Only investigational RNAi therapy in development for all three known types of PH
We are developing nedosiran (formerly referred to as DCR-PHXC), our most advanced therapy utilized with our GalXC™ technology, for the treatment of patients with primary hyperoxaluria (PH). PH is a family of rare, genetic liver disorders characterized by overproduction of oxalate that is normally eliminated as waste through the kidneys. Currently, there is no available therapy approved specifically for the treatment of PH. Nedosiran is the only RNAi therapy in development for the treatment of all three known types of PH.
Preventing excess oxalate production
We are evaluating nedosiran in the PHYOX™ clinical program. The three known genetic types of PH result from mutations in three different genes in the glyoxylate metabolism pathway, AGXT, GRHPR and HOGA1. These genetic mutations manifest in the overproduction of oxalate. Nedosiran inhibits the Lactate Dehydrogenase enzyme in the final common step of this pathway, and thereby attempts to prevent this overproduction of oxalate. This LDH enzyme inhibition occurs specifically in the liver due to the incorporation of GalNAc targeting ligands in nedosiran that bind specifically to the Asialoglycoprotein receptors (ASGPR) on hepatic cell surfaces.