Hitching a Ride to Transduce Barriers: Nonclinical Safety Considerations for Developing Transcriptome Modulating Therapies (S08)

Symposium Chair(s)

• Sheroy Minocherhomji, PhD

  Senior Director
  Toxicology
  Eli Lilly and Company
  Indianapolis, Indiana, United States

• Eileen Blasi, PhD, DABT

  Sr Director, Toxicology
  Avidity Biosciences
  San Diego, California, United States

Symposium Speaker(s)

• James Wild, PhD

  Senior Pharmacologist
  Division of Pharmacology/Toxicology: Infectious Diseases (DPT-ID)
  US FDA
  Silver Spring, Maryland, United States

• Tae-Won Kim, PhD

  Vice President of Preclinical Development
  Toxicology
  Ionis Pharmaceuticals
  Carlsbad, California, United States

• Laura Leung, PhD

  Principal Scientist
  Avidity Biosciences
  San Diego, California, United States

• René Meisner, DVM, DACVP, DABT

  Vice President
  Nonclinical Development
  TCG Labs Soleil
  South San Francisco, California, United States

• Katie Sokolowski, PhD, DABT

  Principle Toxicologist
  Safety Assessment / Development Sciences
  Denali Therapeutics
  South San Francisco, California, United States

Novel nucleic acid-based therapeutics targeting specific tissues, including antibody-conjugated oligonucleotides have recently begun to revolutionize the field of genetic medicine. In addition to GalNac conjugated oligonucleotides, newer modalities such Antibody-conjugated oligonucleotides have the potential to improve selectivity targetability and overall safety by targeting specific cell/tissue types involved in the pathogenesis of difficult-to-treat diseases with high unmet medical needs such as neurodegenerative and neuromuscular diseases. These novel modalities are composed of innovative components and have unique mechanisms of action that often require specific considerations for the assessment of nonclinical safety and pharmacodynamic responses. This symposium aims to provide (A) the current-state-of-the-art for novel biologics-based oligonucleotide therapeutics, (B) present on considerations and best practices to assess putative toxicities, (C) and highlight nonclinical safety assessment strategies including, predictive safety and in vivo toxicology studies that serve to enable first-in-human clinical trials in patients. The speakers will share recent experiences with nonclinical development strategies for these novel modalities including regulatory risk assessment approaches and technical considerations that differ from more classical biologicals.

Presentations:

• 9:00 AM – 9:10 AM CT

  Introduction
  

  Symposium Speaker: Sheroy Minocherhomji, PhD – Eli Lilly and Company
• 9:10 AM – 9:40 AM CT

  Targeted Delivery of Oligonucleotides with Antibody or Peptide Conjugates: An FDA Perspective
  

  Symposium Speaker: James S. Wild, PhD – US FDA
• 9:40 AM – 10:15 AM CT

  Adapting Nonclinical Strategies to Accommodate Evolution of Antisense Oligonucleotide Technologies
  

  Symposium Speaker: Tae-Won Kim, PhD – Ionis Pharmaceuticals
• 10:15 AM – 10:45 AM CT

  Break
• 10:45 AM – 11:15 AM CT

  Nonclinical Safety Assessment of Antibody-Oligo Conjugates from IND-enabling through Late-Stage Clinical Trials
  

  Symposium Speaker: Laura Leung, PhD – Avidity Biosciences
• 11:15 AM – 11:45 AM CT

  Targeting Transferrin Receptor to Transport Antisense Oligonucleotides Across the Blood-Brain Barrier
  

  Symposium Speaker: René Meisner, DVM, DACVP, DABT – TCG Labs Soleil

  Symposium Speaker: Katie B. Sokolowski, PhD, DABT – Denali Therapeutics
• 11:45 AM – 12:00 PM CT

  Panel Discussion