Senior Advisor Eli Lilly and Company, Inc. Indianapolis, Indiana, United States
GalNAc siRNAs are one of the most advanced areas of oligonucleotide development. To date most of the approved GalNAc siRNAs have been for rare or orphan diseases; however, they do have the potential for use in larger disease populations. The advantages of GalNAc siRNAs for patients is that they have a longer duration of pharmacodynamics which means less frequent dose administration. The toxicological advantage of GalNAc siRNAs is that the deliver mechanism allows minimal off-target knockdown and directed deliver to the hepatocytes. This talk will highlight the development strategy for a first-in-human regulatory package which includes assessment of repeat dose studies, genetic toxicity studies and safety pharmacology. The strategy of using a surrogate approach when a clinical candidate is not active in the rodent will be discussed for assessing reproductive toxicity. Given the well characterization of GalNAc siRNAs, the talk will highlight standard class effect findings as well as any future considerations.
