Novel Candidates Show Promise in Turning Cold and Refractory Tumors into Responsive Targets

Agenus Inc. (“Agenus”) (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, today announced the presentation of new data on two of its promising investigational immunotherapy candidates, botensilimab and AGEN1721, at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting in Houston, Texas. The data, showcasing potential breakthroughs in treating immune-resistant tumors, will be presented by Dhan Chand, Ph.D., Vice President of Research at Agenus.

The first two presentations will spotlight botensilimab, an innovative, investigational, Fc-enhanced anti-CTLA-4 antibody that has shown remarkable efficacy in overcoming immune barriers across several treatment-resistant cancers, including glioblastoma, melanoma, colorectal, pancreatic, and breast cancers. Botensilimab’s unique mechanism of action enhances both innate and adaptive immunity to promote optimal T-cell priming, stimulate antigen-presenting cells, and deplete immune suppressing regulatory T cells in the tumor microenvironment, creating a multi-pronged attack on cold and refractory tumors.

“These findings represent a significant milestone in understanding how botensilimab can be optimally combined with both established and emerging therapies,” said Dr. Chand. “What’s particularly compelling is the profound efficacy we’re seeing in traditionally ‘cold’ tumors and treatment-resistant cancers—offering potential new options for patients with limited therapeutic choices.”

Featured botensilimab presentations:

Preclinical dose-pharmacokinetic-efficacy modeling of botensilimab using a mouse surrogate of the Fc-enhanced anti-CTLA-4 antibody

527

Location: Exhibit Halls A B George R. Brown Convention Center

Date: Friday, Nov. 8, 2024 - Odd Number Posters

Poster Hall Hours: 9 a.m.–7 p.m.

Fc-enhanced anti-CTLA-4 antibody, botensilimab, enhances the efficacy of multiple therapeutic modalities in immunotherapy-refractory tumor models

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Location: Exhibit Halls A B George R. Brown Convention Center

Date: Saturday, Nov. 9, 2024 - Even Number Posters

Poster Hall Hours: 9 a.m.–8:30 p.m.

An additional presentation will cover AGEN1721, a first-in-class, Fc-enhanced bifunctional antibody targeting FAP and TGFβ. AGEN1721 is engineered to remodel the tumor microenvironment by depleting cancer-associated fibroblasts (CAFs) and neutralizing TGFβ’s immunosuppressive effects. By facilitating T-cell infiltration and activation, AGEN1721 effectively transforms cold tumors into "hot," immune-responsive environments.

“AGEN1721 represents a breakthrough in addressing the challenges of immune-excluded tumors by targeting key elements that suppress immune activity within the tumor microenvironment,” said Dr. Chand. “The data we’re presenting at SITC 2024 highlight how AGEN1721’s dual-action approach can dismantle barriers to immune infiltration, offering renewed hope for more durable and effective responses against resistant cancers.”

Featured AGEN1721 presentation:

AGEN1721, a first-in-class Fc-enhanced bifunctional antibody targeting FAP and TGFβ, remodels the tumor microenvironment to overcome cancer-associated fibroblast-mediated immune suppression

1355

Location: Exhibit Halls A B George R. Brown Convention Center

Date: Friday, Nov. 8, 2024 - Odd Number Posters

Poster Hall Hours: 9 a.m.–7 p.m.

About Botensilimab

Botensilimab is an investigational human Fc enhanced CTLA-4 blocking 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. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 1,100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

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 (through SaponiQx). 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 www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels.

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 2023, 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.

Investors 917-362-1370 investor@agenusbio.com Media 612-839-6748 communications@agenusbio.com

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