Abstract 1799: BH3120, a bispecific antibody targeting 4-1BB and PD-L1 simultaneously, stimulates T cells in tumor tissue preferred manner

Abstract BH3120 is a heterodimeric bispecific antibody, designed to target 4-1BB and PD-L1 simultaneously with Pentambody™ platform, to stimulate anti-tumor immune response in a tumor microenvironment (TME) specific manner. BH3120 showed strong antitumor efficacy in multiple tumor models, and combination of BH3120 with a PD-1 antagonist showed synergic effects eradicating tumor. While BH3120 consistently activates T cells, both as a monotherapy and in combination with a PD-1 antagonist, modulation of immune system in the tumor tissue is clearly de-coupled from that in peripheral blood, suggesting reduced risks of immune related adverse events (irAEs) with BH3120. To verify this hypothesis, BH3120 was compared with reference bispecific antibodies. Combination of BH3120 with a PD-1 antogonist does not result in elevation of transaminase enzymes, while the reference bispecific antibodies, when combined with the same PD-1 antagonist, show significant increase of the enzymes and macrophage in liver. In the toxicology studies conducted so far with cynomolgus monkeys, NOAEL of BH3120 was determined to be 200 mg/kg (QW X 5). Citation Format: Jing Wang, Jun Wang, Yang Liu, Yan Pang, Aihong Zhang, Jie Feng, Aibo Sun, Xiao Ma, Jingmei Cai, Jiangcheng Xu, Jiawang Liu, Kyoungwoo Lee. BH3120, a bispecific antibody targeting 4-1BB and PD-L1 simultaneously, stimulates T cells in tumor tissue preferred manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1799.