Vincere Biosciences, a small molecule drug developer, has received a USD 1.3 million SBIR Phase II grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to advance a USP30 inhibitor through investigational new drug (IND)-enabling studies for acute kidney injury (AKI).
AKI affects a broad patient population, with cardiac surgery-associated AKI (CSA-AKI) alone estimated to occur in up to 42% of the approximately 2 million patients undergoing cardiac surgery annually in the US. Progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD) represents a significant clinical and economic burden, and standard of care remains supportive.
Vincere's approach centers on inhibiting USP30, a deubiquitinase that suppresses mitophagy — the cellular clearance mechanism for damaged mitochondria — via the PINK1/Parkin pathway. Accumulated dysfunctional mitochondria are considered a driver of AKI pathogenesis. The company reported that USP30 inhibitor (USP30i) candidates demonstrated renal functional improvement in three preclinical AKI models, including ischemia-reperfusion injury, cisplatin-induced nephrotoxicity, and rhabdomyolysis, with high USP30 potency, selectivity over other deubiquitinases, and favorable pharmacokinetic profiles in rodents.