DIA/FDA Oligonucleotide-Based Therapeutics Conference

This session will explore the evolving landscape of translational safety for genetically targeted oligonucleotide therapeutics, with a focus on understanding, assessing, and mitigating class-specific and emerging risks. We will begin by framing the key mechanistic safety considerations associated with oligonucleotides, including class-related adverse events such as liver function test (LFT) elevations, thrombocytopenia, and proteinuria. Building on this foundation, speakers will examine approaches to evaluating and de-risking immunogenicity and QTc liability, drawing on clinical and long-term data from GalNAc-siRNAs as a well-characterized platform. The session will then address safety challenges associated with newer modalities, including linker-containing antibody–oligonucleotide conjugates (AOCs), and discuss how lessons learned from established platforms can inform risk assessment for emerging chemistries, including CNS-targeted approaches. Overall, this session aims to foster shared learning and advance strategies to proactively manage safety across the next generation of oligonucleotide therapeutics.