Evaluating DDI Risk in Emerging Drug Modalities

Full Title: Evaluating DDI Risk: Practical Insights into In Vitro ADME Studies with a Deep Dive into Peptide Metabolism via Proteomics, Clearance, and Biotransformation In vitro ADME and DDI studies are critical decision-making tools for identifying safety and potential drug interaction risks in early development. With appropriate design and interpretation, they can be effectively applied beyond small molecules to support emerging modalities, including peptides. This session examines how complementary in vitro systems, combined with proteomics-driven insights, can improve the understanding of metabolic clearance, biotransformation pathways, and DDI risk assessment. As the prevalence of non-CYP substrate small molecules and new modality drugs in development increases, so does the need for reliable preclinical assays to model human tissue metabolism by non-traditional drug metabolizing enzymes. The second half of this presentation features a case study assessing differences across key in vitro test systems by comparing clearance and metabolic profiles in human hepatocytes, liver/kidney S9 and liver lysosome subcellular fractions for the GLP-1 receptor agonists semaglutide, tirzepatide and orforglipron. Marked differences in both clearance and metabolites formed were observed and then correlated with enzyme expression profiles in the various test systems based on a global proteomics profile derived for each of the test systems of interest. This case study involving both peptide and non-peptide GLP-1 drugs demonstrates the complementary utility of each of the test systems and experimental approaches applied, in conjunction with proteomics data, to aid in better understanding the tissue metabolic clearance of drugs of varying modalities. Key topics include: Evaluating DDI risk across emerging drug modalities Comparative metabolic profiling of GLP-1 therapeutics Proteomics applications in tissue-specific metabolism ADME and biotransformation best practices Download the slides: https://bioivt.com/educational-conten... Additional resources on this and other topics: https://bioivt.com/resources/educatio... Questions, comments and requests: https://bioivt.com/about/contact-us Access BioIVT's products and services: https://bioivt.com Other previously aired webinars: https://bioivt.com/educational-conten...) Upcoming webinar notifications: https://bioivt.com/resources/newslett... About the Presenters Dr. Tina Mueller is a Scientific Advisor for ADME-Tox Services at BioIVT. She joined BioIVT in 2023 and consults with customers and internal teams on in vitro ADME programs with a focus on in vitro DDI studies and compliance with regulatory guidelines. Tina obtained her PhD in Biochemistry and Microbiology and earned a Master’s in Environmental Sciences from the Swiss Federal Institute of Technology in Zurich, Switzerland. Before joining BioIVT, she was an Associate Director, Research at Cybin where she led the company’s research programs from early through late discovery. Additionally, Dr. Mueller served as a Research Associate Professor at Michigan State University, Senior Staff Scientist at Scripps Florida, and Professor for Biomedical Sciences at Keiser University. Dr. Joanna Barbara served as Vice President of Scientific Operations when XenoTech was acquired by BioIVT in 2022 and now serves as the BioIVT Kansas City Site Lead. Joanna obtained her Ph.D. in Analytical Chemistry from the University of Florida. She joined XenoTech in 2007. In that time, Joanna has served in Mass Spectrometry Specialist roles as the Division Director of Analytical Services and Division Director of Scientific Operations at XenoTech. Dr. Barbara also serves as an Adjunct Graduate Professor of Pharmaceutical Sciences for the College of Pharmacy at the University of Missouri – Kansas City. She has authored or co-authored numerous scientific posters and papers and has represented XenoTech as an invited speaker at various analytical and drug metabolism conferences. Joanna is quality-oriented with extensive experience in DMPK, regulatory compliance, and process and project management. Dr. Barbara is responsible for the development, operation, and improvement of the BioIVT Kansas City site.