On March 10, 2021 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, cell therapies, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported that two abstracts on AGEN1181, Agenus’ Fc-enhanced next-generation anti-CTLA-4 antibody, were accepted for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 10 – 15, 2021 (Press release, Agenus, MAR 10, 2021, View Source [SID1234576517]).

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In a Phase 1/2 clinical study, AGEN1181 has shown responses in tumors previously unresponsive to immune therapies, including ovarian cancer and MSS endometrial and colorectal cancers. The AACR (Free AACR Whitepaper) presentation will cover the most up to date data. AGEN1181 is active even in patients with the low affinity FcγRIIIA allele, a genetic polymorphism which makes them generally unresponsive to first generation anti-CTLA-4. Further, AGEN1181 has demonstrated the ability to deplete intratumoral Tregs. Tregs are immunosuppressive T cells, and their depletion can allow for an improved antitumor immune response. Importantly, AGEN1181 is active without the neuroendocrine toxicities or hypophysitis observed with first generation agents.

The data to be presented at AACR (Free AACR Whitepaper) will showcase the optimal performance of AGEN1181 in preclinical models and in clinical trials. Preclinical data show that AGEN1181’s Fc enhancement allows it to engage the immune system even in cases of patients with the low affinity FcyRIIIA allele, which first-generation molecules do not do. These data also show that across all observed populations, AGEN1181 has increased efficacy over first-generation antibodies, and that combinations with multiple agents including checkpoint inhibitors such as anti-PD-1 and anti-TIGIT, iNKT-activating therapy, and adoptive T cell therapy, could further increase that efficacy.

In addition, clinical data to date provide evidence that these observations are being borne out in patients. Responses have been observed in patients with in the low-affinity FcyRIIIA allele. Further, AGEN1181 is the first anti-CTLA-4 to show intratumoral Treg depletion in the clinic.

AGEN1181 is currently advancing in a Phase 2 trial in colorectal cancer alone and in combination with balstilimab, Agenus’ anti-PD-1 antibody. As of February 9, Agenus has reported 6 confirmed objective clinical responses in its AGEN1181 Phase 1/2 trial and no complement-mediated toxicities.

Presentation Details:

Abstract title: Fc-enhanced anti-CTLA-4 antibody, AGEN1181: New mechanistic insights for potent antitumor immunity and combination potential in treatment-resistant solid tumors
Presenting author: Antoine Tanne, PhD

Abstract title: Characterization of the pharmacodynamic activity of AGEN1181, an Fc-enhanced CTLA-4 antibody, alone and in combination with the PD-1 antibody balstilimab
Presenting author: Irina Shapiro, PhD