MAC-8001

MAC-8001 is a first-in-class molecular glue-antibody conjugate (MAC) developed by DaCure Therapeutics for the treatment of KRAS-mutant cancers. It consists of an anti-B7-H3 monoclonal antibody site-specifically conjugated to a KRAS-modulating molecular glue payload via a cleavable linker, with a drug-to-antibody ratio (DAR) of approximately 8.0. The molecular glue payload is designed to disrupt the interaction between KRAS (including G12C, G12D, and G12V mutants) and the BRAF Ras-binding domain (RBD), thereby inhibiting downstream MAPK and PI3K/AKT signaling pathways. By utilizing an antibody-directed delivery system, MAC-8001 aims to enhance the therapeutic window of pan-RAS modulators by limiting systemic exposure and improving pharmacokinetics. Preclinical studies presented at AACR 2026 have demonstrated potent antitumor activity in xenograft models of KRAS-driven malignancies, including pancreatic ductal adenocarcinoma.