TS2: INTRODUCTION TO SMALL MOLECULE DRUG METABOLISM AND APPLICATIONS TO DISCOVERY AND DEVELOPMENT

NEW DATES - AUGUST 26-27, 2020
DAY 1: 1:30 PM - 6:00 PM | DAY 2: 8:00 AM - 5:50 PM

DAY 1: WEDNESDAY AFTERNOON
Follows schedule of main event, including refreshment breaks in exhibit hall for poster viewing and networking
Breakout Discussions

DAY 2: THURSDAY ALL DAY
Plenary Keynote Session
Lunch Provided

About this Training Seminar: This 1.5-day lecture-based interactive seminar, which focuses on small molecule drug metabolism, will begin with a historical background in the origin of the field before reviewing the both well-recognized and more recently discovered drug metabolism pathways. In vitro assays used to access metabolic clearance and medicinal chemistry strategies for modifying structures to overcome metabolism-dependent clearance during lead optimization will be discussed. The topic of drug toxicity will be discussed in the context of drugs that are toxic through bioactivation to reactive metabolites, with examples of drug structure-toxicity relationships and the relevance of idiosyncratic toxicity to the pharmaceutical industry. The role of metabolite identification studies in preclinical and clinical development will be compared and the steps involved in identifying and characterizing metabolites by mass spectrometry will be explained. Advances in the use of in silico tools in the context of drug metabolism will be explored. An overview of the pharmacological properties and functions of drug transporters and some preclinical approaches to investigate drug transport mechanisms will be presented as well as current regulatory guidance on transporters.

Participants will see the importance of understanding drug metabolism in the different stages and processes required to advance a new chemical entity from discovery through development into the clinic, through examples and case studies. This seminar is intended for scientists in either academia or industry who would like to become more familiar with small molecule drug metabolism.

Topics to be covered in the seminar:

• Historical background in the field of drug metabolism
• Basic drug biotransformation reactions and the enzymes responsible
• Newly recognized drug biotransformation reactions
• In vitro assays used to access metabolism-based clearance
• Medicinal chemistry strategies for overcoming poor metabolic stability
• Bioactivation pathways to reactive drug metabolites
• Role of reactive metabolites in drug toxicity, including idiosyncratic toxicity
• Role of metabolite identification studies in discovery and development
• Four steps for identifying and characterizing drug metabolites by mass spectrometry
• In silico tools to address drug metabolism and reactive metabolite formation
• Pharmacological properties and functions of drug transporters
• Preclinical approaches to investigate drug transport mechanisms
• Role of transporters in drug PK, PD, efficacy, safety, and drug-drug interactions (DDI)
• Impact of transporter studies on drug discovery and development
• Recommendations from the current regulatory guidance and International Transporter Consortium (ITC) white papers on transporter evaluation during drug development

Instructor Biographies:

John Erve, PhD, DABT, Jerve Scientific Consulting, Inc.

John Erve is from Chicago and received degrees in Chemistry (BS, MS) from the University of Chicago and earned a PhD in Toxicology at Oregon State University under the supervision of Dr. Donald Reed. Following postdoctoral work at Vanderbilt (1995-1999) he joined BD-Biosciences (Woburn, MA) as a Study Director. In 2002, he joined AstraZeneca (Sweden) where he was involved in characterizing reactive metabolites and their protein adducts in an effort to better understand the role of reactive intermediates in drug toxicity. In 2004 he joined Wyeth (Collegeville, PA) as a Principal Scientist responsible for metabolite identification. Following the merger with Pfizer in 2010, John joined Novartis Institutes of Biomedical Research (Cambridge, MA) as a Lab Head in Analytical Sciences. John returned to the field of drug metabolism by joining Elan Pharmaceuticals (San Francisco, CA) in 2012 and after Elan was sold, created Jerve Scientific Consulting focusing on helping small biotech companies in the Bay area with their drug discovery efforts. His research interests include mechanistic toxicology and using mass spectrometry to characterize metabolites and metabolic pathways.

Yurong Lai, PhD, Senior Director, Drug Metabolism, Gilead Sciences

Dr. Lai is a Senior Director of Drug Metabolism at Gilead Sciences. He is a fellow of American Association of Pharmaceutical Scientists and Adjunct Faculty position in the Department of Pharmacy of the University of Rhode Island. His current role in Gilead is to manage DMPK-drug disposition group and implement in vitro/in vivo preclinical and clinical strategies for compound advancement to regulatory filing. He received his MD from Fujian Medical University in China and his PhD (Toxicology) from Sapporo Medical University in Japan in 1998. Prior to joining Gilead, Dr. Lai led research programs at Pfizer and BMS in transporter research and ADME-PK-Tox. He is the associate editor/editorial board member of top-ranking DMPK journals, including DMD, BDD, JPS and "Frontiers in Pharmacology," etc. He is a patent inventor and the author of a book, book chapters, and over 150 original publications.

Training Seminar Information

Each CHI Training Seminar offers 1.5 days of instruction with start and stop times for each day shown above and on the Event-at-a-Glance published in the onsite Program & Event Guide. Training Seminars will include morning and afternoon refreshment breaks, as applicable, and lunch will be provided to all registered attendees on the full day of the class.

Each person registered specifically for the Training Seminar will be provided with a hard copy handbook for the seminar in which they are registered. A limited number of additional handbooks will be available for other delegates who wish to attend the seminar, but after these have been distributed, no additional books will be available.

Though CHI encourages track hopping between conference programs, we ask that Training Seminars not be disturbed once they have begun. In the interest of maintaining the highest quality learning environment for Training Seminar attendees, and because seminars are conducted differently than conference programming, we ask that attendees commit to attending the entire program, and not engage in track hopping, as to not disturb the hands-on style instruction being offered to the other participants.