PDGFR and KDR Inhibitors for Liver Fibrosis

 描述（由申请人提供）：酒精性和非酒精性肝病的发病率和患病率正在增加。代谢综合征是NAFLD-NASH-肝纤维化的一个关键风险因素，其人群正在膨胀。如果不及时治疗，肝纤维化可能进展为肝硬化或终末期肝病，甚至肝细胞癌。今天，治疗策略主要是通过饮食调整，运动和药物治疗来减轻NAFLD-NASH。不幸的是，除了器官移植外，目前还没有批准的治疗肝纤维化的方法。拟议的转化研究计划旨在为临床试验带来一种出色的和非常有前途的口服生物可利用的小分子抗纤维化药物，用于治疗肝纤维化的临床试验。Anion Biomedica已经确定了ANG 3070，这是一种有效的，高水溶性的，口服生物利用度的小分子血小板衍生生长因子受体（PDGFR）和血管内皮生长因子受体（KDR）抑制剂。在两种肝病模型中的高度令人信服的数据表明了这种候选药物的抗纤维化活性。此外，为一套研究性 这种候选药物的新药（IND）安全性研究已从NIH和DoD获得批准。拟议的SBIR II期计划旨在获得ANG 3070在两种肝病饮食模型中的剂量功效信息，这两种模型在一定程度上模拟了人NAFLD-NASH-肝纤维化表型。本研究的疗效数据以及安全性数据将确定药物治疗指数，并构成向FDA提交IND申请的基础，以使该药物进入临床试验。1

 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