PDGFR and KDR Inhibitors for Liver Fibrosis

 描述(申请人提供)：酒精性和非酒精性肝病的发病率和流行率都在增加。代谢综合征是NAFLD-NASH-肝纤维化的一个关键危险因素，其出现的人口正在膨胀。如果不进行治疗，肝纤维化可能会发展为肝硬化或终末期肝病，甚至是肝细胞癌。今天，治疗策略主要是通过改变饮食、锻炼和药物治疗来缓解NAFLD-NASH。不幸的是，除了器官移植之外，还没有被批准的治疗方法来治疗已建立的肝纤维化。拟议的转化研究计划旨在将一种杰出的、极具前景的口服生物可用小分子抗纤维化药物带入临床试验，用于治疗肝纤维化。ANG3070是一种高效的、高度水溶性的口服生物利用型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。两种肝病模型的极具说服力的数据说明了该候选药物的抗纤维化活性。此外，为调查套件提供资金 新药(IND)-该候选药物的启用安全性研究已从NIH和国防部获得。拟议的SBIR第二阶段计划寻求在两种肝病饮食模型中获得ANG3070的剂量效应信息，这两种饮食模型在一定程度上模拟了人类NAFLD-NASH-肝纤维化表型。这项研究的疗效数据和安全性数据将确定药物治疗指数，并形成IND向FDA提交的将该药物投入临床试验的基础。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