GS-8823

GS-8823 (formerly known as TUB-030) is a next-generation antibody-drug conjugate (ADC) targeting the oncofetal antigen 5T4 (trophoblast glycoprotein). Originally developed by Tubulis and subsequently acquired by Gilead Sciences, GS-8823 consists of a humanized, Fc-silenced IgG1 monoclonal antibody directed against 5T4, site-specifically conjugated to the cytotoxic DNA topoisomerase I inhibitor exatecan via a cleavable linker using Tubulis' proprietary P5 conjugation chemistry (ethynylphosphonamidate chemistry) with a homogeneous drug-to-antibody ratio (DAR) of 8. Upon binding to 5T4-expressing tumor cells, the ADC is internalized, releasing exatecan to induce DNA damage and apoptosis, while also exerting a potent bystander effect on neighboring tumor cells. GS-8823 is currently being evaluated in a Phase I/IIa clinical trial (5-STAR 1-01) for the treatment of advanced solid tumors, including head and neck cancer and non-small cell lung cancer.

Other names

5T4 ADC5T4-directed antibody-drug conjugate