Abstract 2397: Pre-clinical evaluation of PE0116: A potent cross-linking depednet 4-1BB agonist antibody

Abstract

Abstract 4-1BB is a member of the tumor necrosis factor superfamily and plays a critical role in activation of cytotoxic T cells to promote anti-tumor immunity. As a co-stimulatory molecule, it is ideally suited for activation via agonist therapeutic antibodies in order to reactivate the immune system and promote cytolytic activity through CD8+ T cells. Clinical trials of two agonist antibodies (Urelumab and Utomilumab) are ongoing. Urelumab has shown clinical efficacy but been hampered by inflammatory liver toxicity at doses above 1 mg/kg, suggesting potential safety concerns at higher doses. Utomilumab has a superior safety profile, but is a less potent 4-1BB agonist. Hence, it may be necessary to achieve potent immune activation while avoiding limiting immune-related adverse events. PE0116 is a fully human monoclonal antibody generated from immunization of Harbour H2L2 human transgenic mice with recombinant human 4-1BB protein. It blocks the binding of 4-1BB to its ligand 4-1BBL and its activity in T cell activation is crosslinking dependent. After crosslinking, PE0116 strongly increases IFNg secretion from T cells in the presence of anti-CD3 antibody and its activity is superior to Utomilumab analog. More importantly, PE0116 has demonstrated robust anti-tumor activity and better potency than both benchmark antibodies in MC38 tumor model with human 4-1BB KI mice. PE0116 has also demonstrated good safety profile in a non-GLP safety study in cyno monkey. Currently the antibody is under late stage IND-enabling study. Its safety and efficacy will be further tested in patients. Citation Format: Ningning Song, Zhengwu Li, Shan He, Teddy Yang, Qing Duan. Pre-clinical evaluation of PE0116: A potent cross-linking depednet 4-1BB agonist antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2397.