Director, WuXi AppTec DMPK Department WuXi AppTec Shanghai, Shanghai, China (People's Republic)
Since 2018, the FDA has approved over ten oligonucleotide-based drugs, highlighting their rapid rise as a promising therapeutic modality. A key challenge in their development is assessing metabolic stability using in vitro models. However, many current models fail to accurately predict in vivo metabolism, leading to potential gaps in understanding efficacy and safety.
To address this, there is a growing need for improved in vitro systems that better replicate in vivo metabolic conditions. Such models are critical for evaluating oligonucleotide stability and identifying metabolites that may affect pharmacokinetics and pharmacodynamics.
In this study, we systematically develop and assess in vitro metabolic models and metabolite identification strategies tailored for oligonucleotides. This presentation will share our approaches and insights aimed at enhancing preclinical evaluation, optimizing therapeutic profiles, and supporting the efficient translation of oligonucleotide therapeutics into clinical use.
Learning Objectives:
Upon completion, participants will be able to understand the importance of in vitro metabolic stability screening and the relevant experimental systems for oligonucleotide drug development.
Upon completion, participants will be able to describe limitations of current in vitro models and apply strategies to select suitable systems for oligonucleotide metabolic stability assessment and metabolite identification.
Upon completion, participants will be able to understand strategies for oligonucleotide metabolite identification.
