AGENUS INC

Agenus is a clinical-stage biotechnology company focused on discovering and developing immunotherapies for cancer and infectious disease. Our primary business is immuno-oncology ("I-O"), where we are advancing antibody-based programs to activate innate and adaptive immunity, overcome tumor immune evasion and expand the population of patients who may benefit from immunotherapy. Our lead clinical program is botensilimab (“BOT” or “AGEN1181”), alone and in combination with balstilimab (“BAL”). We also maintain select clinical-stage immuno-oncology assets, which may be used as standalone agents or be complimentary to botensilimab plus balstilimab (“BOT/BAL”). Agenus also maintains an equity investment in MiNK Therapeutics, Inc. ("MiNK"), with an approximate fair value of $24.3 million as of December 31, 2025, and a majority ownership of a vaccine adjuvant business through our subsidiary SaponiQx, Inc. ("SaponiQx").

We use internal discovery, translational, clinical and regulatory capabilities together with selected collaborations to advance product candidates. Following our strategic realignment announced in December 2024, we prioritized the botensilimab/balstilimab program and temporarily paused certain non-core preclinical and clinical activities while we evaluate partnering, as well as targeted funding opportunities. Our common stock is listed on The Nasdaq Capital Market under the symbol "AGEN."

Recent Developments

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We, together with the Canadian Cancer Trials Group (“CCTG”), are conducting BATTMAN/CO.33, a global Phase 3 trial of botensilimab plus balstilimab versus best supportive care in refractory MSS/mismatch repair proficient ("pMMR") colorectal cancer, with sites activated and prepared to enroll patients.

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At the 2025 European Society for Medical Oncology Congress (“ESMO”) data in more than 400 heavily pretreated patients across more than nine tumor types was presented, in which BOT plus BAL demonstrated approximately 39% two-year OS, including activity in colorectal, ovarian, sarcoma, PD(L)-1 refractory NSCLC, and hepatocellular cancers. To date, approximately 1,200 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials.

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France’s national Autorisation d’Accès Compassionnel (“AAC”) program provides hospital-based access to BOT plus BAL for eligible patients with certain refractory cancers, with treatment reimbursed through the national health system. In September 2025, the AAC protocol was updated to include botensilimab plus balstilimab for patients with refractory microsatellite‑stable (“MSS”) metastatic colorectal cancer (“mCRC”) without active liver metastases. In January 2026, France further expanded the AAC protocol for botensilimab plus balstilimab to include certain ovarian cancers and soft-tissue sarcomas.

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In January 2026, we closed our previously announced strategic collaboration with Zydus Lifesciences Ltd. ("Zydus"), including the sale of our Emeryville and Berkeley biologics manufacturing facilities. With a total consideration of $91.0 million.

Strategy

Our strategy is to focus capital on execution of programs that we believe have the clearest path to meaningful clinical and commercial value, led by BOT/BAL in colorectal cancer and selected other tumor types. We intend to advance late-stage development and support responsible paid patient access programs as well as clinical trials. We maintain manufacturing flexibility through strategic collaborations with an emphasis on our Zydus collaboration.

Discovery Platforms

Our internal discovery and translational platforms support target identification, antibody generation, biomarker analysis and candidate selection. We use these capabilities to advance wholly owned and partnered programs directed at tumor immune escape, the tumor microenvironment and myeloid cell biology. These capabilities have supported the development of our clinical and preclinical portfolio, including agents directed to CTLA-4, PD-1, CD137, CD73/TGF-beta, ILT2, LAG-3, TIM-3 and TIGIT, all of which remain as proprietary assets of Agenus.

Lead Program: Botensilimab and Balstilimab

Botensilimab is a multifunctional anti-CTLA-4 antibody designed to activate both innate and adaptive anti-tumor immune responses. Its design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care and to conventional PD-1/CTLA-4 therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells (bad actors of the immune system in the context of treating cancer), activating myeloid cells and inducing long-term memory responses (those two latter are known as the good actors of the immune system). Balstilimab is a fully human monoclonal immunoglobulin G4 (IgG4) anti-PD-1 antibody designed to block PD-1 from interacting with PD-L1 and PD-L2. BOT and BAL are investigational therapies and have not been approved by the FDA or the European Medicines Agency for commercial sale, however they are accessible through government reimbursement programs in France as well as through out of pocket pay in select European and South American countries.

BOT, alone and in combination with BAL, has been evaluated in approximately 1,200 patients across more than 60 centers worldwide and across nine tumor types, including colorectal cancer, sarcoma, non-small cell lung cancer, hepatocellular cancer, pancreatic cancer, melanoma, ovarian cancer and triple negative breast cancer. Because much of this dataset comes from early-stage, single-arm or investigator-sponsored studies, these results may not be predictive of outcomes in later-stage trials or of regulatory approval.

Refractory MSS Metastatic Colorectal Cancer

In April 2023, BOT in combination with BAL received Fast Track designation from the FDA for the treatment of patients with non-microsatellite instability-high (“MSI-H”) and/or deficient mismatch repair (“dMMR”) metastatic colorectal cancer without active liver involvement. We completed enrollment in our Phase 1 study in this population in October 2023. These data informed the design of our randomized, global Phase 2 study (n=234), which compared BOT plus BAL against standard treatments (regorafenib or trifluridine/tipiracil) in refractory MSS mCRC without active liver metastases.

In July 2024, we held an end-of-Phase 2 meeting with the FDA. The FDA agreed on a Phase 3 dosing regimen of 75 mg of BOT every six weeks (up to four doses) in combination with 240 mg of BAL every two weeks (up to two years). The FDA advised against pursuing an accelerated approval strategy based on the data then available, suggesting that the objective response data may not directly translate into a survival benefit.

In January 2025, at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (“ASCO GI”), we reported results from the randomized Phase 2 trial. The BOT 75 mg plus BAL regimen achieved a 19% objective response rate ("ORR") and a 55% disease control rate in this heavily pretreated population, while the control arm showed no objective responses. At the data cutoff, 70% of responses remained ongoing. Safety findings were consistent with prior experience, with no new safety signals or treatment-related deaths reported. The most common immune-mediated adverse events (“imAEs”) at BOT 75mg plus BAL included diarrhea/colitis and hypothyroidism, all grades, 35% and 13%, respectively.

In July 2025, long-term follow-up data from an expanded cohort of 123 patients with MSS mCRC without active liver metastases from the Phase 1b study were presented at the European Society for Medical Oncology Gastrointestinal Cancers Congress (“ESMO GI”). In this heavily pretreated population, BOT plus BAL showed approximately 42% two-year overall survival and median overall survival of approximately 21 months. Subgroup analyses showed ORR of 20% in third-line or later patients and 19% in fourth-line or later patients, with median duration of response of 16.6 months in each cohort. No new safety signals were reported. GI-related imAEs were the most common and reversible side effects.

Also in July 2025, we conducted a follow-up end-of-Phase 2 meeting with the FDA. Based on the data then available, the FDA aligned that BAL's contribution to the combination's clinical activity supported a registrational Phase 3 study without a BOT monotherapy arm. We, together with CCTG and participating cooperative groups, are conducting BATTMAN/CO.33, a global Phase 3 trial evaluating BOT plus BAL versus best supportive care in 4L+ refractory, unresectable MSS/pMMR colorectal cancer. The trial is expected to enroll approximately 830 patients across more than 100 sites in Canada, France, Australia and New Zealand and is intended to support potential regulatory filings in the United States and Europe.

Authorized Early Access Pathways

BOT plus BAL is available only through clinical trials or country-specific authorized access mechanisms where permitted. BOT plus BAL is not approved for commercial marketing in the United States, France or elsewhere.

In France, the AAC framework, authorized in September 2025, provides hospital-based access under a nationally validated protocol. The French protocol includes eligible patients with MSS mCRC without active liver metastases and in January 2026 was expanded to include eligible patients with certain platinum-refractory or platinum-resistant ovarian cancers and certain advanced or metastatic soft-tissue sarcomas. Treatment provided under the AAC protocol is reimbursed through the French national health system.

Outside France, select countries permit physician-initiated, patient-specific named-patient access programs where allowed under local law.

In second half of 2025 we began recognizing revenue from treatment supplied through the above-mentioned programs. These programs do not constitute marketing approval, may be modified or discontinued by applicable authorities, and do not assure future regulatory approvals.

Near Term Regulatory Plans

Based on existing data, we intend in 2026 to seek Accelerated Approval in the United States and Conditional Approval in the European Union for BOT plus BAL in refractory microsatellite-stable metastatic colorectal cancer without active liver metastases.

Additional Colorectal Cancer Studies

Investigator sponsored trials are also studying BOT plus BAL in earlier-line and neoadjuvant colorectal cancer settings.

Neoadjuvant data presented at the ASCO GI in January 2025 were derived from two independent studies: UNICORN and NEST.

Data from the NEST study demonstrated promising results, with no clinical recurrences observed after a median follow-up of 18 months for the NEST-1 arm and 9 months for the NEST-2 arm. The pathological complete response (“pCR”) rate improved to 47% in MSS tumors when the median time to surgery was extended, suggesting a potential benefit from a longer pre-operative window. The combination therapy was well tolerated, with no grade 4 events, no unresolved imAEs, and no surgery delays due to imAEs.

The UNICORN Phase 2 study is evaluating pre-operative BOT plus BAL combination treatment in resectable colon cancer. Pathological complete and major responses ("pMR") were observed in both pMMR/MSS and dMMR/MSI-H tumors. Patients with dMMR/MSI-H tumors achieved a 93% pCR and 100% pMR, while patients with pMMR/MSS colorectal cancer had a 29% pCR and 36% pMR rate. Serious adverse events (“AEs”) were reported in 16% of patients, with treatment-related AEs in 5%, and only one surgery was delayed due to an adverse event.

Collectively, these two studies of the BOT plus BAL combination suggest the potential to improve outcomes for patients with early-stage colorectal cancer. The results indicate a possible improvement in recurrence-free survival and overall survival, while also creating the potential to de-escalate the need for chemotherapy, radiotherapy, and surgery in selected patients. This approach may enable organ preservation and improve long-term quality of life.

Data from the Phase 1/2 study of BOT plus BAL in combination with FOLFOX and bevacizumab ("FOLFOX 3B") in MSS mCRC was also presented at ASCO GI in January 2025. Preliminary data demonstrated promising efficacy, including in patients with liver metastases, showing that the combination achieved a 71% ORR, with a 67% ORR specifically in patients with liver metastases. The regimen was well tolerated without dose limiting toxicities.

These studies have informed our evaluation of potential future registration-enabling trial designs in neoadjuvant, first-line and later-line colorectal cancer. Whether and when any additional registration-enabling trials will be initiated will depend on capital availability and strategic transactions, including partnerships, licensing arrangements and joint ventures.

Other Tumor Types and Translational Data

Clinical data generated in other tumor types continue to inform potential expansion opportunities for BOT plus BAL. In October 2025, pan-tumor data from more than 400 heavily pretreated patients in the Phase 1b C-800-01 study were presented in an oral session at the European Society for Medical Oncology Congress. The dataset showed approximately 39% two-year overall survival and median overall survival of 17.2 months across multiple tumor types, including MSS mCRC, sarcoma, ovarian cancer, PD-(L)1 relapsed or refractory non-small cell lung cancer and hepatocellular cancer.

In January 2025, data from a Phase 1b open-label, multicenter study evaluating the BOT/BAL combination across multiple sarcoma subtypes were published in the Journal of Clinical Oncology. Durable responses were observed across several sarcoma types, including visceral angiosarcoma and leiomyosarcoma, both of which are considered an immunologically cold tumor. The overall response rate for the study population (n=52) was 19.2%. Among patients with angiosarcoma (n=18), ORR was 27.8% overall, including 33.3% in visceral angiosarcoma and 22.2% in cutaneous angiosarcoma. The disease control rate was 65.4%, with a median progression-free survival of 4.4 months. At a median follow-up of 9.1 months, median overall survival had not been reached, and the 12-month OS rate was 69%.

In December 2025, data from the ovarian cancer cohort of the same Phase 1b study were published in the Journal for ImmunoTherapy of Cancer (“JITC”). In this heavily pretreated population, the BOT+BAL combination demonstrated clinically meaningful activity and durable benefit in women with treatment-refractory ovarian cancer, a population with few remaining treatment options. The combination achieved a 23% overall response rate and a 31% clinical benefit rate, including durable responses with a median duration of 9.7 months. Median overall survival reached 14.8 months, with an estimated 75% of patients alive at 12 months.

The BOT plus BAL combination demonstrated a manageable and reversible safety profile consistent with CTLA-4 and PD-1 therapies. The most common treatment-related adverse events included diarrhea/colitis (43%; 16% grade 3), fatigue, and nausea (36%), which were effectively managed using established treatment guidelines.

Other Clinical and Preclinical Programs

In addition to BOT and BAL, we own or control a portfolio of earlier-stage immuno-oncology programs directed to multiple targets, including CD137 (“AGEN2373”), CD73/TGFβ TRAP (“AGEN1423”), ILT2 (“AGEN1571”), and TIGIT bispecific (“AGEN1777”). As part of our December 2024 strategic realignment, we temporarily postponed preclinical and clinical programs that were not directly related to BOT plus BAL. We may resume internal development, seek partners or pursue other strategic alternatives for selected assets depending on capital availability and portfolio priorities.

AGEN2373, our CD137 agonist antibody, has been evaluated in a Phase 1 study alone and in combination with BOT in patients with advanced solid tumors. Updated data presented at the American Society of Clinical Oncology Annual Meeting in June 2023 showed single-agent responses without hepatic toxicities, grade 3 or higher treatment-related adverse events, or dose-limiting toxicities at doses up to 10 mg/kg.

Partnered Programs

Bristol Myers Squibb

In May 2021, we entered into a License, Development and Commercialization Agreement with Bristol Myers Squibb ("BMS") under which we granted BMS an exclusive license to develop, manufacture and commercialize our TIGIT bispecific antibody program, AGEN1777. We received a non-refundable upfront payment of $200.0 million and were eligible for development, regulatory and commercial milestones plus royalties on worldwide net sales. In October 2021, the first patient was dosed in the Phase 1 trial, triggering a $20.0 million milestone, and in December 2023 the first patient was dosed in a Phase 2 trial, triggering a $25.0 million milestone. In July 2024, BMS notified us that it was voluntarily terminating the license agreement effective January 26, 2025, and rights to AGEN1777 were returned to us.

Incyte

In January 2015, we entered into a collaboration with Incyte to discover, develop, and commercialize novel immuno-therapeutics using our antibody platforms. The collaboration initially focused on four immunotherapy programs targeting GITR, OX40, TIM-3, and LAG-3. In November 2015, the alliance was expanded to include three additional undisclosed immunotherapy targets. Pursuant to the terms of the original agreement, Incyte paid us $25.0 million in upfront cash. Under the collaboration, targets were designated as either profit-share programs or royalty-bearing programs. For profit-share programs, the parties shared all costs and profits equally. For royalty-bearing programs, Incyte funded all development costs, and we were eligible to receive milestones and royalties. Under the original agreement, programs targeting GITR, OX40, and two undisclosed targets were designated as profit-share programs, while the remaining targets were royalty-bearing programs. For each profit-share product, we were eligible to receive up to $20.0 million in future contingent development milestones. For each royalty-bearing product, we were eligible to receive (i) up to $155.0 million in future contingent development, regulatory, and commercialization milestones and (ii) tiered royalties on global net sales generally ranging from 6% to 12%.

In February 2017, we and Incyte amended the collaboration agreement to, among other things, convert the GITR and OX40 programs from profit-share to royalty-bearing programs, each with royalties on global net sales at a flat 15% rate. In addition, the two undisclosed profit-share programs were removed from the collaboration, with one reverting to Incyte and the other reverting to us (our Fc-enhanced TIGIT program), each with royalties on global net sales at a flat 15% rate. The remaining three royalty-bearing programs targeting TIM-3, LAG-3, and one undisclosed target remained unchanged, and the collaboration no longer included any profit-share programs. Pursuant to the amended agreement, we received accelerated milestone payments of $20.0 million from Incyte related to the clinical development of INCAGN1876 (GITR agonist) and INCAGN1949 (OX40 agonist).

Incyte terminated the OX40 program effective October 2023 and terminated both the GITR program and the undisclosed program effective May 2024. Upon termination, the rights to the OX40, GITR, and undisclosed programs were returned to us. In July 2024, Incyte announced it would discontinue further development of the LAG-3 and TIM-3 monoclonal antibodies. In February 2025, we received formal notice from Incyte terminating the collaboration effective February 2026. Upon termination, Incyte returned all rights to LAG-3 and TIM-3 to us.

Merck & Co.

In April 2014, we entered into a collaboration and license agreement with Merck to discover and optimize fully human antibodies against two undisclosed immunotherapy targets. Merck selected MK-4830, a monospecific antibody targeting ILT4, for advancement into preclinical studies in 2016 and later initiated a Phase 1 trial in August 2018 and a Phase 2 trial in November 2020, which triggered a $10.0 million milestone payment to us. Merck is responsible for all future product development expenses for MK-4830, and we remain eligible to receive additional milestone payments and royalties on any future sales. In 2024, Merck notified us that further clinical development of MK-4830 would be limited to an ongoing neoadjuvant ovarian study in combination with pembrolizumab and chemotherapy with or without bevacizumab.

XOMA

On September 20, 2018, through our wholly owned subsidiary Agenus Royalty Fund, LLC, we entered into a Royalty Purchase Agreement with XOMA (US) LLC. XOMA paid us $15.0 million in exchange for the right to receive 33% of certain future royalties and 10% of certain future milestones then payable to us under our Incyte and Merck agreements, net of specified third-party obligations.

Ligand

In May 2024, we entered into a Purchase and Sale Agreement with Ligand Pharmaceuticals Incorporated ("Ligand") covering specified economic interests in selected partnered programs and in BOT and BAL. Under that agreement, Ligand acquired (i) 31.875% of the development, regulatory and commercial milestones then payable to us under agreements with BMS, UroGen, Gilead, Merck and Incyte, (ii) 18.75% of the royalties under those agreements and (iii) a 2.625% synthetic royalty on worldwide net sales of BOT and BAL. The total amounts payable to Ligand are subject to a 50% reduction if total payments to Ligand exceed a specified return hurdle. The synthetic royalty is also subject to reduction if annual worldwide net sales exceed a specified level and is subject to a cap on annual worldwide net sales if sales exceed a higher specified level. In addition, the synthetic royalty may increase by 1% upon the occurrence of certain future events.

After taking into account our obligations under the Ligand Purchase Agreement, the XOMA Royalty Purchase Agreement, and the current status of our collaboration agreements, we remain eligible to receive up to approximately $49.4 million in potential development, regulatory, and commercial milestone payments from Merck & Co..

Equity Investment in MiNK and Subsidiary SaponiQx

MiNK Therapeutics

In October 2021, MiNK completed its initial public offering and its common stock trades on The Nasdaq Capital Market under the symbol "INKT." MiNK is a clinical-stage biopharmaceutical company focused on developing allogeneic invariant natural killer T (iNKT) cell therapies to treat cancer and other life-threatening immune diseases. MiNK's most advanced product candidate, agenT-797, is an off-the-shelf, allogeneic native iNKT cell therapy. MiNK is expanding clinical programs, including a Phase 2 trial in second-line gastric cancer at Memorial Sloan Kettering Cancer Center, and is also evaluating agenT-797 in viral acute respiratory distress syndrome and graft-versus-host disease.

In July 2025, our ownership percentage of MiNK dropped below 50%. Although we continue to exercise significant influence, this change resulted in a loss of control, and MiNK was deconsolidated in the quarter ended September 30, 2025. Subsequent to the deconsolidation, we account for our investment in MiNK under the equity method of accounting with the fair value option. As of December 31, 2025, we owned approximately 46% of MiNK.

SaponiQx

Founded in 2021, SaponiQx is our subsidiary focused on saponin-based adjuvant discovery and manufacturing. Its objective is to provide scalable and affordable vaccine adjuvants, support sustainable manufacturing approaches and help expand secure supply for known and novel adjuvants.

SaponiQx and QS-21 STIMULON

QS-21 STIMULON is a saponin adjuvant used to enhance immune responses in vaccines and other immunotherapies. Historically, QS-21 has been purified from the bark of the Chilean soapbark tree, Quillaja.

Partnered QS-21 STIMULON Programs

In 2006, we entered into a license agreement and a supply agreement with GlaxoSmithKline Biologicals, S.A. ("GSK") for the use of QS-21 STIMULON. In 2009, we entered into an amended and restated technology transfer and supply agreement under which GSK obtained the right to manufacture all of its commercial grade QS-21 requirements. In 2012, we amended the agreements to clarify and expand certain rights and received a $9.0 million upfront payment, $2.5 million of which was creditable against future royalties.

Under the GSK agreements, we are generally entitled to a 2% royalty on net sales of prophylactic vaccines for a period of 10 years after the first commercial sale of a resulting GSK product; however, we are no longer entitled to any additional milestone payments under those agreements and we have monetized and sold the entire royalty stream associated with GSK’s vaccine products containing QS-21 STIMULON, including Shingrix and Arexvy.

In September 2015, we monetized a portion of the GSK royalty stream through a non-dilutive transaction with an investor group led by Oberland Capital Management for up to $115.0 million. In January 2018, we sold 100% of the GSK royalty rights to Healthcare Royalty Partners III, L.P. and certain affiliates for approximately $190.0 million at closing, using approximately $161.9 million to extinguish the obligation to Oberland Capital Management, yielding us approximately $28.0 million in net proceeds. We also became eligible for two sales-based milestones totaling $40.35 million. Those milestones were achieved and paid in 2020 and 2022.

SaponiQx

SaponiQx is developing an integrated vaccine platform based on scalable manufacturing of QS-21 STIMULON and other saponin-based adjuvants, including a cultured plant cell-derived form of QS-21 known as cpcQS-21.

The commercial importance of durable vaccine responses and secure adjuvant supply was underscored during the COVID-19 pandemic. Shingrix has demonstrated long-lasting protection, but traditional bark extraction is complicated, expensive and dependent on a limited natural supply. To address these constraints, SaponiQx is working with Phyton Biotech and Ginkgo Bioworks to optimize a plant cell culture process for scalable manufacturing of cpcQS-21 and next-generation saponin adjuvants. In January 2019, the Bill & Melinda Gates Foundation awarded us a grant to support this development effort.

In 2023, SaponiQx announced the availability of cGMP cultured plant cell QS-21. In August 2024, SaponiQx announced the availability of STIMULON cpcQS-21 through InvivoGen's international retail infrastructure. In December 2024, preclinical data relating to cpcQS-21 were published in the journal Vaccines.

Manufacturing

Botensilimab and Balstilimab Manufacturing

In June 2025, we announced a strategic collaboration with Zydus Lifesciences to accelerate clinical development, scale global manufacturing, and expand patient access to BOT and BAL. The collaboration included the sale of Agenus’ state-of-the-art biologics CMC facilities in Emeryville, CA and Berkeley, CA.

Under the agreement, we will become Zydus’ first BioCDMO customer through an exclusive manufacturing arrangement supporting BOT+BAL supply for our clinical trials, global access programs, and potential future commercialization. The transaction closed in January 2026.

QS-21 STIMULON Manufacturing

Except in the case of GSK, we have retained worldwide manufacturing rights for QS-21 STIMULON and the right to subcontract manufacturing for QS-21 STIMULON.