Autogene cevumeran

BioNTech on track for a catalyst-rich year with six late-stage data readouts expected across immunomodulators, antibody-drug conjugates and mRNA cancer immunotherapies Increased focus on PD-L1 1 /VEGF-A bispecific immunomodulator pumitamig with e ight global Phase 3 clinical trials planned to be ongoing for year-end in collaboration with Bristol Myers Squibb Full year 2025 revenues of €2.9 billion 2 , net loss of €1.1 billion (adjusted 3 net loss of €0.1 billion) and diluted loss per share of €4.70 ($5.31 4 ) (adjusted 3 diluted loss per share of €0.48 ($0.55 4 )) Strong financial position continues to de-risk execution with cash, cash equivalents and security investments of €17.2 billion 5 Expect 2026 total revenues of €2.0 billion to €2.3 billion, adjusted 3 R&D expenses between €2.2-2.5 billion and adjusted 3 SG&A expenses 7 between €700-800 million BioNTech co-founders Ugur Sahin and Özlem Türeci to establish an independent company  with a focus on next-generation mRNA innovations; management transition by end of 2026 Conference call and webcast scheduled for March 10, 2026, at 8:00 a.m. EDT (1:00 p.m. CET) MAINZ, Germany, March 10, 2026 (GLOBE NEWSWIRE) -- BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) today reported financial results for the three months and full year ended December 31, 2025 and provided an update on its corporate progress. “2025 was a year of strong execution and pipeline momentum, marked by substantial progress in delivering on our strategy. We advanced our oncology pipeline by moving multiple programs into late-stage development and initiated trials assessing novel-novel combination approaches with the aim of delivering differentiated therapeutic pro ” said Prof. Ugur Sahin, M.D., Chief Executive Officer and Co-Founder of BioNTech . “With our unique pipeline and strong financial position, we remain committed to leveraging our pioneering position in the immuno-oncology space with next-generation agents designed to elevate outcomes for patients with cancer. 2026 is poised to be a pivotal year with multiple readouts expected across our portfolio, representing a significant step toward our objective of becoming a multi-product company by 2030.” Financial Review for Fourth Quarter and Full Year 2025 3 in millions €, except per share data Full Year 2025 Full Year 2024 IFRS Results Adjusted Results 3 IFRS Results Adjusted Results 3 Revenues 2,869.9 2,869.9 2,751.1 2,751.1 Net profit / (loss) (1,136.1) (117.1) (665.3) 121.7 Diluted earnings / (loss) per share (4.70) (0.48) (2.77) 0.50 in millions €, except per share data Fourth Quarter 2025 Fourth Quarter 2024 IFRS Results Adjusted Results 3 IFRS Results Adjusted Results 3 Revenues 907.4 907.4 1,190.0 1,190.0 Net profit / (loss) (305.0) (79.5) 259.5 432.4 Diluted earnings / (loss) per share (1.25) (0.33) 1.08 1.79 Revenues for the three months ended December 31, 2025 were €907.4 million, compared to €1,190.0 million for the comparative prior year period. For the year ended December 31, 2025, revenues were €2,869.9 million, compared to €2,751.1 million for the comparative prior year period. The quarterly year-on-year decrease was primarily driven by lower sales of the Company’s COVID-19 vaccines due to reduced market demand. The full year revenue increase was primarily driven by revenues related to BioNTech’s collaboration with Bristol Myers Squibb Company (“BMS”) that were recognized in the third quarter of 2025. Research and development (“R&D”) expenses were €505.4 million for the three months ended December 31, 2025, compared to €611.8 million for the comparative prior year period. For the year ended December 31, 2025, R&D expenses were €2,104.9 million, compared to €2,254.2 million for the comparative prior year period. Both quarterly and full year year-on-year decreases were mainly driven by cost savings resulting from active portfolio management and positive effects resulting from our pumitamig cost sharing with BMS, partly offset by the acceleration of late-stage trials for immuno-oncology (“IO”) and antibody-drug conjugate (“ADC”) development programs. Adjusted R&D expenses were €505.4 million for the three months ended December 31, 2025, compared to €530.3 million for the comparative prior year period. For the year ended December 31, 2025, adjusted R&D expenses were €2,019.5 million, compared to €2,172.7 million for the comparative prior year period. For 2025 and 2024, the Company’s adjusted R&D expenses exclude impairments. Sales, general and administrative (“SG&A”) expenses 7 were €217.9 million for the three months ended December 31, 2025, compared to €132.1 million for the comparative prior year period. For the year ended December 31, 2025, SG&A expenses were €624.4 million, compared to €599.0 million for the comparative prior year period. Both quarterly and full year year-on-year increases were mainly driven by our ongoing commercial build-up, partly offset by lower costs for external services. Other operating result was negative €173.6 million during the three months ended December 31, 2025, compared to negative €54.0 million for the comparative prior year period. For the year ended December 31, 2025, other operating result was negative €903.7 million compared to negative €670.9 million for the prior year period. Both quarterly and full year year-on-year decreases were primarily driven by expenses from settlements of contractual disputes, expenses in connection with our pipeline prioritization and foreign exchange differences. Adjusted other operating result was €21.4 million during the three months ended December 31, 2025, compared to negative €1.6 million for the comparative prior year period. For the year ended December 31, 2025, other operating result was negative €0.6 million compared to negative €13.5 million for the prior year period. For fiscal years 2025 and 2024, our quarterly and full year adjusted other operating results exclude expenses in connection with the settlements of legal proceedings. In addition, our quarterly and full year adjusted other operating results during fiscal year 2025 exclude employee-related costs in connection with our pipeline prioritization and a bargain purchase. Net loss was €305.0 million for the three months ended December 31, 2025, compared to a net income of €259.5 million for the comparative prior year period. For the year ended December 31, 2025, net loss was €1,136.1 million, compared to a net loss of €665.3 million for the comparative prior year period. Adjusted net loss was €79.5 million for the three months ended December 31, 2025, compared to an adjusted net profit of €432.4 million for the comparative prior year period. For the year ended December 31, 2025, adjusted net loss was €117.1 million, compared to an adjusted net profit of €121.7 million for the comparative prior year period. Diluted loss per share was €1.25 for the three months ended December 31, 2025, compared to diluted earnings per share of €1.08 for the comparative prior year period. For the year ended December 31, 2025, diluted loss per share was €4.70, compared to diluted loss per share of €2.77 for the comparative prior year period. Adjusted diluted loss per share was €0.33 for the three months ended December 31, 2025, compared to adjusted diluted earnings per share of €1.79 for the comparative prior year period. For the year ended December 31, 2025, adjusted diluted loss per share was €0.48, compared to adjusted diluted earnings per share of €0.50 for the comparative prior year period. Cash, cash equivalents and security investments as of December 31, 2025 were €17,235.6 million, comprising €7,675.4 million in cash and cash equivalents, €7,158.5 million in current security investments disclosed as financial assets and €2,401.7 million in non-current security investments disclosed as financial assets. Shares outstanding as of December 31, 2025 were 251,325,340, excluding 7,702,147 shares held in treasury. “Our strong financial position fuels and de-risks our R&D activities as we prepare for multiple product launches in the coming years. Our financial discipline, active portfolio management and targeted investments will continue to drive innovation and create long-term value for BioNTech’s stakeholders,” said Ramón Zapata, Chief Financial Officer at BioNTech . 2026 Financial Year Guidance 6 : Revenues for the 2026 financial year €2,000 – €2,300 m In 2026, BioNTech anticipates lower COVID-19 vaccine revenues compared to 2025, driven by declines in both the European and United States markets. The United States continues to be a competitive and dynamic market, where as a result, lower revenues are expected. In Europe, we expect lower revenues as we defend our market share and begin managing the transition of multi-year contracts. In Germany, specifically, BioNTech recognizes direct sales of its COVID-19 vaccines as revenue. Hence, the anticipated declines in the Company’s sales of COVID-19 vaccines in the country will have a direct impact on its topline, whereas revenues outside of Germany only affect the Company’s topline as part of the 50% gross profit split with our partner Pfizer Inc. (“Pfizer”). Per the outlined partnership terms, revenues from the collaboration with BMS in 2026 are expected to be broadly in line with 2025. Revenues from the pandemic preparedness contract with the German government and service businesses are expected to remain stable. Planned 2026 Financial Year Adjusted Expenses 6 : Adjusted R&D expenses €2,200 – €2,500 m Adjusted SG&A expenses €700 – €800 m BioNTech will continue to focus investments on R&D and scaling the business for late-stage development and commercial readiness in oncology, while remaining cost-disciplined. Strategic capital allocation will continue to foster innovation and be a key driver of the Company’s trajectory. As part of BioNTech’s strategy, the Company may continue to evaluate appropriate corporate development opportunities with the aim of driving sustainable long-term growth and creating future value. The full audited consolidated financial statements as of and for the year ended December 31, 2025, can be found in BioNTech’s Annual Report on Form 20-F filed today with the U.S. Securities and Exchange Commission (“SEC”) and available at . Endnotes 1 An overview of abbreviations is compiled in a directory at the end of this press release. 2 All numbers in this press release have been rounded. 3 In addition to BioNTech’s results determined in accordance with International Financial Reporting Standards (“IFRS”), or IFRS Accounting Standards, or IFRS results, BioNTech reports certain adjusted, non-IFRS measures used internally as a supplemental measure of our business performance (each referred to with the prefix “Adjusted” or, as a whole, “Adjusted Results”). The calculation of these measures and the adjusted results as a whole is based on the concepts of the applicable IFRS Accounting Standards, but includes certain adjustments. Reconciliation of the adjusted results to BioNTech’s measures based on IFRS Accounting Standards and more information can be found at the end of this press release and in BioNTech’s Report on Form 20-F for the year ended December 31, 2025 filed on March 10, 2026, which is available at . While non-IFRS measures may offer additional insights, BioNTech’s non-IFRS measures are not, and should not be viewed as, a substitute for their most directly comparable IFRS Accounting Standards measures, and should always be considered alongside our financial statements prepared in accordance with IFRS Accounting Standards. 4 Calculated applying the average foreign exchange rate for the year ended December 31, 2025, as published by the German Central Bank (Deutsche Bundesbank). 5 As of December 31, 2025. 6 Excludes risks that are not yet known and/or quantifiable and related activities. It includes effects identified from licensing arrangements, collaborations and Merger & Acquisitions (“M&A”) transactions to the extent disclosed. The guidance is based on non-IFRS measures and excludes certain effects compared to measures based on IFRS Accounting Standards. More information can be found in BioNTech’s Report on Form 20-F for the year ended December 31, 2025 filed on March 10, 2026, which is available at . 7 Sales, general and administrative expenses (“SG&A”) include sales and marketing expenses as well as general and administrative expenses. Adjusted SG&A expenses include adjusted sales and marketing expenses as well as adjusted general and administrative expenses. Operational Review for the Fourth Quarter and Full Year 2025, Key Post Period-End Events and Outlook on 2026 Corporate Update for the Fourth Quarter 2025 and Post Period Events On March 10, 2026, BioNTech announced plans for an independent company to be established and led by BioNTech co-founders Prof. Ugur Sahin, M.D., and Prof. Özlem Türeci, M.D. The new company with distinct resources, operations and funding options will advance next-generation mRNA innovations. BioNTech plans to contribute related rights and mRNA technologies to the new company to enable and support the prioritized development of next-generation mRNA innovations with disruptive potential. With both companies focusing on their respective strategic priorities, BioNTech expects to maximize value for patients and shareholders alike. Ugur Sahin and Özlem Türeci will transition into the management of their new company by the end of 2026 after their current service agreements end. BioNTech’s Supervisory Board has initiated an executive search to identify successors for the positions to ensure a smooth transition and seamless execution of BioNTech’s strategy. On March 1, Kylie Jimenez joined BioNTech’s Management Board as Chief People Officer (“CPO”). The appointment is in line with BioNTech’s strategy to become a multi-product biopharmaceutical company by 2030 and underscores the importance of its global, highly skilled workforce in achieving this objective. Kylie will focus on attracting, developing and retaining talent, while strengthening an inclusive culture. Select Oncology Pipeline Updates Next-Generation Immunomodulators and Combinations Pumitamig (BNT327/BMS986545) is a bispecific immunomodulator candidate combining PD-L1 checkpoint inhibition with VEGF-A neutralization that is being developed in collaboration with BMS. A global Phase 3 clinical trial in patients with first-line triple-negative breast cancer (“TNBC”) (ROSETTA Breast-01; NCT07173751 ) is enrolling. A global Phase 2/3 clinical trial to evaluate pumitamig in first-line microsatellite stable colorectal cancer (“CRC”) (ROSETTA CRC-203; NCT07221357 ) is enrolling. A global Phase 2/3 clinical trial to evaluate pumitamig in first-line gastric cancer (ROSETTA Gastric-204; NCT07221149 ) is enrolling. A global Phase 2/3 clinical trial (ROSETTA Lung-02; NCT06712316 ) is ongoing to evaluate pumitamig in combination with chemotherapy compared to pembrolizumab and chemotherapy in patients with first-line non-small cell lung cancer (“NSCLC”). The Phase 2 part of the seamless Phase 2/3 trial achieved full enrollment and the Phase 3 portion is currently recruiting. Data from the Phase 2 part of the trial are expected in 2026. Additional pivotal Phase 2/3 and Phase 3 trials are planned to start in 2026, in unresectable stage III NSCLC (ROSETTA Lung-201, NCT07361497 ), first-line PD-L1 ≥ 50% NSCLC (ROSETTA Lung-202, NCT07361510 ) and first-line head and neck squamous cell carcinoma (“HNSCC”) (ROSETTA HNSCC-205). Pumitamig is also being evaluated in additional solid tumor indications, including first-line hepatocellular carcinoma (“HCC”), second-line glioblastoma (“GBM”), first-line pancreatic ductal adenocarcinoma (“PDAC”) and first-line renal cell carcinoma (“RCC”) in various Phase 1/2 and Phase 2 trials, both as monotherapy and in combination with standard of care. In 2025, BioNTech initiated several signal-seeking clinical trials to evaluate pumitamig with the Company’s proprietary assets. These trials will inform the dose selection for pumitamig and explore anti-tumor activity in multiple tumors for later-stage development. Gotistobart (BNT316/ONC-392) is a tumor microenvironment-selective regulatory T cell depletion candidate that targets CTLA-4 and is being developed in collaboration with OncoC4, Inc. (“OncoC4”). A global Phase 3 clinical trial (PRESERVE-003; NCT05671510 ) is ongoing to evaluate the efficacy and safety of gotistobart as monotherapy in patients with metastatic squamous NSCLC (“sqNSCLC”) that progressed under previous platinum-based chemotherapy and PD-(L)1-inhibitor treatment. In December 2025, data from the non-pivotal dose-confirmation stage, the first of two stages of the global Phase 3 clinical trial, were presented at the International Association for the Study of Lung Cancer (“IASLC”) American Society of Clinical Oncology (“ASCO“) 2025 North America Conference on Lung Cancer (“NACLC”). Gotistobart demonstrated a clinically meaningful overall survival benefit compared to standard of care chemotherapy and a manageable safety pro patients with squamous NSCLC whose disease had progressed following anti-PD-(L)1 therapy and platinum-based chemotherapy. Based on current event accrual projections, interim data from the pivotal stage of the two-stage Phase 3 clinical trial are expected in 2026. In January 2026, gotistobart received Orphan Drug Designation from the U.S. Food and Drug Administration (“FDA”) for the treatment of squamous NSCLC. In 2022, gotistobart received Fast Track Designation from the FDA for the treatment of patients with metastatic NSCLC whose disease progressed on prior anti-PD-(L)1 therapy. Antibody-Drug Conjugates Trastuzumab pamirtecan (BNT323/DB-1303) is an ADC candidate targeting HER2 that is being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. (“DualityBio”). A Phase 1/2 clinical trial ( NCT05150691 ) is ongoing to evaluate trastuzumab pamirtecan in patients with advanced HER2-expressing tumors. A potentially registrational cohort with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) patients with recurrent endometrial cancer is ongoing. Data are expected to be shared at a medical conference in 2026. BioNTech and DualityBio plan to biologics license application (“BLA”) in 2026, subject to regulatory feedback from the FDA. A global Phase 3 clinical trial (DYNASTY-Breast02, NCT06018337 ) to evaluate trastuzumab pamirtecan in patients with HR-positive, HER2-low metastatic breast cancer is ongoing. Based on current event accrual projections, data are expected in 2026. BNT324 /DB-1311 is an ADC candidate targeting B7H3 that is being developed in collaboration with DualityBio. In February 2026, updated data from a Phase 1/2 clinical trial ( NCT05914116 ) were presented at the ASCO Genitourinary Cancers Symposium. BNT324/DB-1311 demonstrated durable efficacy in heavily pretreated metastatic castration-resistant prostate cancer (“mCRPC”) patients with no new safety signals reported. A Phase 3 clinical trial ( NCT07365995 ) to evaluate BNT324/DB-1311 compared to docetaxel in patients with mCRPC is expected to initiate in 2026. mRNA Cancer Immunotherapies BNT113 is an mRNA cancer immunotherapy candidate and based on BioNTech’s fully owned, off-the-shelf FixVac platform, encoding the two oncoproteins E6 and E7 that are frequently found in human papillomavirus type 16 positive (“HPV16+”) solid tumors. In December 2025, the FDA granted Fast Track designation to BNT113 for the treatment of patients with PD-L1+, HPV16+ HNSCC. Based on current event accrual projections, data are expected in 2026 from the first interim analysis of the Phase 3 part of the ongoing Phase 2/3 clinical trial (AHEAD-MERIT; NCT04534205 ) evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment for patients with unresectable recurrent or metastatic, PD-L1+, HPV16+ HNSCC. Autogene cevumeran (BNT122/RO7198457) is an mRNA cancer immunotherapy candidate for individualized neoantigen-specific immunotherapy (“iNeST”) that is being developed in collaboration with Genentech, Inc. (“Genentech”), a member of the Roche Group (“Roche”). An update from the ongoing Phase 2 clinical trial in Stage II (high-risk)/Stage III circulating tumor DNA positive (“ctDNA+”) adjuvant colorectal cancer (“CRC”) is expected in early 2026. Data read-out from the final analysis of this trial has been updated from 2026 to 2027, given that events have accrued more slowly than projected. BioNTech and Roche, the sponsor of the trial, have decided to discontinue the Phase 2 clinical trial (IMcode004; NCT06534983 ) evaluating autogene cevumeran as an adjuvant treatment in combination with nivolumab compared to nivolumab alone in patients with high-risk muscle-invasive urothelial carcinoma due to the rapidly emerging treatment landscape and shifting standard of care. The companies will focus on advancing autogene cevumeran in the currently ongoing randomized Phase 2 clinical trials in adjuvant pancreatic ductal adenocarcinoma (“PDAC”) and adjuvant CRC. Expected 2026 Milestones Program Modality Trial Readout Phase Indication Late-Stage Trial Readouts Trastuzumab pamirtecan 3 ADC Single-arm Phase 2 2L+ HER2-expressing endometrial cancer Phase 3 interim analysis Chemo naïve HR+ HER2-low breast cancer Gotistobart 2 Immunomodulator Phase 3 interim analysis 2L+ sqNSCLC Phase 2 2L+ mCRPC BNT113 mRNA cancer immunotherapy Phase 3 interim analysis 1L HPV16+ PD-L1+ HNSCC Pumitamig 1 Immunomodulator Phase 3 in China interim analysis 1L TNBC Early-Stage Pumitamig & ADC Trial Readouts Pumitamig 1 Immunomodulator Phase 2 1L NSCLC Phase 2 1L extensive-stage small-cell lung cancer (“ES-SCLC”) Phase 2 in China 1L HCC Phase 2 in China 1L microsatellite stable colorectal cancer (“MSS-CRC”) Pumitamig 1 + Trastuzumab pamirtecan (HER2-ADC) 3 Immunomodulator + ADC Phase 1/2 Breast cancer Pumitamig 1 + BNT324/DB-1311 (B7H3-ADC) 3 Phase 1/2 Advanced solid tumors Phase 2 NSCLC/SCLC Pumitamig 1 + BNT325/DB-1305 (TROP2-ADC) 3 Phase 2 TNBC Pumitamig 1 + BNT326/YL202 (HER3-ADC) 4 Phase 1/2 NSCLC BNT324/DB-1311 (B7H3-ADC) 3 ADC Phase 1/2 2L+ mCRPC Phase 3 Trial Initiations Pumitamig 1 Immunomodulator Phase 3 1L MSS-CRC Phase 3 1L HER2- PD-L1+ gastric cancer Phase 3 1L HNSCC Phase 3 NSCLC stage 3 unresectable Phase 3 1L NSCLC PD-L1 high BNT324 /DB-1311 (B7H3-ADC) 3 ADC Phase 3 1L mCRPC BLA Submission Trastuzumab pamirtecan (HER2-ADC) 3 ADC - 2L+ HER2-expressing endometrial cancer Partnered with: 1. BMS; 2. OncoC4; 3. DualityBio; 4. MediLink Therapeutics (Suzhou) Co., Ltd. (“MediLink"). Upcoming Investor and Analyst Events BioNTech First Quarter 2026 Financial Results and Corporate Update: May 5, 2026 BioNTech Annual General Meeting: May 15, 2026 Conference Call and Webcast Information BioNTech invites investors and the general public to join a conference call and webcast with investment analysts today, March 10, 2026, at 8:00 a.m. EDT (1:00 p.m. CET) to report its financial results and provide a corporate update for the fourth quarter and full year 2025. To access the live conference call via telephone, please register via this link . Once registered, dial-in numbers and a PIN number will be provided. The slide presentation and audio of the webcast will be available via this link . Participants may also access the slides and the webcast of the conference call via the “Events & Presentations” page of the Investor section of the Company’s website at A replay of the webcast will be made available shortly after the closing of the call and archived on the Company’s website for 30 days following the call. About BioNTech Biopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel investigative therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic modalities with the intent of rapid development of novel biopharmaceuticals. Its diversified portfolio of oncology product candidates aiming to address the full continuum of cancer includes mRNA cancer immunotherapies, next-generation immunomodulators and targeted therapies such as antibody-drug conjugates (ADCs) and innovative chimeric antigen receptor (CAR) T cell therapies. Based on its deep expertise in mRNA development and in-house manufacturing capabilities, BioNTech and its collaborators are researching and developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Bristol Myers Squibb, Duality Biologics, Genentech, a member of the Roche Group, Genmab, MediLink, OncoC4, Pfizer and Regeneron. For more information, please visit Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: expected changes to BioNTech’s leadership and the transition of responsibilities at the Management Board, including identification and recruitment of successors; the terms of the preliminary discussions between BioNTech and the co-founders regarding the potential contribution of certain BioNTech assets to an independent company; BioNTech’s expected revenues and net profit/(loss) related to sales of BioNTech’s COVID-19 vaccine in territories controlled by BioNTech’s collaboration partners, particularly for those figures that are derived from preliminary estimates provided by BioNTech’s partners; the rate and degree of market acceptance of BioNTech’s COVID-19 vaccine and, if approved, BioNTech’s investigational medicines; expectations regarding anticipated changes in COVID-19 vaccine demand; the initiation, timing, progress, results, and cost of BioNTech’s research and development programs, including BioNTech’s current and future preclinical studies and clinical trials, including statements regarding the expected timing of initiation, enrollment, and completion of studies or clinical trials and related preparatory work and the availability of results, and the timing and outcome of applications for regulatory approvals and marketing authorizations; BioNTech’s expectations regarding potential future commercialization in oncology, including goals regarding timing and indications; the targeted timing and number of additional potentially registrational clinical trials, and the registrational potential of any clinical trial BioNTech may initiate; discussions with regulatory agencies; BioNTech’s expectations with respect to intellectual property; the impact of BioNTech’s collaboration and licensing agreements, including BioNTech’s partnership with Bristol Myers Squibb; BioNTech’s expectations with respect to developments in law, public policy, and international trade; BioNTech’s estimates of revenues, research and development expenses, selling, general and administrative expenses and capital expenditures for operating activities; BioNTech’s expectations for upcoming scientific and investor presentations; and BioNTech’s expectations of net profit/(loss). In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are based on BioNTech’s current expectations and beliefs of future events, and are neither promises nor guarantees. You should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond BioNTech’s control and which could cause actual results to differ materially and adversely from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to: the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, projected data release timelines, regulatory submission dates, regulatory approval dates and/or launch dates, as well as risks associated with preclinical and clinical data, including the data discussed in this release, and including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the nature of the clinical data, which is subject to ongoing peer review, regulatory review and market interpretation; BioNTech’s pricing and coverage negotiations with governmental authorities, private health insurers and other third-party payors; the future commercial demand and medical need for initial or annual booster doses of a COVID-19 vaccine; the impact of tariffs and escalations in trade policy; competition from other COVID-19 vaccines or related to BioNTech’s other product candidates; the timing of and BioNTech’s ability to obtain and maintain regulatory approval for its product candidates; the ability of BioNTech’s COVID-19 vaccines to prevent COVID-19 caused by emerging virus variants; BioNTech’s ability to identify research opportunities and discover and develop investigational medicines; the ability and willingness of BioNTech’s third-party collaborators to continue research and development activities relating to BioNTech's development candidates and investigational medicines; unforeseen safety issues and potential claims that are alleged to arise from the use of products and product candidates developed or manufactured by BioNTech; BioNTech’s and its collaborators’ ability to commercialize and market its product candidates, if approved; BioNTech’s ability to manage its development and related expenses; regulatory and political developments; BioNTech’s ability to effectively scale its production capabilities and manufacture its products and product candidates; risks relating to the global financial system and markets; and other factors not known to BioNTech at this time. You should review the risks and uncertainties described under the heading “Risk Factors” in BioNTech’s Annual Report on Form 20-F for the period ended December 31, 2025 and in subsequent filings made by BioNTech with the SEC, which are available on the SEC’s website at . These forward-looking statements speak only as of the date hereof. Except as required by law, BioNTech disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. CONTACTS Investor Relations Douglas Maffei, PhD Investors@biontech.de Media Relations Jasmina Alatovic Media@biontech.de Abbreviation Overview 1L First line 2L Second line adj. Adjuvant B7H3 B7 homologue B3 (MSS-)CRC (Microsatellite stable-) colorectal cancer ctDNA Circulating tumor DNA CTLA-4 Cytotoxic T-lymphocyte-associated protein ES-SCLC Extensive-stage small cell lung cancer GBM Glioblastoma HCC Hepatocellular carcinoma HER2 (or HER3) Human epidermal growth factor receptor 2 (or 3) HNSCC Head and neck squamous cell carcinoma HPV16 Human papilloma virus 16 HR Hormone receptor IHC3+, 2+, 1+ Immunohistochemistry score 1+ (or 2+ or 3+) ISH-positive In-situ hybridization positive mCRPC Metastatic castration resistant prostate cancer RCC Renal cell carcinoma (sq) NSCLC (Squamous) non-small cell lung cancer PDAC Pancreatic ductal adenocarcinoma PD-(L)1 Programmed cell death protein (death-ligand) 1 TNBC Triple-negative breast cancer TROP2 Trophoblast cell-surface antigen 2 VEGF-A Vascular endothelial growth factor A Consolidated Statements of Profit or Loss (IFRS Results) Three months ended December 31, Years ended December 31, 2025 2024 2025 2024 (in millions €, except per share data) (unaudited) (unaudited) Revenues 907.4 1,190.0 2,869.9 2,751.1 Cost of sales (333.3) (243.5) (641.8) (541.3) Research and development expenses (505.4) (611.8) (2,104.9) (2,254.2) Sales and marketing expenses (49.3) (21.3) (110.0) (67.9) General and administrative expenses (168.6) (110.8) (514.4) (531.1) Other operating expenses (208.0) (91.6) (1,088.3) (811.5) Other operating income 34.4 37.6 184.6 140.6 Operating profit / (loss) (322.8) 148.6 (1,404.9) (1,314.3) Finance income 99.6 165.2 423.9 664.0 Finance expenses (4.2) (12.6) (69.8) (27.4) Profit / (Loss) before tax (227.4) 301.2 (1,050.8) (677.7) Income taxes (77.6) (41.7) (85.3) 12.4 Net profit / (loss) (305.0) 259.5 (1,136.1) (665.3) Earnings / (Loss) per share Basic earnings / (loss) per share (1.25) 1.08 (4.70) (2.77) Diluted earnings / (loss) per share (1.25) 1.08 (4.70) (2.77) Condensed Consolidated Statements of Profit or Loss (Adjusted Results) Adjusted Results (non-IFRS measures) 1 Three months ended December 31, Years ended December 31, 2025 2024 2025 2024 (in millions €, except per share data) (unaudited) (unaudited) Adjusted cost of sales (302.8) (204.5) (611.3) (493.2) Adjusted research and development expenses (505.4) (530.3) (2,019.5) (2,172.7) Adjusted other operating expenses (13.0) (39.2) (170.2) (154.1) Adjusted other operating income 34.4 37.6 169.6 140.6 Adjusted operating profit / (loss) (97.3) 321.5 (385.9) (527.3) Adjusted profit / (loss) before tax (1.9) 474.1 (31.8) 109.3 Adjusted net profit / (loss) 2 (79.5) 432.4 (117.1) 121.7 Adjusted earnings / (loss) per share Adjusted basic earnings / (loss) per share (0.33) 1.80 (0.48) 0.51 Adjusted diluted earnings / (loss) per share (0.33) 1.79 (0.48) 0.50 1 Certain adjusted results presented in this table are identical to our results under IFRS Accounting Standards. Reconciliation of all other adjusted results to our IFRS results can be found at the end of this press release and in BioNTech’s Report on Form 20-F for the year ended December 31, 2025, filed on March 10, 2026, which is available at 2 Tax effects are not considered as part of our non-IFRS adjustments Consolidated Statements of Financial Position December 31, December 31, (in millions €) 2025 2024 Assets Non-current assets Goodwill 367.9 380.6 Other intangible assets 1,606.0 790.4 Property, plant and equipment 1,080.9 935.3 Right-of-use assets 210.2 248.1 Contract assets 2.0 9.8 Other financial assets 2,554.2 1,254.0 Other non-financial assets 7.3 26.3 Deferred tax assets 13.5 81.7 Total non-current assets 5,842.0 3,726.2 Current assets Inventories 110.7 283.3 Trade and other receivables 924.2 1,463.9 Contract assets 8.1 10.0 Other financial assets 7,201.8 7,021.7 Other non-financial assets 173.8 212.7 Income tax assets 52.6 50.0 Cash and cash equivalents 7,675.4 9,761.9 Total current assets 16,146.6 18,803.5 Total assets 21,988.6 22,529.7 Equity and liabilities Equity Share capital 259.0 248.6 Capital reserve 2,473.3 1,398.6 Treasury shares (7.7) (8.6) Retained earnings 17,961.9 19,098.0 Other reserves (1,462.3) (1,325.5) Total equity 19,224.2 19,411.1 Non-current liabilities Lease liabilities, loans and borrowings 215.2 214.7 Other financial liabilities 94.9 46.9 Provisions 35.5 20.9 Contract liabilities 88.0 183.0 Other non-financial liabilities 104.2 87.5 Deferred tax liabilities 84.3 42.4 Total non-current liabilities 622.1 595.4 Current liabilities Lease liabilities, loans and borrowings 52.2 39.5 Trade payables and other payables 534.9 426.7 Other financial liabilities 351.7 1,443.4 Income tax liabilities 65.6 4.5 Provisions 145.3 144.8 Contract liabilities 754.9 294.9 Other non-financial liabilities 237.7 169.4 Total current liabilities 2,142.3 2,523.2 Total liabilities 2,764.4 3,118.6 Total equity and liabilities 21,988.6 22,529.7 Consolidated Statements of Cash Flows Three months ended December 31, Years ended December 31, 2025 2024 2025 2024 (in millions €) (unaudited) (unaudited) Operating activities Net profit / (loss) (305.0) 259.5 (1,136.1) (665.3) Income taxes 77.6 41.7 85.3 (12.4) Profit / (Loss) before tax (227.4) 301.2 (1,050.8) (677.7) Adjustments to reconcile loss before tax to net cash flows: Depreciation, amortization and impairment of property, plant, equipment, intangible assets and right-of-use assets 164.8 165.4 382.8 298.0 Share-based payment expenses 24.1 23.5 106.2 100.9 Net foreign exchange differences (43.0) (32.1) (6.6) (109.5) (Gain) / Loss on disposal of property, plant and equipment (0.8) (0.1) (2.5) (0.3) Finance income excluding foreign exchange differences (99.1) (149.7) (423.9) (648.5) Finance expense excluding foreign exchange differences 4.3 12.6 21.4 27.4 Government grants (19.5) (4.7) (63.0) (31.5) Other non-cash (income) / loss 600.4 — 585.4 — Unrealized (gain) / loss on derivative instruments at fair value through profit or loss 2.5 3.9 (10.4) 4.6 Working capital adjustments: (Increase) / Decrease in trade and other receivables, contract assets and other assets 81.0 (879.9) 1,083.7 387.7 Decrease in inventories 116.2 19.9 177.9 74.5 (Decrease) / Increase in trade payables, other financial liabilities, other liabilities, contract liabilities, refund liabilities and provisions (424.6) 167.7 (723.8) 758.4 Interest received and realized gains from cash and cash equivalents 61.8 121.6 337.0 474.9 Interest paid and realized losses from cash and cash equivalents (2.8) (6.6) (11.0) (13.5) Income tax received / (paid), net 40.5 (198.4) 3.8 (389.2) Share-based payments (6.0) (10.9) (25.3) (154.5) Government grants received 37.1 3.3 75.1 106.0 Net cash flows from operating activities 309.5 (463.3) 456.0 207.7 Investing activities Purchase of property, plant and equipment (63.2) (66.6) (175.1) (286.5) Proceeds from sale of property, plant and equipment 0.6 0.7 4.5 1.2 Purchase of intangible assets 1.1 (24.5) (573.9) (165.8) Acquisition of subsidiaries and businesses, net of cash acquired 264.8 — 186.3 — Investment in other financial assets (4,375.8) (2,068.8) (11,422.5) (12,370.3) Proceeds from maturity of other financial assets 1,446.9 2,765.9 9,512.2 10,740.2 Net cash flows used in investing activities (2,725.6) 606.7 (2,468.5) (2,081.2) Financing activities Proceeds from loans and borrowings 6.7 — 6.7 — Repayment of loans and borrowings (8.6) — (18.0) (2.3) Payments related to lease liabilities (10.4) (7.3) (39.6) (43.6) Transaction costs related to issuance of share capital (2.0) — (2.0) — Net cash flows used in financing activities (14.3) (7.3) (52.9) (45.9) Net decrease in cash and cash equivalents (2,430.4) 136.1 (2,065.4) (1,919.4) Change in cash and cash equivalents resulting from exchange rate differences 1.4 13.6 (27.0) 14.8 Change in cash and cash equivalents resulting from other valuation effects 11.5 (12.4) 5.9 2.8 Cash and cash equivalents at the beginning of the period 10,092.9 9,624.6 9,761.9 11,663.7 Cash and cash equivalents as of December 31 7,675.4 9,761.9 7,675.4 9,761.9 Non-IFRS Reconciliation Non-IFRS Reconciliation for the year ended December 31, 2025 non-IFRS adjustments (in millions €, except per share data) IFRS Results Expenses and income from legal proceedings Impairment and reversal Employee-related expenses from restructuring Income from bargain purchase and income and expenses from divestiture related items Adjusted Results Cost of sales (641.8) — 30.5 — — (611.3) Research and development expenses (2,104.9) — 85.4 — — (2,019.5) Other operating expenses (1,088.3) 789.5 71.6 57.0 — (170.2) Other operating income 184.6 — — — (15.0) 169.6 Operating loss (1,404.9) 789.5 187.5 57.0 (15.0) (385.9) Loss before tax (1,050.8) 789.5 187.5 57.0 (15.0) (31.8) Net loss 1 (1,136.1) 789.5 187.5 57.0 (15.0) (117.1) Loss per share Basic loss per share (4.70) (0.48) Diluted loss per share (4.70) (0.48) 1 Tax effects are not considered as part of our non-IFRS adjustments. Non-IFRS Reconciliation for the three months ended December 31, 2025 non-IFRS adjustments (in millions €, except per share data) IFRS Results Expenses and income from legal proceedings Impairment and reversal Employee-related expenses from restructuring Income from bargain purchase and income and expenses from divestiture related items Adjusted Results (unaudited) Cost of sales (333.3) — 30.5 — — (302.8) Other operating expenses (208.0) 111.4 71.6 12.0 — (13.0) Operating loss (322.8) 111.4 102.1 12.0 — (97.3) Loss before tax (227.4) 111.4 102.1 12.0 — (1.9) Net loss 1 (305.0) 111.4 102.1 12.0 — (79.5) Loss per share Basic loss per share (1.25) (0.33) Diluted loss per share (1.25) (0.33) 1 Tax effects are not considered as part of our non-IFRS adjustments. Non-IFRS Reconciliation for the year ended December 31, 2024 non-IFRS adjustments (in millions €, except per share data) IFRS Results Expenses and income from legal proceedings Impairment and reversal Employee-related expenses from restructuring Income from bargain purchase and income and expenses from divestiture related items Adjusted Results Cost of sales (541.3) — 48.1 — — (493.2) Research and development expenses (2,254.2) — 81.5 — — (2,172.7) Other operating expenses (811.5) 657.4 — — — (154.1) Operating loss (1,314.3) 657.4 129.6 — — (527.3) Profit / (Loss) before tax (677.7) 657.4 129.6 — — 109.3 Net profit / (loss) 1 (665.3) 657.4 129.6 — — 121.7 Earnings / (Loss) per share Basic earnings / (loss) per share (2.77) 0.51 Diluted earnings / (loss) per share (2.77) 0.50 1 Tax effects are not considered as part of our non-IFRS adjustments. Non-IFRS Reconciliation for the three months ended December 31, 2024 non-IFRS adjustments (in millions €, except per share data) IFRS Results Expenses and income from legal proceedings Impairment and reversal Employee-related expenses from restructuring Income from bargain purchase and income and expenses from divestiture related items Adjusted Results (unaudited) Cost of sales (243.5) — 39.0 — — (204.5) Research and development expenses (611.8) — 81.5 — — (530.3) Other operating expenses (91.6) 52.4 — — — (39.2) Operating profit 148.6 52.4 120.5 — — 321.5 Profit before tax 301.2 52.4 120.5 — — 474.1 Net profit 1 259.5 52.4 120.5 — — 432.4 Earnings per share Basic earnings per share 1.08 1.80 Diluted earnings per share 1.08 1.79 1 Tax effects are not considered as part of our non-IFRS adjustments. For the three months ended and the year ended December 31, 2023, our adjusted results were identical to our results under IFRS Accounting Standards.

New-generation ICIs set to break biological ceiling With PD-1/CTLA-4 franchises such as Merck’s Keytruda (>$30bn in sales in 2025) reaching maturity, incremental value is shifting to next-generation checkpoints that can address adaptive resistance, extend duration of response, expand responder populations and support lifecycle management. Bristol Myers Squibb’s (BMS’s) Opdualag (LAG-3/PD-1 combination) provides the first commercial proof that dual-checkpoint strategies can extend durability and defend PD-1 backbones. We expect assets showing additive efficacy with PD-1/CTLA-4s and favourable safety are most likely to secure partnering and premium valuations. Cancer vaccines as immune-priming platforms Next-generation cancer vaccines are transitioning from monotherapy setbacks to high-value immune-priming partners capable of generating high-avidity, tumour-specific responses and converting immunologically cold tumours into ‘hot’ tumours. Moderna/Merck’s mRNA vaccine V940/mRNA-4157 provides the clearest validation in melanoma studies. We see cancer vaccines’ strongest commercial positioning in combination treatments, earlier-stage and minimal residual disease settings, where durable immune memory supports long treatment windows. Platform scalability, precision biomarker strategies and consistent combination benefit across tumour types will be critical to partnering activity and peak-sales realisation. CAR-T therapies at an inflection point CAR-T therapies (such as Gilead’s Yescarta and Novartis’s Kymriah) deliver potentially curative outcomes in select haematological cancers, but uptake remains constrained by limited solid-tumour efficacy, manufacturing complexity, high cost and toxicities. Next-wave strategies, including allogeneic platforms, bi-specific/multi-targeting constructs programmes and CRS-mitigation approaches, promise to reduce infrastructure intensity and enable earlier-line use, and will determine CAR-T’s evolution from niche therapy to a broader commercial modality. Immuno-oncology: The next phase of value creation Our immune system is naturally built to detect and eliminate abnormal cells while sparing healthy tissue. However, cancer has evolved several ways to evade immune recognition, allowing unchecked tumour growth. While traditional treatments like chemotherapy and radiation can be effective, they are associated with significant side effects. In contrast, IO is a class of cancer therapies that harness, activate or engineer the body’s natural defence mechanisms to recognise and destroy tumour cells, effectively removing the ‘brakes’ that cancer places on the immune system. Since approval, IO has reshaped cancer care, led by ICIs that have become the backbone treatment across multiple solid tumour types. Yet the first ICI wave has also exposed clear constraints: response rates remain limited in many indications, resistance emerges frequently and some tumour types remain stubbornly ‘cold’. In parallel, haematological malignancies remain an untapped frontier where ICIs have delivered more modest outcomes. The growing challenge is no longer whether immunotherapy works, but how to make it work for the majority of patients, across a broader range of tumours, with acceptable safety, cost and scalability. The next phase of value creation is therefore less about a single breakthrough drug and more about expanding the responder pool and durability of benefit through new checkpoint targets beyond the current PD-(L)1 and CTLA-4 combination strategies that address tumour-resistance mechanisms and new immunotherapy modalities such as therapeutic cancer vaccines and next-generation cell/CAR-T therapies. Commercially, this evolution should continue to drive partnering: big pharma’s PD-(L)1/CTLA-4 franchises, broad oncology footprints and overhang from the upcoming patent cliff (>$200bn in revenues at risk by 2030) create a natural pull for differentiated add-ons (novel checkpoints, vaccines, intratumoural immunotherapies) and for technologies that reduce toxicity and the healthcare burden in cell therapies. This report explores the scientific rationale for next-generation IO approaches, showcases leading biotech innovators advancing the field, examines the commercial dynamics driving deal-making and presents the investment case for biotechs at the forefront of this evolution. Market context: Oncology dominates therapeutic development Oncology remains the largest and most innovation-intensive therapeutic area in pharma, reflecting a combination of large addressable patient populations, persistent unmet need and the high economic value of clinically meaningful survival improvements. According to Evaluate Pharma, oncology accounted for 39% of global pharmaceutical R&D spend in 2023, with projected sales of $375bn by 2030, more than twice that of the next largest therapeutic area, immunology, at $165bn (Exhibit 1). Exhibit 1: Therapeutic area market size projections (2030) Source: Evaluate Pharma, Edison Investment Research Within oncology, IO has become a central pillar of R&D and commercial strategy. PD-(L)1 inhibitors have created a large, durable market, but the competitive dynamics have shifted from ‘who has a PD-1’ to ‘who has the best combination ecosystem and differentiated biology’. This matters for how value is likely to accrue. In the next phase, winners are likely to be those that can: (a) take immunotherapy into harder-to-treat tumours and patient subgroups; (b) move effective approaches earlier in the disease course (adjuvant/maintenance/minimal residual disease); and (c) reduce toxicity and delivery friction so that therapies can be used more widely and earlier. ICIs: Revolution and limitations What are ICIs? ICIs are immunotherapies or drugs that modulate immune ‘brakes’ that ordinarily prevent excessive immune activation, such as by T cells. Tumours exploit these brakes to avoid immune destruction. By blocking these inhibitory brakes, ICIs restore anti-tumour immune activity, thereby enabling the immune system to recognise and attack cancer cells (Exhibit 2). The two foundational inhibitory pathways to date have been PD-1/PD-L1 (dominant in the tumour microenvironment (TME); affects peripheral effector function) and CTLA-4 (more upstream; affects T-cell priming/activation in lymphoid tissues). By releasing these brakes, ICIs can convert an existing anti-tumour immune response into deep, durable remissions in a subset of patients, an outcome rarely achieved with historical cytotoxic treatments or reliably matched by targeted therapy. Exhibit 2: ICIs’ mechanism of action Source: Adapted from Poto R, Troiani T, Criscuolo G, Marone G, Ciardiello F, Tocchetti CG and Varricchi G (2022) Holistic Approach to Immune Checkpoint Inhibitor-Related Adverse Events. Front. Immunol. 13:804597. (CC by 4.0)https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.804597/full Clinically, the impact has been most visible in immunogenic tumours (with multiple neoantigens; proteins exclusively expressed by cancer cells) and where a pre-existing anti-tumour immune response can be amplified (eg ‘hot’ tumours such as melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma and classical Hodgkin lymphoma). However, mechanistically this is not a simple ‘on/off’ switch: the effectiveness of ICIs depends on antigen presentation, T-cell trafficking and infiltration, TME suppressive factors and the dynamic expression of multiple immune checkpoints. Current ICI landscape limited to PD-(L)1s The current ICI market (Exhibit 3) has been dominated by PD-1 and PD-L1 inhibitors, which have achieved broad approvals, frequent label expansions and deep integration into treatment pathways, with Merck’s Keytruda (generic name: pembrolizumab) leading the pack with $31.7bn in annual sales in 2025 and approval across 20+ indications, with an additional 20+ indications in clinical development. CTLA-4 inhibition (BMS’s Yervoy) remains important in select high-intensity combinations. More recently, LAG-3 joined the approved checkpoint set through BMS’s Opdivo (nivolumab) + relatlimab fixed-dose combination, Opdualag, in melanoma (approved in 2022), the first successful next-generation checkpoint beyond CTLA-4. Opdualag’s approval validates the potential clinical relevance of additional checkpoints, in our view. Exhibit 3: Approved ICIs Source: Evaluate Pharma, Edison Investment Research According to Global Markets Insights, the global ICI market was valued at $66.2bn in 2025, with double-digit growth expected over the next decade, driven by earlier lines/adjuvant settings, new combinations and next-generation mechanisms that can extend benefit beyond today’s responder ceiling (discussed in further detail below). Limitations of current ICIs Hitting the biological ceiling: Despite transformative outcomes in some tumour types, only a minority of patients benefit from PD-(L)1 and CTLA-4 blockade, in what is termed a ‘biological ceiling’ issue. Large reviews commonly cite 20–40% of the patients benefiting across broad populations depending on tumour type, biomarker enrichment and treatment regimen. While response rates can vary, the key issue is that a large proportion of patients either do not respond at all or respond transiently before disease progression. This constrains the ceiling of benefit for monotherapy and forces the field toward combination strategies, better patient selection and immune priming approaches. Resistance mechanisms – innate and acquired resistance: The variability in ICI efficacy is fundamentally driven by tumour immune resistance mechanisms, which can be broadly classified as innate (primary) or acquired (secondary). In primary resistance, tumours lack the biological prerequisites for response, including effective antigen presentation, baseline immune activation and pre-existing T-cell infiltration. In acquired resistance, initial responders subsequently relapse as tumours undergo immune editing, downregulate antigen presentation, activate alternative inhibitory checkpoints or remodel the TME to exclude effector T cells. Together, these adaptive escape processes cap response rates and durability. Haematological malignancy limitations: While ICIs have transformed outcomes in multiple solid tumours, their performance has often been more variable in haematological cancers. Many haematological malignancies have lower levels of tumour-specific mutations (so the immune system has fewer abnormal targets to recognise) and exist in the bone marrow and lymph node environment, which is naturally immunosuppressive and can physically limit effective T-cell activity. As a result, releasing a single immune brake is often not enough to generate a meaningful anti-tumour response. The key exception is classical Hodgkin lymphoma, where the PD-1 pathway is genetically overactive, making it particularly sensitive to checkpoint blockade. This has created space for other immunotherapy modalities (including cellular therapies and vaccines) to become central to innovation and value creation in haematology. Toxicity and immune-related adverse events: ICIs work by activating the immune system, but this broad activation can also cause the immune system to attack normal healthy tissues, leading to immune-related adverse events (irAEs). These side effects can affect multiple organs (most commonly the skin, gut, liver, lungs and hormone-producing glands) and range from mild inflammation to, in rare cases, severe or life-threatening complications. In clinical practice, most irAEs are manageable with early detection and immunosuppressive treatment, but they remain a key factor in treatment selection and in the design of next-generation IO combinations. TME complexity: ICIs are also less effective in many cancers because of the complex TME (the community of non-cancer cells, blood vessels and signalling molecules that surround the tumour). In some tumours, this environment acts like a protective shield, keeping cancer-killing immune cells out, switching them off, or flooding the area with signals that suppress immune activity. This means that even if an ICI releases the ‘brakes’ on the immune system, the T cells either cannot reach the tumour or cannot function properly once they get there. As a result, the treatment has little effect. Overcoming this barrier is a major focus for next-generation IO, with new strategies aimed at making these tumours more immune-friendly (such as intratumoral therapies, vaccines and myeloid-targeting approaches) so checkpoint inhibitors can work more effectively. Cold tumours (eg pancreatic, prostate, ovarian, colorectal cancer): ICIs tend to work best when there is already an active immune response against the tumour. In so-called ‘cold’ tumours, this immune activity is largely absent (there are very few cancer-fighting T cells in or around the tumour), and the cancer often does not produce enough abnormal signals to attract them. As a result, giving an ICI is like releasing the brakes on a car that has no engine running – the drug removes the immune block, but there are not enough immune cells present to attack the cancer. In addition, these tumours often create a strongly suppressive environment that keeps immune cells out. To address this, a key focus of current research is on combination approaches that first ‘heat up’ the tumour by bringing immune cells in, and then use ICIs to activate them. Upcoming newer generation ICI strategies To transcend current limitations, the field is aggressively exploring novel immune checkpoints and innovative modalities, with the goal of improving response rates, overcoming resistance and broadening benefit to more tumour types and patients. Expansion into earlier treatment lines: One of the key commercial upsides for ICIs will come from increasing use in the adjuvant, peri-operative and minimal residual disease (MRD) settings, where patient numbers are higher, treatment duration is longer and curative intent supports premium pricing. This is already evident with pembrolizumab in adjuvant melanoma and peri-operative NSCLC (KEYNOTE-671), nivolumab in adjuvant melanoma and resected oesophageal/gastroesophageal junction (GEJ) cancer (CheckMate-577) and atezolizumab in adjuvant NSCLC (IMpower010). With metastatic markets largely penetrated, future growth and blockbuster potential for next-generation IO will depend on demonstrating meaningful benefit in earlier-stage disease. New-generation checkpoint targets – LAG-3, TIGIT, TIM-3, VISTA: Most solid tumours can express multiple inhibitory checkpoints at the same time, often five to 10 or more across tumour cells, building the biological basis for a ‘multiple brakes’ concept and for the move toward dual- and multi-checkpoint strategies. Beyond PD-(L)1 and CTLA-4, multiple inhibitory pathways have emerged as potential levers to overcome resistance and improve response. However, translating target biology into consistent clinical benefit has been uneven. Combination treatments – two better than one?: With growing proof of the ability of tumours to activate multiple immune ‘brakes’ simultaneously, combination checkpoint strategies are increasingly being evaluated. These aim to widen the responder pool by targeting complementary resistance pathways, deepen responses by enhancing T-cell activation and reduce the likelihood of tumour escape via single-pathway adaptation. One thing is clear from the above – to win adoption, combinations need either a clear efficacy step-up (eg overall survival benefit) or a tolerability/convenience advantage that enables broader eligible populations. Bispecific and multi-specific agents: Bispecific and multi-specific agents attempt to integrate the aforementioned combination logic into a single molecule, potentially improving pharmacology and co-targeting engagement, convenience of administration and intellectual property differentiation. These agents can be designed to simultaneously block multiple inhibitory pathways, bring immune effector cells into proximity with tumours, or combine inhibitory checkpoint blockade with immune stimulation. Early clinical and regulatory validation is emerging, with PD-1 × CTLA-4 bispecifics such as Akeso’s cadonilimab approved in China in first-line treatment in gastric/GEJ cancer in combination with chemotherapy. PD-1 × LAG-3 bispecifics represent a mechanistically validated optionality following Opdualag, with assets such as EpimAb/BeiGene’s EMB-02, aiming to co-target the commonly co-expressed pathways and show activity in PD-1–refractory disease. However, challenges remain, as evidenced by the clinical discontinuations of MacroGenics’s tebotelimab and Roche’s tobemstomig, underscoring execution risk. PD-1 × TIGIT formats, led by AstraZeneca’s rilvegostomig, are higher risk but offer potential upside if bispecific architecture can outperform prior TIGIT monoclonal antibodies. The challenge will be to demonstrate meaningful differentiation, efficacy or tolerability versus simply co-administering two agents, while maintaining manufacturability and safety. More recently business development activity in ICI bispecifics has increasingly converged on the PD-(L)1 × VEGF axis, which has emerged as one of the most competitive post-PD-1 backbone strategies. VEGF (vascular endothelial growth factor) is a key signalling protein that tumours use to stimulate the formation of new blood vessels (angiogenesis). VEGF-targeted therapies disrupt this process, effectively starving the tumour and normalising its abnormal vasculature. By simultaneously blocking immune checkpoints and normalising tumour vasculature, these agents may help address two of the key limitations of first-generation PD-1 therapy: poor T-cell infiltration and an immunosuppressive microenvironment. A series of large transactions, including multi-billion-dollar collaborations, the largest being the $11.1bn deal between BMS and BioNTech (for pumitamig) in June 2025, highlights big pharma’s urgency to secure next-generation platforms that combine immune activation with TME normalisation. Exhibit 4 lists the major ICI bispecific licensing deals since 2022, the largest volume and value of which have been in PD-1 x VEGF bispecifics. Exhibit 4: Major ICI bispecific licensing deals Source: Edison Investment Research, Evaluate Pharma Value in the ICI space is shifting from new PD-1 monotherapies to combination-enabling assets that expand responder populations, overcome resistance and move treatment into earlier lines. The biological ceiling creates strong partnering demand for next-generation checkpoints, TME modulators and immune-priming approaches. Bispecific deal activity highlights big pharma’s urgency to secure differentiated, franchise-extending platforms. Therapies that demonstrate additive efficacy with manageable toxicity and clear biomarker strategy are most likely to achieve premium valuations and early monetisation. Cancer vaccines: From disappointment to resurgence Unlike traditional preventative vaccines, therapeutic cancer vaccines are designed to treat patients who already have cancer by training the immune system to recognise and attack tumour-specific targets, mainly by activating cancer-killing T cells. This is more challenging because cancer comes from the body’s own cells and often hides from the immune system, but the same fact also makes these vaccines a strong partner for checkpoint inhibitors. The vaccine helps create more tumour-fighting immune cells, and the checkpoint drug keeps them active. Earlier-generation cancer vaccines delivered only modest clinical benefit and struggled commercially due to weak immunogenicity, suboptimal antigen selection and deployment in late-stage disease, where immune dysfunction is profound. However, recent randomised clinical data provide the first clear evidence that newer-generation vaccines can significantly reduce recurrence risk when used in the early or minimal residual disease setting and/or in combination with PD-1 inhibitors. This represents a fundamental shift in how the modality is positioned: not as a monotherapy for metastatic disease, but as an immune-priming platform capable of inducing durable, tumour-specific T-cell responses. Historical clinical development and limited early impact First-generation cancer vaccines were based on several technological approaches, including peptide vaccines, whole-cell tumour vaccines and autologous dendritic cell therapies. While these strategies demonstrated proof of principle that immune responses could be generated against cancer, they failed to produce consistent and clinically meaningful tumour regression. The approval of Dendreon Corp’s sipuleucel-T (Provenge) in 2010 for metastatic castration-resistant prostate cancer represented a landmark for the field, as it showed an overall survival benefit in a randomised trial. However, the absence of objective tumour responses, the complexity of autologous manufacturing, high cost of goods and logistical challenges limited physician adoption and ultimately constrained commercial success. More broadly, these early programmes suffered from a lack of biomarker-driven patient selection (such as MSI-H/dMMR), poor antigen immunogenicity due to immune tolerance and clinical trial designs that evaluated vaccines in heavily pre-treated metastatic patients with advanced immune dysfunction. Collectively, these factors led to the perception that cancer vaccines were biologically interesting but clinically impractical. Core scientific and clinical limitations of earlier approaches Antigen selection (shared TAAs) and immune tolerance: Most first-generation therapeutic cancer vaccines were built around shared tumour-associated antigens (TAAs), proteins overexpressed in cancer cells but also present at low levels in normal tissues. Because the immune system is trained to tolerate self-antigens, these targets had limited capacity to generate strong cytotoxic T-cell responses. This biological constraint was reflected in several high-profile late-stage failures including GSK’s MAGE-A3 programme (in melanoma and NSCLC), Merck KGaA’s tecemotide (L-BLP25), which targeted the MUC1 glycoprotein in NSCLC, and Bavarian Nordic’s PROSTVAC, a PSA-targeted viral vaccine for prostate cancer. TME and immune escape: A second major limitation was the inability of early vaccine strategies to overcome the TME. First-generation cancer vaccines were commonly administered as monotherapies in patients with advanced metastatic disease, where tumour burden is high and immunosuppressive signalling is well established. Even when tumour-specific T cells were successfully generated in the periphery, their infiltration and cytotoxic function within the tumour were actively inhibited by a complex network of suppressive signals. This included upregulation of immune checkpoints such as PD-L1, recruitment of regulatory T cells and myeloid-derived suppressor cells (MDSCs) and secretion of inhibitory cytokines such as TGF-β and IL-10. Disease setting and tumour burden: Clinical positioning was another critical determinant of failure. Early vaccine trials were conducted predominantly in late-stage, heavily pre-treated patients with high tumour burden and often impaired immune function. In this context, the time required to generate an adaptive immune response, typically several weeks to months, is biologically and clinically mismatched with the rapid disease progression typical of advanced cancer. In contrast, it is now widely recognised that cancer vaccines are most effective in the minimal residual disease or adjuvant setting, where tumour burden and subclonal diversity are lower and immune competence is relatively preserved. Platform and delivery limitations: Many peptide-based vaccines lacked sufficiently potent or appropriately tailored adjuvants to stimulate dendritic cell maturation and effective cross-presentation through MHC Class I pathways, which is essential for generating CD8+ cytotoxic T-cell responses. Without robust innate immune activation, adaptive responses remained quantitatively and qualitatively inadequate. Modern platforms, including mRNA, viral vectors and next-generation dendritic cell approaches (Exhibit 5) are specifically designed to address this limitation by integrating antigen delivery with strong innate immune stimulation. Exhibit 5: Different types of therapeutic cancer vaccines Source: mRNA vaccines for cancer immunotherapy, Yashavantha Vishweshwaraiah, Nikolay Dokholyan. 2022. Frontiers of Immunology Field at an inflection point The resurgence of cancer vaccines is not driven by a single breakthrough but by the convergence of multiple enabling technologies. Neoantigen targeting – moving beyond shared self-antigens: Next-generation cancer vaccines prioritise tumour-specific neoantigens rather than shared TAAs, avoiding central immune tolerance and enabling high-avidity cytotoxic T-cell responses. This shift materially improves the probability of meaningful tumour control, as neoantigens are recognised as non-self and can drive polyclonal immune activation through multi-epitope designs. Clinical validation is emerging across multiple platforms. Moderna/Merck’s V940 has demonstrated a significant reduction in melanoma recurrence in the adjuvant setting in a randomised Phase IIb trial, while BioNTech/Genentech’s autogene cevumeran has generated strong neoantigen-specific T-cell responses in pancreatic cancer. Viral and epitope-based approaches from Nouscom (NOUS-PEV), OSE Immunotherapeutics (Tedopi) and Transgene (TG4050) further underscore the central importance of antigen selection, alongside optimised delivery technologies, in driving immunogenicity and clinical activity. Genetic delivery platforms – mRNA and DNA as scalable backbones: New-generation cancer vaccines are increasingly using genetic material, such as mRNA or DNA, to instruct the body’s own cells to produce tumour antigens, rather than introducing the antigens directly as proteins or peptides. This approach helps the immune system recognise the targets more effectively and generates both killer (CD8+) and helper (CD4+) T cell responses. It also naturally activates the early immune signals needed for a strong and durable reaction, reducing the need for additional adjuvants. Moderna’s personalised mRNA vaccines and BioNTech’s personalised and shared antigen programmes (including BNT111) highlight the speed and flexibility of this technology, while Scancell’s DNA ImmunoBody platform (iSCIB1+) shows how a potent off-the-shelf option can be combined with checkpoint inhibitors. Designed for checkpoint inhibitor synergy: Newer cancer vaccines are also being positioned as immune primers for checkpoint blockade rather than as standalone therapies. The vaccine trains the immune system to recognise the tumour and brings T cells into the tumour, while drugs such as PD-1, PD-L1 or CTLA-4 inhibitors stop those T cells from being switched off. Together, this helps overcome two key problems: many tumours do not already have tumour-fighting T cells, and the tumour environment suppresses immune activity. The positive data for V940 with pembrolizumab show this approach can work in practice. Similar combination strategies, including Scancell’s iSCIB1+ with dual checkpoint blockade, also make it easier for vaccines to fit into current treatment pathways. Earlier disease settings – MRD, adjuvant and maintenance therapy: Cancer vaccine development is moving away from use in very late-stage disease and focusing instead on earlier settings, such as after surgery or when only small amounts of cancer remain (minimal residual disease). At this stage, the immune system is stronger and the tumour burden is low, giving vaccine-activated T cells a better chance to clear remaining cancer cells and provide long-term protection. This also fits better with how vaccines work, as they need time to build an immune response and are less effective in fast-growing metastatic disease. Mendus’s vididencel in acute myeloid leukaemia (AML) after remission and V940 in post-surgery melanoma are good examples. Earlier use also means larger patient populations and longer treatment duration, which improves commercial potential. Exhibit 6 presents a list of the most clinically advanced cancer vaccine programmes in development. Exhibit 6: Selection of ongoing clinical-stage cancer vaccine programmes Source: Edison Investment Research, Evaluate Pharma Deal activity in cancer vaccines is re-accelerating after a prolonged period of limited partnering, reflecting renewed confidence in the modality as clinical data and platform maturity improve. The c $1.25bn BioNTech acquisition of German mRNA vaccine developer CureVac in December 2025 is a clear inflection point. This follows earlier large platform alliances such as BioNTech-Genentech and Moderna-Merck and signals that large pharma now views cancer vaccines as a core long-term pillar of IO. For the broader sector, the transaction raises the strategic value of companies with validated antigen-selection technologies, combination data with checkpoint inhibitors and scalable manufacturing infrastructure, and points to a more competitive partnering and M&A environment. Cancer vaccines are transitioning from a historically high-risk modality to a combination-driven, platform opportunity, supported by randomised clinical validation in the adjuvant and MRD settings. The shift to neoantigen targeting, genetic delivery and PD-1 synergy materially improves probability of success and commercial scalability. Earlier-line positioning expands patient populations and treatment duration, while recent large-scale transactions signal renewed big pharma appetite. Companies with biomarker-led development, checkpoint-combination data and scalable manufacturing are therefore best placed to secure premium partnering and valuation re-rating. CAR-Ts: Expanding beyond first-generation constraints CAR-Ts – mechanism and therapeutic concept Chimeric antigen receptor-T cell therapies (CAR-Ts) are a form of adoptive cell therapy in which a patient’s immune cells are genetically engineered to recognise and kill cancer cells. The process begins with the collection of T cells from the patient, which are then modified ex vivo to express a synthetic receptor, the chimeric antigen receptor, that binds to a specific tumour surface antigen independently. These engineered cells are expanded and reinfused into the patient, where they proliferate, directly eliminate antigen-expressing tumour cells and can persist as a living drug capable of long-term immune surveillance (Exhibit 7). Exhibit 7: How CAR-Ts work Source: Zhou Y, Wei S, Xu M, Wu X, Dou W, Li H, Zhang Z and Zhang S (2024) CAR-T cell therapy for hepatocellular carcinoma: current trends and challenges. Front. Immunol. 15:1489649. (CC BY 4.0) https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1489649/full Limitations and next-generation solutions Curative potential but concentrated to haematology: To date, CAR-Ts have been applied in the treatment of haematological cancers by targeting the CD19 and BCMA antigens. Approved CAR-T therapies from companies such as Gilead/Kite (Yescarta, Tecartus), BMS (Breyanzi, Abecma) and Johnson & Johnson/Legend (Carvykti) have transformed outcomes in relapsed or refractory B-cell malignancies and multiple myeloma, delivering deep and durable responses in heavily pre-treated patients (Exhibit 8). This success stems from several structural advantages over conventional therapies: high target specificity, in vivo expansion after infusion and the potential for durable remission following a single treatment. However, the treatment is also associated with unique immune-mediated toxicities. Complex autologous manufacturing and the need for specialised centres for treatment delivery currently limit scalability. More importantly, clinical activity in solid tumours has been modest (due to tumour heterogeneity), highlighting that first-generation autologous CAR-T designs are highly effective in liquid cancers but not yet broadly applicable across oncology. Exhibit 8: FDA-approved CAR-T therapies Source: Edison Investment Research Antigen escape – The shift to multi-target constructs: Antigen escape in CAR-T cell therapy is a mechanism of treatment resistance where tumour cells evade destruction by losing or reducing the specific surface protein (antigen) that the CAR-T cells are engineered to recognise. Relapse driven by antigen loss is a major limitation of single-target CAR-Ts. Dual and multi-antigen targeting is now a central development focus, designed to address this limitation by simultaneously recognising more than one tumour antigen, reducing the probability of immune evasion and improving depth and duration of response. Academic and China-based programmes evaluating dual CD19/CD22 CAR-Ts, as well as BCMA/CD19 constructs being explored by multiple developers, exemplify this strategy. In parallel, next-generation single-target approaches such as Autolus’s obe-cel (Aucatzyl), approved by the FDA in November 2024 for adults with relapsed/refractory B-cell precursor ALL, use a fast off-rate CD19 binder to enhance T-cell persistence and reduce exhaustion, representing an alternative strategy to improve durability of response. This strategy is particularly relevant in B-cell malignancies and multiple myeloma, where antigen downregulation is well documented. These designs are expected to become increasingly important as CAR-Ts move into earlier lines of therapy where durability requirements are higher. Toxicity and safety – Enabling broader adoption: Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain key barriers to treatment in community settings Engineering approaches to reduce tonic signalling and control CAR activation are being pursued by Autolus and Allogene, while pharmacological strategies targeting inflammatory pathways are emerging as a complementary solution. In parallel, adjunctive therapies specifically targeting CRS are being developed. A notable example is Poolbeg Pharma’s POLB-001, an oral p38 MAP kinase inhibitor, being developed to prevent CRS associated with CAR-T and bispecific antibodies. The asset has completed Phase I human challenge work demonstrating broad cytokine suppression and is now entering a Phase IIa (TOPICAL) proof-of-concept study in r/r multiple myeloma patients receiving the bispecific T-cell engaging antibody teclistamab, with interim data expected in summer 2026. The programme has received FDA Orphan Drug Designation for CRS prevention, positioning it as a potential first-in-class prophylactic that could enable outpatient delivery and broader adoption of cell and T-cell-redirecting therapies. Manufacturing bottlenecks – the move to allogeneic, off-the-shelf platforms: Off-the-shelf (allogeneic) CAR-T therapies use pre-made immune cells from healthy donors instead of creating a custom product for each patient. This could allow treatment to be given much faster, at lower cost and with more consistent quality. Gene editing removes the donor cell’s natural receptor so it does not attack the patient and is less likely to be rejected, an approach being developed by companies such as Allogene and Cellectis. Newer ‘immune-cloaked’ versions use CRISPR to help the cells stay in the body longer, which is important for long-lasting benefit. Another step forward is induced pluripotent stem cell (iPSC)-derived CAR-Ts, where stem cells are used to produce a large, standardised supply. If these therapies work as well as current CAR-T therapies, they could be delivered more widely and earlier in treatment. Alternative effector cells: CAR-NK and CAR-iNKT: Other immune cells such as natural killer (NK) cells and invariant natural killer T (iNKT) cells offer several structural merits over conventional CAR-T cells. They are inherently allogeneic, have a lower risk of graft-versus-host disease and appear to produce less severe CRS. Nkarta and Fate Therapeutics are advancing CAR-NK programmes in both haematological and solid tumours, while Arovella Therapeutics is developing CAR-iNKT therapies, with encouraging early data. These platforms may be particularly important for solid tumours and outpatient delivery models. A key current limitation however is the relatively short in-vivo persistence and limited clinical durability particularly for CAR-NK approaches, which may necessitate repeat dosing to match the long-term efficacy achieved with autologous CAR-T therapies. CAR-T for solid tumours – the largest expansion opportunity: Extending CAR-T therapies into solid tumours represents the biggest long-term growth opportunity for the modality, but also the most complex biologically due to the immunosuppressive TME and heterogeneous antigen expression. Armoured CAR-T cells, designed to secrete stimulatory cytokines such as IL-12 or IL-15, aim to remain active within this hostile environment and recruit other immune cells; this approach is being explored in multiple early-stage clinical and academic–industry programmes. To improve tumour specificity and safety, logic-gated CAR designs that require the presence of more than one tumour antigen for activation are also under development. Modular adaptor CAR platforms, such as Prescient Therapeutics’ OmniCAR, provide an alternative strategy by enabling controllable and retargetable tumour recognition. Most of these approaches remain in early phases of clinical development. Expanding beyond oncology: CAR-T therapies are emerging as a potentially transformative modality in autoimmune disease by delivering deep and durable depletion of pathogenic B cells, creating the possibility of a one-time immune reset rather than chronic immunosuppression. Early academic CD19 CAR-T studies in systemic lupus erythematosus have demonstrated drug-free remissions, catalysing rapid industry investment. A key requirement for broader adoption in immunology is an improved safety and tolerability profile suitable for outpatient use. Immix Biopharma’s NXC-201, a BCMA-targeted CAR-T in Phase Ib/II for AL amyloidosis with registrational intent, uses a sterically optimised design that has shown low neurotoxicity and short-duration CRS. This profile underpins planned expansion into B-cell-driven non-oncology indications, where risk tolerance is lower but the commercial opportunity is significantly larger. In-vivo CAR-T: Next-generation cell therapy without ex-vivo manufacturing: An area of development that has been gaining increasing interest is in-vivo CAR-T therapy, an emerging approach in which a patient’s T cells are genetically programmed directly inside the body using targeted delivery technologies such as lipid nanoparticles or viral vectors, removing the need for complex ex-vivo cell processing. This has the potential to significantly reduce manufacturing time, lower cost of goods and enable treatment in outpatient or community settings, addressing key access and scalability barriers associated with current autologous CAR-T therapies. The modality may also allow repeat dosing and more controlled cell expansion, although this remains to be demonstrated clinically. This field has seen increasing M&A and licensing activity in the past year and is becoming one of the most commercially attractive areas of development within the cell therapy space. Exhibit 9 highlights some of the major deals in this space, the most recent being the acquisition of Orna Therapeutics by Eli Lilly for up to $2.4bn in February 2026. Exhibit 9: Recent in-vivo CAR-T deals Source: Edison Investment Research, Evaluate Pharma Competitive pressure from bispecific antibodies: Bispecific T-cell engagers from companies such as Amgen (Blincyto), Regeneron and Roche are achieving high response rates in haematological malignancies with an off-the-shelf format, creating both a competitive threat and a complementary treatment option. Their ease of administration and lower upfront cost are accelerating adoption, particularly in earlier lines of therapy. As a result, CAR-T developers are increasingly focused on demonstrating superior durability and curative potential to maintain differentiation. The long-term value of CAR-T therapy will depend on its evolution from an autologous, late-line therapy into a scalable, earlier-line treatment modality. Off-the-shelf manufacturing, improved safety profiles and expansion into solid tumours are the key inflection points. Companies that can demonstrate durable responses with faster delivery and outpatient administration are likely to capture a disproportionate share of future growth. Other promising treatment modalities Emerging intratumoural modalities Intratumoural delivery is gaining traction as a strategy to activate the anti-tumour immune response directly at the tumour site while minimising systemic toxicity. By converting immune-cold lesions into inflamed, T cell-infiltrated tumours, these approaches can generate systemic immunity and improve responses to checkpoint inhibitors. Rather than competing with established backbones, most intratumoural therapies are being developed as immune-priming combination partners, with their greatest potential in accessible solid tumours and earlier treatment settings where immune function is less compromised. Immuno-modulatory antibodies – reprogramming the TME Immuno-modulatory antibodies are an emerging class of IO agents that work by changing the tumour’s immune environment rather than attacking cancer cells directly. They act on both the innate and adaptive immune system to improve antigen presentation, boost antibody-driven tumour killing and help overcome resistance to PD-1 inhibitors and other targeted antibodies, making them important combination partners. BioInvent’s BI-1206, a first-in-class FcγRIIB-blocking antibody in Phase I/II, is a key example, restoring sensitivity to rituximab in lymphoma with early signs of re-sensitising tumours to pembrolizumab in solid tumours. Overall, these therapies act as immune amplifiers that increase response rates to established checkpoint backbones and are an important source of the next wave of IO value. Pharma patent cliff – implications The healthcare sector is approaching an unprecedented loss-of-exclusivity cycle, with >$200bn of branded drug revenue at risk by 2030 (Exhibit 10). The concentration of exposure in a small number of megabrands means the impact will be both financially material and strategically disruptive for large pharma, which will be looking to acquire new assets to replenish pipelines and future revenues. Exhibit 10: Worldwide sales at risk from patent expiration (2025–30) Source: Edison Investment Research, Evaluate Pharma The notable event in this cycle is the expected biosimilar exposure of Merck’s Keytruda from 2028, currently the world’s largest oncology drug with c $31.7bn in sales in 2025. BMS’s Opdivo, with over $10bn in revenue in 2025, faces a similar timeline. Together, these two PD-1 inhibitors account for over $40bn of at-risk revenue, making IO one of the largest contributors to the late-decade patent cliff. This is structurally different from previous cycles because PD-1 therapy is not a single indication franchise, but a treatment backbone across multiple tumour types and lines of therapy. What it means for the biotech sector Lifecycle management is necessary but not sufficient: Large pharma is already implementing lifecycle strategies to defend these franchises, most visibly through subcutaneous formulations of PD-1 antibodies such as Keytruda and Opdivo. However, lifecycle management alone is unlikely to offset the scale of the revenue decline. The more durable strategy is to build proprietary combination regimens that extend the clinical relevance of the checkpoint backbone, which in turn increases reliance on external innovation. Combination-driven innovation – a structural tailwind for biotechs: The Merck-Moderna collaboration around the personalised cancer vaccine V940 illustrates how the patent cliff is reshaping deal-making. Positive Phase II melanoma data in combination with Keytruda led to a global profit-share agreement, reflecting the value of assets that increase responder rates and enable earlier-line use. BioNTech’s neoantigen vaccine partnership with Genentech follows the same logic. These therapies do not compete with PD-1; they expand its addressable population, which makes them strategically attractive and allows smaller companies to monetise early clinical proof of concept. Cell therapy/CAR-T platform acquisitions and modality leadership: A similar dynamic is evident in cell therapy, where the focus has shifted to scalable next-generation platforms. AbbVie’s acquisition of Capstan for up to $2.1bn, AstraZeneca’s purchase of EsoBiotec for up to $1bn and Gilead/Kite’s acquisition of Interius for $350m all target in-vivo cell-engineering technologies that remove the manufacturing bottlenecks of autologous CAR-T therapies. Eli Lilly’s recent acquisition of Orna for up to $2.4bn reinforces the strategic importance of programmable immune-engineering platforms. These transactions show that modality leadership alone can crystallise significant value for small biotechs, often before pivotal data. Targeting resistance – the rise of immune-modulatory combinations: Overcoming resistance to PD-1 and other targeted therapy is another major investment theme. BioInvent’s BI-1206, which restores sensitivity to rituximab and pembrolizumab by targeting FcγRIIB. CD47/SIRPα programmes, including assets originating from Trillium (Pfizer) and the AbbVie/I-Mab collaboration, aim to enhance macrophage-mediated tumour cell clearance, although recent clinical setbacks across the class have increased the focus on differentiated safety and combination positioning. By increasing response rates rather than competing with established backbones, these therapies extend the commercial lifespan of PD-1 and are therefore highly attractive combination partners. From single-asset licensing to platform consolidation: The urgency to replace multi-billion-dollar revenues is also changing the structure of deal-making. Large pharma is increasingly acquiring entire technology platforms, as seen in BioNTech’s $1.25bn acquisition of CureVac and Eli Lilly’s acquisition of Orna. Owning the underlying technology allows rapid generation of multiple clinical assets and shortens time to impact. For small biotechs, this creates an opportunity to monetise platform value earlier and reduces dependence on late-stage, capital-intensive development. Financing and valuation implications for the biotech sector: The patent cliff creates a multi-year period of structural demand for external innovation. Assets that demonstrate clear synergy with PD-1, durable responses, or the ability to move into earlier lines of therapy are likely to attract partnering interest earlier, at Phase I or II, bringing forward value inflection points. At the same time, the bar for differentiation is rising, with increasing emphasis on biomarker selection, durability and health-economic benefit. Tougher evidence bar and payer friction post-loss of exclusivity: As pricing dynamics intensify around megabrands, payers will push harder on incremental benefit. Biotechs should expect increasing emphasis on: clear biomarkers, durable endpoints, health-economic outcomes (reduced hospital time, fewer cycles) and differentiated safety/route of administration. In the US, the Inflation Reduction Act and Medicare price negotiation for high-spend biologics further increase long-term pricing pressure, reinforcing the need for clinically differentiated, earlier-line and combination-driven strategies to sustain premium reimbursement. What it means for investors Lower commercial risk: From an investor standpoint, IO remains one of the most compelling areas in biotechnology because it combines large commercial markets, multiple value-creation inflection points and strong strategic demand from large pharma. Unlike many therapeutic areas where new entrants must displace entrenched standards of care, most next-generation IO assets are largely developed as combination partners to existing treatments. This significantly lowers commercial adoption risk and increases the probability of partnering at an early clinical stage. For investors, this creates a model in which Phase I/II proof-of-concept data can drive disproportionate valuation re-rating, well ahead of registrational timelines. Pipeline-in-a-product optionality: Many IO modalities are inherently modular and can be expanded across multiple tumour types and treatment settings. Personalised cancer vaccines, cell therapies and immune-modulatory antibody platforms can generate several clinical programmes from a single technology base. This supports higher risk-adjusted valuations, multiple deal opportunities and lifecycle expansion, which is particularly valuable for small and mid-cap companies. Accelerated development pathways: IO assets often target high-unmet-need or biomarker-selected populations, making them well suited for expedited regulatory pathways and smaller, faster clinical trials. The use of durable endpoints such as long-term survival or MRD clearance can shorten development timelines and reduce funding requirements, improving the return profile for investors. Premium pricing: Therapies that deliver deep and durable responses, particularly those with curative potential, can command premium pricing despite high upfront costs. This is already evident in the CAR-T space (eg Kymriah and Yescarta come with list price of $47k and $373k, respectively) and is likely to extend to immune-reset approaches in both oncology and autoimmune disease. Strong pricing power translates into attractive peak-sales potential and supports higher valuation multiples. Structural deal flow driven by the patent cliff: The loss of exclusivity for major ICIs is creating a multi-year need for revenue replacement among large pharmaceutical companies. This is accelerating licensing and M&A activity for assets that can expand the PD-1 ecosystem or overcome resistance. For investors, this provides a clear and recurring exit pathway through strategic transactions. Multiple value inflection points across the development cycle: IO programmes typically generate several catalysts, including early immune-response readouts, combination data, expansion into new indications and regulatory designations. This steady flow of milestones supports sustained investor engagement and allows value to be realised progressively rather than only at approval. From a capital markets perspective, IO offers earlier value inflection than most therapeutic areas. Immune-response readouts, durability signals and initial combination data can drive meaningful re-rating well ahead of approval, while sustained M&A demand provides a clear monetisation pathway. Risk-reward considerations Investment risks Despite its transformational clinical impact and strong deal activity, immuno-oncology investments continue to carry meaningful risk. Clinical development risks: Commercial risks: Company-specific risks: Mitigating factors Several factors help mitigate traditional IO investment risks. Strong external demand for innovation Increasingly validated biology Large and durable market opportunity Platform and lifecycle optionality Investment conclusions The IO landscape represents one of the most compelling long-term investment themes in healthcare today, driven by scientific validation, platform technologies and the need to replace multibillion-dollar checkpoint revenues. The shift from monotherapy checkpoints to combination-based, immune-ecosystem control marks the next phase of value creation. Several factors make the current investment environment particularly attractive. The upcoming PD-1 patent cliff is accelerating external innovation and increasing partnering appetite for assets that expand responder populations or overcome resistance. At the same time, advances in biomarker-driven development, cell-engineering, mRNA and in-situ tumour-priming approaches are improving clinical success probabilities and shortening development timelines. The commercial opportunity remains substantial. Oncology continues to be the largest therapeutic area globally, with immuno-oncology capturing a disproportionate share of drug spending. Movement into earlier lines of therapy, adjuvant and MRD settings is expanding the addressable population, while durable responses and treatment-free remission support premium pricing and strong pharmacoeconomic value. For investors, immuno-oncology offers multiple avenues for exposure. Large-cap pharmaceutical companies provide franchise stability and lifecycle management of checkpoint backbones, mid-cap innovators offer focused exposure to next-generation modalities and small-cap platform companies present the most asymmetric risk-reward, particularly where early data can unlock partnering or acquisition. The companies highlighted in this report reflect the breadth of innovation across the field. From personalised cancer vaccines and next-generation cell therapies to immune-modulatory antibodies and intratumoural immune-priming approaches, these platforms are designed to extend the PD-1 ecosystem rather than compete with it, which lowers commercial adoption risk. Risk mitigation comes from the structural demand for external innovation and the modular nature of many IO technologies. Multiple value inflection points, accelerated regulatory pathways and the ability to monetise assets at Phase I/II through partnerships help offset traditional biotech funding and development risks. As this next phase of immuno-oncology unfolds, investors who position themselves early in differentiated platforms and combination-relevant assets are likely to benefit from sustained deal flow and valuation re-rating. The sector combines a large market opportunity, strong strategic buyer demand and scalable technologies, creating a highly attractive long-term investment landscape. Appendix: Company showcase The following companies represent a selection of the most innovative approaches across the immuno-oncology landscape, each targeting a key biological or commercial bottleneck such as responder expansion, resistance reversal, immune priming or scalable cell therapy delivery (Edison clients are indicated with an asterisk). BioInvent International BioInvent International AB (Nasdaq Stockholm: BINV) is a clinical-stage biotech focused on developing first-in-class immune-modulatory antibodies to address key limitations in cancer immunotherapy, particularly treatment resistance and low response rates. Its antibodies target immune checkpoints and tumour microenvironment biology to unlock new mechanisms of action. The company’s discovery engine is built on its proprietary F.I.R.S.T platform, which enables the simultaneous identification of novel targets and corresponding antibodies directly from patient-derived tumour material. This is complemented by the n-CoDe antibody library, supporting rapid generation of differentiated candidates. Following a strategic portfolio prioritisation in August 2025, BioInvent is focusing resources on its two lead assets, BI-1206 and BI-1808. BI-1206 (anti-FcγRIIB) is designed to restore sensitivity to anti-CD20 therapies in non-Hodgkin’s lymphoma and enhance responses to PD-1 inhibitors in solid tumours. In a Phase I/IIa trial with rituximab and acalabrutinib, early data from the triple-combination arm showed 100% disease control and a 63% objective response rate. Subsequent data for the Phase IIa safety run-in (n=15) showed an overall response rate of 80%, with 47% achieving complete responses. The disease control rate was 100%. A second Phase IIa study combining BI-1206 with pembrolizumab in first-line NSCLC and uveal melanoma marks its entry into treatment-naïve settings. The asset has also been reformulated for subcutaneous delivery to improve convenience, safety and durability. BI-1808 targets TNFR2 to counter tumour immune evasion by depleting regulatory T cells and expanding CD8+ T cells. In Phase IIa cutaneous T-cell lymphoma, it has demonstrated strong immune engagement with 100% disease control and a 45% response rate, alongside ongoing evaluation in combination with pembrolizumab in solid tumours. Both programmes have received supportive FDA designations, including Orphan Drug and Fast Track status, highlighting their potential in high-unmet-need indications. BioInvent’s integrated GMP manufacturing provides scalable, cost-efficient biologics production and ensures reliable global clinical supply, strengthening its operational and partnering position. Immix Biopharma* Immix Biopharma (NASDAQ: IMMX) is a clinical-stage company focused on advancing next-generation CAR-T therapies for patients with relapsed/refractory AL amyloidosis, a rare plasma cell disorder characterised by rapid organ deterioration and poor outcomes with conventional treatments. Its lead and wholly owned programme, NXC-201, is a BCMA-directed autologous CAR-T therapy designed with the objective of inducing deep haematologic responses and enabling meaningful and potentially durable organ recovery. Clinical data generated to date highlight compelling efficacy in a heavily pretreated patient population, including high overall and complete response rates and early signals of organ improvement. Recent interim data (20 patients) presented from the ongoing Phase Ib/II NEXICART-2 trial (n=40) showed a 75% complete response (CR) rate, with 15/20 patients achieving deep haematological responses. Of the five patients without a CR, four were MRD negative. Importantly, NXC-201 has demonstrated a favourable safety and tolerability profile, with low rates of high-grade CRS and neurotoxicity, a critical consideration in AL amyloidosis patients who are often frail and ineligible for intensive therapies. This safety profile, combined with rapid manufacturing turnaround and reliable product delivery, supports the potential use of NXC-201 in a broader treatment setting and in patients with significant organ involvement. The ongoing US-based NEXICART-2 study is intended to support a registrational pathway for AL amyloidosis with a biologics licence application planned before end-FY26. The company was recently granted the Breakthrough Therapy Designation for NXC-201 by the FDA based on the strength of the interim data. NXC-201 also holds the Regenerative Medicine Advanced Therapy designation by the US FDA and Orphan Drug Designation by FDA and the EMA. With CAR-T increasingly recognised as a transformative modality in non-oncology indications, NXC-201 is positioned to address a critical gap for AL amyloidosis patients who have limited therapeutic options and poor prognosis following relapse. Immutep Immutep (ASX: IMM) is a late-stage biotechnology company and a pioneer in therapies targeting the MHC Class II and LAG-3 pathways for cancer and autoimmune diseases. Its scientific leadership is rooted in the discovery of LAG-3 by CSO Dr Frédéric Triebel, positioning the company at the forefront of this immune checkpoint field. Immutep’s approach focuses on modulating key regulators of the immune response to enhance anti-tumour activity and improve outcomes for patients who derive limited benefit from existing immunotherapies. The oncology pipeline is anchored by two clinical-stage assets that employ complementary strategies to stimulate anti-cancer immunity. Efti (eftilagimod alpha) is a first-in-class MHC Class II agonist that directly activates antigen-presenting cells (APCs), including dendritic cells and monocytes. By engaging this central immune control point, efti drives a broad and durable immune response, priming CD8+ cytotoxic T cells and expanding multiple immune effector populations. This mechanism has demonstrated strong synergy with anti-PD-(L)1 therapy, chemotherapy and radiotherapy, alongside a favourable safety profile across combinations. Efti is currently being evaluated in TACTI-004 (KEYNOTE-F91), a pivotal Phase III trial in partnership with MSD (n=750), in combination with pembrolizumab and chemotherapy as first-line treatment for advanced/metastatic NSCLC (50% enrolment completed). The study builds on positive data from TACTI-002 and INSIGHT-003 (>165 patients), which showed high response rates and encouraging survival outcomes. Notably, efficacy has been observed across the full PD-L1 expression spectrum, including the large low/negative PD-L1 population with significant unmet need. Efti is also being explored in multiple additional solid tumours, including head and neck, urothelial, breast cancer and soft tissue sarcoma. Immutep’s second clinical asset, LAG525 (ieramilimab), the first anti-LAG-3 antibody, is out-licensed to Novartis, validating the company’s leadership in LAG-3 biology. Earlier-stage programmes include a small-molecule LAG-3 inhibitor and IMP761, the first LAG-3 agonist antibody for autoimmune disease, which has generated promising initial Phase I data (single ascending dose part completed). Lytix Biopharma Lytix Biopharma (Euronext Growth Oslo: LYTIX) is developing a novel class of oncolytic immunotherapies designed to harness the full potential of the immune system by directly reprogramming the tumour microenvironment. Its lead asset, ruxotemitide (LTX-315), is a first-in-class intratumoral therapy that rapidly disrupts tumour cell membranes, releasing a broad repertoire of tumour antigens and danger signals that drive immune activation. By initiating immune recognition rather than relying on pre-existing anti-tumour immunity, the approach is positioned to convert immunologically ‘cold’ tumours into ‘hot’ tumours and expand the benefit of checkpoint inhibitors beyond current responder populations. This mechanism enables broad T-cell priming and durable systemic immune responses, providing a strong biological rationale for combination with PD-1/PD-L1 inhibitors in indications where response rates to checkpoint blockade alone remain limited. Clinically, the company is prioritising injectable and resectable solid tumours, where intratumoral delivery is both feasible and therapeutically meaningful. In partnership with Verrica Pharmaceuticals, ruxotemitide has completed a Phase II study in non-metastatic skin cancer, demonstrating a 97% objective response rate, 51% pathological complete responses and an 86% mean tumour reduction across treated lesions, alongside a favourable safety profile with no serious adverse events. Based on these data and FDA alignment on trial design, Verrica is preparing a pivotal Phase III programme in basal cell carcinoma. Lytix retains rights in metastatic and neoadjuvant settings, including melanoma, triple-negative breast cancer and Merkel cell carcinoma, where combination strategies with checkpoint inhibitors represent a key value driver. The pipeline also includes LTX-401, an oncolytic candidate targeting liver metastases, extending the platform to deep-seated tumours. With a validated mechanism, encouraging clinical activity and a flexible partnering strategy, Lytix is positioning intratumoral immunotherapy as a complementary modality within the immuno-oncology landscape, aimed at delivering a durable systemic benefit for patients underserved by current treatments. Mendus* Mendus (OMX: IMMU) is a clinical-stage immuno-oncology company developing off-the-shelf cellular cancer vaccines designed to induce durable, tumour-specific immune responses and reduce relapse in haematological malignancies and solid tumours. Its lead programme, vididencel, is an allogeneic dendritic cell-based therapy aimed at establishing long-term immune surveillance in patients with AML and CML. By priming and expanding tumour-specific T cells, vididencel is intended to eliminate residual malignant cells and deliver sustained disease control without the toxicity associated with intensive consolidation treatments. The off-the-shelf format enables rapid treatment, scalable manufacturing and favourable logistics compared with autologous cell therapies. Clinical data to date from the ADVANCE II trial has demonstrated encouraging immune responses, a favourable safety profile and signals of relapse reduction in AML patients following first line intensive induction chemotherapy. The programme is now being repositioned to address a broader AML population, including ‘chemo-unfit’ patients receiving venetoclax-based regimens, with new studies (CADENCE and DIVA) expected to inform the design of a potential global registrational trial. Mendus is also expanding into CML, where vididencel is being developed as a potential treatment-free remission, enabling therapy for patients on long-term TKI therapy, representing a large and well-defined commercial opportunity. Vididencel is also being explored in ovarian cancer and has potential applicability in additional tumour settings where immune priming in the minimal residual disease setting could improve long-term outcomes. Manufacturing is supported through a dedicated GMP partnership with NorthX Biologics, providing scalable, commercial-ready production capabilities and strengthening the pathway to late-stage development and potential out-licensing. The company is funded into 2027 and is seeking partnerships to support late-stage development and maximise the platform’s potential. See below for our most recently conducted Edison TV executive interview with Mendus. Exhibit 11: Executive interview with Erik Manting, CEO of Mendus, and Tariq Mughal, CMO Source: Edison Investment Research OSE Immunotherapeutics* OSE Immunotherapeutics (PAR: OSE) is a clinical-stage biotechnology company developing first-in-class immunotherapies across oncology and immuno-inflammation, with a strategy centred on biomarker-driven precision medicine and differentiated T-cell modulation. Its lead oncology programme, Tedopi, is an off-the-shelf, multi-epitope therapeutic cancer vaccine designed to induce tumour-specific cytotoxic T-cell responses in HLA-A2–positive patients and address resistance to ICIs. Tedopi is being advanced in NSCLC after ICI failure, a setting with high unmet need and limited treatment options. The vaccine targets five tumour-associated antigens and is engineered to generate durable CD8+ T-cell immunity with a favourable tolerability profile compared with chemotherapy. In the Phase III ATALANTE-1 study, Tedopi demonstrated a clinically meaningful survival benefit versus standard chemotherapy in the ICI-resistant population, establishing proof of concept and supporting its ongoing registrational strategy. The confirmatory ARTEMIA Phase III trial, comparing Tedopi with docetaxel, represents the final step toward potential approval, with a futility analysis expected in 2026. Beyond oncology, OSE’s immunology pipeline provides additional value creation and partnering optionality. The most advanced asset, lusvertikimab (anti-IL-7R), targets a central pathway in T-cell expansion and is being developed in chronic inflammatory diseases (ulcerative colitis, chronic pouchitis and hidradenitis suppurativa) offering a complementary and potentially less capital-intensive route to late-stage development through partnerships. See below for our most recently conducted Edison TV executive interview with OSE Immunotherapeutics. Exhibit 12: Executive interview with Silvia Comis MD, chief clinical and medical research officer at OSE Immunotherapeutics Source: Edison Investment Research Percheron Therapeutics* Percheron Therapeutics (ASX: PER) is a clinical-stage immuno-oncology company developing next-generation checkpoint inhibitors to address resistance to PD-1/PD-L1 therapies. Its lead asset, HMBD-002, targets VISTA (V-domain Ig suppressor of T-cell activation), an emerging immune checkpoint strongly associated with poor response to existing immunotherapies and with tumours that remain largely unresponsive to current treatment, including pancreatic, ovarian and prostate cancers. By expanding the number of patients who can benefit from checkpoint blockade, VISTA inhibition represents a key opportunity in the evolution of the IO landscape. HMBD-002 is differentiated by its IgG4 backbone, the same isotype used in pembrolizumab and nivolumab, which is designed to minimise unwanted immune activation and improve tolerability, an important advantage in a class where earlier candidates have been limited by toxicity. Preclinical studies have demonstrated broad anti-tumour activity both as monotherapy and in combination with PD-1 inhibitors, including in triple-negative breast cancer models (UT Southwestern) and in radiotherapy combinations in head and neck cancer (Stanford), supporting a strong biological rationale for use in CPI-resistant disease. The completed US Phase I study (n=48) showed an excellent safety profile across doses from 20–1,400mg, with no maximum tolerated dose reached due to the low incidence of dose-limiting toxicities. Early signs of clinical activity included tumour shrinkage and durable stable disease in heavily pre-treated patients, supporting advancement into later-stage trials. A modular Phase II study is expected to commence within 2026. See below for our most recently conducted Edison TV executive interview with Percheron Therapeutics. Exhibit 13: Executive interview with Percheron Therapeutics CEO, Dr James Garner Source: Edison Investment Research Poolbeg Pharma Poolbeg Pharma (LSE: POLB) is developing POLB 001, a first-in-class, orally administered p38 MAPK inhibitor designed to prevent cancer immunotherapy-induced CRS, one of the most serious and resource-intensive toxicities associated with T-cell-engaging bispecific antibodies and CAR-T therapies. CRS affects more than 70% of patients receiving certain T-cell-redirecting treatments and currently necessitates administration in specialised centres, leading to prolonged hospitalisation, high healthcare utilisation and constrained patient access. With no approved preventative therapies, POLB 001 is positioned to address a critical bottleneck in the delivery and scalability of next-generation immuno-oncology treatments. By selectively modulating excessive inflammatory signalling without causing broad immunosuppression, POLB 001 aims to improve the safety profile of T-cell-engaging therapies while preserving anti-tumour immune function, an important consideration in heavily pre-treated cancer populations. Enabling safer outpatient or community-hospital administration could significantly expand treatment capacity, improve patient quality of life and unlock additional commercial value across the rapidly growing cell therapy and bispecific antibody markets. The initial commercial opportunity, focused on multiple myeloma and diffuse large B-cell lymphoma, is estimated to exceed US$10bn, with further upside as T-cell-engaging therapies move into earlier lines of treatment and into solid tumours. The programme has demonstrated a favourable safety and pharmacodynamic profile in preclinical studies and in a human lipopolysaccharide (LPS) challenge model, providing important translational validation ahead of patient studies. The Phase IIa open-label, single-arm trial is in advanced preparation and will evaluate POLB 001 in approximately 30 relapsed/refractory multiple myeloma patients receiving an approved bispecific antibody (teclistamab), with interim data expected in summer 2026. The study is being led by The Christie NHS Foundation Trust and the Accelerating Clinical Trials network. FDA Orphan Drug Designation provides additional regulatory validation and commercial optionality. On positive data, Poolbeg expects to pursue a partnering strategy, positioning POLB 001 as a potential enabling therapy for the broader immuno-oncology ecosystem. Scancell Scancell (LSE: SCLP) is a clinical-stage immuno-oncology company developing targeted active immunotherapies designed to generate durable, tumour-specific T-cell responses and address the large proportion of patients who fail to benefit from checkpoint inhibitors (ICIs). With approximately half of patients not responding to ICIs and five-year survival in stage IV melanoma below 23%, Scancell’s off-the-shelf platforms aim to enhance efficacy without adding toxicity while improving accessibility versus personalised approaches. The lead asset, iSCIB1+ (DNA Immunobody), is a needle-free DNA vaccine that induces high-avidity T cells against gp100 and TRP-2 melanoma antigens, selected from patients with spontaneous tumour regression. In the Phase II SCOPE study (n=140), iSCIB1+ in combination with ICIs has demonstrated clinically meaningful improvements over historical CPI outcomes. Progression-free survival in the target HLA population reached 78% at 11 months versus ~46% for nivolumab/ipilimumab, with 69% PFS at 22 months across cohorts. Updated data remained encouraging with PFS of 74% at 16 months in the target population. These data support the potential to establish a new standard of care in advanced melanoma. With FDA IND clearance in place, development is being accelerated towards a randomised registrational study in 2026, likely incorporating a precision biomarker. A commercial-scale GMP manufacturing process with strong stability has already been established, supporting future scalability. The second clinical programme, Modi-1 (Moditope), is a peptide-based active immunotherapy targeting post-translationally modified tumour antigens and is currently in Phase II evaluation in hard-to-treat solid tumours, including head and neck cancer, with further data expected in early 2026. Beyond vaccines, Scancell’s GlyMab platform, developed within its Glymab Therapeutics subsidiary, generates high-affinity antibodies against tumour-specific glycans, with two assets already licensed to Genmab, providing external validation and potential non-dilutive value. See below for our recent Edison TV executive interview with Scancell. Exhibit 14: Executive Interview with Scancell Holdings’ chief medical officer, Dr Nermeen Varawalla Source: Edison Investment Research Transgene Transgene (FRA: TNG) is a clinical-stage biotechnology company developing virus-based immunotherapies, with a strategic focus on individualised neoantigen therapeutic vaccines (INTVs) to prevent cancer relapse in early-stage disease. Its lead programme, TG4050, is based on the proprietary myvac platform and is currently being evaluated in the randomised Phase II part of a Phase I/II trial in operable head and neck cancer (HNSCC). The myvac platform integrates viral vector engineering, artificial intelligence and translational data to deliver precision immunotherapy at clinically relevant timelines. Using a Modified Vaccinia Ankara (MVA) vector, TG4050 encodes patient-specific neoantigens identified through AI-driven algorithms developed with NEC. This approach is designed to generate potent and durable CD8+ T-cell responses against tumour mutations unique to each patient, with the aim of establishing long-term immune surveillance following surgery and standard-of-care treatment. A digitalised, in-house GMP manufacturing process supports scalable production within a timeframe compatible with routine clinical practice. Clinical data presented at ASCO 2025 demonstrated the feasibility, safety and strong immunogenicity of TG4050, with 100% disease-free survival at a median 30-month follow-up (n=32). Neoantigen-specific CD8+ T-cell responses persisted for more than two years and showed effector and memory phenotypes consistent with durable protection against relapse. Additional translational analyses presented at SITC 2025 confirmed the induction of polyclonal cytotoxic T cells, expansion of both de novo and pre-existing tumour-reactive clones and the development of tissue-resident immune populations, highlighting the potential to overcome resistance in immunologically ‘cold’ tumours. With proof of concept established, Transgene is advancing TG4050 towards a registrational pathway and exploring expansion into additional early-stage solid tumours. More broadly, myvac represents a scalable platform for a pipeline of individualised vaccines, positioning the company at the forefront of next-generation precision immuno-oncology.