在一项概念验证的第一阶段中，Aligos Therapeutics在慢性乙型肝

StephenW

Aligos Therapeutics Begins Dosing with STOPS™ Molecule Drug Candidate, ALG-010133, in First Cohort of Chronic Hepatitis B Patients in a Phase 1 Proof-of-Concept Study

Published: Mar 10, 2021

SOUTH SAN FRANCISCO, Calif., March 10, 2021 (GLOBE NEWSWIRE) -- Aligos Therapeutics, Inc. (Nasdaq: ALGS), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in viral and liver diseases, today announced that the company has started dosing in the first cohort of chronic hepatitis B (CHB) patients in the ongoing ALG-010133-101 study (NCT04485663). This trial is evaluating ALG-010133, a proprietary oligonucleotide S-antigen Transport-inhibiting Oligonucleotide Polymer (STOPS™) molecule, which was developed to reduce viral S-antigen (or HBsAg) levels in CHB patients.

“S-antigen suppresses immune responses and plays a major role in maintaining HBV replication in patients with CHB,” said Lawrence Blatt, Ph.D., MBA, Chief Executive Officer of Aligos. “Our lead STOPS candidate, ALG-010133, has demonstrated potent inhibition of S-antigen levels in preclinical studies. This observation, coupled with the drug’s clinical profile to date, led us to initiate dosing with ALG-010133 in CHB patients to assess its ability to suppress S-antigen levels. It is exciting to have taken the first step in evaluating ALG-010133 in CHB patients. Our goal is to develop a therapeutic regimen that can lead to functional cure for patients living with CHB.”

ALG-010133-101 (NCT04485663) is a multi-part umbrella trial that is evaluating the safety, pharmacokinetics and antiviral activity of up to twelve weekly doses of subcutaneously administered ALG-010133 in healthy volunteers (HVs) and virologically suppressed patients with CHB. Seventy-two healthy volunteers have been dosed to date, and preliminary data indicate that ALG-010133 has an acceptable safety and PK profile after as many as three weekly subcutaneous doses. The drug levels achieved at doses evaluated in HVs are expected to result in antiviral activity, thus supporting further evaluation of ALG-010133 in CHB patients.

Matthew W. McClure, M.D., Chief Medical Officer of Aligos, added, “This is an exciting next step for Aligos. We have now entered an important phase in the ALG-010133-101 study where we will define the clinical profile of ALG-010133 in our target population, patients with CHB. We expect to begin reporting safety, pharmacokinetic, and antiviral activity data for ALG-010133 from the initial patient cohorts of this study in the second half of 2021.”

Professor Ed Gane, MB ChB, Principal Investigator for the ALG-010133-101 study, added, “I believe that drugs that reduce S-antigen levels will play an important role in achieving much higher rates of functional cure than can be achieved with current therapies and look forward to evaluating the potential role that this promising drug candidate may play in future treatment regimens.”

Aligos’ STOPS program represents one of several in the company’s CHB portfolio that target different clinically validated mechanisms of action in the hepatitis B virus life cycle. The portfolio also includes capsid assembly modulator (CAM), antisense oligonucleotide (ASO), and small interfering RNA (siRNA) drug candidates. The properties of these candidates indicate that their use in combination could yield potentially best-in-class treatment regimens that may achieve higher rates of functional cure than current standard of care. For each of these drug candidates, Aligos plans to initially establish proof of concept as monotherapy in Phase 1 umbrella trials before evaluating them in combination in subsequent trials.

StephenW

在一项概念验证的第一阶段中，Aligos Therapeutics在慢性乙型肝炎患者的首批研究中开始使用STOPS™分子候选药物ALG-010133进行给药

发行时间：2021年3月10日

2021年3月10日，加利福尼亚州南旧金山-全球领先的生物制药公司Aligos Therapeutics，Inc.（纳斯达克股票代码：ALGS）今天致力于开发新颖的疗法，以满足未满足的病毒和肝病医疗需求。宣布该公司已开始正在进行的ALG-010133-101研究（NCT04485663）中的第一批慢​​性乙型肝炎（CHB）患者用药。该试验正在评估ALG-010133，这是一种专有的抑制寡核苷酸S抗原转运的寡核苷酸聚合物（STOPS™）分子，其开发目的是降低CHB患者的病毒S抗原（或HBsAg）水平。

“ S抗原抑制了CHB患者的免疫反应，并在维持HBV复制中起着重要作用，” Aligos首席执行官MBA博士Lawrence Blatt说道。 “我们的主要STOPS候选药物ALG-010133在临床前研究中已证明有效抑制S抗原水平。这一观察结果，加上迄今为止该药的临床概况，使我们开始在CHB患者中开始使用ALG-010133给药，以评估其抑制S抗原水平的能力。迈出评估CHB患者ALG-010133的第一步是令人兴奋的。我们的目标是开发一种治疗方案，以导致CHB病人的功能治愈。”

ALG-010133-101（NCT04485663）是一项包括多个部分的总括试验，旨在评估健康志愿者（HVs）和经病毒学抑制的CHB患者中，每周皮下给药ALG-010133的剂量（多达十二周）的安全性，药代动力学和抗病毒活性。迄今为止，已有72名健康志愿者接受了剂量，初步数据表明，经过每周三次皮下给药，ALG-010133具有可接受的安全性和PK特性。在HV中评估的剂量下达到的药物水平有望产生抗病毒活性，从而支持对CHB患者进行ALG-010133的进一步评估。

Aligos首席医学官Matthew W. McClure，医学博士补充说：“这是Aligos激动人心的下一步。我们现在已经进入ALG-010133-101研究的重要阶段，我们将在目标人群CHB患者中定义ALG-010133的临床概况。我们希望从2021年下半年开始，从本研究的最初患者队列中报告ALG-010133的安全性，药代动力学和抗病毒活性数据。”

ALG-010133-101研究的首席研究员MB ChB的Ed Gane教授补充说：“我相信，降低S抗原水平的药物将在实现功能治愈率方面比目前的方法高得多。疗法，并期待评估这种有前途的候选药物在未来治疗方案中可能发挥的潜在作用。”

Aligos的STOPS计划代表了公司CHB产品组合中的几个，这些产品的目标是在乙肝病毒生命周期中经过临床验证的不同作用机制。该产品组合还包括衣壳装配调节剂（CAM），反义寡核苷酸（ASO）和小干扰RNA（siRNA）候选药物。这些候选药物的特性表明，它们的组合使用可能会产生潜在的同类最佳治疗方案，与目前的护理标准相比，可以实现更高的功能治愈率。对于每种这些候选药物，Aligos计划首先在1期总括试验中确立单一疗法的概念验证，然后在随后的试验中对它们进行联合评估。