anti-DLL3 antibody-drug conjugate FZ-AD005

An antibody-drug conjugate (ADC) composed of FZ-A038, a monoclonal antibody directed against the tumor-associated antigen (TAA) delta-like protein 3 (DLL3), conjugated, via a valine-alanine (Val-Ala) dipeptide linker, to the cytotoxic DNA topoisomerase I inhibitor and exatecan derivative DXd (MAAA-1181a; MAAA-1181), with potential antineoplastic activity. Upon administration, anti-DLL3 ADC FZ-AD005 targets and binds to DLL3-expressing tumor cells. Upon binding and internalization, DXd is released. DXd inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of DLL3-expressing tumor cells. FZ-AD005 is also able to induce a bystander effect on neighboring cells in the tumor environment. This further inhibits the proliferation of tumor cells. In addition, FZ-AD005 is Fc-silenced, which may prevent Fc gamma receptor (FcgR)-mediated toxicities. DLL3, a Notch pathway protein, is overexpressed on a variety of cancer cell types. It plays a key role in embryonic development, tumor initiation and proliferation.