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DIA/FDA Oligonucleotide-Based Therapeutics Conference

Session 3 Track B: Toxicology Updates on Renal and Platelet Effects of ASOs and 2’-Fluoro Nucleotide Effects of siRNAs

Session Chair(s)

Ronald L. Wange, PhD

Ronald L. Wange, PhD

  • Associate Director for Pharm/Tox ODE3, CDER
  • FDA, Office of New Drugs, United States
Jeffery  Engelhardt, DVM, PhD

Jeffery Engelhardt, DVM, PhD

  • Vice President, Pathology and Nonclinical Drug Safety
  • Ionis Pharmaceuticals, Inc., United States
This session will examine the renal accumulation of ASOs in animals, mechanisms of ASO-related glomerular injury, and the broader experience of clinical renal toxicity with the class. The current hypothesis on the pathogenesis of ASO-related thrombocytopenia in nonhuman primates and potential strain dependence will be discussed along with potential clinical ramifications. The safety studies of 2’-deoxy-2’-fluoro nucleotides in GalNAc-siRNA conjugates will also be discussed in view of toxicity concerns from previous drugs containing 2’-F-modified nucleobases, such as fialuridine.


Kendall  Frazier, DVM, PhD

Examination of Glomerular Toxicity Risk Across ASO Platforms and Trials

Kendall Frazier, DVM, PhD

  • Director, Cellular and Molecular Pathology
  • GlaxoSmithKline, United States
Padma Kumar  Narayanan, DVM, PhD, MS

Understanding the Mechanism for Dose-Dependent Thrombocytopenia Associated with 2' MOE ASOs

Padma Kumar Narayanan, DVM, PhD, MS

  • Executive Director
  • Ionis Pharmaceuticals, Inc., United States
Ivan  Zlatev, PhD

Safety Evaluation of 2'-Deoxy-2'-Fluoro Nucleotides in GalNAc-siRNA Conjugates

Ivan Zlatev, PhD

  • Principal Scientist, Research
  • Alnylam Pharmaceuticals, Inc., United States