IQ Webinar: Biodistribution, PK/PD & related bioanalytical considerations - AAV based Gene Therapies

March 26, 2021

Webinar

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.