Biotransformation Stories

Abstract:

Biotransformation science is critical to understanding the metabolic fate, pharmacokinetics, safety, and efficacy of new therapeutics. Biotransformation Stories highlights emerging research from doctoral trainees applying both established and evolving approaches to drug and xenobiotic metabolism. Emily Gracey will explore advanced human in vitro models for studying drug metabolism and toxicology, including 3D cultures, organoids, induced pluripotent stem cell-derived models, and microphysiological systems. These technologies offer opportunities to better recapitulate human physiology, improve preclinical translation, and complement conventional 2D cultures and animal models. Ian Levasseur’s presentation will examine the metabolism of BKI-1708, a promising anti-Cryptosporidium agent that forms an unusual, pharmacologically active hemiaminal metabolite. Using human liver microsomes, selective CYP inhibition, recombinant enzymes, and LC-MS/MS, CYP2C8 was identified as the primary enzyme responsible for metabolite formation, illustrating how mechanistic biotransformation studies can inform pharmacokinetics and drug–drug interaction risk. These stories will showcase how emerging scientists are addressing contemporary biotransformation challenges and provide a forum for engagement between academic trainees and industrial DMPK scientists.

Educational Needs Statement: 

A trained biotransformation scientist is becoming increasingly difficult to find for industrial biotransformation bench scientist positions. Intellectual property concerns have long limited access to novel compounds and metabolism studies, and recent decreases in funding available to support basic DMPK science have created additional challenges for doctoral students and postdocs in biotransformation and related fields. We see an urgent need to give exposure to those working on projects in this space both to highlight their exciting work and to inspire them and their peers to continue working on projects with a focus on drug and xenobiotic metabolism. 

Learning Objectives: 

• Give a platform for trainees to highlight their emerging science. 
• Provide an opportunity for industrial scientists to interact with a few of the next generation of biotransformation scientists. 
• Provide the audience with a few examples of how academia is tackling biotransformation questions.