anti-TROP2/EGFR bispecific antibody-drug conjugate DM001

An antibody-drug conjugate (ADC) composed of a bispecific antibody directed against the tumor associated antigens (TAAs) trophoblast cell surface protein 2 (trophoblast antigen 2; calcium signal transducer 2; TROP2; TROP-2; TACSTD2; GA733-1; M1S1) and human epidermal growth factor receptor (EGFR), conjugated, via a protease-cleavable linker, to the auristatin derivative and microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, the antibody moiety of anti-TROP2/EGFR bispecific ADC DM001 targets and binds to TROP2 and EGFR expressed on tumor cells. Upon binding, internalization, proteolytic cleavage of linker, and the release of MMAE, MMAE targets and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in TROP2 and EGFR-expressing tumor cells. TROP2 and EGFR are co-expressed in a variety of cancer cells. TROP2, a transmembrane protein overexpressed in various tumors, is associated with enhanced tumor aggressiveness, metastasis, drug resistance and increased tumor cell survival. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.