Agenus’ CD137 Agonist Advances in the Clinic, Triggering Milestone Payment From Gilead

Agenus Inc. recently announced receipt of a $5-million clinical milestone payment for AGEN2373 (conditionally active CD137 agonist). AGEN2373 is being evaluated in a Phase 1b combination study with botensilimab (Fc-enhanced anti-CTLA-4), in melanoma patients who had relapsed on, or were refractory to, prior anti-PD-1 therapy.

“The majority of patients treated with anti-PD-1 progress within a year and are in need of more effective treatment options,” said Steven O’Day, MD, Chief Medical Officer of Agenus. “Botensilimab has shown promising activity in a wide range of treatment-resistant cancers, including melanoma. The rationale to combine botensilimab and AGEN2373 is based on preclinical evidence we reported of enhanced tumor control with this approach in a PD-1 resistant melanoma model. This study represents a rationally designed combination strategy to bring novel therapies to cancer patients.”

AGEN2373 has demonstrated preliminary clinical benefit and has been well tolerated without signs of liver toxicity, an adverse event that has impacted competitor antibodies in the clinic. Gilead currently has an exclusive option to license AGEN2373. Agenus retains the right to opt-in to share Gilead’s development and commercialization costs in the United States in exchange for a 50:50 profit share and US co-commercialization rights.

AGEN2373 is a fully human monoclonal antibody designed to boost the immune response to cancer cells by enhancing CD137 co-stimulatory signaling in activated immune cells. The unique binding properties of AGEN2373 are expected to limit its activity outside of the tumor site and mitigate toxicities that may be associated with systemic activation of CD137 in humans.

Botensilimab (also known as AGEN1181) is a next-generation, Fc-enhanced, immunoglobulin G1 (IgG1) antibody designed to block CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) inhibitory function from interacting with its ligands CD80 and CD86. The Fc region of the antibody was engineered to enhance immune activation and tumor killing, improve safety, and benefit a broader patient population versus first-generation anti CTLA-4 antibodies. CTLA-4 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market.

Agenus is a clinical-stage immuno-oncology company focused on the discovery and development of therapies that engage the body’s immune system to fight cancer. The Company’s vision is to expand the patient populations benefiting from cancer immunotherapy by pursuing combination approaches that leverage a broad repertoire of antibody therapeutics, adoptive cell therapies (through its subsidiary MiNK Therapeutics), and adjuvants (through its subsidiary SaponiQx). The Company is equipped with a suite of antibody discovery platforms and a state-of-the-art GMP manufacturing facility with the capacity to support clinical programs. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com.