AAPS Webinar: Advancing In Vitro Metabolic Models and Metabolite Identification for Oligonucleotide Therapeutics

Since 2018, the FDA has approved over ten new oligonucleotide drugs, highlighting the rapid emergence of oligonucleotide therapeutics as a promising drug modality. A critical aspect of developing these therapies is their metabolic stability, which necessitates the selection of appropriate in vitro metabolism models for thorough investigations. However, many existing in vitro models often fail to predict in vivo metabolism, leading to potential discrepancies in therapeutic efficacy and safety.

To address this challenge, there is a growing need for in vitro models that can effectively simulate the complex metabolic environments found in vivo. Such models are essential for conducting comprehensive metabolic stability assessments and identifying metabolites that may influence the pharmacokinetics and pharmacodynamics of oligonucleotide therapies.

In our systematic study, we focus on developing suitable in vitro metabolic systems and metabolite identification strategies specifically tailored for oligonucleotides. Through this talk, we aim to share our insights and methodologies designed to facilitate the optimization and development of oligonucleotide therapeutics, ultimately enhancing their therapeutic potential and accelerating their translation into clinical practice.

Learning Objectives:

1. The current trend in the development of oligonucleotide drugs.

2. The Importance of in vitro metabolic systems for oligonucleotides.

3. How to choose suitable in vitro models to perform metabolic stability assessment and metabolite profiling, and identification of oligonucleotides.

4. Strategies for oligonucleotide metabolite identification.

Speaker

Hong Zhang, Ph.D.

Dr. Hong Zhang, Ph.D. of Pharmacy, is mainly responsible for the metabolite profiling and identification of oligonucleotides in the DMPK Service Department of WuXi AppTec. He has over 10 years of working experience in the metabolite identification by LC-HRMS and extensive experience in the preclinical development of drugs. Dr. Zhang worked as Associate Professor in School of Pharmacy, Shanghai University of Traditional Chinese Medicine prior to joining WuXi AppTec. He has authored over 40 peer-reviewed papers in internationally renowned journals, including Pharmacological Research, Analytica Chimica Acta, Journal of Chromatography A, and Journal of Natural Products, among others.