Enanta Pharmaceuticals在2019年国际肝脏大会上发布针对乙型肝炎病

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Enanta Pharmaceuticals Presents New Preclinical Data on Compounds Targeting Hepatitis B Virus and Non-Alcoholic Steatohepatitis at The International Liver Congress™ 2019
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WATERTOWN, Mass.--(BUSINESS WIRE)--Apr 11, 2019--Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, announced that new preclinical data from Enanta’s wholly-owned development programs for hepatitis B virus (HBV) and non-alcoholic steatohepatitis (NASH) will be presented at The International Liver Congress™ (ILC) 2019, in Vienna, Austria.

New data include a presentation on development candidate EDP-514, Enanta’s core inhibitor for HBV that is expected to enter into a Phase 1 clinical study in the second half of 2019. Presentations also focus on Enanta’s NASH program, featuring new data on the FXR agonist EDP-305, and including in vivo data on EP-027315 and EP-026856, two prototype compounds from Enanta’s ASK-1 (apoptosis signal-regulating kinase 1 ) inhibitor project.

“Enanta continues to generate an abundance of preclinical and clinical data on our development candidates EDP-514 for HBV, and EDP-305 for NASH,” stated Jay R. Luly, President and CEO, Enanta. “Our extensive scientific research provides us the knowledge and confidence to move forward our best candidates with the highest likelihood of success. We look forward to announcing clinical results of EDP-305 in our ARGON-1 Phase 2 study in NASH patients in the third quarter and to initiating a phase 1 study with EDP-514 during the second half of 2019.”

A summary of the poster presentations at The International Liver Congress™ (ILC) 2019 are below.

Full abstracts can be found at http://ilc-congress.eu.

April 11, 2019 - 09:00 - 19:00
THU-084: “A comparative study of anti-Fibrotic therapeutics using aptamer-based quantitative proteomics in a rat model of non-alcoholic steatohepatitis cirrhosis,” Smitha Krishnan, United States

Data in this poster demonstrate that in a preclinical rat model of NASH cirrhosis utilizing an aptamer-based proteomics assay, it was possible to identify non-invasive biomarkers of treatment response and potential pathways activated by different mechanisms currently under study in clinical trials by Enanta and others. Three anti-fibrotic compounds were evaluated: two ASK-1 inhibitors, Enanta compound EP-026856 and Gilead’s selonsertib, and one FXR agonist, Enanta compound EDP-305. While all three drugs were effective in inhibiting fibrosis development in this 12-week treatment model, EP-026856 showed the greatest effect on returning non-invasive serum markers back to baseline.

April 12, 2019 - 09:00 - 17:00

FRI-191: “EDP-514, a novel HBV core inhibitor with potent antiviral activity both in vitro and in vivo, ” Kai Lin, United States

Data in this poster demonstrate that EDP-514, a novel class II HBV core inhibitor, is a potent inhibitor of HBV replication, and prevents the de novo formation of new cccDNA in primary human hepatocytes when given early during infection. Data also show that EDP-514 is pan-genotypic, and that combinations of EDP-514 with nucleoside reverse-transcriptase inhibitors (NRTIs, current anti-viral therapies for HBV) or a class I core inhibitor result in additive to synergistic antiviral effects in vitro. ln vivo, EDP-514 demonstrates excellent in vivo efficacy with >4-log viral load reduction in HBV-infected PXB mice.

FRI-340: “In vivo effects of a novel inhibitor of apoptosis signal-regulating kinase 1 in mouse models of liver injury and metabolic disease,” Manuel Roqueta-Rivera, United States

Data in this poster demonstrate that EP-027315 is a potent and highly selective inhibitor of ASK-1. It inhibits hepatic ASK-1 and decreases liver pJNK (one of the stress-activated protein kinase signaling pathways influencing inflammation in liver cells), plasma ALT (a common marker of potential liver damage), and apoptosis (cell death) in a dose-dependent manner in a mouse acute injury model. EP-027315 also protects against liver injury in a diet-induced obesity model. Suppression of markers of liver injury, inflammation, and apoptotic pathways are observed at both a transcriptional and protein level.

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Enanta Pharmaceuticals在2019年国际肝脏大会上发布针对乙型肝炎病毒和非酒精性脂肪性肝炎的化合物的新临床前数据
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马萨诸塞州WATERTOWN  - （美国商业资讯） -  2019年4月11日 -  Enanta Pharmaceuticals，Inc。（纳斯达克股票代码：ENTA），一家专注于研究和开发的生物技术公司，致力于为病毒感染和肝脏疾病制造小分子药物，宣布Enanta的乙肝病毒（HBV）和非酒精性脂肪性肝炎（NASH）全资开发项目的新临床前数据将在奥地利维也纳举行的国际肝病会议（ILC）2019年上发布。

新数据包括关于开发候选物EDP-514的介绍，Enanta的HBV核心抑制剂预计将于2019年下半年进入第一阶段临床研究。报告还关注Enanta的NASH计划，其中包含有关FXR激动剂的新数据EDP​​-305，包括来自Enanta的ASK-1（凋亡信号调节激酶1）抑制剂项目的两种原型化合物EP-027315和EP-026856的体内数据。

Enanta总裁兼首席执行官Jay R. Luly表示：“Enanta继续为我们的HBV开发候选人EDP-514和NASH的EDP-305提供丰富的临床前和临床数据。 “我们广泛的科学研究为我们提供了最有可能取得成功的最佳候选人的知识和信心。我们期待在第三季度在NASH患者的ARGON-1期研究中宣布EDP-305的临床结果并在2019年下半年开始用EDP-514进行第一阶段研究。“

以下是国际肝病大会（ILC）2019年海报展示的摘要。

完整的摘要可以在http://ilc-congress.eu找到。

2019年4月11日 -  09:00  -  19:00
THU-084：“在非酒精性脂肪性肝炎肝硬化大鼠模型中使用基于适体的定量蛋白质组学的抗纤维化治疗的比较研究”，Smitha Krishnan，美国

该海报中的数据表明，在使用基于适体的蛋白质组学测定的NASH肝硬化的临床前大鼠模型中，有可能鉴定Enanta等临床试验中目前正在研究的不同机制激活的治疗反应和潜在途径的非侵入性生物标志物。评估了三种抗纤维化组合物：两种ASK-1抑制剂，Enanta化合物EP-026856和Gilead's selonsertib，以及一种FXR激动剂Enanta化合物EDP-305。尽管在这12周治疗模型中所有三种药物都有效抑制纤维化发展，但EP-026856显示出将非侵入性血清标志物返回基线的最大效果。

2019年4月12日 -  09:00  -  17:00

FRI-191：“EDP-514，一种新型HBV核心抑制剂，在体外和体内具有强大的抗病毒活性，”Kai Lin，美国

该海报中的数据表明EDP-514是一种新型II类HBV核心抑制剂，是HBV复制的有效抑制剂，可防止感染早期给予原代人肝细胞中新的cccDNA的重新形成。数据还显示EDP -514是泛基因型，EDP-514与核苷逆转录酶抑制剂（NRTI，HBV的当前抗病毒疗法）或I类核心抑制剂的组合导致增加协同抗病毒作用。体外。在体内，EDP-514表现出优异的体内功效，在HBV感染的PXB小鼠中具有> 4-log病毒载量减少。

FRI-340：“一种新的细胞凋亡信号调节激酶1抑制剂在肝损伤和代谢疾病小鼠模型中的体内作用，”Manuel Roqueta-Rivera，美国

该海报中的数据表明EP-027315是一种有效且高选择性的ASK-1抑制剂。它抑制肝脏ASK-1和治疗性肝脏pJNK（影响肝细胞炎症的应激激活蛋白激酶信号通路之一），血浆ALT（潜在肝损伤的常见标志物）和细胞凋亡（细胞死亡）的剂量 - 依赖于小鼠急性损伤模型的方式。 EP-027315还在饮食诱导的肥胖模型中预防肝损伤。在转录和蛋白质水平均观察到肝损伤，炎症和凋亡途径的标志物的抑制。