anti-c-Met/MMAE ADC MYTX-011

An antibody-drug conjugate (ADC) composed of an engineered pH-dependent humanized immunoglobulin G1 (IgG1) monoclonal antibody against the tumor-associated antigen (TAA) proto-oncogene c-Met (hepatocyte growth factor receptor; HGFR) and conjugated, via a valine-citrulline (VC) peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon intravenous administration of anti-c-Met/MMAE ADC MYTX-011, the monoclonal antibody moiety targets and binds to c-Met expressed on tumor cells. Upon binding, internalization, and proteolytic cleavage, MMAE is released. MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. This induces cell death in c-Met-expressing cancer cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis and tumor angiogenesis. The engineered pH-dependent anti-c-Met antibody allows enhanced binding and thus uptake into c-Met-expressing cancer cells while reducing binding to and uptake in healthy cells. This may increase efficacy and improve tolerability.