Chronic kidney disease (CKD) remains an unsolved challenge for the nephrologist, as it almost inevitably leads to end-stage renal failure, a life-threatening condition that necessitates renal replacement therapy. Few, if any, of the currently practiced therapeutic strategies oppose the molecular and cellular program of fibrosis that drives renal disease. There is now mounting evidence that certain receptor tyrosine kinases including platelet derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) are promising targets for development of anti-fibrotic strategies. Under the aegis of the SBIR Phase I program and harnessing a drug discovery engine comprising molecular modeling, rational drug design, medicinal chemistry and in vitro biology, Angion Biomedica has synthesized a highly water soluble, orally bioavailable, small molecule PDGFR+KDR inhibitor, ANG3070. Critical and highly compelling data indicate that ANG3070 is therapeutic in experimental CKD, reducing microalbuminuria and urine TGF21, decreasing renal interstitial collagen accumulation and other markers of renal fibrosis and preserving renal parenchymal microarchitecture. The goal of this proposed milestone driven SBIR Phase II translational research program is to conduct the comprehensive gamut of Investigational New Drug (IND)-enabling studies required to advance our novel, orally bioavailable, small molecule therapeutics to clinical trials in CKD, one of the largest markets of unmet clinical need.
