What changed in this filing

/stocks — the workspaceLOADING

Item 1A. Risk Factors

2026-02-25 compared with 2025-02-26 · 195 added, 238 removed, 1645 unchanged (21% of the section changed)

6 unchanged sentences

We have incurred significant losses in every year since our inception.

We expect to continue to incur losses over the next several years and may never achieve or maintain profitability.

We may continue to incur losses over the next several years and may never achieve or maintain profitability.

While we are a commercial-stage biotechnology company, we have incurred net losses in each year since our inception.

32 unchanged sentences

We are focusing a significant portion of our commercial activities and resources on KIMMTRAK, and we believe our ability to grow our long-term revenues, and a significant portion of the value of our company, relates to our ability to successfully commercialize KIMMTRAK in the United States and Europe.

While we have established commercial teams, we expect to develop these teams further and otherwise continue to develop commercialization strategies in order to continue to successfully commercialize KIMMTRAK in the longer term.

We expect to develop our commercial teams further and to continue to develop commercialization strategies in order to continue to successfully commercialize KIMMTRAK in the longer term.

There are many factors that could cause commercialization of KIMMTRAK to be unsuccessful, including many that are outside our control.

37 unchanged sentences

In addition, global macroeconomic factors, such as supply chain disruptions and rising inflation, may increase these expenses beyond what we currently anticipate.

As of December 31, 2024 , we had working capital (defined as total current assets less total current liabilities) of $717.7 million and cash and cash equivalents of $455.7 million , and marketable securities of $364.6 million.

As of December 31, 2025 , we had working capital (defined as total current assets less total current liabilities) of $750.0 million, cash and cash equivalents of $467.7 million , and marketable securities of $396.4 million .

We expect that our existing cash and cash equivalents with the inclusion of expected revenue for KIMMTRAK will provide sufficient funds to continue to meet our liabilities as they fall due and for at least 12 months from the issuance of our Annual Report.

42 unchanged sentences

If the market opportunities for our product candidates are smaller than we estimate, our revenue and ability to achieve profitability will be adversely affected, possibly materially.

The total addressable market opportunity for KIMMTRAK and our programs will ultimately depend upon, among other things, acceptance by the medical community and patient access, product pricing and reimbursement as well as expansion into additional markets.

The total addressable market opportunity for KIMMTRAK and our other programs will ultimately depend upon, among other things, acceptance by the medical community and patient access, product pricing and reimbursement as well as expansion into additional markets.

The number of patients with cancers, solid tumors, HIV, and chronic HBV and test positive for HLA-A*02:01 may turn out to be lower than expected, patients may not be otherwise amenable to treatment with our products, or new patients may become increasingly difficult to identify or gain access to, all of which would adversely affect our results of operations and our business.

8 unchanged sentences

Our commercial prospects will be heavily dependent on product candidates identified and developed using our ImmTAX platform.

To date, we have invested substantially all of our efforts and financial resources to identify, acquire intellectual property for, and develop our ImmTAX platform technology and our programs, including conducting pre-clinical studies, as well as early- and late-stage clinical trials, and providing general and administrative support for these operations.

To date, we have invested substantially all of our efforts and financial resources to identify, acquire intellectual property for, and develop our ImmTAX platform technology and our programs, including conducting pre-clinical studies, as well as early- and late-stage clinical trials and commercialization of KIMMTRAK that emerged from the ImmTAX platform and providing general and administrative support for these operations.

We may not be successful in our efforts to further develop our ImmTAX platform technology and current product candidates.

2 unchanged sentences

We, and the third parties on whom we rely in part for sales, marketing and distribution capabilities, may not be able to continue to effectively market, sell and distribute KIMMTRAK or effectively market, sell and distribute our other product candidates, if approved.

We have invested, and expect to continue to invest, significant financial and management resources to further develop internal sales, distribution and marketing capabilities, some of which, in territories prior to any confirmation that tebentafusp will be approved in that territory.

We utilize a hybrid model that includes an in-house sales force in the United States and contracted resources in the United States and Europe, and we have engaged third parties and may engage additional third parties to provide services related to the marketing of KIMMTRAK.

We have entered into agreements with Syneos Health, Inc.("Syneos"), Medison, and other third parties, to develop our commercial infrastructure for the commercial launch and continued sale of KIMMTRAK, including to potentially retain, train and deploy a direct sales force, but we do not have control over third parties beyond contractual agreements.

We have invested, and expect to continue to invest, significant financial and management resources to further develop internal sales, distribution and marketing capabilities of product candidates, some of which in territories prior to any confirmation that the product candidate will be approved in that territory.

We have entered into agreements with Syneos Health, Inc.("Syneos"), Er-Kim, Medison, and other third parties, to develop our commercial infrastructure for the commercial launch and continued sale of KIMMTRAK, including to potentially retain, train and deploy a direct sales force, but we do not have control over third parties beyond contractual agreements.

There can be no assurance that the capabilities of the Syneos sales organization or other third parties will be more effective than an internally developed sales organization.

13 unchanged sentences

• unforeseen costs and expenses associated with creating an independent sales and marketing organization.

If we enter into arrangements with third parties to perform sales, marketing and distribution services, our revenue from sale of therapies or the profitability to us from these revenue streams is likely to be lower than if we were to market and sell any product candidates that we develop ourselves.

If we enter into arrangements with third parties to perform sales, marketing and distribution services, our revenue from sale of therapies or the profitability from these revenue streams is likely to be lower than if we were to market and sell any product candidates that we develop ourselves.

In addition, we may not be successful in entering into arrangements with third parties to sell and market our product candidates or may be unable to do so on terms that are favorable to us.

1 unchanged sentence

If we do not establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we may not be successful in commercializing our product candidates.

Health epidemics or pandemics could materially adversely impact our business, including the commercialization of KIMMTRAK, our supply chain, our pre-clinical studies and our clinical trials, our liquidity and access to capital markets and our business development activities, as well as the business or operations of our CROs or other third parties with whom we conduct business.

Our business could be adversely affected by health epidemics or pandemics in regions where we have concentrations of clinical trial sites or other business operations, and could cause significant disruption in the operations of third-party manufacturers and CROs upon whom we rely.

Public health directives and executive orders in response to potential future health epidemics or pandemics may negatively impact productivity, disrupt our business and delay our clinical programs and timelines, the magnitude of which will depend, in part, on the length and severity of the restrictions and other limitations on our ability to conduct our business in the ordinary course.

These and similar, and perhaps more severe, disruptions in our operations could negatively impact our business, operating results and financial condition.

Quarantines, shelter-in-place and similar government orders, shutdowns or other restrictions on the conduct of business operations have occurred and could occur in the future, and could impact personnel at third-party manufacturing facilities, or the availability or cost of materials, which would disrupt our supply chain.

The effects of future health epidemics or pandemics may also negatively impact our clinical trials and the operations or our CROs or CMOs in the future, including:

• delays or difficulties in enrolling and retaining patients in our clinical trials, including patients that may not be able or willing to comply with clinical trial protocols such as weekly dosing regimens if quarantines impede patient movement or interrupt healthcare services;

• delays or difficulties in clinical site initiation, including difficulties in recruiting and retaining clinical site investigators and clinical site staff;

• increased rates of patients withdrawing from our clinical trials following enrollment, as a result of risks of exposure to disease, being forced to quarantine or being unable to visit clinical trial locations or otherwise comply with clinical trial protocols;

• diversion or prioritization of healthcare resources away from the conduct of clinical trials and towards the epidemic or pandemic, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials, including because they, as healthcare providers, may have heightened exposure to disease, which would adversely impact our clinical trial operations;

• interruption of our clinical supply chain or key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal, state/provincial or municipal governments, employers and others; and

• limitations in employee resources that would otherwise be focused on the conduct of our clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people.

For our clinical trials that we expect to conduct at sites outside the United States, particularly in countries which in the future could experience heightened impact future pandemics, in addition to the risks listed above, we may also experience the following adverse impacts:

• delays in receiving approval from local regulatory authorities to initiate our planned clinical trials;

• delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials;

• interruption in global shipping that may affect the transport of clinical trial materials, such as investigational drug product and comparator drugs used in our clinical trials;

• changes in supranational, national, federal, state/provincial or municipal regulations as part of a response to outbreak of disease which may require us to change the ways in which our clinical trials are conducted, which may result in unexpected costs, or to discontinue the clinical trials altogether;

• delays in necessary interactions with local regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government employees; and

• the refusal of the FDA or comparable foreign regulatory authorities to accept data from clinical trials in these affected geographies.

Epidemics or pandemics may in the future, impact our business and clinical trials, and such impact will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the duration of the outbreak, the emergence, infectiousness and severity of new variants, travel restrictions and social distancing, business closures or business disruptions and the effectiveness of actions taken in the United Kingdom, United States, and other countries to contain and treat the disease.

The ultimate impact potential epidemics is highly uncertain and subject to change.

Our products, even if approved for commercial sale, may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for continued commercial success.

Our products, even if approved for commercial sale by the FDA, the European Commission or other comparable regulatory authorities, may not achieve or maintain market acceptance among physicians, patients, hospitals, including pharmacy directors, and third-party payors and, ultimately, may not become or remain commercially successful.

The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including:

• the clinical indications for which our product candidates are approved;

• physicians, hospitals, cancer treatment centers, and patients considering our product candidates as a safe and effective treatment;

• hospitals and cancer treatment centers establishing the infrastructure required for the administration of the product candidate;

• the potential and perceived advantages of our product candidates over alternative treatments;

KIMMTRAK and our other product candidates, even if approved for commercial sale, may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for continued commercial success.

KIMMTRAK and our other product candidates, even if approved for commercial sale by the FDA, the European Commission or other comparable regulatory authorities, may not achieve or maintain market acceptance among physicians, patients, hospitals, including pharmacy directors, and third-party payors and, ultimately, may not become or remain commercially successful.

The degree of market acceptance of KIMMTRAK or any of our product candidates, if approved for commercial sale, will depend on a number of factors, including:

• the clinical indications for which our medicines are approved;

• physicians, hospitals, cancer treatment centers, and patients considering our medicines as a safe and effective treatment;

• hospitals and cancer treatment centers establishing the infrastructure required for the administration of the medicine;

• the potential and perceived advantages of our medicines over alternative treatments;

• the prevalence and severity of any side effects, including cytokine release syndrome ("CRS"), for which KIMMTRAK has a boxed warning recommending at least 16 hours of patient monitoring after each of the first three infusions, and as clinically indicated thereafter;

1 unchanged sentence

• limitations or warnings contained in the labeling approved by the FDA or the European Commission;

• the timing of market introduction of our product candidates compared to competitive products;

• the timing of market introduction of our medicines compared to competitive products;

• the cost of treatment in relation to alternative treatments;

• the amount of upfront costs or training required for physicians to administer our product candidates;

• the amount of upfront costs or training required for physicians to administer our medicines;

• the pricing of our products and the availability of coverage and adequate reimbursement by third-party payors and government authorities;

5 unchanged sentences

Even if our products achieve market acceptance, we may not be able to maintain that market acceptance over time, including if new products or technologies are introduced that are more favorably received than our products, are more cost effective or render our products obsolete.

Because we expect sales of KIMMTRAK and our other product candidates, if approved, to generate substantially all of our revenue for the foreseeable future, the failure of our product candidates to find or maintain market acceptance would harm our business and could require us to seek additional financing.

We may be unable to successfully complete additional large-scale, pivotal clinical trials for any product candidates we develop after KIMMTRAK in mUM.

Because we expect sales of KIMMTRAK and our other product candidates, if approved, to generate substantially all of our revenue for the foreseeable future, the failure of our medicines to find or maintain market acceptance would harm our business and could require us to seek additional financing.

We may be unable to successfully complete additional large-scale, pivotal clinical trials for any product candidates we develop.

We cannot be sure that issues will not arise that require us to suspend or terminate our clinical trials.

34 unchanged sentences

Clinical product development involves a lengthy and expensive process, with an uncertain outcome.

While we plan to pursue additional regulatory approvals, it is uncertain whether tebentafusp will receive further marketing approval beyond the approval which KIMMTRAK has received in the United States, the EU, Canada and certain other territories.

Furthermore, it is impossible to predict when or if tebentafusp for the treatment of advanced melanoma or adjuvant uveal (ocular) melanoma, brenetafusp , IMC-I109V, IMC-M113V, IMC-P115C, IMC-T119C, IMC-R117C, IMC-S118AI, or IMC-U120AI, or any of our future product candidates, will prove effective and safe in humans or will receive regulatory approval.

While we plan to pursue additional regulatory approvals, it is uncertain whether we will receive further marketing approval for tebentafusp beyond the approval we have received for KIMMTRAK for mUM in the United States, the EU, Canada and certain other territories.

For example, it is impossible to predict when or if tebentafusp for the treatment of advanced melanoma or adjuvant uveal (ocular) melanoma, brenetafusp , IMC-I109V, IMC-M113V, IMC-P115C, IMC-R117C, IMC-S118AI, or IMC-U120AI, or any of our future product candidates, will prove effective and safe in humans or will receive regulatory approval.

Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, we must complete pre-clinical studies and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans.

4 unchanged sentences

Our pre-clinical studies and future clinical trials may not be successful.

From time to time, we may publish interim top-line or preliminary data from our clinical trials.

Interim data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available.

Preliminary or top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published.

As a result, interim and preliminary data should be viewed with caution until the final data are available.

Adverse differences between preliminary or interim data and final data could significantly harm our business prospects.

We also rely, and expect to continue to rely in part, on outside vendors (for example, independent contractors and CROs) to conduct, supervise or monitor some or all aspects of clinical trials involving our products.

6 unchanged sentences

Before we can commercialize further product candidates, we must obtain marketing approval.

Currently, the majority of our product candidates are in development, and we have not received approval to market any of our product candidates from regulatory authorities, with the exception of KIMMTRAK.

It is possible that our product candidates, including any product candidates we may seek to develop in the future, will never obtain regulatory approval.

We have only limited experience in filing and supporting the applications necessary to gain regulatory approvals and expect to rely on third-party CROs and/or regulatory consultants to assist us in this process.

Securing regulatory approval requires the submission of extensive pre-clinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy.

Securing regulatory approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority.

Obtaining regulatory approval requires the submission of extensive pre-clinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy.

Obtaining regulatory approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority.

Our product candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use.

162 unchanged sentences

Our decisions concerning the allocation of research, collaboration, management and financial resources toward particular proprietary molecules in our library, product candidates or therapeutic areas are subject to change over time, and these decisions may not lead to the development of viable commercial products and may divert resources away from better opportunities.

For example, in 2025 we decided to pause our IMC-T119C (PRAME-A24) program.

Similarly, our decisions to delay, terminate or collaborate with third parties in respect of certain product development programs may also prove not to be optimal and could cause us to miss valuable opportunities.

If we make incorrect determinations regarding the market potential of our product candidates, abandon products that we have devoted significant resources toward in favor of other product candidates, or misread trends in the biopharmaceutical industry, in particular for our lead product candidate, our business, financial condition and results of operations could be materially adversely affected.

If we make incorrect determinations regarding the market potential of our product candidates, abandon or pause products that we have devoted significant resources toward in favor of other product candidates, or misread trends in the biopharmaceutical industry, in particular for our lead product candidate, our business, financial condition and results of operations could be materially adversely affected.

We conduct clinical trials for our product candidates outside the United States, and the FDA and similar foreign regulatory authorities may not accept data from such trials.

43 unchanged sentences

If the defective product candidates cannot be replaced in a timely fashion, we may incur significant delays in our development programs that could adversely affect the value of such product candidates.

For example, in June 2025, we initiated a global recall for one batch of KIMMTRAK (tebentafusp) relating to an unexpected result in routine stability testing.

As of the date of this Annual Report, based on all available data to date, we do not expect there will be a material impact on the supply of KIMMTRAK or our financial statements.

A failure to comply with these requirements may result in regulatory enforcement actions against our manufacturers or us, including fines and civil and criminal penalties, which could result in imprisonment, suspension or restrictions of production, suspension, injunctions, delay or denial of product approval or supplements to approved products, clinical holds or termination of clinical trials, warning or untitled letters, regulatory authority communications warning the public about safety issues with the biologic, refusal to permit the import or export of the products, product seizure, detention, or recall, operating restrictions, suits under the civil False Claims Act ("FCA"), corporate integrity agreements, consent decrees, or withdrawal, suspension or variation of product approval.

34 unchanged sentences

We face competition from segments of the pharmaceutical, biotechnology and other related markets that pursue the development of TCR-based therapeutics to address unmet needs in cancer including:

Adaptimmune Therapeutics plc, Immatics, Adaptive, pure MHC, LLC, BioNTech SE, Genentech, Matterhorn Biosciences AG, Enara Bio Limited, Boehringer Ingelheim International GmbH, and Regeneron, who are also seeking to identify peptide HLA targets and develop product candidates; Immatics, Anocca AB, T-Knife GmbH, Adaptive, 3T Biosciences, Inc., MediGene AG, Regeneron, Takara Bio Inc., BMS, GSK plc, Kite Pharma , Inc., Lion TCR Pte.

Adaptimmune Therapeutics plc, Immatics, Adaptive, pure MHC, LLC, BioNTech SE, Genentech, Enara Bio Limited, and Boehringer Ingelheim International GmbH, who are also seeking to identify peptide HLA targets and develop product candidates; Immatics, Anocca AB, T-Knife GmbH, Adaptive, 3T Biosciences, Inc, Regeneron, Takara Bio Inc., AstraZeneca PLC, Lion TCR Pte.

Ltd., TCRCure Biopharma Ltd., Corregene Biotechnology Co.

LTD, and TScan who are developing TCR-based cell therapies; and F.

Hoffmann-La Roche Ltd, Amgen, Inc., Genmab, Inc., Molecular Partners AG, 3T Biosciences, Inc., Crossbow Therapeutics, Inc.

LTD, and TScan who are developing TCR-based cell therapies; and Immatics, Molecular Partners AG, 3T Biosciences, Inc., Crossbow Therapeutics, Inc.

and CDR-Life Inc.

4 unchanged sentences

This system is marketed in the European Union as a CE Marked medical device under the trade name Delcath Hepatic CHEMOSAT® Delivery System for Melphalan (CHEMOSAT).

We are aware of several other companies with product candidates in clinical development, including an anticipated readout from Ideaya Biosciences’ first-line non-HLA-A2 mUM registrational Phase 2/3 clinical trial in 2025.

We are also aware of various companies initiating registrational Phase 3 clinical trials in uveal melanoma ("UM"), including Ideaya Biosciences, Inc.’s initiation of a registrational Phase 3 clinical trial in high-risk neoadjuvant UM, and Replimune Group, Inc.’s initiation of a registration Phase 3 clinical trial in immune-checkpoint naïve UM, both anticipated in 2025.

We are aware of several other companies with product candidates in clinical development, including an anticipated readout from Ideaya Biosciences’ first-line HLA-A*02:01 negative mUM registrational Phase 2/3 clinical trial in 2026.

We are also aware of various companies conducting registrational Phase 3 clinical trials in uveal melanoma ("UM"), including Ideaya Biosciences, Inc.’s registrational Phase 3 clinical trial in high-risk neoadjuvant UM, and Replimune Group, Inc.

registrational Phase 2/3 clinical trial in immune-checkpoint naïve UM.

We are aware of various companies and academic institutions that are developing TCR transduced cell therapies against a range of pHLA targets, some of which may overlap with product candidates in our pipeline such as PRAME.

3 unchanged sentences

There can be no assurance that our competitors are not currently developing, or will not in the future develop, products that are equally or more effective or are more economically attractive than any of our current or future product candidates.

Competing products may gain faster or greater market acceptance than our products, if any, and medical advances or rapid technological development by competitors may result in our product candidates becoming non-competitive or obsolete before we are able to recover our research and development and commercialization expenses.

Competing products may gain faster or greater market acceptance than our products, if any, and medical advances or rapid technological development by competitors, including increased use of artificial intelligence-based technologies, may result in our product candidates becoming non-competitive or obsolete before we are able to recover our research and development and commercialization expenses.

If we or our product candidates do not compete effectively, it may have a material adverse effect on our business, financial condition and results of operations.

15 unchanged sentences

Therefore, coverage and adequate reimbursement is critical to new medical product acceptance.

In addition, recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S.

Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under government payor programs, and review the relationship between pricing and manufacturer patient programs.

For example, the Inflation Reduction Act (IRA) among other things, (1) requires the U.S.

Department of Health and Human Services (HHS) to negotiate the price of certain single-source biologics that have been on the market for at least 11 years covered under Medicare as part of the Medicare Drug Price Negotiation Program, and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation on an annual basis.

Each year up to twenty (20) products will be selected by HHS for the Medicare Drug Price Negotiation Program.

Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

Outside the United States, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.

9 unchanged sentences

The extent to which pricing and reimbursement decisions are influenced by the HTA of the specific medicinal product currently varies between Member States.

In December 2021, Regulation No 2021/2282 on HTA amending Directive 2011/24/EU, was adopted in the European Union.

This Regulation, which entered into force in January 2022 and applies as of January 12, 2025, is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at the level of the European Union for joint clinical assessments in these areas.

The Regulation permits Member States to use common HTA tools, methodologies, and procedures across the European Union, working together in four main areas, including joint clinical assessment of the innovative health technologies with the most potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas.

Individual Member States continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technologies, and making decisions on pricing and reimbursement.

On January 12, 2025, the HTA Regulation entered into application through a phased implementation.

It is intended to increase cooperation among EU Member States in assessing health technologies, including new medicinal products, by establishing a framework for joint clinical assessments, joint scientific consultations, and the early identification of emerging health technologies.

The Regulation permits Member States to use common tools, methodologies, and procedures and requires them to rely on EU‑level joint clinical assessment reports for the clinical components of their national HTA evaluations.

Member States, however, remain responsible for assessing non‑clinical aspects, such as economic, ethical, and social considerations, and for making pricing and reimbursement decisions at the national level.

As implementation of the HTA Regulation is phased in and key methodological and procedural guidance continues to evolve, there remains uncertainty regarding the evidence requirements, timing, and impact of joint clinical assessments on national reimbursement processes.

The new framework may result in additional or differently structured evidentiary expectations, misalignment between assessment and regulatory timelines, or delays in national decisions.

If we are unable to maintain favorable pricing and reimbursement status in Member States for product candidates that we may successfully develop and for which we may obtain regulatory approval, any anticipated revenue from and growth prospects for those products in the EU could be negatively affected.

In light of the fact that the United Kingdom has left the European Union, Regulation No 2021/2282 on HTA does not apply in the United Kingdom.

However, the MHRA is working with UK HTA bodies and other national organizations, such as the SMC, the NICE, and the All-Wales Medicines Strategy Group, to introduce new pathways supporting innovative approaches to the safe, timely and efficient development of medicinal products.

Legislators, policymakers and healthcare insurance funds in the European Union and the United Kingdom may continue to propose and implement cost-containing measures to keep healthcare costs down, particularly due to the financial strain that the COVID-19 pandemic has placed on national healthcare systems of European countries.

3 unchanged sentences

For example, we must enter into pricing agreements with individual Member States in order to be reimbursed for KIMMTRAK in such Member States.

For Germany, we had entered into a pricing agreement, which is subject to certain conditions, for KIMMTRAK that was published in September 2023.

Because the sales of KIMMTRAK exceeded the orphan drug threshold (€30 million) in Germany in 2023, German law requires a new benefit assessment and renegotiation of the price.

For Germany, we had entered into a pricing agreement with the German government for KIMMTRAK.

As the sales of KIMMTRAK exceeded the orphan drug threshold (€30 million) in Germany in 2023, German law required a new benefit assessment and renegotiation of the price.

The outcome of the benefit assessment remained unchanged;

the Federal Joint Committee (G-BA) granted KIMMTRAK a Considerable Added Benefit (published May 16, 2024).

Price negotiations are ongoing and we cannot guarantee that the price of KIMMTRAK will not change in Germany.

Simultaneously with the renegotiation of pricing agreements in Germany, we are negotiating pricing agreements with other Member States, including France.

the Federal Joint Committee (G-BA) granted KIMMTRAK a Considerable Added Benefit, and we negotiated and entered into a new pricing agreement with Germany in 2025.

In 2025, we also entered into a pricing agreement with France regarding retrospective and future pricing of KIMMTRAK, however we are disputing one element of the agreement related to certain prior periods.

We are also negotiating pricing agreements with other Member States, and we cannot guarantee that the price of KIMMTRAK will not change in certain countries in the future.

Limitations on our ability to price KIMMTRAK, or our future product candidates, if approved, may have a significant impact on our results of operations.

43 unchanged sentences

In addition, we have entered and may enter in the future into collaboration agreements whereby we investigate the therapeutic benefit of our own products or product candidates in combination with a product or product candidate of a third party.

For example, in February 2024, we entered into a clinical trial collaboration and supply agreement with Bristol-Myers Squibb ("BMS"), pursuant to which we will sponsor and fund the PRISM-MEL-301 clinical trial of our candidate brenetafusp + BMS’s nivolumab versus a control arm of either nivolumab or nivolumab + BMS’s relatlimab, depending on the country where the patient is enrolled, in first line advanced cutaneous melanoma, and BMS will provide nivolumab.

For example, in February 2024, we entered into a clinical trial collaboration and supply agreement with BMS, pursuant to which we will sponsor and fund the PRISM-MEL-301 clinical trial of our candidate brenetafusp + BMS’s nivolumab versus a control arm of either nivolumab or nivolumab + BMS’s relatlimab, depending on the country where the patient is enrolled, in first line advanced cutaneous melanoma, and BMS will provide nivolumab.

Any future collaborations we enter into, may pose a number of risks, including the following:

33 unchanged sentences

Subject to certain specified exceptions, each of our existing therapeutic collaborations contains an exclusivity restriction on our engaging in activities that are the subject of the collaboration with third parties for specified periods of time.

We rely on CROs and other third parties to conduct our Phase 1, Phase 2 and Phase 3 pivotal clinical trials and expect to rely on CROs and other third parties to conduct future clinical trials, as well as investigator-sponsored clinical trials of our product candidates.

We rely on CROs and other third parties to conduct our clinical trials and expect to rely on CROs and other third parties to conduct future clinical trials, as well as investigator-sponsored clinical trials of our product candidates.

If these CROs and other third parties do not successfully carry out their contractual duties, comply with regulatory requirements or meet expected deadlines, we may not be able to obtain regulatory approval for or commercialize our product candidates and our business could be substantially harmed.

We rely and expect to continue to rely on CROs, medical institutions, clinical investigators, contract laboratories and other third parties to conduct or otherwise support clinical trials for our product candidates, including our TEBE-AM Phase 3 advanced melanoma tebentafusp trial, our EORTC-sponsored ATOM Phase 3 trial of KIMMTRAK in adjuvant uveal (ocular) melanoma, our PRISM-MEL-301 Phase 3 clinical trial of brenetafusp in first line advanced cutaneous melanoma, our Phase 1/2 clinical trial of brenetafusp in multiple solid tumors, our Phase 1 clinical trial of IMC-M113V in people who live with HIV, and our Phase 1 clinical trial of IMC-I109V in people who live with HBV.

We rely and expect to continue to rely on CROs, medical institutions, clinical investigators, contract laboratories and other third parties to conduct or otherwise support clinical trials for our product candidates, including our TEBE-AM Phase 3 advanced melanoma tebentafusp trial, our EORTC-sponsored ATOM Phase 3 trial of KIMMTRAK in adjuvant uveal (ocular) melanoma, our PRISM-MEL-301 Phase 3 clinical trial of brenetafusp in first line advanced cutaneous melanoma, our Phase 1/2 clinical trial of brenetafusp in multiple solid tumors, our Phase 1/2 clinical trial of IMC-M113V in people who live with HIV, and our Phase 1 trial with IMC-R117C in colorectal cancer.

We may also rely on academic and private non-academic institutions to conduct and sponsor clinical trials relating to our product candidates.

97 unchanged sentences

Collaborations with pharmaceutical or biotechnology companies and other third parties often are terminated or allowed to expire by the other party.

For example, our collaborations with GlaxoSmithKline Intellectual Property Development Ltd and with Eli Lilly were terminated in 2022, and in February 2023, we elected to withdraw from co-funding the MAGE-A4 HLA-A02 program, IMC-C103C with Genentech.

Any such termination or expiration would adversely affect us financially and could harm our business reputation.

16 unchanged sentences

Compliance with applicable environmental laws and regulations is expensive, and current or future environmental regulations may impair our research, development and production efforts, which could impact our business, prospects, financial condition or results of operations.

Risks Related to Our International Operations

As a company based outside of the United States, we are subject to economic, political, regulatory and other risks associated with international operations.

As a company based in the United Kingdom, our business is subject to risks associated with conducting business outside of the United States.

Many of our suppliers and clinical trial relationships are located outside the United States.

Accordingly, our future results could be harmed by a variety of factors, including:

• economic weakness, including inflation, or political instability in particular non-U.S.

economies and markets;

• differing and changing regulatory requirements for product approvals;

• differing jurisdictions could present different issues for securing, maintaining or obtaining freedom to operate in such jurisdictions;

• potentially reduced protection for intellectual property and proprietary rights;

• difficulties in compliance with different, complex and changing laws, regulations and court systems of multiple jurisdictions and compliance with a wide variety of foreign laws, treaties and regulations;

• changes in global regulations and customs, tariffs and trade barriers;

• changes in exchange rates of the pound sterling, U.S.

dollar and euro;

• changes in a specific country’s or region’s political or economic environment;

• trade protection measures, import or export licensing requirements or other restrictive actions by governments;

• differing reimbursement regimes and price controls in certain non-U.S.

• negative consequences from changes in tax laws;

• compliance with tax, employment, immigration and labor laws for employees living or traveling abroad, including, for example, the variable tax treatment in different jurisdictions of options or restricted share units granted under our share option schemes or equity incentive plans;

• workforce uncertainty in countries where labor unrest is more common than in the United States;

• litigation or administrative actions resulting from claims against us by current or former employees or consultants individually or as part of class actions, including claims of wrongful terminations, discrimination, misclassification or other violations of labor law or other alleged conduct;

• difficulties associated with staffing and managing international operations, including differing labor relations;

• production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and

• business interruptions resulting from geo-political actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires.

For example, in July 2025, the United States and the European Union announced a bilateral framework on tariffs and trade, which was further detailed in a joint statement on August 21, 2025.

Under this framework, the United States committed to an all inclusive ceiling of 15% on most tariffs applied to goods originating from the European Union, including pharmaceuticals.

These proposed tariffs under the framework are subject to ongoing negotiations, European Parliament and Member State approval, as well as further review and implementation by the U.S.

On February 20, 2026, the Supreme Court of the United States invalidated certain tariffs imposed by the U.S.

government under emergency statutory authority.

In response to this ruling, President Trump signed an executive order implementing a new 10% global tariff pursuant to an alternative statutory authority, which may be raised up to 15%.

As of the date of this Annual Report, it is unclear when and which level of alternative tariffs will be imposed, whether such tariffs would apply to our supply of drug, which is manufactured in the European Union and whether such alternative tariffs, if challenged in court, would be upheld.

We are monitoring the developments and assessing the impact tariffs would have on our cost of importing clinical and commercial product into the United States, which is expected to increase the cost of revenue from sale of therapies and reduce our margins on the sale of our products.

Unlike many industries, our ability to pass increased costs to customers is limited by the structure of pharmaceutical pricing and reimbursement systems.

The complexity of announced or future tariffs may also increase the risk that we or our customers or suppliers may be subject to civil or criminal enforcement actions in the United States or non-U.S.

jurisdictions related to compliance with trade regulations.

In addition, the United States and other governments have imposed and may continue to impose additional sanctions, such as trade restrictions or trade barriers, which could restrict us from doing business directly or indirectly in or with certain countries or parties and may impose additional costs and complexity to our business.

Trade disputes, tariffs, restrictions and other political tensions between the United States and other countries may also exacerbate unfavorable macroeconomic conditions including inflationary pressures, foreign exchange volatility, financial market instability, and economic recessions or downturns.

The ultimate impact of current or future tariffs and trade restrictions remains uncertain and could materially and adversely affect our business, financial condition, and prospects.

Additionally, due to the Russia-Ukraine conflict, the United States, United Kingdom, EU, and other nations announced various sanctions against Russia and Belarus.

The military conflict and the retaliatory measures that have been taken, or could be taken in the future, by the United States, United Kingdom, EU, and other countries, as well as the conflict in the Middle East, have created global security concerns and global geopolitical tension that could result in a lasting impact on regional and global economies, any or all of which could disrupt our supply chain, adversely affect our ability to conduct ongoing and future clinical trials of our product candidates, and adversely affect our ability to commercialize our products (subject to regulatory approval) in these regions and have wider implications globally that could impact our business outside of these regions.

Ongoing military conflict will likely impact our ability to conduct clinical trials in Ukraine, Russia and potentially in other Eastern European countries, and may prevent us from continuing follow-up for patients previously enrolled or enrolling patients in future trials at sites in these countries, and may also prevent us from commercializing our products (subject to regulatory approval) in this region.

In addition, there could be an impact on our international operations because of the conflict in the Middle East, because our distributor outside the US and Western Europe has significant exposure in the region.

This could negatively impact the anticipated timing and completion of future clinical trials and/or analyses of future clinical results, and negatively impact our plans to commercialize our product (subject to regulatory approval) in this region, which could harm our business.

Exchange rate fluctuations may materially affect our results of operations and financial condition.

Owing to the international scope of our operations, fluctuations in exchange rates, particularly between the pound sterling and the U.S.

dollar, may adversely affect us.

Although the majority of our employees, offices and research facilities are based in the United Kingdom, we source some of our research and development, manufacturing, consulting and other services from the United States and the EU.

Further, significant current and future revenue is and may continue to be derived from abroad, including the United States, EU and further territories.

As a result, our business and the price of our ADSs may be affected by fluctuations in foreign exchange rates not only between the pound sterling and the U.S.

dollar, but also the euro, and other currencies, which may impact our results of operations and cash flows from period to period.

Risks Related to Intellectual Property

If we are unable to adequately protect our proprietary technology or obtain, maintain, protect and enforce patent and other intellectual property protection for our technology and products or if the scope of the protection obtained is not sufficiently broad, our competitors and other third parties could develop and commercialize technology and products similar or identical to ours, and our ability to successfully commercialize our technology and products may be impaired.

Our commercial success will depend in part on our ability to obtain and maintain proprietary or intellectual property protection in the United States and other countries for our product candidates and our core technologies, including our novel target discovery technology, our proprietary compound library and other know-how.

We seek to protect our proprietary and intellectual property position by, among other methods, filing patent applications in the United States and abroad related to our proprietary technology, inventions and improvements that are important to the development and implementation of our business.

22 unchanged sentences

Patent prosecution is a lengthy process, during which the scope of the claims initially submitted for examination by the U.S.

Patent and Trademark Office ("USPTO"), or its global equivalents, are often narrowed by the time they issue, if they issue at all.

Accordingly, it is possible that that our present or future pending patent applications (whether owned or licensed) will not lead to issued patents.

Patent and Trademark Office ("USPTO"), or its global equivalents, are often significantly narrowed by the time they issue, if they issue at all.

Accordingly, it is possible that our present or future pending patent applications (whether owned or licensed) will not lead to issued patents.

It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection or that we may not develop additional proprietary technologies that are patentable.

1 unchanged sentence

Therefore, these patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business.

Even if we acquire patent protection that we expect should enable us to maintain a competitive advantage, third parties may challenge the validity, enforceability or scope thereof, which may result in such patents being narrowed, invalidated or held unenforceable.

The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our patents or any patent we may license may be challenged in the courts or patent offices in the United States and abroad.

For example, we may be subject to a third-party submission of prior art to the USPTO challenging the priority of an invention claimed within one of our patents, which submissions may also be made prior to a patent’s issuance, precluding the granting of any of our pending patent applications.

We may become involved in opposition, derivation, re-examination, revocation, inter partes review, post-grant review, interference or other proceedings challenging our patent rights or the patent rights of others from whom we have obtained licenses to such rights.

Competitors or other third parties may claim that they invented the inventions claimed in our issued patents or patent applications prior to us, or may file patent applications before we do.

Third parties may also claim that we are infringing, misappropriating or otherwise violating their patents or other intellectual property rights and that we therefore cannot practice our technology as claimed under our patents, if issued.

Competitors and other third parties may also contest our patents, if issued, by showing the patent examiner that the invention was not original, was not novel or was obvious.

In litigation, a competitor or other third party could claim that our patents, if issued, are not valid for a number of reasons.

If a patent office or court agrees, we would lose our rights to those challenged patents, in whole or in part.

In addition, we may in the future be subject to claims by our former employees or consultants asserting an ownership right in our patents or patent applications, as a result of the work they performed on our behalf.

Although we generally require all of our employees, consultants and advisors and any other third parties who have access to our proprietary know-how, information or technology to assign or grant similar rights to their inventions to us, we cannot be certain that we have executed such agreements with all parties who may have contributed to our intellectual property, nor can we be certain that our agreements with such parties will be upheld in the face of a potential challenge, or that they will not be breached, for which we may not have an adequate remedy.

An adverse determination in any such submission or proceeding may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and products, without payment to us, or could limit the duration of the patent protection covering our technology and product candidates.

Such challenges may also result in our inability to manufacture or commercialize our product candidates without infringing third-party patent rights.

In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates.

Such proceedings also may result in substantial cost and require significant time and attention from our scientists and management.

In addition, given the amount of time required for the development, testing, and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.

4 unchanged sentences

In addition, we may need the cooperation of any such co-owners of our patents in order to enforce such patents against third parties, and such cooperation may not be provided to us.

Our patent portfolio may not provide us with any meaningful protection or prevent competitors from designing around our patent claims to circumvent our patents or any patents we may license now or in the future by developing similar or alternative technologies or products in a non-infringing manner.

Even if unchallenged, our patent portfolio may not provide us with any meaningful protection or prevent competitors from designing around our patent claims to circumvent our patents or any patents we may license by developing similar or alternative technologies or products in a non-infringing manner.

For example, a third party may develop a competitive product that provides benefits similar to one or more of our product candidates but that falls outside the scope of our patent protection.

9 unchanged sentences

In addition to the protection afforded by patents, we rely upon unpatented trade secret protection, unpatented know-how, proprietary information and continuing technological innovation to develop and maintain our competitive position.

With respect to the building of our ImmTAX platform, we consider trade secrets and know-how to be one of our primary intellectual property assets.

With respect to the building of our ImmTAX platform, we consider trade secrets and know-how to be our primary intellectual property.

We seek to protect our proprietary technology and processes, in part, by entering into confidentiality agreements with our collaborators, scientific advisors, employees, CROs and consultants, and invention assignment agreements with our consultants and employees.

9 unchanged sentences

If any of our trade secrets were to be lawfully obtained or independently developed by a competitor or other third party, we would have no right to prevent them, or those to whom they communicate such information, from using that technology or information to compete with us.

For example, a third party may subsequently file a patent application covering our trade secrets or unpatented know-how.

If our trade secrets are not adequately protected so as to protect our market against competitors’ products, our competitive position could be adversely affected, as could our business.

12 unchanged sentences

If a patent holder believes our product or product candidate infringes on its patent, the patent holder may sue us even if we have received patent protection for our technology.

Moreover, we may face patent infringement claims from non-practicing entities that have no relevant revenue and against whom our own patent portfolio may thus have no deterrent effect.

Moreover, we may face patent infringement claims from non-practicing entities that have no relevant product revenue and against whom our own patent portfolio may thus have no deterrent effect.

Even if we believe that such claims are without merit, there is no assurance that a court or patent office would find in our favor on questions of infringement, validity, enforceability, or priority.

19 unchanged sentences

If our defenses to these claims fail, in addition to requiring us to pay monetary damages, a court could prohibit us from using technologies or features that are essential to our product candidates, if such technologies or features are found to incorporate or be derived from the trade secrets or other proprietary information of the former employers.

An inability to incorporate such technologies or features may have a material adverse effect on our business, and may prevent us from successfully commercializing our product candidates.

We may seek licenses to use trade secrets or other proprietary information, but such licenses may not be available on commercially reasonable terms or at all.

If we are unable to incorporate necessary technologies or unable to design around third party technologies or features that we cannot obtain a license to, it may prevent us from successfully commercializing our product candidates, which may have a material adverse effect on our business.

In addition, we may lose valuable intellectual property rights or personnel as a result of such claims.

7 unchanged sentences

We may become involved in opposition, derivation, re-examination, revocation, inter partes review, post-grant review, interference or other administrative proceedings challenging our patent rights or the patent rights of others from whom we have obtained licenses to such rights.

Additionally, our European patents may be involved in opposition proceedings at the European Patent Office, challenging the validity of those patents.

For example, our European patents may be involved in opposition proceedings at the European Patent Office, challenging the validity of those patents.

Opposition proceedings may involve issues including, but not limited to, priority, patentability of the claims involved, and certain procedural formalities.

10 unchanged sentences

In patent litigation in the United States, defendant counterclaims challenging the validity, enforceability or scope of asserted patents are commonplace.

In addition, third parties may initiate legal proceedings against us to assert such challenges to our intellectual property rights.

The outcome of any such proceeding is generally unpredictable.

Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, non-enablement, written description, or lack of patentable subject matter.

2 unchanged sentences

Moreover, it is also possible that prior art may exist that we are aware of but do not believe is relevant to our future patents, should they issue, but that could nevertheless be determined to render our patents invalid.

Third parties may also raise similar validity claims before the USPTO in post-grant proceedings such as ex parte reexaminations, inter partes review or post-grant review, or oppositions or similar proceedings outside the United States, in parallel with litigation or even outside the context of litigation.

An adverse determination in any of the foregoing proceedings could result in the revocation or cancellation of, or amendment to, our patents in such a way that they no longer cover our product candidates or technology.

The outcome following legal assertions of invalidity and unenforceability is unpredictable.

With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which the patent examiner and we or our licensing partners were unaware during prosecution.

If a defendant or third party were to prevail on a legal assertion of invalidity or unenforceability, we could lose at least part, and perhaps all, of the patent protection on one or more of our product candidates or technologies.

Such a loss of patent protection could have a material adverse effect on our business, financial conditions, results of operations, and prospects.

An adverse result in any litigation proceeding could put one or more of our patents at risk of being invalidated or interpreted narrowly.

If a defendant were to prevail on a legal assertion of invalidity or unenforceability of our patents covering one of our product candidates, we could lose at least part, and perhaps all, of the patent protection covering such product candidate.

Competing products may also be sold in other countries in which our patent coverage might not exist or be as strong.

Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations, and prospects.

Intellectual property litigation and proceedings could cause us to spend substantial resources and distract our personnel from their normal responsibilities.

20 unchanged sentences

Competitors may use our technologies and/or conduct research and development activities in jurisdictions where we have not obtained patent protection or in jurisdictions where research and development safe harbor laws exist to develop their own products.

Further, competitors may export otherwise infringing products to territories where we have patent protection, if our ability to enforce our patents to stop infringing activities is inadequate.

These products may compete with our product candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

40 unchanged sentences

Any of the foregoing could have a material adverse effect on our business, financial conditions, results of operations, and prospects.

Changes in U.S.

patent law or the patent law of other countries or jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.

Supreme Court has ruled on several patent cases in recent years with potential impact on the scope of patent protection and patent eligibility, depending on the types of claims being pursued, as well as on the ability of patent owners to defend and challenge patents.

This may result in greater uncertainty with respect to obtaining and ascribing value to patents.

Depending on actions by the U.S.

Congress, the federal courts and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce patents that we have licensed or that we might obtain in the future.

For example, recent decisions could impact how patent term adjustment, which often results in longer patent term, would be accorded for a particular patent.

Similarly, changes in patent law and regulations in other countries or jurisdictions or changes in the governmental bodies that enforce them or changes in how the relevant governmental authority enforces patent laws or regulations may affect our ability to obtain new patents or to enforce patents that we have licensed or that we may obtain in the future.

For example, the landscape of European patent laws has also changed in recent years.

In Europe, a new unitary patent system took effect June 1, 2023, which has the potential to significantly impact European patents, including those granted before the introduction of such a system.

Under the unitary patent system, European applications have the option, upon grant of a patent, of becoming a Unitary Patent which will be subject to the jurisdiction of the Unitary Patent Court (“UPC”).

As the UPC is a new court system, precedent has not yet been established, increasing the uncertainty of any litigation.

Patents granted before the implementation of the UPC have the option of opting out of the jurisdiction of the UPC and remaining as national patents obtained through the European Patent Office.

Patents under the jurisdiction of the UPC will be potentially vulnerable to a single UPC-based revocation challenge that, if successful, could invalidate the patent in all countries who are signatories to the UPC.

We cannot predict with certainty the long-term effects of any potential changes.

If our trademarks and trade names are not adequately protected, then this may impede our ability to build and sustain name recognition in our markets of interest and our business may be adversely affected.

4 unchanged sentences

In addition, there could be potential trade name or trademark oppositions or infringement claims brought by owners of other registered or unregistered trademarks or trade names that incorporate elements which are identical or similar to our trademarks or trade names.

For example, our U.S.

trademark application for ImmTAX was previously subject to an opposition filed by Immatics and we brought counterclaims against three of Immatics’s U.S.

registered trademarks for IMMATICS.

In addition, Immatics previously filed invalidation actions against U.K.

and EU trademark registration for IMMTAX.

While we were successful in defending this opposition and Immatics were required to reimburse our legal costs in 2023, if we are unsuccessful in defending trademark cases in the future that directly relate for example, to our commercial products, we could be required to change our branding or trademarks, which could cause us to incur substantial costs and impede our ability to build and sustain name recognition for such platform.

Over the long term, if we are unable to successfully register our trademarks and trade names and establish name recognition based on effective use of our trademarks and trade names, then we may not be able to compete effectively and our business may be adversely affected.

If we are unsuccessful in defending trademark cases in the future that directly relate for example, to our commercial products, we could be required to change our branding or trademarks, which could cause us to incur substantial costs and impede our ability to build and sustain name recognition for such platform(s).

Over the long term, if we are unable to successfully register our trademarks and trade names and establish name recognition based on effective use of our tr ademarks and trade names, then we may not be able to compete effectively and our business may be adversely affected.

Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources and could adversely impact our financial condition or results of operations.

48 unchanged sentences

For instance, the regulatory landscape related to clinical trials in the EU recently evolved.

The EU Clinical Trials Regulation ("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 Member State, leading to a single decision for each Member State.

The assessment procedure for the authorization of clinical trials has been harmonized as well, including a joint assessment by all Member States concerned, and a separate assessment by each Member State with respect to specific requirements related to its own territory, including ethics rules.

Each Member State’s decision is communicated to the sponsor via the centralized portal of the EU.

Once the clinical trial 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 when all ongoing trials being conducted 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 development plans.

The EU Clinical Trials Regulation ("CTR"), which was adopted in April 2014 and repeals the EU Clinical Trials Directive ("CTD"), became fully applicable on January 31, 2025.

The CTR introduces, among other changes, a centralized application system, coordinated review procedures, and expanded reporting and transparency obligations.

The new requirements, together with evolving guidance from EU authorities, may impose additional operational burdens on us and our CROs and could result in delays in trial initiation, increased compliance costs, or other disruptions to our development programs.

The United Kingdom’s regulatory framework in relation to clinical trials is derived from existing legislation of the EU (as implemented into the United Kingdom’s law of the United Kingdom, through secondary legislation).

On January 17, 2022, the MHRA, launched an eight-week consultation on reframing the United Kingdom’s legislation for clinical trials.

The United Kingdom’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 United Kingdom into closer alignment with the EU.

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 laws of the EU 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.

On April 11, 2025, the UK 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 UK regulatory framework for clinical trials into closer alignment with the CTR.

The changes include risk-proportionate regulation of clinical trials, with low-risk trials able to receive faster approval through automatic authorization, a streamlined approval process that integrates both regulatory and ethics committee approvals, leading to a single UK decision for clinical trials, and new legal obligations mandating the registration of clinical trials in public registries and the publication of trial results within 12 months of trial conclusion.

The amendment will become applicable on April 28, 2026 following a one-year transition period.

To support a smooth transition, the Medicines and Healthcare products Regulatory Agency (“MHRA”) and the Health Research Authority (“HRA”) are working together to provide updated guidance and information about key changes for industry.

In addition, on December 11, 2025, the European Commission, the Parliament and the European Council reached a political agreement on a comprehensive overhaul of EU pharmaceutical legislation (the “Pharma Package”).

The reform has been under negotiation since the European Commission submitted its proposal in April 2023.

This packag e - comprised of a new directive and regulation to replace existing legislation – aims to modernize the EU framework.

The Pharma Package is still subject to formal approval by the European Parliament and 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, capped at a maximum of eleven years.

The reform would also expand the Bolar exemption to permit generic and biosimilar manufacturers to conduct preparatory activities for regulatory submissions, including pricing and reimbursement, and participate in procurement tenders while patent protection remains in force.

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.

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.

59 unchanged sentences

If we become subject to new data privacy or security laws the risk of enforcement action against us could increase because we may become subject to additional obligations, and the number of individuals or entities that can initiate actions against us may increase (including individuals, via a private right of action, and state actors).

Additionally, regulations promulgated pursuant to the federal Health Insurance Portability and Accountability Act of 1996 ("HIPAA,") as amended, establish privacy and security standards that limit the use and disclosure of individually identifiable health information and protected health information, and require the implementation of administrative, physical and technological safeguards to protect the privacy of such information and ensure the confidentiality, integrity and availability of electronic protected health information.

We are also subject to laws governing the privacy of consumer health data, including reproductive, sexual orientation, and gender identity privacy rights.

For example, Washington’s My Health My Data Act (“MHMD”) broadly defines consumer health data, places restrictions on processing consumer health data (including imposing stringent requirements for consents), provides consumers certain rights with respect to their health data, and creates a private right of action to allow individuals to sue for violations of the law.

Other states have passed, are considering, and may adopt similar laws.

Additionally, regulations promulgated pursuant to HIPAA as amended, establish privacy and security standards that limit the use and disclosure of individually identifiable health information and protected health information, and require the implementation of administrative, physical and technological safeguards to protect the privacy of such information and ensure the confidentiality, integrity and availability of electronic protected health information.

Department of Justice issued a rule entitled the Preventing Access to U.S.

Sensitive Personal Data and Government-Related Data by Countries of Concern or Covered Persons, which places additional restriction on certain data transactions involving countries of concern (e.g., China, Russia, Iran) and covered persons (i.e., individuals and entities who are designated as such by the U.S.

Attorney General or considered “foreign persons” and are majority owned by, organized under the laws of, a primary resident in, or a contractor of, a covered person or country of concern, as applicable) that may impact certain business activities such as vendor engagements, sale or sharing of data, employment of certain individuals, and investor agreements.

Violations of the rule could lead to significant civil and criminal fines and penalties.

The rule applies regardless of whether data is anonymized, key-coded, pseudonymized, de-identified or encrypted, which presents particular challenges for companies like ours and may impact our ability to enter into certain transactions or agreements.

In Europe, the Network and Information Security Directive ("NIS2") entered into force on January 17, 2023, aiming to improve the resilience and incident response capabilities of entities operating in a number of sectors, including the health sector.

149 unchanged sentences

There have been executive, judicial and Congressional challenges to certain aspects of the ACA.

On August 16, 2022, President Biden signed the IRA, into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

On August 16, 2022, the IRA was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expiring ACA subsidies.

The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.

It is unclear what effect any such challenges or the healthcare reform measures of the Biden administration will have on the status of the ACA.

Litigation and legislation over the ACA are likely to continue, with unpredictable and uncertain results.

Other legislative changes have been proposed and adopted in the United States since the ACA was enacted.

In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress.

A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs.

This includes aggregate reductions of Medicare payments to providers up to 2% per fiscal year, and, due to subsequent legislative amendments, will remain in effect until 2032, unless additional Congressional action is taken.

There has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices.

Specifically, there have been several recent U.S.

Congressional inquiries and federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs.

The IRA, among other things:

(i) directs HHS to negotiate the price of certain single-source drugs and biologics that have been on the market for at least 7 years covered under Medicare (the “Medicare Drug Price Negotiation Program”) and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions took effect progressively starting in fiscal year 2023.

On August 15, 2024, HHS announced the agreed-upon prices of the first ten drugs that were subject to price negotiations, which take effect in January 2026.

HHS will select up to fifteen additional products covered under Part D for negotiation in 2025.

Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.

Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

For example, on January 5, 2024, the FDA approved Florida’s proposal to import certain drugs from Canada for specific state healthcare programs.

It is unclear if and how this program will be implemented and whether it will be subject challenges in the United States or Canada.

Other states have also submitted proposals that are pending review by the FDA.

Any such approved importation plans, if implemented, may result in lower drug prices for products covered by those programs.

We cannot be sure whether additional legislative changes will be enacted, or whether the FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on obtaining marketing approvals for our drug candidates, if any, may be.

In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs.

On July 4, 2025, the annual reconciliation bill (OBBBA) was signed into law which is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program.

OBBBA also narrows access to ACA marketplace exchange enrollment and declines to extend the ACA enhanced advanced premium tax credits, set to expire in 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance.

The current administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, CMS and related agencies.

These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.

For example, the current administration has announced several agreements with pharmaceutical companies that require the drug manufacturers to offer, through a direct to consumer platform, U.S.

patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues.

Other recent actions, for example, include (1) directives to reduce agency workforce and cut programs;

(2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products;

(3) imposing tariffs on imported pharmaceutical products;

and (4) as part of the Make America Healthy Again (MAHA) Commission’s recent Strategy Report, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising.

These actions and policies may significantly reduce U.S.

drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.

In June 2024, the U.S.

Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program created under the IRA.

Regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs.

These measures could reduce the ultimate demand for KIMMTRAK and our product candidates, if approved, or put pressure on our product pricing.

12 unchanged sentences

Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors, which may adversely affect our future profitability.

In December 2021, the HTA Regulation, was adopted in the EU.

The HTA Regulation is intended to boost cooperation among Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation across the EU for joint clinical assessments in these areas.

The HTA Regulation has applied from January 12, 2025 although it will enter into force iteratively and initially apply to new active substances to treat cancer and to all ATMPs, it will then be expanded to orphan medicinal products in January 2028, and to all centrally authorized medicinal products as of 2030.

Selected high-risk medical devices will also be assessed under the HTA Regulation as of 2026.

The HTA Regulation is intended to harmonize the clinical benefit assessment of HTA across the EU.

In light of the fact that the United Kingdom has left the EU, Regulation No 2021/2282 on HTA does not apply in the United Kingdom.

Our relationships with customers and third-party payors are subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to significant penalties, including criminal sanctions, civil penalties, exclusion from government healthcare programs, contractual damages, reputational harm and diminished profits and future earnings.

50 unchanged sentences

Oxfordshire, England where we are headquartered, Pennsylvania and Maryland.

We may also experience further competition as a result of Brexit.

Many of the other pharmaceutical companies that we compete against for qualified personnel have greater financial and other resources, different risk profiles and a longer history in the industry than we do.

20 unchanged sentences

Activities subject to these laws also involve the improper use of information obtained in the course of clinical trials or creating fraudulent data in our pre-clinical studies or clinical trials, which could result in regulatory sanctions and cause serious harm to our reputation.

We have adopted a Code of Business Conduct and Ethics applicable to all of our employees, but it is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations.

We have adopted a Code of Business Conduct and Ethics applicable to all of our employees, however, it is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations.

Additionally, we are subject to the risk that a person could allege such fraud or other misconduct, even if none occurred.

5 unchanged sentences

If a natural disaster, power outage or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical infrastructure, such as our research facilities or the manufacturing facilities of our third-party contract manufacturers, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible, for us to continue our business for a substantial period of time.

A disruption in our operations or those of our CROs or CMOs may also negatively impact our clinical trials, including delays or difficulties in enrolling and retaining patients in our clinical trials, and delays or difficulties in clinical site initiation, including difficulties in recruiting and retaining clinical site investigators and clinical site staff.

The disaster recovery and business continuity plans we have in place may prove inadequate in the event of a serious disaster or similar event.

6 unchanged sentences

For example, ongoing military conflict will likely impact our ability to conduct clinical trials in Ukraine, Russia and potentially in other Eastern European countries, and may prevent us from continuing follow-up for patients previously enrolled or enrolling patients in future trials at sites in these countries, and may also prevent us from commercializing our products (subject to regulatory approval) in this region.

In addition, there could be an impact on our international operations because of the conflict in the Middle East, because our distributor outside the United States and Western Europe has significant exposure in the region.

23 unchanged sentences

While we have implemented security measures designed to protect our information technology systems and data, there can be no assurance that these measures will be effective.

We have not always been able in the past to protect against security breaches (for example, we experienced two minor phishing attacks in 2018 and 2019).

We have not always been able in the past to protect against security breaches (for example, we were impacted by two minor phishing attacks in 2018 and 2019).

We take steps designed to detect, mitigate, and remediate vulnerabilities in our information systems (such as our hardware and/or software, including that of third parties upon which we rely).

43 unchanged sentences

As a result, it may be more difficult to attract and retain qualified individuals to serve on our board of directors or the board committees.

Risks Related to Our International Operations

As a company based outside of the United States, we are subject to economic, political, regulatory and other risks associated with international operations.

As a company based in the United Kingdom, our business is subject to risks associated with conducting business outside of the United States.

Many of our suppliers and clinical trial relationships are located outside the United States.

Accordingly, our future results could be harmed by a variety of factors, including:

• economic weakness, including inflation, or political instability in particular non-U.S.

economies and markets;

• differing and changing regulatory requirements for product approvals;

• differing jurisdictions could present different issues for securing, maintaining or obtaining freedom to operate in such jurisdictions;

• potentially reduced protection for intellectual property and proprietary rights;

• changes in global regulations and customs, tariffs and trade barriers;

• changes in non-U.S.

currency exchange rates of the pound sterling, U.S.

dollar, euro and currency controls;

• changes in a specific country’s or region’s political or economic environment, including the longer-term implications of Brexit;

• trade protection measures, import or export licensing requirements or other restrictive actions by governments;

• differing reimbursement regimes and price controls in certain non-U.S.

• negative consequences from changes in tax laws;

• workforce uncertainty in countries where labor unrest is more common than in the United States;

• difficulties associated with staffing and managing international operations, including differing labor relations;

• production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and

• business interruptions resulting from geo-political actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires.

For example, the U.S.

government has threatened to impose new tariffs on imported products from the European Union.

As we produce our clinical and commercial supply of drug in the European Union, the import of clinical and commercial supply of our products into the United States could be impacted to the extent any such tariffs are imposed and applicable to pharmaceutical products.

The impact of such tariffs would be subject to a number of factors, including the effective date and duration of such tariffs, changes in the amount, scope and nature of the tariffs in the future, any retaliatory responses to such actions that the target countries may take and any mitigating actions that may become available.

Tariffs on our products would increase our cost of importing clinical and commercial product into the United States, which would increase the cost of revenue from sale of therapies and reduce our margins on the sale of our products.

Additionally, due to the Russia-Ukraine conflict, the United States, United Kingdom, EU, and other nations announced various sanctions against Russia and Belarus.

Exchange rate fluctuations may materially affect our results of operations and financial condition.

Owing to the international scope of our operations, fluctuations in exchange rates, particularly between the pound sterling and the U.S.

dollar, may adversely affect us.

Further, significant current and future revenue is and may continue to be derived from abroad, including the United States, EU and further territories.

As a result, our business and the price of our ADSs may be affected by fluctuations in foreign exchange rates not only between the pound sterling and the U.S.

dollar, but also the euro, and other currencies, which may impact our results of operations and cash flows from period to period.

Risks Related to Our Indebtedness

55 unchanged sentences

• changes in the market valuations of similar companies;

• general economic, industry, political and market conditions, including, but not limited to, the war in Ukraine, the conflict in the Middle East, global geopolitical tension, changes in inflation and interest rates, supply chain disruptions, and volatility in the capital markets;

• general economic, industry, political and market conditions, including, but not limited to, those resulting from the war in Ukraine, the conflict in the Middle East, global geopolitical tension, changes in inflation and interest rates, supply chain disruptions, and volatility in the capital markets;

• sales of our ADSs or ordinary shares by us or our shareholders in the future;

24 unchanged sentences

In addition, some of these persons or entities may have interests different than yours.

For example, because many of these shareholders purchased their ordinary shares at prices substantially below our current trading price and have held their ordinary shares for a longer period, they may be more interested in selling our company to an acquirer than other investors or they may want us to pursue strategies that deviate from the interests of other shareholders.

We may be required to repurchase for cash all, or to facilitate the purchase by a third party of all, the shares of our company held by the Bill & Melinda Gates Foundation if we default under the global access commitments agreement, which could have an adverse impact on us and limit our ability to make distributions to our shareholders.

For example, because many of these shareholders purchased their ordinary shares (including ordinary shares in the form of ADSs) at prices substantially below our current trading price and have held their ordinary shares for a longer period, they may want us to pursue strategies that deviate from the interests of other shareholders.

We may be required to repurchase for cash, or to facilitate the purchase by a third party of, all the shares of our company held by the Bill & Melinda Gates Foundation if we default under the global access commitments agreement, which could have an adverse impact on us and limit our ability to make distributions to our shareholders.

We entered into a global access commitments agreement with our shareholder, the Bill & Melinda Gates Foundation (the "Gates Foundation"), in September 2017, which was amended and restated in March 2020 and February 2021, pursuant to which we are required to take certain actions to support the Gates Foundation’s mission.

10 unchanged sentences

Shares registered under these registration statements on Form S-8 will be available for sale in the public market subject to vesting arrangements and exercise of options, as well as, in the case of our affiliates, the restrictions of Rule 144 under the Securities Act.

We have registered approximately 1.2 million of our ordinary shares for resale by certain holders of our ordinary shares pursuant to registration rights agreements with such holders.

Additionally, as of December 31, 2024 , unless such holders have sold their shares without our knowledge, the holders of an aggregate of approximately 2.9 million of our ordinary shares, or their transferees, have rights, subject to conditions, to require us to file one or more registration statements covering their shares or to include their shares in registration statements that we may file for ourselves or other shareholders, as well as to cooperate in certain public offerings of such ordinary shares.

Upon registration, these shares are, or will be, as applicable, available to be freely sold in the public market subject, in the case of our affiliates, to the restrictions of Rule 144 under the Securities Act.

If these additional shares are sold, or if it is perceived that they will be sold, in the public market, the trading price of our ADSs could decline.

In addition, we may issue up to approximately 6 million ADSs representing ordinary shares upon conversion of our Notes based on the maximum conversion rate of the Notes, subject to customary anti-dilution adjustments.

94 unchanged sentences

Inadequate internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our ADSs.

If a United States person is treated as owning at least 10% of our ordinary shares or ADSs, such holder may be subject to adverse U.S.

federal income tax consequences.

holder is treated as owning, directly, indirectly or constructively, at least 10% of the value or voting power of our ordinary shares or ADSs, such U.S.

holder may be treated as a “United States shareholder” with respect to each “controlled foreign corporation” in our group, if any.

Because our group includes U.S.

subsidiaries, our current and future non-U.S.

subsidiaries will be treated as controlled foreign corporations, regardless of whether we are treated as a controlled foreign corporation.

A United States shareholder of a controlled foreign corporation may be required to report annually and include in its U.S.

taxable income its pro rata share of “Subpart F income,” “global intangible low-taxed income” and investments in U.S.

property by controlled foreign corporations, regardless of whether we make any distributions.

An individual that is a United States shareholder with respect to a controlled foreign corporation generally would not be allowed certain tax deductions or foreign tax credits that would be allowed to a United States shareholder that is a U.S.

Failure to comply with controlled foreign corporation reporting obligations may subject a United States shareholder to significant monetary penalties.

We cannot provide any assurances that we will furnish to any United States shareholder information that may be necessary to comply with the reporting and tax payment obligations applicable under the controlled foreign corporation rules of the Internal Revenue Code of 1986, as amended (the "Code").

holders should consult their tax advisors regarding the potential application of these rules to their investment in our ordinary shares or ADSs.

If we are a passive foreign investment company ("PFIC"), for any taxable year, there could be adverse U.S.

federal income tax consequences to U.S.

Under the Code, we will be a PFIC, for any taxable year in which (1) 75% or more of our gross income consists of passive income or (2) 50% or more of the value of our assets (generally determined in the basis of a weighted quarterly average) consists of assets that produce, or are held for the production of, passive income (including cash).

Under the Internal Revenue Code of 1986, as amended (the "Code"), we will be a PFIC, for any taxable year in which (1) 75% or more of our gross income consists of passive income or (2) 50% or more of the value of our assets (generally determined in the basis of a weighted quarterly average) consists of assets that produce, or are held for the production of, passive income (including cash).

For purposes of these tests, passive income includes dividends, interest, gains from the sale or exchange of investment property and certain rents and royalties.

12 unchanged sentences

The composition of our income and assets also is affected by how we spend the cash we raise in any offering.

We have only recently begun to generate revenues and therefore we may be a PFIC for any taxable year in which we do not generate sufficient amounts of active income to offset our passive financing income.

We may be a PFIC for any taxable year in which we do not generate sufficient amounts of active income to offset our passive financing income.

Therefore, we cannot give any assurance regarding our PFIC status for the current or any future taxable year.

8 unchanged sentences

corporation tax.

As of December 31, 2024 , we had cumulative carry forward tax losses of $277.4 million.

As of December 31, 2025 , we had cumulative carry forward tax losses of $525.5 million in the U.K.

and $73.6 million in the United States.

Subject to any relevant utilization criteria and restrictions (including the Corporate Income Loss Restriction that, broadly, restrict the amount of carried forward losses that can be utilized to 50% of group profits arising above £5.0 million per tax year), we expect these to be eligible for carry forward and utilization against future operating profits.

5 unchanged sentences

R&D tax credit regime may mean that we no longer qualify for it or have a material impact on the extent to which we can make claims (or benefit from them).

We may benefit in the future from the United Kingdom’s “patent box” regime, which allows certain profits attributable to revenues from patented products (and other qualifying income) to be taxed at an effective rate of 10% by giving an additional tax deduction.

We are able to benefit from the United Kingdom’s “patent box” regime, which allows certain profits attributable to revenues from patented products (and other qualifying income) to be taxed at an effective rate of 10% by giving an additional tax deduction.

We are the exclusive licensee or owner of several patent applications which, if issued, would cover our product candidates, and accordingly, future upfront fees, milestone fees, revenues and royalties could be eligible for this deduction.

When taken in combination with the enhanced relief available on our R&D expenditures, we expect a long-term rate of corporation tax lower than the statutory to apply to us.

When taken in combination with the enhanced relief available on our R&D expenditures, we maintain long-term rate of corporation tax lower than the statutory to apply to us.

If, however, there are unexpected adverse changes to the U.K.

69 unchanged sentences

English law provides that a board of directors may only allot shares (or rights to subscribe for or convert any security into shares) with the prior authorization of shareholders, such authorization stating the aggregate nominal amount of shares that it covers and being valid for a maximum period of five years, each as specified in the articles of association or relevant shareholder resolution.

At a general meeting of shareholders held on February 3, 2021, we obtained authority from our shareholders to allot new shares or to grant rights to subscribe for or to convert any security into shares in the company up to a maximum aggregate nominal amount of £150,000 for a period of five years from the date of such general meeting of shareholders, which authorization will need to be renewed upon expiration (i.e., at least every five years) but may be sought more frequently for additional five-year terms (or any shorter period).

At our 2025 Annual General Meeting held on May 15, 2025, we obtained authority from our shareholders to allot new shares or to grant rights to subscribe for or to convert any security into shares in the company up to a maximum aggregate nominal amount of £150,000 for a period ending on May 14, 2030, which authorization will need to be renewed upon expiration (i.e., at least every five years) but may be sought more frequently for additional five-year terms (or any shorter period).

English law also generally provides shareholders with preemptive rights when new shares are issued for cash.

2 unchanged sentences

In either case, this disapplication would need to be renewed by our shareholders upon its expiration (i.e., at least every five years).

At a general meeting of shareholders held on February 3, 2021, we obtained authority from our shareholders to disapply preemptive rights in respect of allotments made pursuant to the authorization described above for a period of five years from the date of such general meeting of shareholders which disapplication will need to be renewed upon expiration (i.e., at least every five years), but may be sought more frequently for additional five-year terms (or any shorter period).

At our 2025 Annual General Meeting held on May 15, 2025, we obtained authority from our shareholders to disapply preemptive rights in respect of allotments made pursuant to the authorization described above or pursuant to a sale of shares held as treasury shares up to a maximum aggregate nominal amount of £150,000 for a period ending on May 14, 2030, which disapplication will need to be renewed upon expiration (i.e., at least every five years), but may be sought more frequently for additional five-year terms (or any shorter period).

English law also generally prohibits a public company from repurchasing its own shares without the prior approval of shareholders by ordinary resolution, being a resolution passed by a simple majority of votes cast, and other formalities.

10 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1A. Risk Factors