Background

• Autosomal Dominant Polycystic Kidney Disease (ADPKD) affects >600,000 in US population; 12.5 M worldwide
• ~4% of prevalent End-Stage Renal Disease (ESRD)
• ADPKD has orphan condition designation (2012) with estimated prevalence in US 1:2000
• One approved therapy: Tolvaptan (Jinarc) – approved April, 2018
• Targets low level proliferation and secretion in cysts originating from collecting duct; unknown long term efficacy and significant sideeffects including liver toxicity (Hy’s law)

Innovation

• Identified the Ireα-Xbp1 pathway as a modulator of cyst growth
• Inhibition of this pathway at the genetic level slows down disease progression in orthologous animal models through specific apoptosis of mutant cells
• Generated a pre-clinical efficacy package around a novel use for an Ireα inhibitor previously tested in human trials