtain regulatory approval for our product candidates. ● We intend to rely on third parties to manufacture product candidates and supply raw materials used in our product candidates, such as 212 Pb, which increases the risk that we will not have sufficient quantities of such product candidates or products or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts. ● If we are unable to obtain and maintain patent and other intellectual property protection for our products and product candidates, or if the scope of the patent and other intellectual property protection obtained is not sufficiently broad, our competitors could develop and commercialize products similar or identical to ours, and our ability to successfully commercialize our products and product candidates may be adversely affected. ● If we are sued for infringing intellectual property rights of third parties, such litigation could be costly and time consuming and could prevent or delay us from developing or commercializing our product candidates. ● Our recent workforce reductions were undertaken to significantly reduce our ongoing operating expenses, but they may not result in our intended outcomes and may yield unintended consequences and additional costs. ● The market price of our ADSs is highly volatile, and holders of our ADSs may not be able to resell their ADSs at or above the price at which they purchased their ADSs. ● As a company with operations outside of the United States, we are subject to economic, political, regulatory and other risks associated with international operations.
Since inception, we have incurred recurring losses, including net losses of $219.0 million, $169.0 million and $180.7 million for the years ended December 31, 2025, 2024 and 2023, respectively.
As of December 31, 2025, we had an accumulated deficit of $899.8 million.
Net losses and negative cash flows have had, and will continue to have, an adverse effect on our shareholders’ equity and working capital. We anticipate that our expenses will increase substantially if and as we: ● continue to develop and conduct clinical trials with respect to our BDC and BRC programs and our other pipeline programs; ● initiate and continue research, preclinical and clinical development efforts for any future product candidates; ● seek to discover and develop additional product candidates and further expand our clinical product pipeline; ● seek marketing and regulatory approvals for any product candidates that successfully complete clinical trials; ● require the manufacture of larger quantities of product candidates for clinical development and, potentially, commercialization; ● maintain, expand and protect our intellectual property portfolio; ● expand our research and development infrastructure, including hiring and retaining additional personnel, such as clinical, quality control and scientific personnel; ● establish sales, marketing, distribution and other commercial infrastructure in the future to commercialize products for which we obtain marketing approval, if any; ● add operational, financial and management information systems and personnel, including personnel to support our product development and commercialization and help us comply with our obligations as a public company; and ● add equipment and physical infrastructure to support our research and development. Our ability to become and remain profitable depends on our ability to generate revenue.
Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our revenue to date has been primarily generated from our current and former research collaborations with Bayer Consumer Care AG, or Bayer, Novartis Pharma AG, or Novartis, Ionis Pharmaceuticals, Inc., or Ionis, and Genentech Inc., or Genentech.
Our failure to raise capital as and when needed would have a negative impact on our financial condition and our ability to pursue our business strategy. We believe that our existing cash and cash equivalents of $628.1 million as of December 31, 2025, will enable us to fund our operating expenses and capital expenditure requirements for at least 12 months from the date of filing of this Annual Report.
Our future funding requirements, both short-term and long-term, will depend on many factors, including: ● the scope, progress, timing, costs and results of clinical trials of, and research and preclinical development efforts for, our current and future product candidates; ● our ability to enter into, and the terms and timing of, any collaborations, licensing or other arrangements; ● our ability to identify one or more future product candidates for our pipeline; ● the number of future product candidates that we pursue and their development requirements; ● the outcome, timing and costs of seeking regulatory approvals; ● the costs of commercialization activities for any of our product candidates that receive marketing approval to the extent such costs are not the responsibility of any collaborators, including the costs and timing of establishing product sales, marketing, distribution and manufacturing capabilities; ● subject to receipt of marketing approval, revenue, if any, received from commercial sales of our current and future product candidates; ● our headcount and associated costs as we progress our research and development and establish a commercial infrastructure; ● the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights including enforcing and defending intellectual property related claims; and ● the costs of operating as a public company. While the long-term economic impact of geopolitical risks, including evolving impacts from tariffs, sanctions or other trade tensions between the United States and other countries, or demand or supply shocks from events such as major terrorist attacks, war, natural disasters or actual or threatened public health pandemics or other emergencies is difficult to assess or predict, these events have caused or may cause significant disruptions to the global financial markets and have contributed or may contribute to a general global economic slowdown.
Furthermore, inflation rates, particularly in the United States and the United Kingdom, recently increased to levels not seen in decades and, despite recent decreases, remain high.
Future increases in interest rates, especially if coupled with reduced government spending and volatility in financial markets and the global banking system, may further increase economic uncertainty and heighten these risks. Raising additional capital may cause dilution to our existing shareholders or holders of our ADSs , restrict our operations or cause us to relinquish valuable rights . We may seek additional capital through a combination of public and private equity offerings, debt financings, strategic partnerships and alliances, licensing arrangements or monetization transactions.
If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves . Risks Related to the Discovery , Development and Regulatory Approval of Our Product Candidates We are substantially dependent on the success of our internal development programs and of our product candidates from our BDC and BRC programs, which may not successfully complete clinical trials , receive regulatory approval or be successfully commercialized . Our future success will depend heavily on the success of our internal development programs and of product candidates from our BDC and BRC programs. Within our BDC programs, we are evaluating nuzefatide pevedotin, formerly BT5528, a BDC molecule that targets Ephrin type-A receptor 2, or EphA2 and carries a MMAE cytotoxin payload, in an ongoing, company-sponsored Phase I/II clinical trial to assess safety, pharmacokinetics and preliminary clinical activity in patients with advanced malignancies historically associated with EphA2 expression as well as an ongoing, company-sponsored Phase II clinical trial to evaluate the efficacy, safety and pharmacokinetics of nuzefatide pevedotin in adult patients with recurrent metastatic pancreatic ductal adenocarcinoma.
In addition, IND-enabling activities are currently ongoing for BT1702, a theranostic BRC molecule targeting MT1-MMP and carrying a 212 Pb radioisotope payload.
There can be no assurance our BDC or BRC molecules will ever demonstrate evidence of safety or effectiveness for any use or receive regulatory approval in the United States, the European Union, or any other country in any indication.
Even if clinical trials show positive results, there can be no assurance that the FDA in the United States, or the European Commission, whose decision is based on an opinion from the EMA in Europe or similar regulatory authorities will approve our BDC or BRC molecules or any of our other product candidates for any given indication for several potential reasons, including the failure to follow Good Clinical Practice, or GCP, a negative assessment of the risks and benefits, insufficient product quality control and standardization, failure to have Good Manufacturing Practices, or GMP, compliant manufacturing facilities, or the failure to agree with regulatory authorities on clinical endpoints . Our ability to successfully commercialize our BDC molecules, BRC molecules, and our other product candidates will depend on, among other things, our ability to: ● successfully complete preclinical studies and clinical trials, which may be delayed; ● receive regulatory approvals from the FDA, the European Commission based on an opinion from the EMA and other similar regulatory authorities; ● establish and maintain collaborations with third parties for the development and/or commercialization of our product candidates, or otherwise build and maintain strong development, sales, distribution and marketing capabilities that are sufficient to develop products and launch commercial sales of any approved products; ● obtain coverage and adequate reimbursement from payors such as government health care systems and insurance companies and achieve commercially attractive levels of pricing; ● secure acceptance of our product candidates from physicians, health care payors, patients and the medical community; ● produce, through a validated process, in manufacturing facilities inspected and approved by regulatory authorities, including the FDA, sufficiently large quantities of our product candidates to permit successful commercialization; ● manage our spending as expenses increase due to clinical trials and commercialization; and ● obtain and enforce sufficient intellectual property rights for any approved products and product candidates and maintain freedom to operate for such products with respect to the intellectual property rights of third parties. Of the large number of drugs in development in the pharmaceutical industry, only a small percentage result in the submission of a new drug application, or NDA, to the FDA or comparable foreign applications to competent regulatory authorities abroad, and even fewer are approved for commercialization.
The CTR, which was adopted in April 2014 and repeals the CTD, became applicable on January 31, 2022.
The CTR introduces, among other changes, a centralized application system, coordinated review procedures, expanded reporting and increased transparency obligations.
Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our developments plans. In addition, on December 11, 2025, the European Commission, European Parliament and European Council reached a political agreement on a comprehensive overhaul of EU pharmaceutical legislation, or the Pharma Package.
The reform has been under negotiation since the European Commission submitted its proposal in April 2023.
This package, composed of a new directive and regulation to replace existing legislation, aims to modernize the EU framework.
The political agreement is still subject to formal approval by the European Parliament and European Council.
If approved in the form proposed, the Pharma Package will, among other changes, reduce the baseline market protection period by one year, with limited opportunities for extensions; reshape the incentives regime for orphan medicinal products; and expand the Bolar exemption.
A decrease in market exclusivity opportunities for our product candidates in the EU, combined with the expanded Bolar exemption, could open them to generic or biosimilar competition earlier than under the current regime, potentially impacting reimbursement status and the commercial prospects of our product candidates. Moreover, following a public consultation that began in 2022, the United Kingdom government has enacted new legislation to overhaul the clinical trials regulatory framework.
In April 2025, the United Kingdom adopted an amendment to the Medicines for Human Use (Clinical Trials) Regulations 2004 intended to support a more streamlined and flexible regulation of clinical trials, remove unnecessary administrative burdens on trial sponsors, and protect the interests of trial participants.
It also intends to bring the U.K. regulatory framework for clinical trials into closer alignment with the EU’s CTR.
The amendment will become applicable on April 28, 2026 following a one-year transition period.
While these changes introduce efficiencies and align with some principles of the CTR, divergence between the United Kingdom and EU regulatory systems remains.
Any significant divergence could affect the cost and complexity of conducting clinical trials in the United Kingdom and may impact the acceptability of United Kingdom-based trial data for seeking marketing authorizations in the EU, and vice versa. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, our development plans may be impacted. We are at an early stage in our development efforts , and our product candidates and those of our collaborators represent a new category of medicines and may be subject to heightened regulatory scrutiny until they are established as a therapeutic modality . Bicycle molecules are fully synthetic short peptides constrained to form two loops which stabilize their structural geometry.
If preclinical or clinical trials of our or their product candidates fail to satisfactorily demonstrate safety and efficacy to the FDA , the EMA and the European Commission and any other comparable regulatory authority , additional costs may be incurred or delays experienced in completing , the development of these product candidates , or their development may be abandoned . The FDA in the United States, the European Commission based on a positive opinion from the EMA, or national competent regulatory authorities in the EEA, countries and any other comparable regulatory authorities in other jurisdictions must approve product candidates before they can be marketed, promoted or sold in those territories.
Patient enrollment and trial completion is affected by factors including the : ● size of the patient population and process for identifying subjects; ● design of the trial protocol; ● eligibility and exclusion criteria; ● safety profile, to date, of the product candidate under study; ● perceived risks and benefits of the product candidate under study; ● perceived risks and benefits of our approach to treatment of diseases; ● availability of competing therapies and clinical trials; ● severity of the disease under investigation; ● degree of progression of the subject’s disease at the time of enrollment; ● proximity and availability of clinical trial sites for prospective subjects; ● ability to obtain and maintain subject consent; ● risk that enrolled subjects will drop out before completion of the trial; ● patient referral practices of physicians; and ● ability to monitor subjects adequately during and after treatment. In addition, clinical testing of our product candidates generally is performed in multiple jurisdictions, including countries outside of the United States.
Our ability to successfully initiate, enroll and complete a clinical trial in any foreign country is subject to numerous risks unique to conducting business in foreign countries, including: ● difficulty in establishing or managing relationships with academic partners or CROs and physicians; ● different standards for the conduct of clinical trials; ● the absence in some countries of established groups with sufficient regulatory expertise for review of protocols related to our novel approach; ● our inability to locate qualified local consultants, physicians and partners; and ● the potential burden of complying with a variety of foreign laws, medical standards and regulatory requirements, including the regulation of pharmaceutical and biotechnology products and treatment. If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay, limit or terminate ongoing or planned clinical trials, any of which would have an adverse effect on our business, financial condition, results of operations and prospects. Results of preclinical studies and early clinical trials may not be predictive of results of future clinical trials . The outcome of preclinical studies and early clinical trials may not be predictive of the success of later clinical trials, and preliminary or interim results of clinical trials do not necessarily predict success in the results of completed clinical trials.
For example, the interim results of our company-sponsored Phase I/II clinical trials of nuzefatide pevedotin, zelenectide pevedotin and BT7480, including specific patient responses we have observed and disclosed, may not be replicated in the completed data sets or in future trials at global clinical trial sites in a later stage clinical trial conducted by us or our collaborators.
We have limited experience in designing late-stage clinical trials and may be unable to design and execute a clinical trial to support marketing approval. Preclinical and clinical data are often susceptible to varying interpretations and analyses.
In the EEA (and Northern Ireland), in order to place an in vitro diagnostic medical device on the market, the device must be designed, developed, manufactured and marketed in compliance with the Regulation on In-Vitro Diagnostic Devices (Regulation (EU) 2017/746), which is a lengthy and costly process. We do not develop companion diagnostics internally and thus we will be dependent on the sustained cooperation and effort of our third-party collaborators in developing and obtaining approval or certification for these companion diagnostics.
So far, we have not demonstrated, and we cannot predict if ongoing or future clinical trials will demonstrate, that nuzefatide pevedotin, zelenectide pevedotin, BT7480 or any other of our product candidates are safe in humans. Moreover, clinical trials of our product candidates are conducted in carefully defined sets of patients who have agreed to enter into clinical trials.
If we fail to identify and develop additional potential product candidates, we may be unable to grow our business and our results of operations could be materially harmed . We may expend our limited resources to pursue a particular development strategy, product candidate or indication and fail to capitalize on strategies, product candidates or indications that may be more profitable or for which there is a greater likelihood of success . In March 2026, we announced the strategic reprioritization of our clinical portfolio to focus on our promising pipeline of next-generation therapeutics, including nuzefatide pevedotin as well as next-generation Bicycle conjugates, including BRC molecules.
While dose selection data from the Phase II/III Duravelo-2 clinical trial for zelenectide pevedotin are promising, demonstrating response rates comparable to published rates for existing standards of care and a differentiated safety profile, we plan to convert the Phase II/III Duravelo-2 registrational trial to a randomized Phase II clinical trial and deprioritize the program for internal development while we evaluate next steps for zelenectide pevedotin following preliminary feedback from regulatory agencies.
In addition, as part of the strategic reprioritization, we plan to discontinue the Phase I/II clinical trials evaluating zelenectide pevedotin in patients with NECTIN4 amplified advanced breast cancer and NECTIN4 amplified advanced or metastatic non-small cell lung cancer.
Further enrollment in these trials will be closed and patients already enrolled will complete their course of treatment. Because we have limited financial and managerial resources, we intend to focus on developing product candidates for specific indications that we identify as most likely to succeed, in terms of both their potential for marketing approval and commercialization.
As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that may prove to have greater commercial potential. Our past resource allocation decisions, and those we may make in the future, may cause us to fail to capitalize on viable commercial products or profitable market opportunities.

and 164 more.

Gone since FY2024

These risks and uncertainties include, among others, the following: ● We have a history of significant operating losses and expect to incur significant and increasing losses for the foreseeable future, and we may never achieve or maintain profitability. ● We may need substantial additional funding, and if we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our product discovery and development programs or commercialization efforts. ● Raising additional capital may cause dilution to our existing shareholders or holders of our ADSs, restrict our operations or cause us to relinquish valuable rights. ● We are substantially dependent on the success of our internal development programs and of our product candidates from our Bicycle ® Toxin Conjugate, or BTC ® , and Bicycle Tumor-Targeted Immune Cell Agonist ® , or Bicycle TICA ® , programs, which may not successfully complete clinical trials, receive regulatory approval or be successfully commercialized. ● We are at an early stage in our development efforts, and our product candidates and those of our collaborators represent a new category of medicines and may be subject to heightened regulatory scrutiny until they are established as a therapeutic modality. ● We may find it difficult to enroll patients in our clinical trials, which could delay or prevent us from proceeding with clinical trials of our product candidates. ● Results of preclinical studies and early clinical trials may not be predictive of results of future clinical trials. ● Our current or future product candidates may cause undesirable side effects or have other properties when used alone or in combination with other approved products or investigational new drugs, or IND, that could halt their clinical development, prevent their marketing approval, limit their commercial potential or result in significant negative consequences. ● We may be delayed or not be successful in our efforts to identify or discover additional product candidates. ● We may expend our limited resources to pursue a particular development strategy, product candidate or indication and fail to capitalize on strategies, product candidates or indications that may be more profitable or for which there is a greater likelihood of success. ● We may seek designations for our product candidates with the U.S.
Our (and third parties with whom we work) actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions, litigation, fines and penalties, disruptions of our business operations, reputational harm, loss of revenue or profits, and other adverse business consequences. ● We rely on third parties, including independent clinical investigators and clinical research organizations, or CROs, to conduct and sponsor some of the clinical trials of our product candidates.
Any failure by a third party to meet its obligations with respect to the clinical development of our product candidates may delay or impair our ability to obtain regulatory approval for our product candidates. ● We intend to rely on third parties to manufacture product candidates, which increases the risk that we will not have sufficient quantities of such product candidates or products or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts. ● If we are unable to obtain and maintain patent and other intellectual property protection for our products and product candidates, or if the scope of the patent and other intellectual property protection obtained is not sufficiently broad, our competitors could develop and commercialize products similar or identical to ours, and our ability to successfully commercialize our products and product candidates may be adversely affected. ● If we are sued for infringing intellectual property rights of third parties, such litigation could be costly and time consuming and could prevent or delay us from developing or commercializing our product candidates. ● The market price of our ADSs is highly volatile, and holders of our ADSs may not be able to resell their ADSs at or above the price at which they purchased their ADSs. ● As a company based outside of the United States, we are subject to economic, political, regulatory and other risks associated with international operations.
Since inception, we have incurred recurring losses, including net losses of $169.0 million, $180.7 million and $112.7 million for the years ended December 31, 2024, 2023 and 2022, respectively.
As of December 31, 2024, we had an accumulated deficit of $680.8 million.
Net losses and negative cash flows have had, and will continue to have, an adverse effect on our shareholders’ equity and working capital. We anticipate that our expenses will increase substantially if and as we: ● continue to develop and conduct clinical trials with respect to our BTC and Bicycle TICA programs and our other pipeline programs, including for the ongoing Phase II/III Duravelo-2 registrational trial; ● initiate and continue research, preclinical and clinical development efforts for any future product candidates; ● seek to discover and develop additional product candidates and further expand our clinical product pipeline; ● seek marketing and regulatory approvals for any product candidates that successfully complete clinical trials; ● require the manufacture of larger quantities of product candidates for clinical development and, potentially, commercialization; ● maintain, expand and protect our intellectual property portfolio; ● expand our research and development infrastructure, including hiring and retaining additional personnel, such as clinical, quality control and scientific personnel; ● establish sales, marketing, distribution and other commercial infrastructure in the future to commercialize products for which we obtain marketing approval, if any; ● add operational, financial and management information systems and personnel, including personnel to support our product development and commercialization and help us comply with our obligations as a public company; and ● add equipment and physical infrastructure to support our research and development. Our ability to become and remain profitable depends on our ability to generate revenue.
Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our revenue to date has been primarily generated from our research collaborations with Bayer Consumer Care AG, or Bayer, Novartis Pharma AG, or Novartis, Ionis Pharmaceuticals, Inc., or Ionis, and Genentech Inc., or Genentech.
Our failure to raise capital as and when needed would have a negative impact on our financial condition and our ability to pursue our business strategy. We believe that our existing cash and cash equivalents of $879.5 million as of December 31, 2024, will enable us to fund our operating expenses and capital expenditure requirements for at least 12 months from the date of filing of this Annual Report.
Our future funding requirements, both short-term and long-term, will depend on many factors, including: ● the scope, progress, timing, costs and results of clinical trials of, and research and preclinical development efforts for, our current and future product candidates; ● our ability to enter into, and the terms and timing of, any collaborations, licensing or other arrangements; ● our ability to identify one or more future product candidates for our pipeline; ● the number of future product candidates that we pursue and their development requirements; ● the outcome, timing and costs of seeking regulatory approvals; ● the costs of commercialization activities for any of our product candidates that receive marketing approval to the extent such costs are not the responsibility of any collaborators, including the costs and timing of establishing product sales, marketing, distribution and manufacturing capabilities; ● subject to receipt of marketing approval, revenue, if any, received from commercial sales of our current and future product candidates; ● our headcount growth and associated costs as we expand our research and development and establish a commercial infrastructure; ● the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights including enforcing and defending intellectual property related claims; and ● the costs of operating as a public company. While the long-term economic impact of public health crises or geographical tensions and wars, such as the ongoing wars involving Ukraine and Israel, is difficult to assess or predict, these events have caused or may cause significant disruptions to the global financial markets and have contributed or may contribute to a general global economic slowdown.
Furthermore, inflation rates, particularly in the United States and the United Kingdom, have increased recently to levels not seen in decades.
Federal Reserve has raised, and may further raise, interest rates in response to concerns about inflation.
Increases in interest rates, especially if coupled with reduced government spending and volatility in financial markets and the global banking system, may further increase economic uncertainty and heighten these risks. Raising additional capital may cause dilution to our existing shareholders or holders of our ADSs , restrict our operations or cause us to relinquish valuable rights . We may seek additional capital through a combination of public and private equity offerings, debt financings, strategic partnerships and alliances, licensing arrangements or monetization transactions.
If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves . Risks Related to the Discovery , Development and Regulatory Approval of Our Product Candidates We are substantially dependent on the success of our internal development programs and of our product candidates from our BTC and Bicycle TICA programs, which may not successfully complete clinical trials , receive regulatory approval or be successfully commercialized . Our future success will depend heavily on the success of our internal development programs and of product candidates from our BTC and Bicycle TICA programs. Within our BTC programs, we are evaluating zelenectide pevedotin, formerly BT8009, a BTC molecule that targets Nectin-4 and carries a monomethyl auristatin E, or MMAE, cytotoxin payload, in both an ongoing company-sponsored Phase I/II clinical trial to assess safety, pharmacokinetics and preliminary clinical activity in patients with Nectin-4 expressing advanced malignancies and an ongoing Phase II/III registrational trial called Duravelo-2, and BT5528, a BTC molecule that targets Ephrin type-A receptor 2, or EphA2 and carries a MMAE cytotoxin payload, in an ongoing, company-sponsored Phase I/II clinical trial to assess safety, pharmacokinetics and preliminary clinical activity in patients with advanced malignancies associated with EphA2 expression.
We are also evaluating BT7480, a Bicycle TICA molecule targeting Nectin-4 and agonizing CD137, in a company-sponsored Phase I/II clinical trial to assess the safety and tolerability of BT7480, and to determine a recommended Phase II dose.
There can be no assurance our BTC molecules or Bicycle TICA molecules will ever demonstrate evidence of safety or effectiveness for any use or receive regulatory approval in the United States, the European Union, or any other country in any indication.
Even if clinical trials show positive results, there can be no assurance that the FDA in the United States, or the European Commission, whose decision is based on an opinion from the European Medicines Agency, or EMA, in Europe or similar regulatory authorities will approve our BTC molecules or any of our other product candidates for any given indication for several potential reasons, including the failure to follow Good Clinical Practice, or GCP, a negative assessment of the risks and benefits, insufficient product quality control and standardization, failure to have Good Manufacturing Practices, or GMP, compliant manufacturing facilities, or the failure to agree with regulatory authorities on clinical endpoints . Our ability to successfully commercialize our BTC molecules, Bicycle TICA molecules, and our other product candidates, including our BRC molecules, will depend on, among other things, our ability to: ● successfully complete preclinical studies and clinical trials, which may be delayed; ● receive regulatory approvals from the FDA, the European Commission based on an opinion from the EMA and other similar regulatory authorities; ● establish and maintain collaborations with third parties for the development and/or commercialization of our product candidates, or otherwise build and maintain strong development, sales, distribution and marketing capabilities that are sufficient to develop products and launch commercial sales of any approved products; ● obtain coverage and adequate reimbursement from payors such as government health care systems and insurance companies and achieve commercially attractive levels of pricing; ● secure acceptance of our product candidates from physicians, health care payors, patients and the medical community; ● produce, through a validated process, in manufacturing facilities inspected and approved by regulatory authorities, including the FDA, sufficiently large quantities of our product candidates to permit successful commercialization; ● manage our spending as expenses increase due to clinical trials and commercialization; and ● obtain and enforce sufficient intellectual property rights for any approved products and product candidates and maintain freedom to operate for such products with respect to the intellectual property rights of third parties. Of the large number of drugs in development in the pharmaceutical industry, only a small percentage result in the submission of a new drug application, or NDA, to the FDA or comparable foreign applications to competent regulatory authorities abroad, and even fewer are approved for commercialization.
The EU Clinical Trials Regulation, or CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022.
The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each EU Member State, leading to a single decision for each EU Member State.
The assessment procedure for the authorization of clinical trials has been harmonized as well, including a joint assessment by all EU Member States concerned, and a separate assessment by each EU Member State with respect to specific requirements related to its own territory, including ethics rules.
Each EU Member State’s decision is communicated to the sponsor via the centralized EU portal.
Once the clinical trial is approved, clinical study development may proceed.
The CTR foresees a three-year transition period.
The extent to which ongoing and new clinical trials will be governed by the CTR varies.
For clinical trials in relation to which application for approval was made on the basis of the Clinical Trials Directive before January 31, 2023, the Clinical Trials Directive continued to apply on a transitional basis until January 31, 2025 , by which date, all ongoing trials under the Clinical Trials Directive became subject to the provisions of the CTR and all new trials since January 31, 2023 have been subject to the CTR.
Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our developments plans. In addition, on April 26, 2023, the European Commission adopted a proposal for a new Directive and Regulation to revise the existing 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 recent European Commission proposals to revise the existing EU laws governing authorization of medicinal products 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. The U.K.’s regulatory framework in relation to clinical trials is derived from existing legislation of the EU (as implemented into the law of the U.K., through secondary legislation).
On January 17, 2022, the MHRA launched an eight-week consultation on reframing the U.K.’s legislation for clinical trials.
The U.K.’s government published its response to the consultation on March 21, 2023 confirming that it would bring forward changes to the legislation.
These changes were laid before parliament on December 12, 2024 and if adopted will bring the U.K. into closer alignment with the EU. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, our development plans may be impacted. We are at an early stage in our development efforts , and our product candidates and those of our collaborators represent a new category of medicines and may be subject to heightened regulatory scrutiny until they are established as a therapeutic modality . Bicycle molecules are fully synthetic short peptides constrained to form two loops which stabilize their structural geometry.
If preclinical or clinical trials of our or their product candidates fail to satisfactorily demonstrate safety and efficacy to the FDA , the EMA and the European Commission and any other comparable regulatory authority , additional costs may be incurred or delays experienced in completing , the development of these product candidates , or their development may be abandoned . The FDA in the United States, the European Commission based on a positive opinion from the EMA, or national competent regulatory authorities in the European Economic Area, or EEA, countries and any other comparable regulatory authorities in other jurisdictions must approve product candidates before they can be marketed, promoted or sold in those territories.
Patient enrollment and trial completion is affected by factors including the : ● size of the patient population and process for identifying subjects; ● design of the trial protocol; ● eligibility and exclusion criteria; ● safety profile, to date, of the product candidate under study; ● perceived risks and benefits of the product candidate under study; ● perceived risks and benefits of our approach to treatment of diseases; ● availability of competing therapies and clinical trials; ● severity of the disease under investigation; ● degree of progression of the subject’s disease at the time of enrollment; ● proximity and availability of clinical trial sites for prospective subjects; ● ability to obtain and maintain subject consent; ● risk that enrolled subjects will drop out before completion of the trial; ● patient referral practices of physicians; and ● ability to monitor subjects adequately during and after treatment. In addition, clinical testing of zelenectide pevedotin, BT5528, and BT7480 is currently taking place outside of the United States.
Our ability to successfully initiate, enroll and complete a clinical trial in any foreign country is subject to numerous risks unique to conducting business in foreign countries, including: ● difficulty in establishing or managing relationships with academic partners or contract research organizations, or CROs, and physicians; ● different standards for the conduct of clinical trials; ● the absence in some countries of established groups with sufficient regulatory expertise for review of protocols related to our novel approach; ● our inability to locate qualified local consultants, physicians and partners; and ● the potential burden of complying with a variety of foreign laws, medical standards and regulatory requirements, including the regulation of pharmaceutical and biotechnology products and treatment. If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay, limit or terminate ongoing or planned clinical trials, any of which would have an adverse effect on our business, financial condition, results of operations and prospects. Results of preclinical studies and early clinical trials may not be predictive of results of future clinical trials . The outcome of preclinical studies and early clinical trials may not be predictive of the success of later clinical trials, and preliminary or interim results of clinical trials do not necessarily predict success in the results of completed clinical trials.
For example, our company-sponsored Phase I/II clinical trials of zelenectide pevedotin, BT5528 and BT7480 are ongoing, and the interim results of these trials, including specific patient responses we have observed and disclosed, may not be replicated in the completed data sets or in future trials at global clinical trial sites in a later stage clinical trial conducted by us or our collaborators.
While we aligned with the FDA on the design of a Phase II/III registrational trial for zelenectide pevedotin, called Duravelo-2, which is currently enrolling, we otherwise have limited experience in designing clinical trials and may be unable to design and execute a clinical trial to support marketing approval. Preclinical and clinical data are often susceptible to varying interpretations and analyses.
We do not develop companion diagnostics internally and thus we will be dependent on the sustained cooperation and effort of our third-party collaborators in developing and obtaining approval or certification for these companion diagnostics.
So far, we have not demonstrated, and we cannot predict if ongoing or future clinical trials will demonstrate, that zelenectide pevedotin, BT5528, BT7480, or any other of our product candidates are safe in humans. Moreover, clinical trials of our product candidates are conducted in carefully defined sets of patients who have agreed to enter into clinical trials.
If we fail to identify and develop additional potential product candidates, we may be unable to grow our business and our results of operations could be materially harmed . We may expend our limited resources to pursue a particular development strategy, product candidate or indication and fail to capitalize on strategies, product candidates or indications that may be more profitable or for which there is a greater likelihood of success . 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.

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Sentence-level comparison of Item 1A in the two most recent 10-Ks (FY2024 ↗, FY2025 ↗). A reworded sentence counts as one dropped and one added, so heavy edits read as low “kept”. Headings and page furniture are stripped; nothing is summarised by a model.

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