Abstract 694: Novel conditionally active bispecific EpCAM x CD3 T cell engagers targeting solid tumors

Abstract

Abstract Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that plays many roles in cancer biology. EpCAM is an attractive therapeutic target due to its expression on most solid tumors. However, targeting of EpCAM protein has been limited since it is also expressed on normal epithelial tissues. In fact, initial attempts to develop EpCAM-specific T cell engagers were not successful due to severe cytokine release effects as well as serious on-target off-tumor drug related toxicities. Conditionally Active Biologic (CAB) technology is a proprietary platform that generates bispecific antibodies which have no or very little binding to CD3 or to the target antigen in healthy tissue (normal physiological conditions), but have strong binding in the context of diseased tissues (tumor microenvironment) based on the glycolytic tumor metabolism (Warburg effect). Using our CAB technology, we have developed CD3 mono-CAB (WT EpCAM x CAB CD3) and CD3/EpCAM dual-CAB (CAB EpCAM x CAB CD3) bispecific antibodies. In vitro and in vivo efficacy data as well as toxicology studies in non-human primates for mono- and dual-CAB EpCAM x CD3 bispecific antibodies targeting EpCAM will be presented. Our data demonstrate that both mono- and dual-CAB EpCAM x CD3 bispecific antibodies have potent anti-tumor activities in vivo and have much lower toxicity compared to non-CAB bispecific antibodies. The mono- and dual-CAB EpCAM x CD3 bispecific antibodies generated by the CAB technology represent a new class of potent, effective T-cell engagers with potential for increased safety margin and therapeutic index in the clinic. Citation Format: Ana Paula G. Cugnetti, Haizhen Liu, Jing Wang, Charles Xing, Christina Wheeler, Matthew Lucas, Cathy Chang, Gerhard Frey, William Boyle, Jay Short. Novel conditionally active bispecific EpCAM x CD3 T cell engagers targeting solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 694.