Abstract 4560: Conditionally active biologics (CAB): A novel class of molecules targeting solid tumors

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Abstract Conditionally Active Biologics (CAB) technology is a proprietary platform that selects antibodies binding to target antigens in the context of diseased tissues, but not normal tissues, taking advantage of the unique conditions in the tumor microenvironment. Using our CAB technology, we have developed CAB ADCs to various well-established tumor associated antigens (TAA), including Nectin-4, Her2 and CD46. Each of these molecules play an important role in cancer biology and are attractive targets for the development of therapeutic antibodies. These targets, however, are expressed on many normal tissues and have been implicated in a wide range of biological processes; therefore, limiting the use of traditional ADCs as cancer therapy. Using CAB technology, we have developed conditionally active ADCs that have no or very little binding 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 (including Warburg effect). In vitro and in vivo efficacy data demonstrating the abilities of CAB ADCs to induce cytotoxicity of human target-expressing tumor cell lines, and to inhibit tumor growth in human tumor xenograft models will be presented. In conclusion, our data is consistent with our previous work on EpCAM, our clinical stage AXL and ROR2 CAB ADCs, and suggests that conditionally active ADCs generated using the CAB technology will provide a new generation of biologics with increased safety margin and therapeutic index in the clinic. Citation Format: Jing Wang, Charles Xing, Haizhen Liu, Ana Paula G. Cugnetti, Christina Wheeler, Matthew Lucas, Gerhard Frey, Cathy Chang, William J. Boyle, Jay M. Short. Conditionally active biologics (CAB): A novel class of molecules targeting solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4560.