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Session 3 Track B: Toxicology Updates on Renal and Platelet Effects of ASOs and 2’-Fluoro Nucleotide Effects of siRNAs
Session Chair(s)
Ronald Wange, PhD
Associate Director for Pharm/Tox, OND, CDER
FDA, United States
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.
Speaker(s)
Examination of Glomerular Toxicity Risk Across ASO Platforms and Trials
Kendall Frazier, DVM, PhD
GlaxoSmithKline, United States
Director, Cellular and Molecular Pathology
Understanding the Mechanism for Dose-Dependent Thrombocytopenia Associated with 2' MOE ASOs
Padma Kumar Narayanan, DVM, PhD, MS
Ionis Pharmaceuticals, Inc., United States
Executive Director
Safety Evaluation of 2'-Deoxy-2'-Fluoro Nucleotides in GalNAc-siRNA Conjugates
Ivan Zlatev, PhD
Alnylam Pharmaceuticals, Inc., United States
Principal Scientist, Research
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