Hello,I’m H. Michael Shepard.
—Ph.D., Scientific Advisor.
Participate with Halozyme management to accomplish three European drug approvals during 2013-2014, and one US FDA approval (with partners: Roche and Baxter). Solved multiple problems related to toxicology and companion diagnostic for Halozyme’s principal development candidate, PEGPH20, enter Phase 3 in pancreatic adenocarcinoma (characterized by tumor-associated hyaluronan).
Lead discovery efforts to demonstrate utility of PEGPH20 in remodeling the tumor microenvironment to facilitate immunotherapy.
Developed a novel selection method to discover therapeutic proteins (including antibodies) that are active in the tumor microenvironment but not in normal tissues, as a way to avoid systemic toxicity. In vivo proof of concept for pegylated PH20 to treat cancer (by remodeling of the tumor microenvironment). First clinical proof of concept that monoclonal antibodies could be used to treat solid tumors (Herceptin/trastuzumab). First clinical proof of concept that inhibiting tyrosine kinase is useful in treating cancer (Herceptin/trastuzumab). Helped to formulate clinical and approval strategy for trastuzumab, including biomarker-driven clinical trials (Herceptin/trastuzumab). Created first EGFR family ligand trap and showed broad anticancer activity. Proof of concept that targeting multiple members of the EGFR family could give better efficacy than targeting a single member of the family. Described specialized phosporamidate derivatives of nucleosides to target upregulated enzymes (e.g. thymidylate synthase) in cancer cells containing inactivated tumor suppressor genes (TP53, RB)—resulting in their conversion to cytotoxic moieties specifically in tumor cells with unregulated thymidylate synthase (NB1011, re. https://en.wikipedia.org/wiki/Thymectacin)