PDGFR and KDR Inhibitors for Liver Fibrosis

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 DESCRIPTION (provided by applicant): The incidence and prevalence of both alcoholic and non-alcoholic liver diseases is increasing. The population presenting with Metabolic Syndrome, a key risk factor for NAFLD-NASH-liver fibrosis is ballooning. Left untreated, liver fibrosis can progress to cirrhosis or end-stage liver disease and even hepatocellular carcinoma. Today, therapeutic strategies are primarily geared toward mitigating NAFLD-NASH via diet modification, exercise and medication. Unfortunately, there is no approved therapy for established liver fibrosis other than organ transplantation. The proposed translational research program is designed to bring to clinical trials an outstanding and highly promising orally bioavailable small molecule antifibrotic to clinical trials for the treatment of liver fibrosis. Anion Biomedica has identified ANG3070, a potent, highly water-soluble, orally bioavailable, small molecule platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (KDR) inhibitor. Highly compelling data in two models of liver disease speak to antifibrotic activity of this drug candidate. Furthermore, funding for the suite of Investigational New Drug (IND)-enabling safety studies for this drug candidate has been appropriated from the NIH and DoD. The proposed SBIR Phase II program seeks to obtain dose efficacy information for ANG3070 in two dietary models of liver disease which simulate to some extent the human NAFLD-NASH-liver fibrosis phenotype. Efficacy data from this study, together with the safety data will determine drug therapeutic index and form the form the basis of an IND submission to FDA to bring this drug to clinical trials. 1