M69-MMAE

**M69-MMAE** is an investigational, preclinical antibody-drug conjugate targeting activated matriptase. It consists of the activated-matriptase-selective M69 monoclonal antibody conjugated to the microtubule-disrupting payload monomethyl auristatin E through a cathepsin B-cleavable valine-citrulline-PABA linker. Binding to activated matriptase on tumor cells promotes internalization and lysosomal payload release, leading to inhibition of microtubule assembly, cell-cycle arrest, and apoptosis. In published mouse and cell-line studies, M69-MMAE showed antitumor activity in activated-matriptase-positive triple-negative breast cancer and mantle cell lymphoma models, including activity in combination with cisplatin or bortezomib. ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC5995259/))