Botensilimab

Botvymo ® (botensilimab) and Evamplix ® (balstilimab) receive separate approvals for use in combination Armenia is the first country to approve marketing authorization of BOT+BAL, following a rigorous review of quality, nonclinical, clinical and pharmacovigilance data Approvals supported by clinical evidence published in peer-reviewed journals and presented at major oncology congresses, including two-year Phase 1b survival findings and randomized Phase 2 data in MSS metastatic colorectal cancer without active liver metastases Agenus will evaluate the potential for approvals in other Eurasian Economic Union countries that support this regulatory path LEXINGTON, Mass.--(BUSINESS WIRE)-- $AGEN #Armenia -- Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, today announced that the Ministry of Health of the Republic of Armenia has granted marketing authorizations for Botvymo ® (botensilimab, BOT) and Evamplix ® (balstilimab, BAL), each approved for use in combination with the other for the treatment of adult patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases who have previously received available standard therapies. These are the first marketing authorizations for either medicine anywhere in the world. The approvals are expected to benefit patients in Armenia as well as patients who travel to Armenia for treatment under the care of Armenian oncologists. Botensilimab is a multifunctional, Fc-enhanced anti-CTLA-4 antibody designed to activate innate and adaptive antitumor immune responses, including in tumors that have historically responded poorly to conventional immunotherapy. Balstilimab is an anti-PD-1 antibody designed to sustain antitumor T-cell activity. The approvals are effective as of October 2, 2026. They follow a rigorous review by Armenia’s regulatory authorities of the complete registration dossier, submitted in the international Common Technical Document format used under Eurasian Economic Union rules. The review covered product quality and manufacturing (chemistry, manufacturing and controls), nonclinical data, clinical efficacy and safety data, and the pharmacovigilance system and risk management plan. BOT and BAL were separately submitted and approved for use as a combination regimen. Under the approved product information, Botvymo is administered at 75 mg intravenously every 6 weeks for up to 4 doses, in combination with Evamplix at 240 mg intravenously every 2 weeks for up to 2 years or until disease progression or unacceptable toxicity. Each marketing authorization is conditional and valid for one year and is renewable based on the clinical updates that Agenus will provide to the Armenian regulator each year. “Armenia is the first country in the world to grant marketing approval for BOT+BAL,” said Garo H. Armen, PhD, Chairman and Chief Executive Officer of Agenus. “The evidence behind this decision has been published in peer-reviewed journals and presented at major cancer conferences, and it has consistently pointed to clinical benefit for patients with metastatic colorectal cancer. We thank Armenia’s health authorities for the depth and care of their review. Patients who have exhausted standard treatments now have a new option, and we are proud to bring it to them.” Clinical Evidence Supporting the Approvals The Armenian approvals were based on the totality of clinical evidence for BOT+BAL in MSS mCRC, including mature results from the fully enrolled MSS mCRC patient cohort from the Phase 1b C-800-01 study and data from the randomized Phase 2 C-800-25 study. Results from this clinical program have been published in peer-reviewed journals, including Nature Medicine and Clinical Cancer Research , and presented at major oncology congresses, including the ASCO Gastrointestinal Cancers Symposium. The efficacy and safety data supporting the approvals are summarized in the approved product information for Botvymo and Evamplix. Regional Opportunities Following the Armenian approvals, Agenus will evaluate the potential to seek marketing authorizations for BOT+BAL in the MSS metastatic colorectal cancer setting in other Eurasian Economic Union member countries. Access to BOT+BAL Outside Armenia The Armenian marketing authorizations apply within the territory of Armenia. In France, the national Autorisation d’Accès Compassionnel (AAC) program provides fully reimbursed, hospital-based access to BOT+BAL for eligible patients with MSS metastatic colorectal cancer without active liver metastases, platinum-resistant or platinum-refractory ovarian cancer, and certain advanced soft-tissue sarcomas. In a growing number of other countries, BOT+BAL is available through physician-initiated named-patient programs under local regulations. BAP Pharma serves as Agenus’ global partner for the French AAC pathway and named-patient access programs. Physicians seeking information about authorized access pathways can visit the Patient Access section of our corporate website. Important Safety Information The approved product information for Botvymo and Evamplix includes warnings and precautions for immune-mediated adverse reactions, including colitis and diarrhea, hepatitis, pneumonitis, endocrinopathies, nephritis, myocarditis and pancreatitis, as well as infusion-related reactions. Healthcare professionals in Armenia should consult the approved product information before prescribing. About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants. Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. About Botensilimab (BOT) Botensilimab (BOT) is a human multifunctional, Fc-enhanced anti-CTLA-4 antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. BOT augments immune responses across a wide range of tumor types by priming and activating T cells, reducing intratumoral regulatory T cells, activating myeloid cells and inducing durable memory responses. BOT+ balstilimab (BAL) has been studied in over 1,500 patients across more than nine tumor types, spanning late-line refractory disease and early-stage neoadjuvant settings. The combination is being developed to expand immunotherapy benefit to more patients, including those with microsatellite stable (MSS) disease and tumors considered immunologically “cold” or resistant to existing immunotherapies. Agenus’ Phase 3 ROBBIN study is designed to evaluate BOT+BAL given before surgery in earlier-stage colon cancer. For more information about botensilimab trials, visit . About Balstilimab (BAL) Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients to date and has demonstrated clinical activity and a favorable tolerability pro several tumor types. Botvymo and Evamplix are authorized in Armenia for use in combination for the treatment of previously treated MSS metastatic colorectal cancer without active liver metastases. Their use in other indications and in other countries remains investigational. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, the conditional Armenian marketing authorizations and their renewal, the availability of treatment to patients who travel to Armenia, potential regulatory submissions in other countries, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2025, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Contacts Investors 917-362-1370 | investor@agenusbio.com Media 781-674-4422 | communications@agenusbio.com

Survival estimate remained at 48% between years two and three, extending evidence of durable benefit Results observed in heavily pretreated, difficult-to-treat population that received a median of four prior lines of therapy; nearly three-quarters of patients had platinum-resistant or refractory cancer LEXINGTON, Mass.--(BUSINESS WIRE)-- $AGEN #AGEN -- Agenus Inc. (Nasdaq: AGEN) , a leader in immuno-oncology innovation, today announced three-year follow-up results from the ovarian cancer cohort of its 400+ patient Phase 1b C-800-01 trial. The study evaluated botensilimab (BOT), Agenus’ multifunctional, Fc-enhanced anti-CTLA-4 antibody, in combination with balstilimab (BAL), Agenus’ anti-PD-1 antibody. The results, including three-year survival and outcomes by sensitivity to platinum-based chemotherapy and by prior treatment, were presented at the 2026 International Gynecologic Cancer Society (IGCS) Annual Global Meeting in Montréal, Canada. Among patients evaluable for efficacy, three-year overall survival was 48% (n=35), unchanged from the two-year estimate, suggesting durable clinical benefit in this population. Responses and long-term survival were observed in both platinum-sensitive and platinum-resistant or refractory disease. At the last follow-up, 25% of patients who received at least one dose of treatment (11 of 44) were alive and off all therapy. These results come from a population with substantial prior treatment. Patients had received a median of four prior lines of therapy, and 66% had received at least four. All had previously received platinum chemotherapy, 77% had received bevacizumab and 57% had received a PARP inhibitor. Nearly three-quarters had platinum-resistant or refractory disease, meaning their cancer had progressed during platinum treatment or returned within six months of it. “In recurrent ovarian cancer, conventional checkpoint immunotherapy has rarely produced lasting benefit, particularly after the disease stops responding to platinum chemotherapy,” said Rebecca L. Porter, MD, of Dana-Farber Cancer Institute, who presented the data . “What stands out with longer follow-up is the survival plateau in patients who had already received multiple treatments. That pattern suggests that a different approach to activating the immune system may offer some patients lasting benefit, even when treatment options have narrowed.” Three-year follow-up findings Overall efficacy results (n=35) Overall survival (OS): Estimated survival was 48% at both two and three years. Median OS was 14.8 months. Objective response rate (ORR): 23% of patients (8/35) had a response, including one complete response and seven partial responses. Duration of response: Responses lasted a median of 9.7 months. Clinical benefit: 31% of patients (11/35) had a response or stable disease lasting at least 24 weeks. Alive and off treatment: At last follow-up, 25% (11 of all 44 patients who received at least one dose of treatment) were alive and off all therapy. Results by patient subgroup Platinum-resistant or refractory disease (n=25): Estimated three-year survival was 47%. ORR was 20% (5/25), including one complete and four partial responses. Platinum-sensitive disease (n=10): Estimated three-year survival was 45%. Thirty percent (3/10) of patients had a partial response. Four or more prior lines of therapy (n=23): Estimated three-year survival was 48%. ORR was 17% (4/23), with all four responses being partial responses. Disease progression on a PARP inhibitor (n=17): I n patients whose cancer had progressed during PARP inhibitor treatment or maintenance, estimated three-year survival was 61%. Two patients (12%) had partial responses. Safety remained consistent with the known BOT+BAL profile. No new safety signals or treatment-related deaths were reported. “The most compelling finding is that the survival curve extends beyond two years in women who had already received multiple treatments, including those with platinum-resistant or refractory disease,” said Steven J. O’Day, MD, Chief Medical Officer of Agenus . “We have seen a similar pattern of durable survival in other difficult-to-treat cancers studied with BOT+BAL. This three-year ovarian update strengthens our conviction that the combination can deliver meaningful, lasting benefit to a subset of patients who have had few effective immunotherapy options.” The three-year ovarian results add to a pattern of long-term survival across difficult-to-treat cancers studied with BOT+BAL. In the broader 400+ patient Phase 1b pan-tumor analysis, estimated two-year survival was 39%. In a separate cohort of patients with refractory MSS metastatic colorectal cancer without active liver metastases, estimated survival was 41% at two years and 33% at three years. These findings are particularly notable in cancers where conventional immunotherapy has historically offered limited benefit. The consistent and durable BOT+BAL activity in heavily pretreated cancers that are poorly immunogenic or resistant to prior immunotherapy, reinforced by deep pathologic responses in neoadjuvant studies, strengthens the rationale for moving treatment earlier in the course of disease. Before surgery, when the primary tumor and surrounding lymph nodes remain intact, BOT+BAL may have the greatest opportunity to generate lasting antitumor immunity, reduce recurrence and ultimately increase the number of patients who may be cured. The full presentation can be found on the publications section of the Agenus website at . BOT and BAL are in development and have not been approved by the U.S. Food and Drug Administration. Presentation details Abstract Title: Next Generation Immune Checkpoint Inhibition with Botensilimab Plus Balstilimab in Recurrent Ovarian Cancer: Results by Platinum Sensitivity Status and 3-Year Overall Survival Presenter: Rebecca L. Porter, MD; Dana-Farber Cancer Institute, Boston, MA, USA Poster Presentation number: 969 Session Title: Poster Rounds with Professors Session, Ovarian Cancer 03 Session Date/Time: Saturday, October 3, 2026 | 10:50am-10:55am EDT About the C-800-01 Study C-800-01 (NCT03860272) is a multicenter Phase 1b trial evaluating BOT with or without BAL in advanced solid tumors. The ovarian cancer cohort included patients with recurrent disease for whom no standard therapy was available or whose cancer had progressed after standard treatment. The efficacy analysis included 35 patients who had at least one tumor scan after starting therapy. The safety population included all 44 patients who received treatment. The data cutoff for this analysis was December 13, 2025. About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants. Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. Agenus’ Commitment to Patient Access Until marketing authorization is granted, BOT+BAL is accessible only through clinical trials and authorized early access mechanisms where permitted and available under each country’s regulatory framework. For eligible French patients treated in hospitals under AAC and meeting the predefined criteria, BOT+BAL is fully reimbursed by France’s national health system. Outside France, access may be available in select countries through paid named-patient programs, which may involve out-of-pocket costs to the patient or coverage under applicable national or private reimbursement arrangements. These programs are physician-driven and are not promotional. About Botensilimab (BOT) Botensilimab (BOT) is a human multifunctional, Fc-enhanced anti-CTLA-4 antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. BOT augments immune responses across a wide range of tumor types by priming and activating T cells, reducing intratumoral regulatory T cells, activating myeloid cells and inducing durable memory responses. Approximately 1,500 patients have been treated with BOT and balstilimab (BAL) in phase 1 and phase 2 clinical trials. The combination with Agenus’ investigational PD-1 antibody, BAL, has shown clinical responses across more than nine cancers. For more information about BOT trials, visit . About Balstilimab (BAL) Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients to date and has demonstrated clinical activity and a favorable tolerability pro several tumor types. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2025, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Contacts Investors 917-362-1370 | investor@agenusbio.com Media 781-674-4422 | communications@agenusbio.com