Aligos Therapeutics将在2020年EASL数字国际肝脏大会上展示慢性乙

StephenW

Aligos Therapeutics to Present Nonclinical Data for All Components of Chronic Hepatitis B Combination Therapy at EASL Digital International Liver Congress 2020
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August 27, 2020 10:17 ET | Source: Aligos Therapeutics

SOUTH SAN FRANCISCO, Calif., Aug. 27, 2020 (GLOBE NEWSWIRE) -- Aligos Therapeutics, Inc. (Aligos), a private biopharmaceutical  company focused on developing novel therapeutics to address unmet medical needs in viral and liver diseases, including  chronic hepatitis B (CHB), COVID-19 and therapeutics for NASH, will present four abstracts highlighting nonclinical data for drug candidates in the company’s CHB portfolio at the European Association for the Study of the Liver (EASL) Digital International Liver Congress™ 2020.

“Taken together, our findings show promising progress across our chronic hepatitis B portfolio, both individually and in pairwise combinations,” said Lawrence Blatt, Ph.D., MBA, chief executive officer of Aligos. “As our lead candidates advance in the clinic, we are gratified to see that our approach of designing purpose-built drug candidates targeting clinically validated mechanisms of action have shown promising activity in our nonclinical studies to date.”

The presentations provide new information for many of the company’s classes of drug candidates designed for use in combination therapy to develop high rates of functional cure in CHB. Of note, an abstract related to Aligos’ STOPSTM program, entitled “Structural requirements for ’S-antigen transport-inhibiting oligonucleotide polymer inhibition of hepatitis B surface antigen secretion,” was selected for inclusion in the meeting’s ‘Best of ILC’ category, which highlights the most noteworthy contributions to the meeting’s scientific program. The titles of each abstract, the class(es) of candidates highlighted and the findings are as follows:

S-antigen Transport-inhibiting Oligonucleotide PolymerS (STOPSTM)

Title: Structural requirements for S-antigen Transport-inhibiting Oligonucleotide Polymer inhibition of hepatitis B surface antigen secretion

Summary: Aligos’ proprietary STOPS candidates were evaluated for S-antigen (or HBsAg) reduction and cytotoxicity in cell culture to optimize activity relative to structurally similar nucleic acid polymers (NAPs). Upon varying sequence, length, and chemical modifications of STOPS, it was found that STOPS’ activity is dependent on length, with the highest potency observed at over 34 nucleotides. Sequence was critical for STOPS activity: when the AC dinucleotide repeat was changed to AG, the antiviral activity was completely lost. However, activity was retained when the base identities were maintained, such as with a CA repeat. Site-specific incorporation of backbone chemistries such as a stereospecific phosphorothioate bond also improved potency.

Note: This abstract will be available publicly after the meeting as part of EASL’s ‘Best of ILC’ summary slide deck.

Capsid Assembly Modulators (CAMs)

Title: ALG-000184, a prodrug of capsid assembly modulator ALG-001075, demonstrates best-in-class preclinical characteristics for the treatment of chronic hepatitis B

Summary:  ALG-001075 was found to be a potent inhibitor of HBV DNA production in HepG2.117 cells with EC50/EC90 values of 0.63/3.17 nM (n = 12), respectively. This level of potency exceeds that of all other known reported CAMs that have entered clinical development, efficiently blocking both HBV genome encapsidation and de novo cccDNA formation. ALG-000184, a prodrug of ALG-001075, showed improved pharmacokinetic properties, including improved aqueous solubility, stability and oral absorption across species with efficient conversion to ALG-001075 in vivo.

Antisense oligonucleotides (ASOs)

Title: Best in class hepatitis B virus anti-sense oligonucleotides: Next generation bridged nucleic acid chemistries significantly improve the therapeutic index by reducing hepatotoxicity and increasing in vivo efficacy in a mouse model

Summary: Although locked nucleic acid (LNA)-modified ASOs can cause liver toxicity, applying bridged nucleic acid and nucleobase gap modifications to LNA ASOs showed improved efficacy and reduced liver toxicity in a mouse model of hepatitis B virus (HBV) infection, suggesting that Aligos’ anti-HBV ASO candidates have potential to be best in class compounds.

STOPS in combination with other agents

Title: Combination drug interactions of hepatitis B virus (HBV) S-antigen Transport-inhibiting Oligonucleotide Polymers in vitro

Summary: STOPS in combination with nucleos(t)ides, core assembly modulators (CAMs), and HBV-specific antisense oligonucleotides (ASOs) were evaluated for inhibition of HBV replication and HBsAg release in HBV-producing hepatic cells. When tested in pairwise combinations with the other HBV inhibitors, STOPS demonstrated synergy or additivity. Overall, the activity of STOPS warrants further study as a component of a combination therapy in CHB.

About Chronic Hepatitis B (CHB)

CHB is a major cause of chronic liver disease that the World Health Organization estimates affects ~257 million people worldwide, more people than hepatitis C virus (HCV) and HIV infection combined. Serious complications of CHB include cirrhosis and liver cancer, which are associated with significant mortality.  Approximately 900,000 people died from CHB-related causes in 2015 alone and the mortality rate has been rising for decades. Although current standard of care for patients with CHB is effective in suppressing HBV, it is associated with very low rates of functional cure, which is the main goal of CHB treatment.

About Aligos

Aligos Therapeutics, Inc., is a privately held, clinical stage biopharmaceutical company that was founded in 2018 with the mission to become a world leader in the treatment of viral infections and liver diseases. Aligos is focused on the development of targeted antiviral therapies for chronic hepatitis B (CHB) and coronaviruses as well as leveraging its expertise in liver diseases to create targeted therapeutics for nonalcoholic steatohepatitis (NASH). Aligos’ strategy is to harness the deep expertise and decades of drug development experience its workforce has in liver disease, particularly viral hepatitis, to rapidly advance its pipeline of potentially best-in-class molecules.

Please visit www.aligos.com for more information.

Media Contact
Amy Jobe, Ph.D.
LifeSci Communications
+1 315 879 8192
[email protected]

Investor Contact
Corey Davis, Ph.D.
LifeSci Advisors
+1 212 915 2577
[email protected]

StephenW

Aligos Therapeutics将在2020年EASL数字国际肝脏大会上展示慢性乙型肝炎联合治疗所有成分的非临床数据
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东部时间2020年8月27日10:17 |资料来源：Aligos Therapeutics

加利福尼亚州南旧金山，2020年8月27日（全球新闻）-Aligos Therapeutics，Inc.（Aligos）是一家私人生物制药公司，致力于开发新颖的疗法，以满足未满足的病毒和肝脏疾病（包括慢性肝炎）的医疗需求B（CHB），COVID-19和NASH的疗法将在2020年欧洲肝病研究协会（EASL）数字国际肝病大会™上提出四个摘要，重点介绍该公司CHB产品组合中候选药物的非临床数据。

“综合起来，我们的研究结果表明，无论是单独还是成对组合，我们在慢性乙型肝炎产品组合中都有令人鼓舞的进步，” Aligos首席执行官MBA劳伦斯·布拉特博士说。 “随着我们的主要候选药物在临床上的发展，我们很高兴看到我们设计针对临床验证的作用机制的特制候选药物的方法迄今为止在我们的非临床研究中显示出令人鼓舞的活性。”

演讲为该公司的许多候选药物类别提供了新信息，这些类别的药物被设计用于联合治疗，以提高CHB的功能性治愈率。值得注意的是，与Aligos的STOPSTM程序有关的摘要，题为“抑制S抗原转运的寡核苷酸聚合物抑制乙型肝炎表面抗原分泌的结构要求”被选为会议的“最佳ILC”类别，强调了对会议科学计划最值得关注的贡献。每个摘要的标题，突出显示的候选类别和发现如下：

抑制S抗原转运的寡核苷酸聚合物（STOPSTM）

标题：抑制S-抗原转运的寡核苷酸的结构要求聚合物抑制乙型肝炎表面抗原的分泌

摘要：对Aligos专有的STOPS候选药物进行了细胞培养物中S抗原（或HBsAg）的减少和细胞毒性的评估，以优化相对于结构相似的核酸聚合物（NAP）的活性。发现STOPS的序列，长度和化学修饰各不相同时，发现STOPS的活性取决于长度，在超过34个核苷酸处观察到最高的效力。序列对于STOPS活性至关重要：当将AC二核苷酸重复序列更改为AG时，抗病毒活性将完全丧失。但是，当维持基本身份时（例如CA重复），活性得以保留。骨架化学物质的位点特异性结合（如立体特异性的硫代磷酸酯键）也提高了效能。

注意：会议结束后，此摘要将作为EASL“最佳ILC”摘要幻灯片中的一部​​分公开发布。

衣壳装配调制器（CAM）

发言题目：ALG-000184，衣壳装配调节剂ALG-001075的前药，具有治疗慢性乙型肝炎的同类最佳临床前特性

摘要：发现ALG-001075是HepG2.117细胞中HBV DNA产生的有效抑制剂，EC50 / EC90值分别为0.63 / 3.17 nM（n = 12）。该水平超过了已进入临床开发的所有其他已知报道的CAM的水平，有效地阻断了HBV基因组的衣壳化和从头cccDNA的形成。 ALG-001075的前药ALG-000184显示出改善的药代动力学特性，包括改善的水溶性，稳定性和跨物种的口服吸收，并在体内有效转化为ALG-001075。

反义寡核苷酸（ASO）

标题：一流的乙型肝炎病毒反义寡核苷酸：下一代桥接核酸化学通过降低小鼠模型中的肝毒性并提高体内功效，显着提高了治疗指数

简介：尽管锁核酸（LNA）修饰的ASO可能引起肝毒性，但在乙型肝炎病毒（HBV）感染的小鼠模型中，对LNA ASO应用桥接的核酸和核碱基缺口修饰显示出更高的功效并降低了肝毒性，这表明Aligos的抗HBV ASO候选药物可能是同类化合物中最好的。

停止与其他代理商一起

发言题目：乙型肝炎病毒（SHB）抑制抗原转运的寡核苷酸聚合物的联合药物相互作用

摘要：评估了STOPS与核苷酸，核心组装调节剂（CAM）和HBV特异性反义寡核苷酸（ASO）的结合，以抑制产生HBV的肝细胞中HBV复制和HBsAg释放。当与其他HBV抑制剂配对使用时，STOPS表现出协同作用或可加性。总体而言，STOPS的活性值得进一步研究，作为CHB联合疗法的组成部分。

关于慢性乙型肝炎（CHB）

慢性乙型肝炎是慢性肝病的主要原因，据世界卫生组织估计，这种疾病影响全世界约2.57亿人，人数超过丙型肝炎病毒（HCV）和HIV感染的总和。 CHB的严重并发症包括肝硬化和肝癌，这与死亡率显着相关。仅在2015年，就有约90万人死于与CHB相关的原因，并且死亡率在数十年来一直在上升。尽管当前针对CHB患者的护理标准可有效抑制HBV，但它与极低的功能治愈率相关，这是CHB治疗的主要目标。

关于阿里戈斯

Aligos Therapeutics，Inc.是一家私有的临床阶段生物制药公司，成立于2018年，其使命是成为病毒感染和肝病治疗的全球领导者。 Aligos致力于开发针对慢性乙型肝炎（CHB）和冠状病毒的针对性抗病毒疗法，并利用其在肝脏疾病方面的专业知识来开发针对非酒精性脂肪性肝炎（NASH）的针对性疗法。 Aligos的策略是利用其员工在肝脏疾病（尤其是病毒性肝炎）方面拥有的深厚专业知识和数十年的药物开发经验，以快速推进其潜在最佳分子产品的开发。

请访问www.aligos.com了解更多信息。

媒体联络
艾米·乔布（Amy Jobe）博士
生命科学通讯
+1 315 879 8192
[email protected]

投资者联系
科里·戴维斯（Corey Davis）博士
生命科学顾问
+1 212 915 2577
[email protected]