What changed in this filing

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Item 1. Business

2026-02-25 compared with 2025-02-26 · 151 added, 181 removed, 727 unchanged (31% of the section changed)

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In 2022, we received approval for our lead product, KIMMTRAK, for the treatment of unresectable or metastatic uveal melanoma ("mUM") from the FDA, the European Commission and other health authorities.

KIMMTRAK is now approved in 39 countries for the treatment of unresectable or mUM.

In 2024, we launched KIMMTRAK in 14 additional countries (including Australia, Spain, Poland, and the United Kingdom excluding Scotland, and, reached price agreements with England's National Institute for Clinical Excellence ("NICE"), with further commercial launches planned in additional territories where KIMMTRAK is approved.

KIMMTRAK is now approved in 39 countries and the Company has commercially launched the product in 30 countries, including the United States, Germany and France, among other territories.

KIMMTRAK is the lead product from our ImmTAX platform and was the first approved therapy in mUM.

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We utilize a hybrid commercialization model that includes an in-house sales force in the United States and contracted resources in the United States and Europe.

To support our commercialization efforts, we have entered into an exclusive multi-regional agreement with Medison Pharma Ltd.

("Medison") to help seek regulatory authorization and commercialize KIMMTRAK in Canada, Australia, New Zealand, Israel, Central and Eastern Europe, South and Central America, and the Caribbean.

To support our commercialization efforts, we have an exclusive multi-regional collaboration with Medison Pharma Ltd.

("Medison") to help seek regulatory authorization and commercialize KIMMTRAK in Canada, Australia, New Zealand, Israel, Central and Eastern Europe, South and Central America and the Caribbean and we have entered into a distribution and commercialization agreement with Er-Kim Pharmaceuticals Bulgaria EOOD ("Er-Kim") for commercialization of KIMMTRAK in Turkey, the Middle East, North Africa, Caucasus, and the Commonwealth of Independent States regions.

Unlike antibody targeted immunotherapies that have a relatively small target pool, our approach relies on the power of TCRs, which are naturally occurring receptors found on the surface of T cells that have the ability to target nearly all of the human proteome.

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By engineering these TCRs through our ImmTAX platform, we are developing off-the-shelf, bispecific therapeutics, which are able to precisely target a wide range of proteins uniquely expressed by unhealthy and abnormal cells that cannot be targeted by current antibody-based immunotherapies.

Our ImmTAX bispecific therapeutics couple the targeting power of these engineered TCRs on one end with the other end displaying pre-optimized effector functions, which have the ability to drive a desired immune response at the site of the disease.

Our ImmTAX bispecific therapeutics are designed to couple the targeting power of these engineered TCRs on one end with the other end displaying pre-optimized effector functions, which have the ability to drive a desired immune response at the site of the disease.

This combination is designed to provide us with significant flexibility as we are able to engineer and tailor our ImmTAX therapeutics to target proteins that are specific to the disease we are trying to treat and then modulate the corresponding immune response by either boosting or inhibiting the immune system.

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cancer, infectious diseases, and autoimmune diseases.

Our oncology portfolio includes numerous pre-clinical to late stage programs, including KIMMTRAK in advanced cutaneous melanoma and adjuvant uveal melanoma, brenetafusp in a Phase 3 clinical trial in first-line advanced cutaneous melanoma and in a Phase 1/2 clinical trial in multiple tumor types, IMC-R117C (PIWIL-1) in a Phase 1/2 clinical trial in advanced solid tumors, including colorectal cancer , IMC-P115C (PRAME-HLE-A02) in a Phase 1 clinical trial for patients with tumors that express PRAME.

In 2024, we submitted a clinical trial application ("CTA") for IMC-T119C (PRAME-A24).

In infectious diseases, we are currently evaluating two candidates, IMC-M113V and IMC-I109V, in Phase 1 clinical trials for a potential functional cure in human immunodeficiency virus ("HIV") and hepatitis B virus ("HBV"), respectively.

Our oncology portfolio includes numerous pre-clinical to late stage programs, including Phase 3 clinical trials of KIMMTRAK (tebentafusp) in advanced cutaneous melanoma and adjuvant uveal melanoma, brenetafusp in a Phase 3 clinical trial in first-line advanced cutaneous melanoma and in a Phase 1/2 clinical trial in multiple tumor types, IMC-R117C (PIWIL-1) in a Phase 1/2 clinical trial in advanced solid tumors, including colorectal cancer, and IMC-P115C (PRAME-HLE-A02) in a Phase 1 clinical trial for patients with tumors that express PRAME.

In infectious diseases, we are currently evaluating IMC-M113V, in Phase 1 clinical trials for a potential functional cure in human immunodeficiency virus ("HIV").

We have expanded the ImmTAX platform into autoimmune diseases with the addition of two potential first-in-class new bispecific candidates entering the pipeline:

IMC-S118AI, for which we plan to submit a CTA or Investigational New Drug application ("IND") in the second half of 2025, and IMC-U120AI for which we plan to submit a CTA or IND in 2026.

Ou r current pipeline is below.

IMC-S118AI, for which we have submitted a clinical trial application ("CTA") in December 2025, and IMC-U120AI for which we plan to submit a CTA or investigational new drug application ("IND") in the second half of 2026.

Our current pipeline is below.

Our ImmTAC Platform (Oncology)

Within our ImmTAC platform, KIMMTRAK is approved in 39 countries for HLA-A*02:01-positive adult patients with unresectable or mUM, and is being evaluated in late-stage trials for adjuvant uveal melanoma and advanced cutaneous melanoma.

Brenetafusp, a PRAME-targeted candidate, is being evaluated in an ongoing Phase 3 registrational trial, PRISM-MEL-301, in first-line advanced cutaneous melanoma, after we randomized the first patient in the second quarter of 2024, and we are enrolling patients in multiple expansion arms of the Phase 1/2 clinical trial.

Within our ImmTAC platform, KIMMTRAK is approved in 39 countries for HLA-A*02:01-positive adult patients with unresectable or mUM, and is being evaluated in Phase 3 registrational trials for adjuvant uveal melanoma and advanced cutaneous melanoma.

Brenetafusp, a PRAME-targeted candidate, is being evaluated in an ongoing Phase 3 registrational trial, PRISM-MEL-301, in first-line advanced cutaneous melanoma, and we are enrolling patients in multiple expansion arms of the Phase 1/2 clinical trial.

Additionally, we have initiated a Phase 1/2 trial with IMC-R117C in advanced gastrointestinal cancers, and a Phase 1 trial with IMC-P115C (PRAME-HLE-A02) in patients with tumors that express PRAME.

Finally, we submitted a CTA for IMC-T119C (PRAME-A24).

The pipeline also includes additional undisclosed pre-clinical programs.

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This trial is enrolling patients with advanced CM, excluding only uveal melanoma, who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a prior targeted therapy (BRAF mutant).

The Phase 2/3 trial was converted into a registrational Phase 3 clinical trial in May 2024.

We expect the Phase 3 trial to complete patient enrollment in the first half of 2026 with topline data expected as early as the second half of 2026.

• KIMMTRAK is also being evaluated for the treatment of adjuvant therapy for uveal (or ocular) melanoma in the ATOM registrational Phase 3 trial.

Randomization of the first patient in this trial, led by the European Organisation for Research and Treatment of Cancer ("EORTC"), began in December 2024.

We signed the agreement for this EORTC-sponsored trial in 2023.

This is a global trial led by the European Organisation for Research and Treatment of Cancer ("EORTC") and randomization is ongoing.

We expect the Phase 3 trial to complete enrollment in 2028.

• Brenetafusp, the first PRAME x CD3 ImmTAC bispecific molecule, is being evaluated in patients with first-line advanced CM in our registrational PRISM-MEL-301 Phase 3 clinical trial in combination with nivolumab with a primary endpoint of progression-free survival ("PFS").

PRISM-MEL301, the first Phase 3 clinical trial with brenetafusp, is randomizing patients with HLA-A*02:01-positive, first-line advanced CM to brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled.

The trial was designed based on our analysis of the ongoing Phase 1 data in previously treated CM which demonstrated monotherapy clinical activity including partial responses ("PR"), durable tumor reduction, disease control (PR and stable disease), PFS and circulating tumor DNA ("ctDNA") reduction (consistent with prior reported data for brenetafusp and tebentafusp).

Additional rationale includes safety in combination with checkpoints (from the ongoing Phase 1 data and prior experience with tebentafusp) and evidence from across the platform for increased clinical activity in earlier line patients compared to later line.

The first patient was randomized in this trial in June 2024.

• Brenetafusp is also being tested in a Phase 1/2 trial in combination with non-platinum chemotherapies in platinum-resistant ovarian cancer ("PROC") and with bevacizumab or with platinum chemotherapy in earlier lines of platinum sensitive ovarian cancer ("PSOC").

In the same trial, we continue signal detection in metastatic non-small cell lung cancer ("NSCLC") cohorts, including brenetafusp in combination with docetaxel and with osimertinib in earlier-line NSCLC and additional solid tumors.

We presented updated clinical data from the Phase 1/2 trial:

◦ in patients with late-line CM, at the 2024 American Society of Clinical Oncology annual meeting, showing promising brenetafusp monotherapy disease control (partial response and stable disease), PFS, and ctDNA molecular response.

In PRAME positive patients, the disease control rate ("DCR") was 58% and median PFS was 4.2 months.

This analysis of the initial 18 uveal and cutaneous melanoma patients was an update of the initial data set presented at the 2022 European Society for Medical Oncology (“ESMO”) Congress, which continued to show promising durability of the clinical activity (range of duration of patient response from 6 months to 17 months).

◦ in patients with heavily pre-treated platinum-resistant high grade serous ovarian cancer, at the 2024 ESMO Congress, showing signals of activity in heavily pretreated, platinum-resistant patients.

DCR was 58% in monotherapy patients and 69% for combination patients.

Overall survival ("OS") was still maturing (73% 6 months OS rate in the monotherapy cohort).

ctDNA molecular response rates were 31% and 82% in the monotherapy and combination cohorts, respectively, associated with longer progression PFS and OS.

Following a pre-planned review of safety for all three arms and of efficacy for the two brenetafusp regimens (40 mcg and 160 mcg) in the first 90 randomized patients, the Independent Data Monitoring Committee recommended the dose of 160 mcg as the go-forward dose in PRISM-MEL-301.

Patients who were receiving 40 mcg were given the option to dose-escalate to 160 mcg but will not be included in the intent-to-treat analysis for the primary endpoint.

• Brenetafusp is also being tested in a Phase 1/2 clinical trial in combination with non-platinum chemotherapies in platinum-resistant ovarian cancer ("PROC") and with bevacizumab or with platinum chemotherapy in earlier lines of platinum sensitive ovarian cancer ("PSOC").

In the same trial, we continue to evaluate signal detection in metastatic non-small cell lung cancer ("NSCLC") cohorts, including brenetafusp in combination with docetaxel and with osimertinib in earlier-line NSCLC and additional solid tumors.

We expect to present data from this trial in the second half of 2026.

• IMC-P115C , our half-life extended ImmTAC candidate is being tested in a Phase 1 dose escalation trial in HLA-A*02:01-positive patients with a range of advanced cancers expressing PRAME .

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IMC-P115C targets the same PRAME-A02 peptide, with the same CD3 effector and TCR, specificity as brenetafusp.

We started enrolling patients in this trial in December 2024.

We expect to present data from this trial in the second half of 2026.

• IMC-R117C , our ImmTAC candidate targeting an optimal HLA-A*02:01 PIWIL1, is being tested in a Phase 1/2 trial (first dose was administered in December 2024) for patients with advanced solid tumors, including colorectal cancer, as a single agent and in combination with standards of care.

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We believe IMC-R117C is the first PIWIL1 targeted immunotherapy.

• IMC-T119C, is an ImmTAC molecule targeting an optimal HLA-A*24 PRAME.

We submitted a CTA for IMC-T119C in the fourth quarter of 2024.

HLA-A24 is an HLA-type that is estimated to be present in 60% of people in Japan and 15% - 20% in Western populations.

We expect to present initial data from this trial in 2027.

Our ImmTAV Platform (Infectious Diseases)

We have two programs from our ImmTAV ( I mmune m obilizing m onoclonal T CRs A gainst V irus) platform in the clinic.

Our ImmTAV product candidates are bispecific soluble TCR molecules featuring our ImmTAX TCR-based targeting system with high specificity for low-expression viral antigens, combined with the proprietary anti-CD3 effector module for T cell engagement and activation that has been evidenced by our clinical oncology pipeline.

We are seeking to develop therapeutics that can provide a functional cure to chronic viral disease and are focusing initially on HIV and HBV.

Within our ImmTAV ® ( I mmune m obilizing m onoclonal T CRs A gainst V irus) platform our lead program is IMC-M113V targeting a functional cure for HIV.

Our ImmTAV pre-clinical and clinical candidates are bispecific soluble TCR molecules featuring our ImmTAX TCR-based targeting system with high specificity for low-expression viral antigens, combined with the proprietary anti-CD3 effector module for T cell engagement and activation that has been evidenced by our clinical oncology pipeline.

We shared promising data in 2025 about our programs in HIV and HBV.

We are enrolling patients at higher doses in the HIV trial.

We have completed the SAD portion of the trial for HBV and will determine next steps in 2026.

Our ImmTAV programs include:

• IMC-M113V , our ImmTAV molecule targeting a human immunodeficiency virus gag antigen bispecific TCR molecule, is being evaluated in a Phase 1 clinical trial.

• IMC-M113V , our ImmTAV molecule targeting a human immunodeficiency virus gag antigen bispecific TCR molecule, is being evaluated in a Phase 1/2 clinical trial ("STRIVE").

Initial Phase 1 safety and pharmacodynamic activity data from the single ascending dose ("SAD"), portion of the trial was presented at the Conference on Retroviruses and Opportunistic Infections ("CROI") in 2023.

IMC-M113V was well tolerated at doses where we observed biomarkers of T cell engagement.

We are enrolling up to 28 people living with HIV in the multiple ascending dose ("MAD"), part of the trial, to identify a safe and tolerable dosing schedule that could lead to reduction in the viral reservoir and control of HIV after stopping antiretroviral therapies, or functional cure.

We will present initial data from the MAD portion of the trial in the first quarter of 2025.

• IMC-I109V , our ImmTAV molecule targeting a conserved hepatitis B virus envelope antigen, is being evaluated in a Phase 1 clinical trial in patients with chronic HBV who are non-cirrhotic, hepatitis B e-Antigen negative, and virally suppressed on chronic nucleot(s)ide analogue therapy.

In 2023, we amended the trial design in the ongoing Phase 1 clinical trial with IMC-I109V for people living with HBV to include HBV-positive hepatocellular carcinoma.

We have completed patient enrollment in the SAD portion of the trial and plan to present data in the second half of 2025.

We are enrolling people living with HIV in the multiple ascending dose ("MAD") portion of the trial, to identify a safe and tolerable dosing schedule that could lead to reduction in the viral reservoir and control of HIV after stopping antiretroviral therapies, or functional cure.

We presented initial data from the MAD portion of the trial at the CROI 2025 conference.

The data included 16 people living with HIV ("PLWH") who were stable on antiretroviral therapy ("ART").

All doses were well tolerated and no serious adverse events or dose limiting toxicities were observed.

In the 15 evaluable PLWH, delayed viral rebound and/or viremia control at any point during the analytical treatment interruption ("ATI") was observed in none of five PLWH at 60 mcg, one of five at 120 mcg, and two of five at 300 mcg.

The three PLWH with evidence of viral control had a viral load of approximately 200 copies/mL at week 8.

The historical rate for this observation is 5%.

Furthermore, two of these three PLWH remained off ART for the entire 12-week ATI period that was pre-specified in the protocol.

Patient enrollment continues at higher doses in the multiple ascending dose part of the Phase 1/2 clinical trial to identify a safe and tolerable dose.

We expect to report additional MAD data from the STRIVE trial in the second half of 2026.

• IMC-I109V , our ImmTAV molecule targeting a conserved hepatitis B virus envelope antigen, has been evaluated in a Phase 1 clinical trial in patients with chronic HBV who are non-cirrhotic, hepatitis B e-Antigen negative, and virally suppressed on chronic nucleot(s)ide ana logue therapy.

We presented data at The Liver Meeting, organized by the American Association for the Study of Liver Diseases (AASLD).

Our presentation showed that IMC-I109V is generally well tolerated in all evaluated doses and exhibits pharmacodynamic effects consistent with its mechanism of action, including reduction in HBsAg levels, clearance of which is indicative of resolved hepatitis B infection.

We have completed the SAD portion of the trial and will determine next steps in 2026.

Our ImmTAAI ® Platform (Autoimmune Diseases)

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• IMC-S118AI is our ImmTAAI molecule specifically targeted to the pancreatic beta-cells for disease modifying treatment in type 1 diabetes.

We plan to submit a CTA or IND for IMC-S118AI in the second half of 2025.

We submitted a CTA for IMC-S118AI in December 2025.

IMC-S118AI recognizes a peptide from pre-pro-insulin presented by HLA-A2*01 on beta-cells coupled with a PD1 agonist effector arm.

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We believe IMC-S118AI has the potential to provide a differentiated option for treatment with advantages of tissue-specific down modulation without immunosuppression.

We expect to begin the Phase 1 clinical trial in the first half of 2026.

• IMC-U120AI is a CD1a-tethered PD1 agonist ImmTAAI therapy.

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It plays an important role in triggering allergic inflammation in atopic dermatitis and potentially other immune diseases.

We plan to file a CTA or IND in 2026 for a Phase 1 trial in atopic dermatitis.

We believe that precision targeting of our PD1 agonist based immune inhibitory molecule to these key cells involved in the establishment and maintenance of disease will provide clinical benefit to patients and the potential to modify the course of disease.

We plan to file a CTA or IND in the second half of 2026 for a Phase 1 trial in atopic dermatitis.

Our 2026 Strategic Priorities

Our strategic priorities for 2026 include:

• Building a melanoma franchise – reaching more mUM patients and delivering KIMMTRAK’s lifecycle management program through two ongoing registrational Phase 3 trials (TEBE-AM and the EORTC-sponsored ATOM trial).

We are also enrolling a third registrational trial, PRISM-MEL-301, evaluating brenetafusp in first-line melanoma.

• Advancing the clinical portfolio – enrolling patients in multiple Phase 1 and 1/2 oncology trials with brenetafusp (PRAME-A02), IMC-P115C (PRAME-A02-HLE), IMC-R117C (PIWIL1-A02), and IMC-M113V in HIV.

• Innovating for sustainable growth – planning to submit a CTA or IND for our two autoimmune disease candidates:

IMC-S118AI (PPI x PD1) by year end 2025 and IMC-U120AI (CD1a x PD1) in 2026.

• Grow KIMMTRAK (tebentafusp) and prepare for potential new melanoma indications:

reaching more metastatic uveal melanoma (mUM) patients and delivering KIMMTRAK’s lifecycle management program through two ongoing registrational Phase 3 trials (TEBE-AM and ATOM).

We are also enrolling patients in a third Phase 3 registrational trial, PRISM-MEL-301, evaluating brenetafusp in first-line melanoma.

• Expand beyond melanoma into other tumor types:

in 2026, we anticipate having multiple Phase 1 readouts with our PRAME bispecific candidates – brenetafusp and IMC-P115C (PRAME-A02-HLE) – across multiple tumor types, including ovarian and NSCLC, in combination with multiple therapies.

This data will inform next steps.

We are also enrolling patients in a Phase 1/2 dose escalation trial, including combinations, in colorectal cancer with IMC-R117C (PIWIL1-A02).

• Realize growth opportunities beyond oncology:

in 2025, we showed important proof of concept data for our infectious disease platform and we continue to dose escalate and monitor the viral rebound kinetics in the Phase 1 trial in people living with HIV.

We are also advancing our two autoimmune disease candidates towards the clinic:

initiation of the Phase 1 trial for IMC-S118AI (PPI x PD1), and submission of a CTA for IMC-U120AI (CD1a x PD1).

Overview of ImmTAX Platform

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Medison is the exclusive distribution partner for KIMMTRAK in Canada, Australia, New Zealand, Israel, Central and Eastern Europe, South and Central America, and the Caribbean.

In 2025, we signed a distribution and commercialization agreement with Er-Kim for KIMMTRAK in Turkey, the Middle East, North Africa, Caucasus, and the Commonwealth of Independent States regions.

Reimbursement

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In the United States, it is essential to obtain third-party payor coverage policies, coding mechanisms, and adequate payment to expand market acceptance and adoption of KIMMTRAK as a treatment for mUM.

In 2024 , we continued working with the U.S.

We continue working with the U.S.

commercial third-party payor community in order to maintain coverage for KIMMTRAK.

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The requirements governing pricing vary widely from country to country.

As of December 31, 2024, we have pricing and reimbursement agreements in more than 20 European and other territories, including Germany and Italy.

KIMMTRAK is sold in France according to the government’s early access and commercial programs, while final price negotiations are ongoing.

In order to maximize KIMMTRAK revenue, we are continuing our reimbursement and pricing submissions and negotiations in several additional countries.

As of December 31, 2025, we have pricing and reimbursement agreements in more than 20 European and other territories, including Germany, France, and Italy.

In order to maximize KIMMTRAK's access and revenue, we are continuing our reimbursement and pricing submissions and negotiations in several additional countries.

Manufacturing and Drug Supply

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We have an internal commercial supply chain group that coordinates the supply and distribution of KIMMTRAK.

We do not currently own or operate manufacturing facilities for the production of clinical or commercial ImmTAX product candidates, and we have no intention to build out our own manufacturing capabilities in the foreseeable future.

We do not currently own or operate manufacturing facilities for the production of clinical or commercial ImmTAX product candidates, and we have no current intention to build out our own manufacturing capabilities in the foreseeable future.

Instead, we outsource to contract manufacturing organizations ("CMOs"), for both drug substance and drug product production and have a successful cGMP-compliant manufacturing history of production of cGMP batches.

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However, we expect substantial competition from multiple sources, including major pharmaceutical, specialty pharmaceutical, and existing or emerging biotechnology companies, academic research institutions and governmental agencies and public and private research institutions worldwide.

Many of our competitors, either alone or with their collaborations, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.

Many of our competitors, either alone or with their collaborations, have significantly greater financial, technical and other resources, and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

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Adaptimmune Therapeutics plc, Immatics Biotechnologies GmbH ("Immatics"), Adaptive Biotechnologies Corporation ("Adaptive"), pure MHC, LLC, BioNTech SE, Genentech, Inc.

("Genentech"), Matterhorn Biosciences AG, Enara Bio Limited, Boehringer Ingelheim International GmbH, and Regeneron Pharmaceuticals, Inc.

("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., Bristol-Myers Squibb Company ("BMS"), GSK plc, Kite Pharma, Inc., Lion TCR Pte.

("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 Pharmaceuticals, Inc.

("Regeneron"), Takara Bio Inc., AstraZeneca PLC, Lion TCR Pte.

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

LTD, and TScan Therapeutics, Inc.

("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., and CDR-Life Inc.

("TScan") who are developing TCR-based cell therapies; and Immatics, Molecular Partners AG, 3T Biosciences, Inc., Crossbow Therapeutics, Inc., and CDR-Life Inc.

are developing CD3-based TCR bispecific compounds or TCR mimetic antibodies.

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Specifically in regard to PRAME, we are aware that Immatics, TScan, and Replay Therapeutics, Inc.

(in collaboration with MD Anderson) are conducting Phase 1 clinical trials of PRAME-directed cellular therapies and Immatics has also initiated a Phase 1/2 clinical trial of a PRAME TCRxCD3 half-life extended bispecific approach.

(in collaboration with MD Anderson) are conducting Phase 1 clinical trials of PRAME-directed cellular therapies and Immatics is also conducting a Phase 1/2 clinical trial of a PRAME TCRxCD3 half-life extended bispecific approach.

Any ImmTAC product candidates that we successfully develop and commercialize for oncology indications may compete with existing products and new products that may become available in the future.

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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 registration Phase 2/3 clinical trial in 2025.

We are also aware of various companies initiating registrational Phase 3 clinical trials in uveal melanoma, including Ideaya Biosciences, Inc.'s initiation of a registrational Phase 3 clinical trial in high-risk neoadjuvant uveal melanoma, and Replimune Group Inc.’s initiation of a registrational Phase 3 clinical trial in immune-checkpoint naïve UM, both anticipated to begin 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, including Ideaya Biosciences, Inc.'s registrational Phase 3 clinical trial in high-risk neoadjuvant uveal melanoma, and Replimune Group Inc.’s registrational Phase 2/3 clinical trial in immune-checkpoint naïve UM.

In March 2022, Bristol Myers Squibb announced the approval and launch of Opdualag, a new, first-in-class, fixed-dose combination of nivolumab and relatlimab, administered as a single intravenous infusion for the treatment of unresectable or metastatic melanoma.

We are aware of several other companies with product candidates in clinical development in cutaneous melanoma, including Regeneron’s Phase 3 studies of cemiplimab and fianlimab, Iovance’s Phase 3 trial of lifileucel and pembrolizumab, Immatics’ Phase 3 trial of IMA203 TCR-T, and Moderna’s Phase 3 trial of mRNA4157 (mRNA cancer vaccine) in adjuvant melanoma.

There are now over 30 antiretroviral medications in six drug classes approved for the treatment of HIV.

Antiretroviral therapy ("ART") consists of treatment with a combination of two or three agents targeting different stages of the virus life cycle.

ART consists of treatment with a combination of two or three agents targeting different stages of the virus life cycle.

If started early, ART provides a normal lifespan, prevents immunodeficiency and stops the spread of HIV.

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Intellectual Property

We strive to protect and enhance the proprietary technologies, inventions and improvements that we believe are important to our business, including by seeking, maintaining, enforcing and defending patent rights for our therapeutics and platform, whether developed internally or licensed from third parties.

We strive to protect and enhance the proprietary technologies, inventions and improvements that we believe are important to our business, including by seeking, maintaining, enforcing and defending patent rights for our therapeutics and platforms, whether developed internally or licensed from third parties.

Our success will depend on our ability to obtain and maintain patent, trademark and other intellectual property protection for our therapeutic products, product candidates and platform technology, preserve the confidentiality of our know-how and operate without infringing, misappropriating or otherwise violating the valid and enforceable patents and proprietary rights of third parties.

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The majority of our patents and patent applications are solely owned.

The portfolio includes solely owned patents and patent applications directed to our commercial TCR product (KIMMTRAK), our product candidates (including brenetafusp, IMC-M113V, IMC-I109V, IMC-P115C, IMC-R117C, IMC-T119C, IMC-S118AI and IMC-U120AI), and our platform technology used to identify and generate our therapeutic candidates, novel targets, formulations and methods of treatment.

A minor proportion of the portfolio, comprising certain older platform IP, is jointly owned in equal share with Adaptimmune.

We control the prosecution of the jointly owned patents and patent applications, and we have rights under the joint patents as required to develop and commercialize our therapeutics.

The portfolio includes solely owned patents and patent applications directed to our commercial product KIMMTRAK (tebentafusp), our product candidates (including brenetafusp, IMC-M113V, IMC-I109V, IMC-P115C, IMC-R117C, IMC-T119C, IMC-S118AI and IMC-U120AI), and our platform technologies used to identify and generate our therapeutic candidates, novel targets, formulations and methods of treatment.

A minor proportion of the portfolio that comprises certain older platform technology IP is also solely owned, with the exception of the one patent family jointly owned in equal share with Adaptimmune.

We control the prosecution of this jointly owned patent family, and we have rights under the joint patents as required to develop and commercialize our therapeutics.

For more information on our assignment and exclusive license agreement with Adaptimmune, see “Item 1.

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As of December 31, 2025 , we own granted patents and patent applications covering the composition of matter of our commercial product KIMMTRAK (tebentafusp).

The patents include claims that cover the specific sequence of KIMMTRAK, as well as claims that cover TCR variants with similar biological properties.

Granted patents have been obtained in major territories including two in the United States and 28 in foreign jurisdictions, including Europe (including United Kingdom, France, Germany, Italy, Spain, Ireland, Denmark and the Netherlands), Australia, Canada, China, Hong Kong, Japan, Mexico, Eurasia and South Africa.

These granted patents are set to expire in 2030.

In the United States, a patent term extension ("PTE") application has been filed and is anticipated to extend the patent term such into the first quarter of 2035.

Requests for supplementary protection certificates ("SPC") have been filed and granted in Australia and Canada, extending patent term through the second quarter of 2035 and 2032, respectively.

SPCs have also been filed in Europe (with grants in at least 10 European territories) extending patent term through the second quarter of 2035.

Granted patents have been obtained in major territories including the United States and Europe (including United Kingdom, France, Germany, Italy, Spain, Ireland, Denmark and the Netherlands), as well as other jurisdictions, such as Australia, Canada, China, Hong Kong, Japan, Mexico, Eurasia and South Africa.

The granted patent in the US, including patent term extension ("PTE"), is set to expire in 2035.

Supplementary protection certificates ("SPC"), extending patent term to the second quarter of 2035 have been granted in Australia, and in the majority of European territories where patents have been obtained.

An SPC has also been granted in Canada, extending patent term through the second quarter of 2032.

Granted patents in remaining jurisdictions are set to expire in 2030.

Further patent families have been filed including those directed to dosing regimen, formulation, and methods of treatment.

If granted, these applications would provide possible additional upside protection to at least 2042.

ImmTAX pipeline

If granted, these applications would provide possible additional upside protection with expiries in the range of 2037 to 2042.

Pipeline Products

As of December 31, 2025 , we solely own patent families covering the composition of matter of each of our oncology, infectious disease, and autoimmune pipeline candidates, including issued U.S.

patents covering the composition of matter of brenetafusp, our PRAME-A02 candidate.

In each case, claims of the composition of matter patents or patent applications are directed to the therapeutic candidates and to variants with similar biological properties.

The issued U.S.

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Further patent applications have been filed relating to brenetafusp dosing regimens and methods of treatment.

Our ImmTAX platform

As of December 31, 2024 , we solely own a number of patents and patent applications related to our ImmTAX platform.

The oldest patent families relating to our ImmTAX TCR bispecific format will expire starting in 2030.

We have filed further platform patent families relating to TCR bispecifics with improved therapeutic properties, including formats with extended in vivo half-life and improved anti-CD3 effector functions, as well as therapeutic formats for the treatment of autoimmune indications.

Such pending patent applications, if granted, are expected to expire between 2039 and 2043, excluding any additional term for patent term adjustments or patent term extensions.

We jointly own in 50% equal share with Adaptimmune, platform patent families relating to methods and tools for selecting TCRs in the early pipeline.

The latest of these will expire in 2036.

HLA target peptide patent applications

As of December 31, 2024 , we own a number of patent families relating to novel HLA-restricted peptide targets and their use.

Such patents and pending patent applications, if granted, are expected to expire between 2036 and 2037, excluding any additional term for patent term adjustments or patent term extensions.

Our ImmTAX platform and Other Technology

As of December 31, 2025 , we solely own a number of patents and patent applications related to our platform and other technologies.

The oldest patent families related to our TCR bispecific format will expire starting in 2030.

We have filed further platform patent families relating to molecule formats with improved therapeutic properties, including formats with extended in vivo half-life and improved anti-CD3 effector functions, as well as therapeutic formats for the treatment of autoimmune indications.

Legacy platform patents include a jointly owned patent family with Adaptimmune.

Such legacy patent filings also include ones relating to HLA-restricted peptide targets and their use.

Typically, we file our priority applications at the U.K.

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We also have confidentiality agreements and invention assignment agreements with our collaborators and consultants as required.

These agreements are designed to protect our proprietary information and, in the case of the invention assignment agreements, to grant us ownership of technologies that are developed through a relationship with a third party.

We cannot guarantee, however, that we have executed such agreements with all applicable counterparties.

Furthermore, these agreements may be breached, and we may not have adequate remedies for any breach.

In addition, our trade secrets may otherwise become known or be independently discovered by competitors and other third parties.

To the extent that our collaborators, employees and consultants use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions.

For more information, please see “Item 1A.

Risk Factors—Risks Related to Intellectual Property.”

Third-party rights

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BMS Collaboration

In February 2024, we entered into a clinical trial collaboration and supply agreement with BMS (the "BMS Agreement") to investigate our ImmTAC bispecific TCR candidate targeting PRAME HLA-A*02:01 brenetafusp in combination with BMS’s nivolumab, in first-line advanced cutaneous melanoma.

In February 2024, we entered into a clinical trial collaboration and supply agreement (the "BMS Agreement") with Bristol-Myers Squibb ("BMS") to investigate our ImmTAC bispecific TCR candidate targeting PRAME HLA-A*02:01 brenetafusp in combination with BMS’s nivolumab, in first-line advanced cutaneous melanoma.

Under the terms of the BMS Agreement, we are sponsoring and funding the registrational Phase 3 clinical trial of brenetafusp in combination with nivolumab in first-line advanced cutaneous melanoma (PRISM-MEL-301), and BMS is providing nivolumab.

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We also have an obligation to make available certain research tools on a royalty-free basis to certain entities supported by the Gates Foundation and other third parties and certain obligations relating to publishing of scientific results of our work.

Gadeta Collaboration

In December 2022, we entered into a collaboration, option and license agreement, (the “Gadeta Collaboration”), with Gadeta B.V., (“Gadeta”) which was acquired by Clade Therapeutics, (“Clade”) in October 2023.

Under the Gadeta Collaboration, we collaborated on ‘201 γδ-TCR target discovery, and we had the option to develop ImmTAC therapies derived from the ‘201 TCR.

Following the acquisition of Gadeta by Clade, the rights under the Gadeta Collaboration were transferred to a newly established entity called Ateda Therapeutics (“Ateda”).

Our rights and obligations under the terms of the Gadeta Collaboration did not alter through this transfer.

In April 2024, Clade was acquired by Century Therapeutics.

Our rights and obligations under the Gadeta Collaboration were not affected by this acquisition.

In December 2024, we elected not to exercise the option to develop ImmTAC therapies derived from the ‘201 TCR, bringing to an end any payment obligations related to such activities.

Under the surviving license terms, we retain the right to develop therapies directed to the target recognized by the ‘201 TCR provided such therapies are not derived from the ‘201 TCR.

Should we elect to develop such therapies, then the defined milestones and royalties may be owed to Ateda.

We have incurred amounts totaling $2.8 million under the Gadeta Collaboration as of December 31, 2024 .

Assignment and Exclusive License Agreement with Adaptimmune

In May 2013, we entered into an assignment and exclusive license agreement (the “Adaptimmune License”) with Adaptimmune Limited, which is the U.K.

subsidiary of Adaptimmune Therapeutics plc, relating to the joint ownership and licensing of certain patents, patent applications, rights in know-how and other intellectual property rights.

Pursuant to the Adaptimmune License, we and Adaptimmune jointly own certain identified patents, patent applications, rights in know-how and other intellectual property rights in equal shares.

We each grant the other party an exclusive, royalty-free, irrevocable license, with the right to sub-license, under those jointly owned intellectual property rights in separate fields.

Adaptimmune’s exclusive field relates to treatment of patients with engineered TCR therapeutic candidates and our exclusive field relates to the treatment of patients with soluble TCRs.

There is no royalty payable under the Adaptimmune License but we share equally in the costs associated with the filing, maintenance and prosecution of the jointly owned patents and patent applications covered by the Adaptimmune License.

The Adaptimmune License is effective until the later of the expiration of the last to expire jointly owned patent under the Adaptimmune License or the jointly owned know-how ceasing to be confidential.

The Adaptimmune License cannot be terminated by either party.

Upon the insolvency of either party, the other party has the right to take over patent prosecution of the licensed patents and to request assignment of the insolvent party’s interest in all the licensed patents, know-how and results on commercially reasonable terms.

Government Regulation

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Individual Member States retain the power to authorize the conduct of clinical trials on their territory.

The extent to which on-going clinical trials will be governed by the CTR will depend on the duration of the individual clinical trial.

For clinical trials in relation to which an application for approval was made on the basis of the CTD before January 31, 2023, the CTD continued to apply on a transitional basis until January 31, 2025.

All ongoing trials are now subject to the provisions of the CTR.

Marketing Authorization

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Regulation in the United Kingdom

The withdrawal of the United Kingdom from the EU on January 31, 2020, commonly referred to as Brexit, has changed the regulatory relationship between the United Kingdom and the EU .

The Medicines and Healthcare products Regulatory Agency ("MHRA") is now the United Kingdom’s standalone regulator for medicinal products and medical devices.

The United Kingdom is now no longer a Member State of the European Union and therefore a “third country”.

The Medicines and Healthcare products Regulatory Agency ("MHRA") is the United Kingdom’s standalone regulator for medicinal products and medical devices.

The United Kingdom’s regulatory framework in relation to clinical trials is governed by the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended, which is derived from the CTD, as implemented into the United Kingdom’s national law 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, and such changes were laid in parliament on December 12, 2024.

These resulting legislative amendments will, if implemented in their current form, bring the United Kingdom into closer alignment with the CTR.

In October 2023, the MHRA announced a new Notification Scheme for clinical trials which enables a more streamlined and risk-proportionate approach to initial clinical trial applications for Phase 4 and low-risk Phase 3 clinical trial applications.

On April 10, 2025, the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024 came into force, with a 12-month implementation period before entering into full effect on April 10, 2026.

These amendments modernize the UK clinical trials framework and introduce significant changes including:

(i) a risk-proportionate approach whereby low-risk trials can receive faster approval through automatic authorization without prior regulatory review;

(ii) a combined review process integrating ethics committee and regulatory approvals into a single streamlined approval pathway;

(iii) enhanced transparency requirements mandating registration of clinical trials in a public registry and publication of trial results within 12 months of trial completion;

(iv) provisions to streamline approvals and enable innovation in clinical trial design;

and (v) measures to promote patient and public involvement in clinical trials.

Marketing authorizations in the United Kingdom are governed by the Human Medicines Regulations (SI 2012/1916), as amended.

Since January 1, 2021, an applicant for the EU’s centralized procedure marketing authorization can no longer be established in the United Kingdom.

As a result, since this date, companies established in the United Kingdom cannot use the EU’s centralized procedure.

In order to obtain a UK MA to commercialize products in the United Kingdom, an applicant must be established in the United Kingdom and must follow one of the United Kingdom national authorization procedures or one of the remaining post-Brexit international cooperation procedures.

In order to obtain a United Kingdom MA to commercialize products in the United Kingdom, an applicant must be established in the United Kingdom and must follow one of the United Kingdom national authorization procedures or one of the remaining post-Brexit international cooperation procedures.

Applications are governed by the Human Medicines Regulations (SI 2012/1916) and are made electronically through the MHRA Submissions Portal.

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Applicants can submit initial MAAs to the IRP but the procedure can also be used throughout the lifecycle of a product for post-authorization procedures including line extensions, variations and renewals.

All existing marketing authorizations of the EU for centrally authorized products were automatically converted or grandfathered into the United Kingdom’s marketing authorization, effective in Great Britain only, free of charge on January 1, 2021, unless the marketing authorization holder opted-out of this possibility.

Northern Ireland remained within the scope of authorizations of the EU in relation to centrally authorized medicinal products until January 1, 2025.

However, on January 1, 2025, a new arrangement as part of the so-called “Windsor Framework” came into effect and reintegrated Northern Ireland under the regulatory authority of the MHRA with respect to medicinal products.

The Windsor Framework removes EU licensing processes and EU labelling and serialization requirements in relation to Northern Ireland and introduces a UK-wide licensing process for medicines.

Existing EU marketing authorizations for centrally authorized products were automatically converted into United Kingdom’s marketing authorizations, effective in Great Britain only, free of charge on January 1, 2021, unless the marketing authorization holder opted-out of this possibility.

On January 1, 2025, the Windsor Framework came into effect, reintegrating Northern Ireland under the regulatory authority of the MHRA with respect to medicinal products and introducing a UK-wide licensing process for medicines.

There is no pre-marketing authorization orphan designation for medicinal products in the United Kingdom.

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The start of this market exclusivity period will be set from the date of first approval of the product in the United Kingdom.

Regulation of In Vitro Diagnostic Medical Devices in the United Kingdom

In vitro diagnostic medical devices (“IVDs”), are regulated in the United Kingdom under the Medical Devices Regulations 2002, as amended, which implement requirements derived from the EU In Vitro Diagnostic Medical Devices Directive.

The MHRA is responsible for the regulation of IVDs in the United Kingdom.

Manufacturers must demonstrate conformity with applicable essential requirements, including analytical and clinical performance, before placing IVDs on the UK market.

From July 1, 2023, the UK has required UKCA marking for IVDs placed on the Great Britain market, though CE marking continues to be recognized during a transitional period.

Manufacturers must appoint a UK Responsible Person if they are not established in the United Kingdom.

The United Kingdom is developing a new regulatory framework for IVDs based on a risk-based approach similar to the EU's In Vitro Diagnostic Regulation (EU) 2017/746 with the stated aim of reducing regulatory burden, with UK-specific modifications.

The new regime will include enhanced clinical evidence requirements, increased scrutiny by UK-approved bodies for higher-risk devices, and strengthened post-market surveillance.

The MHRA will provide transitional arrangements for compliance, though specific timelines remain subject to regulatory development and parliamentary approval.

Other Healthcare Laws and Regulations

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In addition, the ACA codified case law that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA;

• HIPAA imposes criminal and civil liability, among other things, for executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

• the Health Insurance Portability and Accountability Act as amended ("HIPAA") imposes criminal and civil liability, among other things, for executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

• the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services ("CMS") information related to payments and other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physicians assistants and nurse practitioners), and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members;

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government, state legislatures and foreign governments have shown significant interest in implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs.

For example, the Inflation Reduction Act of 2022 (“IRA”), among other things, (1) 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 (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit our net revenue and results.

For example, the Inflation Reduction Act of 2022 (“IRA”), among other things, (1) directs the U.S.

Department of Health and Human Services ("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 (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

Adoption of additional price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit our net revenue and results.

A payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved.

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In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by federal and state legislative initiatives, including those designed to limit the pricing, coverage, and reimbursement of pharmaceutical and biopharmaceutical products, especially under government-funded health care programs, and increased governmental control of drug pricing.

By way of example, in March 2010, the ACA was signed into law, which, among other things, was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose taxes and fees on the healthcare industry and impose additional health policy reforms.

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

For example, on June 17, 2021, the U.S.

Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.

Further, 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.

The IRA also eliminated 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.

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

By way of example, 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.

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.

Other legislative changes have been proposed and adopted in the United States.

For example, in August 2011, the Budget Control Act of 2011 was signed into law, which, among other things, created measures for spending reductions by Congress.

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Therefore, we do not currently expect to be required to make refund payments under the CMS Rule.

There also has been heightened governmental scrutiny in the United States of pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics.

Such scrutiny has resulted in several recent Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.

At the federal level, for example, the IRA, among other things:

(i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare 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 in the United States have increasingly passed legislation and implemented 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.

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.

We expect that these initiatives, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and lower reimbursement, and in additional downward pressure on the price that we receive for any approved product.

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The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our product candidates.

Further, additional healthcare reform initiatives may arise from future legislation or administrative action, especially in light of the recent U.S.

Presidential and Congressional elections.

In December 2021, Regulation No 2021/2282 on Health Technology Assessment ("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 at level of 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.

Pricing and reimbursement decisions, based on these assessments, remain the responsibility of individual Member States.

On January 12, 2025, Regulation No 2021/2282 on Health Technology Assessment ("HTA Regulation"), was entered into application through a phased implementation .

The HTA Regulation initially applies to new active substances for oncology and ATMPs.

It will be expanded to orphan medicinal products in January 2028, and to all centrally authorized medicinal products as of 2030.

Select high-risk medical devices will also come into scope in 2026.

The HTA Regulation is intended to boost cooperation among Member States in assessing health technologies, including new medicinal products.

The Regulation establishes a framework for EU‑level joint clinical assessments and increased cooperation among Member States on clinical aspects of health technology evaluation.

Pricing and reimbursement decisions remain under the exclusive authority of individual Member States.

In light of the fact that the United Kingdom has left the EU, the HTA Regulation does not apply in the United Kingdom.

However, the MHRA is working with UK HTA bodies and other national organizations, such as the Scottish Medicines Consortium ("SMC"), the National Institute for Health and Care Excellence ("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.

For example, in March 2021, the UK introduced the Innovative Licensing and Access Pathway (“ILAP”) which brings together the MHRA, NICE, SMC and the All Wales Therapeutics and Toxicology Centre, to accelerate time to market for certain innovative products.

The ILAP temporarily stopped accepting applications on November 20, 2024, and applications under a relaunched ILAP reopened in March 2025 with changes including improvements to interaction with the National Health Service and an amended eligibility and selection criteria.

Data Privacy and Security Laws

We are subject to privacy laws in the jurisdictions in which we operate, have partners, or sell or market our products or run clinical trials, and may in the future become subject to additional laws.

For example, we are subject to the EU’s General Data Protection Regulation ("EU GDPR"), the United Kingdom’s equivalent law ("U.K.

GDPR") (collectively, "GDPR"), and the Health Insurance Portability and Accountability Act as amended ("HIPAA"), in the United States, among others.

For example, we are subject to the EU’s General Data Protection Regulation ("EU GDPR") and, the United Kingdom’s equivalent law ("U.K.

GDPR") (collectively, "GDPR"), among others.

Our regulatory obligations could harm the use or cost of our solution as data protection and privacy laws and regulations around the world continue to evolve.

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state privacy laws exempt some data processed in the context of clinical trials, but these developments may further complicate compliance efforts, and increase legal risk and compliance costs for us.

Certain aspects of our business, including those for which we rely upon collaborators, service providers, contractors or others, are or may become subject to HIPAA and its implementing regulations, which establish standards for covered entities (certain healthcare providers, health plans and healthcare clearinghouses) governing the conduct of certain electronic healthcare transactions and protecting the security and privacy of protected health information, including, among other requirements, mandatory contractual terms and technical safeguards designed to protect the privacy, security and transmission of protected health information and notification to affected individuals and regulatory authorities in the event of certain breaches of security of protected health information.

The American Recovery and Reinvestment Act of 2009, commonly referred to as the economic stimulus package, included sweeping expansion of HIPAA’s privacy and security standards called the Health Information Technology for Economic and Clinical Health Act ("HITECH"), which became effective on February 17, 2010.

Among other things, the HITECH makes HIPAA’s privacy and security standards directly applicable to business associates, or independent contractors or agents of covered entities, that receive or obtain protected health information in connection with providing a service on behalf of a covered entity, as well as their covered subcontractors.

HITECH also increased the civil and criminal penalties that may be imposed against covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions.

Certain states have also enacted consumer health data privacy laws or medical information privacy laws, or amended existing consumer protection laws, to further regulate the collection, use, and sharing of consumer health data and medical information.

These laws further complicate compliance, and many provide a private right of action through which individuals can seek statutory damages for actual or perceived violations.

Additional Regulation

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This is why we are committed to offer a rewarding employee experience and company culture.

As we strive each day to deliver our mission, we have built a strong culture rooted in values, as we strive to create a workplace where all belong and can share ideas to drive innovation, and to create an environment where individual contributions and initiatives can be maximized, while fostering a culture of collaboration, based on respect and integrity.

As we strive each day to deliver our mission, we have built a strong culture rooted in values, as we attempt to create a workplace where all belong and can share ideas to drive innovation, and an environment where individual contributions and initiatives can be maximized, while fostering a culture of collaboration, based on respect and integrity.

We conduct a Performance Development Review ("PDR") at mid- and end-of-year which are important to our pay-for-performance culture.

These PDRs assess and provide feedback on delivery of individual objectives and demonstration of company values but are not a replacement for real-time, informal feedback which we recognize is important to drive business results.

An employee's end of year PDR is used to determine compensation awards so as to drive a pay for performance culture, including annual merit increases, bonuses, and equity awards (offered to every single employee).

Our annual bonus budget is approved by the Remuneration Committee after reviewing the Company annual scorecard achievement relative to delivering on company goals.

An employee's end of year PDR is used to determine compensation awards so as to drive a pay-for-performance culture, including annual merit increases, bonuses, and equity awards (offered to every employee).

Our annual bonus budget is approved by the Remuneration Committee after reviewing our annual scorecard achievement relative to delivering on company goals.

Our merit budget is approved annually by the Remuneration Committee for base pay adjustments for our global organization, taking into account a variety of factors, including competitive, forward-looking benchmarking data.

We believe that continued growth and development are essential to the professional well-being of our team.

We also want each individual employee to own their career, contribute to high-performing teams through access to training, continuous learning programs and other development initiatives, as well as constructive feedback.

During 2024, we introduced a global bonus structure that aligned all employees in the same job level with the same short-term incentive opportunity.

Staying in good health, mind and body, is important to us, which is why we offer employees a range of benefits including those to support retirement, health and wellness, maturity and parental benefits and an employee assistance program among other benefits, so that they can thrive at work as well as at home, but have the protection they need, and enjoy all things in life.

We also want each individual employee to own their career, contribute to healthy high-performing teams through access to training, continuous learning programs and other development initiatives, as well as constructive feedback.

We also have a global bonus structure that aligns all employees in the same job level with the same short-term incentive opportunity.

Staying in good health, mind and body, is important to us, which is why we offer employees a range of benefits including those to support retirement, health and wellness, maternity and parental benefits and an employee assistance program among other benefits, so that they can thrive at work as well as at home, but have the protection they need, and enjoy all things in life.

We always strive to identify ways to improve what we do and how we do.

That is why we regularly conduct an employee survey.

We have a highly engaged workforce and our 2023 employee survey data had a high response rate and showed an improvement in engagement versus the previous survey conducted in 2021.

We have a highly engaged workforce and our 2023 employee survey data had a high response rate and showed a significant improvement in engagement versus the previous survey conducted in 2021.

We will be conducting our next survey in 2026.

Corporate Information

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Our principal executive offices are located at 92 Park Drive, Milton Park, Abingdon, Oxfordshire OX14 4RY, United Kingdom, and the telephone number of our registered office is +44 (0)1235 438600.

We also have offices in the United States at Six Tower Bridge, Suite 200, 181 Washington Street, Conshohocken, Pennsylvania 19428 and 9801 Washingtonian Boulevard, Suite 800, Gaithersburg, Maryland 20878, United States, and our U.S.

We also have offices in the United States at 1 Radnor Corporate Center, 100 Matsonford Road, Suite 100, Radnor, Pennsylvania 19087, United States and 9801 Washingtonian Boulevard, Suite 800, Gaithersburg, Maryland 20878, United States, and our U.S.

telephone number is +1 484-534-5261.

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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 1. Business