Antifibrotic Therapy for Chronic Kidney Disease

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DESCRIPTION (provided by applicant): Chronic kidney disease 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. For decades, Abl, c-KIT, PDGFR, KDR, and EGFR receptor tyrosine kinases have been implicated in growth factor signaling and angiogenesis. They have therefore been the targets for successful molecular targeted anti-neoplastic therapeutics. However, there is a substantial body of evidence that certain receptor tyrosine kinases, including PDGFR and KDR can also be promising targets for anti-fibrotic agents. While anti-neoplastic therapeutics have successfully been developed for use in oncology, it remains unclear whether these small molecules are suitable for use as antifibrotic agents. Angion Biomedica has identified ANG3154, a small molecule with PDGFR and KDR inhibitory activity. In experimental models of pulmonary and renal fibrosis, orally administered ANG3154 has exhibited powerful antifibrotic effects. Based on these compelling preliminary data, the present SBIR Phase I proposal is designed to make an in-depth analysis of the antifibrotic effects of ANG3154 in experimental CKD. PUBLIC HEALTH RELEVANCE: A small molecule orally bioactive antifibrotic has significant clinical potential for treatment of chronic kidney disease.