PYX-201 targets a tumor-restricted antigen that several tumor types overexpress. By using a well-characterized linker and potent toxin, PYX-201 selectively kills tumor cells and enhances a robust anticancer immune response.
PYX-201 is an investigational human IgG1 isotype site-specifically conjugated with an auristatin toxin targeting oncofetal fibronectin extradomain-B (EDB) that we plan to initially develop for the treatment of non-small cell lung cancer. Fibronectin is a glycoprotein found in the extracellular matrix. EDB regulates blood vessel morphogenesis, which provides the tumor access to nutrition and oxygen, a means to remove waste, and a pathway for metastasizing cells. EDB is overexpressed in many malignancies and is minimally expressed in most normal adult tissues. In addition to achieving tumor regression with single-agent PYX-201 in patient derived xenograft, treatment of syngeneic tumor models with PYX-201 resulted in immunogenic cell death enhanced infiltration of T-cells into the tumor microenvironment, enabling synergistic activity in combination with a checkpoint inhibitor.