Monday, March 25, 6:30 – 9:30 PM
SC1: Examining the Safety and Toxicity of Nucleic Acid Therapeutics

Short Course Description:

Nucleic acid drugs continue to deliver on their promise to become a third therapeutic modality, besides small molecules and biologics. Several antisense oligonucleotide drugs have been on the market for some time, while the first RNAi approval was granted last year (2018). In addition, numerous mRNA and CRISPR therapeutic programs have entered clinical stages. Despite the common "nucleic acid" component, the mechanisms of action and of non-specific effects differ for each of these drug types.

6:30 Dinner to be Served

6:50 Introduction and Welcome from the Chair

Dmitry Samarsky, PhD, CTO, Sirnaomics

7:00 Oligonucleotide Drugs and Chemical Modifications Approved By FDA

Muthiah (Mano) Manoharan, PhD, Senior Vice President, Drug Discovery, Alnylam Pharmaceuticals

7:30 Pharmacokinetics of Oligonucleotides and their Chemical Modifications

Richard S. Geary, PhD, Senior Vice President (SVP), Development, Ionis Pharmaceuticals

The pharmacokinetics and pharmacodynamic relationships, as well as exposure related safety margins, have been well-studied for single strand antisense oligonucleotides. Innovations in chemical modifications including cell directed conjugations have further informed safety and efficacy for emerging platforms. Methods, chemical platforms, cross species translation and outcomes will be summarized.

7:50 Coffee and Dessert

8:05 Nonclinical Strategies for GalNAc-conjugated siRNAs from a Dicerna perspective and an Overview of the Oligonucleotide Safety Working Group (OSWG)

Jeffrey Foy, PhD, Senior Director, Toxicology, Dicerna Pharmaceuticals

8:25 Safety Aspects of Therapeutic mRNAs, LNPs and Gene Editing Components

Thomas Madden, PhD, President & CEO, Acuitas Therapeutics

This presentation will discuss the key safety signals from nucleic acid therapeutics and lipid nanoparticles (LNP) and dissect the relative contribution of each in a mRNA-LNP therapeutic. The talk will also cover the sensitivities of different species and their relative value in predicting clinical experience.

8:45 Practical Exercises and/or RoundTable Discussions

Dmitry Samarsky, PhD, CTO, Sirnaomics

9:30 End of Course

Oligonucleotide Discovery and Delivery