Navigating Complexities in Oligonucleotides: DMPK Strategies and CNS-Targeting Solutions

Oligonucleotides have emerged as a rapidly growing class of therapeutics, with nearly 20 oligo-based drugs approved by the U.S. FDA to date. However, due to their novelty, complexity, and limited regulatory guidance, oligonucleotides pose unique technical challenges for drug developers compared to traditional small molecules or biologics. Specialized pharmacokinetic evaluation systems are essential to address these complexities.

Advancements in delivery platforms have heightened the need for customized PK strategies during preclinical development. For in vitro ADME studies, selecting the right metabolic model based on the drug's structure and in vitro-in vivo extrapolation (IVIVE) is critical. In vivo PK studies require tailored administration methods to thoroughly investigate pharmacokinetics. This webinar will discuss strategies for overcoming DMPK challenges and accelerating oligonucleotide drug development, drawing from extensive experience in early-stage screening and IND filings. 

CNS-targeting oligonucleotides add further complexity, primarily entering the brain through nervous system administration methods such as cerebrospinal fluid injections (ventricular, cisterna magna, and lumbar) and nasal administration. Among these, lumbar injection is preferred for its simplicity and feasibility for repeated dosing. Over years of refinement, a standardized platform for lumbar administration in monkeys has been developed.

This webinar is sponsored by WuXi AppTec.