anti-EDB antibody-drug conjugate PYX-201

An antibody-drug conjugate (ADC) composed of a fully human immunoglobulin G1 (IgG1) antibody against extra domain B (EDB) splice variant of fibronectin (EDB-FN; EDB+ FN), conjugated via the cleavable linker mc-Val-Cit-PABC, to the cytotoxic auristatin derivative Aur0101, with potential antineoplastic activity. Upon administration of anti-EDB ADC PYX-201, the antibody moiety targets and binds to EDB in the tumor stroma. Upon binding, the cell-permeable auristatin derivative payload is released, and diffuses across the cell membranes of nearby tumor cells, fibroblasts and tumor vasculature. The auristatin derivative binds to tubulin and inhibits microtubule polymerization, which results in G2/M phase arrest and apoptosis of these cells. Upon tumor cell death, the auristatin derivative is re-released, further killing nearby tumor cells. Tumor cell death may also promote dendritic cell (DC) maturation and anti-tumor immune responses. ED-B splice variant of fibronectin, a marker of tissue remodeling and angiogenesis, is overexpressed in the extracellular matrix in many tumors.