Discovery DMPK Quick Guide

S. Cyrus Khojasteh is a Senior Director and Senior Principal Scientist and heads the Biotransformation Function in DMPK Department at Genentech (South San Francisco). He leads the ADME efforts of macrocyclic peptides and microbiome efforts. His biotransformation research focuses on the mechanisms of biotransformation in drug discovery and development, from small molecules, antibody drug conjugates, and macrocyclic peptides. Cyrus received his PhD in medicinal chemistry from the University of Washington under the direction of Professor Sidney D. Nelson.Harvey Wong is Associate Professor of Pharmacokinetics in the Faculty of Pharmaceutical Sciences at the University of British Columbia. He obtained his BSc in pharmacy and PhD in pharmacokinetics and biopharmaceutics from the University of British Columbia (Canada). Harvey’s expertise is in pharmacokinetics, and modeling and simulation (translational PK/PD analysis, systems pharmacology, and physiologically based pharmacokinetic modeling). He serves on the editorial boards of Biopharmaceutics and Drug Disposition, Xenobiotica, and Clinical and Translational Sciences.Donglu Zhang is a Senior Fellow in DMPK at Genentech. He is interested in applying drug metabolism studies in drug design and development of both small molecule drugs, protein degraders, and antibody-drug conjugates (ADC). He received the Sir James Black Award for discovery of and original research on Eliquis from the British Pharmacological Society (2018), and the Ondetti and Cushman Award for invention of mass defect filtering method (MDF) from Bristol-Myers Squibb (2007). He serves on editorial boards of Drug Metabolism and Disposition and Xenobiotica.Cornelis E.C.A. Hop is Vice President at Genentech and supervises the DMPK Department. He leads a team of about 85 scientists involved in acquisition and interpretation of ADME data in support of drug discovery and development ranging from early stage research to NDA and beyond. Before that he was a senior director at Pfizer and a senior research fellow at Merck, and he received his PhD from the University of Utrecht (the Netherlands). He has extensive experience in ADME sciences with a particular focus on PK optimization, human PK prediction, biotransformation, bioanalysis, and the use of in silico approaches in drug discovery.

• Goals for DMPK during drug optimizations.- Drug Properties.- DMPK in lead optimization.- Candidate tranlational characterization.- Q&A of DMPK issues and tools for drug discovery.- ADME assays.- Regulatory documents for IND to Support FIH.- Appendix: Chemical nomenclature.