IQ Webinar: Biodistribution, PK/PD & related bioanalytical considerations - AAV based Gene Therapies
Presented by Kefeng Sun, PhD (Takeda) and Uma Kavita PhD (Bristol Myers Squibb)
Sponsored by the IQ Translational and ADME Sciences Cell and Gene/Nucleic Acid Based Modalities Working Group
The biodistribution, PK/PD and analytical aspects are crucial for understanding both safety and efficacy of the AAV-based vector gene therapy (GT) and is a component of the nonclinical package required by regulatory agencies prior to first-in-human trials.
Discussion will include:
- Guidelines for nonclinical biodistribution studies
- Important considerations for biodistribution as it relates to species, route of administration, AAV serotype and dose.
- Published examples of biodistribution studies to support these guidelines.
- The challenges of PK/PD analysis and modeling for GT compared with traditional therapeutics
- Approaches applied for GT human dose projection and aspects concerning long-term durability of liver based AAV GTs.
- Bioanalytical considerations related to biodistribution studies of rAAV GTs and transgene expression in target and non-target tissues.
- Bioanalytical process from sample collection, handling and data reporting.
- Non-clinical IND enabling case study where the bioanalytical methods were employed to understand biodistribution, transgene expression, viral shedding and germline transmission.
- Comparison between the traditional qPCR method and the currently trending droplet digital PCR (ddPCR) method for DNA and mRNA quantitation (technical merits of each platform)
- Various aspects of method development and validation
- Pros and cons of qualitative and quantitative methods for transgene protein products
This webinar will provide a comprehensive overview of biodistribution and bioanalytical considerations and how concepts of “PK” apply for AAV based GTs.