AGENUS INC

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

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A MESSAGE TO OUR STOCKHOLDERS FROM OUR CHAIRMAN & CEO

Dear Fellow Stockholders,

Over the past year, Agenus made substantial progress across the areas most critical to long-term value creation: durable clinical data in cancers with limited treatment options, expanding patient access through regulated early-access pathways, advancement of our registrational strategy, and a dramatic reduction in operating burn while preserving focus on the programs at the center of our strategy.

In 2025 and early 2026, we continued to generate data that we believe reinforce the differentiated potential of BOT+BAL, advanced patient access through regulated compassionate-use and named-patient programs, initiated our registrational Phase 3 BATTMAN trial, strengthened our balance sheet, and reduced annualized operating burn from levels above $200 million in prior years to an expected approximately $50 million, as reflected in our public disclosures. We made these choices deliberately and with discipline — to focus resources where we believe they can create the greatest long-term value for patients and stockholders.

What we accomplished in 2025 and early 2026

Durable clinical data across colorectal cancer and other solid tumors. At the 2025 ESMO Congress, BOT+BAL demonstrated approximately 39% two-year overall survival across more than 400 heavily pretreated patients spanning more than nine tumor types, including colorectal, ovarian, sarcoma, PD-(L)1-refractory NSCLC, and liver cancers. In refractory microsatellite stable metastatic colorectal cancer without active liver metastases, we reported that 42% of patients treated with BOT+BAL (n=123) were alive at two years, with median overall survival of 21 months. As of year-end 2025, approximately 1,200 patients had been treated with BOT and/or BAL in Phase 1 and Phase 2 trials. We believe these data continue to support the relevance of BOT+BAL in settings where patients have few effective options and where durability of benefit matters most.

Early access and first revenues realized. In September 2025, France’s medicines agency authorized reimbursed compassionate access for BOT+BAL in refractory MSS metastatic colorectal cancer without active liver metastases. In January 2026, France expanded that access to include platinum-resistant or platinum-refractory ovarian cancer and certain advanced soft-tissue sarcomas. We recognized our first revenues under this program in the fourth quarter of 2025 and, based on continued inquiry levels, expect realized income from France to continue. Outside France, patients have also been treated through regulatory-authorized paid named-patient programs in multiple countries across Europe and South and Central America, where a treating physician determines that BOT+BAL is appropriate for an individual patient based on the clinical data generated to date, medical need, and local regulatory requirements. These programs are important not only because they provide access where permitted, but because they reflect growing physician interest in BOT+BAL and offer early real-world validation of its relevance in settings with significant unmet need.

Registrational momentum. Our registrational Phase 3 BATTMAN/CO.33 trial evaluating BOT+BAL in patients with MSS metastatic colorectal cancer is now enrolling, with the first patient enrolled in March 2026. This study is the first global registrational Phase 3 trial of a next-generation CTLA-4/PD-1 combination in this late-line setting and is being led by the Canadian Cancer Trials Group, together with GI Cancer Trials Australia and the PRODIGE network in France, across more than 100 sites. In July 2025, the FDA agreed that this streamlined two-arm design, without a BOT monotherapy arm, could support a registration package. We view BATTMAN as an important and disciplined step forward in advancing BOT+BAL toward potential approval.

Balance sheet strengthened. In January 2026, we closed our strategic collaboration with Zydus Lifesciences, including the sale of our Emeryville and Berkeley biologics manufacturing facilities, for total consideration of $91.0 million. This transaction provided strategic capital, secured dedicated U.S. biologics manufacturing capacity, and materially improved our financial flexibility. At the same time, we sharply reduced operating burn and strengthened our ability to continue investing in the programs we believe matter most.

Strong management alignment with stockholders. I, together with our Chief Commercial Officer and certain other executives, elected to receive both base salary and annual bonus compensation entirely in Agenus common stock and stock options, with no cash component. That decision reflects a clear principle: management should be aligned directly and visibly with stockholders. The value realized by participating executives depends on the long-term performance of Agenus stock. We have asked stockholders to stay with us through a critical period for the Company, and management has made that same commitment.

Stock price performance and the changing operating environment

Our stock price in 2025 did not reflect the quality of our data, the discipline of our execution, or the progress the Company made. Two factors contributed to that disconnect.

First, the regulatory environment in the United States created headwinds. The FDA’s prior recommendation against pursuing an accelerated approval path for BOT+BAL in MSS metastatic colorectal cancer without active liver metastases required us to invest in and initiate a Phase 3 trial before pursuing a broader filing strategy, delaying both potential approval and broader patient access. Second, biotech market conditions remained challenging, placing sustained pressure on balance sheets across the sector.

We responded with discipline. Rather than pursue unnecessary dilution at depressed valuations, we reduced burn, sharpened our operating focus, strengthened the balance sheet, and continued advancing BOT+BAL.

We also believe aspects of the operating environment are changing. In 2025, the FDA also announced the National Priority Voucher Program, which is intended to accelerate review for therapies that address important national health priorities and unmet medical needs. At the same time, the growing burden of colorectal cancer has become even more visible, including data showing colorectal cancer is now the leading cause of cancer-related death in Americans under 50. Together, these developments suggest a more constructive environment for therapies that address serious unmet need and demonstrate meaningful clinical benefit.

We believe BOT+BAL aligns with the objectives of these evolving FDA initiatives: durable survival data in refractory MSS metastatic colorectal cancer without active liver metastases, activity across multiple difficult-to-treat tumor types, and a persistent lack of effective options in these settings. In 2026, we plan to engage with the FDA regarding potential accelerated pathways in the United States. In parallel, we are evaluating a conditional marketing authorization pathway with the European Medicines Agency, for which the French AAC program may provide an important foundation of real-world evidence.

What we are asking of stockholders this year

This year’s proxy includes two equity-related proposals, Proposals 3 and 4, that I believe are important to keeping our team together, preserving cash, and maintaining alignment through what I believe is a defining period for Agenus.

Proposal 3 asks stockholders to approve an increase of 5,000,000 shares under our 2019 Equity Incentive Plan. This additional pool is important to supporting continued equity-based compensation, paying 2025 bonuses in stock options rather than cash, hiring a new key talent, and making the annual grants we rely on to conserve cash while retaining the people needed to execute our strategy.

Proposal 4 asks stockholders to approve a one-time option exchange for executives, directors, and certain other employees. For executives and directors, any replacement options would carry an exercise price set at a 50% premium to the market price on the exchange date. In other words, those options would have no value unless stockholders first see approximately 50% appreciation from the exchange-date price. For all other participants, replacement options would be granted at fair market value. I believe this structure is both rigorous and aligned: management benefits only if stockholders benefit first.

These proposals are not about rewarding management for the past. They are about preserving the team, the incentives, and the discipline required to execute what comes next. Together with our continued emphasis on equity-based compensation and careful expense management, they are intended to support execution of BATTMAN, continued patient access in additional jurisdictions where permitted, and pursuit of the regulatory pathways described in this Proxy Statement — with continuity of the team that has brought us to this point.

We have faced headwinds, but we have not stood still. We have advanced our science, expanded patient access, strengthened our financial position, and remained focused on building long-term value. I believe Agenus is entering an important period, and what we need now is the continuity and alignment to keep moving. I respectfully ask for your support.

Sincerely,

Garo H. Armen, Ph.D.

Chairman and Chief Executive Officer

If you need assistance with voting, have questions about the proposals or if you need additional copies of the proxy statement or the enclosed proxy card you should contact:

Alliance Advisors, LLC

150 Clove Rd #400

Little Falls Township, NJ 07424

Call Toll-free: 1-844-202-6561

AGEN@AllianceAdvisors.com

NOTICE OF ANNUAL MEETING OF STOCKHOLDERS

A list of stockholders entitled to vote will be open for examination by any stockholder for any purpose germane to the 2026 Annual Meeting of Stockholders for ten days before the meeting during ordinary business hours at our principal offices at 3 Forbes Road, Lexington, Massachusetts 02421.

It is important that your shares be represented at the 2026 Annual Meeting of Stockholders. Therefore, whether or not you plan to attend the meeting virtually, please complete your proxy and return it to us. If you attend the 2026 Annual Meeting of Stockholders virtually and wish to vote at the meeting, your proxy will not be used. You may also vote your shares over the internet or by telephone. Instructions for internet or telephonic voting are printed on your proxy card.

By order of the Board of Directors,

Garo H. Armen, Chief Executive Officer

TABLE OF CONTENTS

3 Forbes Road

Lexington, Massachusetts 02421

Telephone: (781) 674-4400

PROXY STATEMENT

This proxy statement contains information about the 2026 Annual Meeting of Stockholders of Agenus Inc. (the “Annual Meeting”), including any postponements or adjournments of the meeting. The Annual Meeting will be held virtually by live audio web conference at www.virtualshareholdermeeting.com/AGEN2026 on June 16, 2026 at 10:00 A.M., Eastern Time.

In this proxy statement, we refer to Agenus Inc. as “Agenus,” “us,” “we” or the “Company.”

This proxy statement and solicitation is being made on behalf of the Board of Directors of Agenus. In accordance with the “notice and access” rules approved by the Securities and Exchange Commission (“SEC”) and in connection with the solicitation of proxies by our Board of Directors, on or about April 30, 2026 we first sent a Notice of Internet Availability of Proxy Materials and provided access to our proxy materials (consisting of this proxy statement, our Annual Report on Form 10-K for the year ended December 31, 2025 and a form of proxy) over the internet to each stockholder entitled to vote at the Annual Meeting. We intend to mail to requesting stockholders full sets of our proxy materials (consisting of this proxy statement, our Annual Report on Form 10-K for the year ended December 31, 2025 and a form of proxy) on or about April 30, 2026.

Our Annual Report on Form 10-K for the year ended December 31, 2025 is also available on our corporate website athttps://investor.agenusbio.com/financial-information/sec-filingsand through the SEC’s EDGAR system athttp://www.sec.gov. To request a printed copy of our Annual Report on Form 10-K, which we will provide to you without charge, write to Investor Relations, Agenus Inc., 3 Forbes Road, Lexington, Massachusetts 02421. No material on our website is part of this proxy statement.

PROXY SUMMARY

This summary highlights information contained elsewhere in this Proxy Statement. Because it is a summary, it does not contain all of the information you should consider when deciding how to vote. You should read the entire Proxy Statement and our Annual Report on Form 10-K for the year ended December 31, 2025, before voting.

2025 Business Highlights

The 2025 fiscal year was defined by clinical validation, regulatory progress, initial revenue, and disciplined financial execution. The highlights below are drawn directly from our 10-K for the year ended December 31, 2025 and our subsequent public disclosures.

BOT/BAL — A Next-Generation CTLA-4/PD-1 Immunotherapy Combination

Botensilimab (BOT) is a multifunctional, Fc-enhanced CTLA-4 antibody designed to activate both innate and adaptive immunity. Balstilimab (BAL) is a fully human IgG4 PD-1 inhibitor. Together, BOT+BAL has demonstrated clinical activity in tumors historically resistant to checkpoint inhibition. As of year-end 2025, approximately 1,200 patients have been treated with BOT and/or BAL in Phase 1 and Phase 2 clinical trials.

Clinical Milestones

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Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) (no active liver metastases) at ESMO GI 2025.42% two-year overall survival and approximately 21-month median overall survival in 123 heavily pretreated patients — a population with few effective options.

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Tumor-agnostic activity at ESMO 2025. Approximately 39% two-year overall survival in over 400 heavily pretreated patients across more than nine tumor types including colorectal, ovarian, sarcoma, PD-(L)1-refractory non-small cell lung cancer, and hepatocellular cancers.

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BATTMAN Phase 3 enrolling. In March 2026, the first patient was enrolled in BATTMAN (CCTG CO.33) — the first global registrational Phase 3 trial of a next-generation CTLA-4/PD-1 immunotherapy combination in refractory MSS mCRC. The trial spans more than 100 sites across Canada, France, Australia, and New Zealand, led by the Canadian Cancer Trials Group with GI Cancer Trials Australia and the PRODIGE network (Unicancer, GERCOR, FFCD). FDA aligned with the Company on a streamlined two-arm design without a BOT monotherapy arm could support a regulatory package.

First Revenues and Expanding Patient Access

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France AAC — reimbursed through the national health system. In September 2025, France's medicines agency (ANSM) authorized reimbursed compassionate access (Autorisation d'Accès Compassionnel, or AAC) for BOT+BAL in refractory MSS mCRC without active liver metastases — the first government-reimbursed access for BOT+BAL granted by any country. In January 2026, France expanded the AAC protocol to include platinum resistant ovarian cancer and certain soft-tissue sarcomas. Initial revenues under this program were recognized in the fourth quarter of 2025 and are expected to continue as enrollment builds. Beyond the financial result, these revenues are an early real-world validator of physician and patient interest for BOT+BAL.

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Paid named-patient programs. Outside France, patients have also been treated through regulatory-authorized paid named-patient programs in multiple countries across Europe and South and Central America, where a treating physician determines that BOT+BAL is appropriate for an individual patient based on the clinical data generated to date, medical need, and local regulatory requirements. These programs are important not only because they provide access where permitted, but because they reflect real-world physician and patient interest in BOT+BAL.

Strengthened Balance Sheet

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Zydus collaboration closed January 2026. We closed a strategic collaboration with Zydus Lifesciences Ltd. for total consideration of $91.0 million, including the sale of our Emeryville and Berkeley biologics manufacturing facilities. The transaction provided working capital, secured dedicated U.S. biologics production capacity for BOT+BAL, and materially improved financial flexibility.

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Disciplined execution. The Company has substantially reduced annual operational net burn, from over $200 million in recent years to an expected approximately $50 million, as reflected in guidance provided in its public disclosures.

An Evolving U.S. Regulatory Environment

In 2025, the FDA announced the National Priority Voucher Program, which is intended to accelerate review for therapies that address important national health priorities and unmet medical needs. At the same time, the growing burden of colorectal cancer has become even more visible, including data showing colorectal cancer is now the leading cause of cancer-related death in Americans under 50. We believe BOT+BAL — with its durable survival data, tumor-agnostic signal, and profound unmet need in MSS mCRC — fits squarely within the objectives of these new initiatives.

Planned 2026 Regulatory Strategy

In 2026, we plan to engage with the FDA regarding potential accelerated pathways in the United States. In parallel, we are evaluating a conditional marketing authorization pathway with the European Medicines Agency, for which the French AAC program may provide an important foundation of real-world evidence. The basis for that effort rests on three reinforcing elements: (i) the evolving FDA framework described above; (ii) continued maturation of our long-term follow-up data, which reinforces the durability of clinical responses observed across multiple tumor types; and (iii) response criteria — a recognized endpoint for accelerated approval in oncology — that our data meaningfully support. There can be no assurance that any such filing will be accepted or that any accelerated, conditional, or other approval will be granted on the timelines we currently anticipate, or at all. Further details are set forth under “Forward-Looking Statements” later in this Proxy Statement.

Why We Are Asking for Your Support on Proposals 3 and 4

Proposals 3 and 4 are the two most important items on this year's ballot in terms of our ability to retain and motivate the team that produced the results summarized above, preserve cash and maintain alignment. The Board unanimously recommends a vote FOR each proposal for the reasons set out below, which are developed in full in the proposal sections that follow.