Aligos Therapeutics 在 The Liver Meeting® 2021 上展示了其慢性乙型肝

StephenW

Aligos Therapeutics 在 The Liver Meeting® 2021 上展示了其慢性乙型肝炎 (CHB) 和非酒精性脂肪性肝炎 (NASH) 产品组合的数据
阿里戈斯疗法
2021 年 11 月 13 日星期六，上午 12:00·9 分钟阅读

将在会议上展示的几张临床和非临床海报

Aligos 的衣壳组装调节剂 (CAM) 候选物 ALG-000184 在每日服用 28 剂后，在 CHB 患者中实现了乙型肝炎病毒 DNA 和 RNA 的快速、实质性减少

加利福尼亚州南旧金山，2021 年 11 月 12 日（环球新闻社）--Aligos Therapeutics, Inc.（纳斯达克股票代码：ALGS）是一家临床阶段的生物制药公司，专注于开发新型疗法，以满足病毒和肝脏疾病未满足的医疗需求，将在由美国肝病研究协会 (AASLD) 主办的 The Liver Meeting® 2021 上展示几张海报。从今天起和会议结束后，所有这些海报也将在 Aligos 网站上的科学演示和会议上提供。

“随着我们继续通过多方面的方法来解决慢性肝病，我们很高兴通过海报展示我们的进展，这些海报涵盖了我们的 CHB 药物，包括 STOPS™、CAM、ASO 和 siRNA 候选药物，以及令人鼓舞的结果来自一项临床前研究显示，当这些模式中的几种组合在一起时，可以产生协同作用，”Aligos 董事长兼首席执行官 Lawrence Blatt 博士、工商管理硕士说。 “我们相信，将减少乙型肝炎病毒 S 抗原的多种方式与抑制病毒复制的药物相结合，将是提高 CHB 患者功能治愈率的关键。”

Blatt 博士继续说道，“我们特别高兴地提供临床前数据，进一步阐明我们 STOPS 分子的分子作用机制以及我们的 CAM 候选药物 ALG-000184 的临床数据，这些数据显示出良好的耐受性和显着降低 HBV DNA 和口服给药 28 天后的 RNA。我们也很高兴推出我们的 THR-β 激动剂候选药物 ALG-055009，它具有良好的临床前药代动力学特征，支持人体每日一次给药，并且似乎药物相互作用的风险较低。”

慢性乙型肝炎

S-抗原转运抑制寡核苷酸聚合物 (STOPS™)

标题：抑制 S-抗原转运的寡核苷酸聚合物，(STOPS™) 隔离细胞蛋白以减少乙型肝炎病毒 S-抗原表达并增加其蛋白酶体降解
出版号：845
会议名称：乙型肝炎：治疗学：新药剂
主讲人：C. Cheng Kao
总结：作为阐明 STOPS 在乙型肝炎病毒 (HBV) 感染背景下的作用机制的体外研究的一部分，五种宿主蛋白​​被鉴定为与 STOPS 结合。已知这些蛋白质参与 RNA 加工、翻译和蛋白质折叠和降解，支持 STOPS 分子可能通过隔离表达和正确折叠 HBV 所需的宿主蛋白质来抑制 HBV 感染和乙型肝炎病毒表面抗原 (HBsAg) 产生的前提。抗原。

STOPS 是 Aligos 专有的单链寡核苷酸，旨在通过减少 HBsAg 来提高功能性治愈率，HBsAg 被认为可以抑制 CHB 受试者的抗病毒免疫反应。

衣壳组装调制器 (CAM)

标题：衣壳组装调节剂 (CAM) ALG-000184 在慢性乙型肝炎 (CHB) 受试者中的安全性、药代动力学 (PK) 和抗病毒活性
出版号：843
会议名称：乙型肝炎：治疗学：新药剂
主讲人：埃德·盖恩
总结：ALG-000184 是 Aligos 的 II 类 CAM 候选药物，通过干扰 HBV 衣壳组装和病毒复制，导致非感染性空病毒颗粒的形成，从而抑制 HBV 感染。

作为正在进行的三部分、多中心、双盲、随机、安慰剂对照研究 (NCT04536337) 的一部分，队列 1 和 2（n=10/队列；8 个活性：2 个安慰剂）的 E 抗原 (HBeAg) -阴性，目前未治疗 (CNT)/未治疗 (TN) CHB 受试者接受 50 毫克或 100 毫克每日口服剂量的 ALG-000184 或安慰剂，持续 28 天。在两个队列中，ALG-000184 给药与 28 天期间 HBV DNA 和 RNA 的类似快速、显着降低相关，≥75% 和 100% 的可评估受试者的 HBV DNA 和 RNA 降低低于定量下限(LLOQ)，分别。
反义寡核苷酸 (ASO)

标题：针对乙型肝炎病毒的一流​​反义寡核苷酸：下一代桥接核酸化学显着提高小鼠体内功效并降低肝毒性
出版号：820
会议名称：乙型肝炎：治疗学：新药剂
主讲人：黛娜·米斯纳
总结：Aligos 将下一代桥接核酸 (BNA) 化学物应用于已经使用锁定核酸 (LNA) 技术的 ASO 候选药物，在与肝毒性相关的功效方面有望产生一流的 ASO 候选药物。

Aligos 正在推进 ASO 候选药物，作为减少 HBsAg 的组合方法的一部分，HBsAg 抑制患者在 CHB 中的抗病毒免疫反应。从历史上看，肝毒性一直是 ASO 的主要副作用。然而，下一代 BNA 化学物质在包含 LNA 成分的 ASO 中使用时，可以在保持疗效的同时降低肝毒性。

标题：ALG-020572，一种 GalNAc 偶联的反义寡核苷酸，证明了治疗慢性乙型肝炎的体内疗效和良好的临床前特征
出版号：819
会议名称：乙型肝炎：治疗学：新药剂
主讲人：库苏姆·古普塔
总结：Aligos 的 ASO 治疗候选药物 ALG-020572 在体外和体内均显示出有效抑制 HBsAg。皮下给药后 ALG-020572 的抗病毒活性、肝细胞靶向和有利的 PK 特征保证了其作为 CHB 的潜在治疗方法进入临床开发。

siRNA

标题：新型 siRNA 化学物的结合显着提高了 AAV-HBV 小鼠模型中 HBV siRNA 的效力和耐久性
出版号：831
会议名称：乙型肝炎：治疗学：新药剂
主讲人：金红
总结：Aligos 正在开发的 CHB 非临床小干扰 RNA (siRNA) 治疗候选药物在使用新型 siRNA 化学物质进行修饰时在体外和体内表现出更高的效力和/或耐久性。

组合

标题：三联抗乙型肝炎病毒药物在体外表现出协同活性
出版号：852
会议名称：乙型肝炎：治疗学：新药剂
主讲人：华坦
总结：Aligos 正在开发的针对乙型肝炎病毒的 siRNA 化合物 ALG-125755 与该公司的 ASO、ALG-020572 和 STOPS™ 分子 ALG-010133 相结合，在细胞培养中表现出协同活性，在添加时减少 HBsAg与核苷（酸）类似物 (NA)、CAM 或干扰素的各种三联组合分组。

siRNA ALG-125755 和 STOPS ALG-010133 与 ASO ALG-020572 的三重组合在降低 HBsAg 方面表现出相加活性，并证明了对 ASO 的剂量依赖性反应。当将干扰素或 STOPS 添加到 ASO-siRNA 组合中时，效果增强，表明当与其他 HBV 疗法组合时，有可能降低治疗 HBV 所需的剂量。此外，当与 NA 或 CAM 成对组合进行测试时，这些化合物显示出对抑制 HBV DNA 的协同相互作用的加成作用。

非酒精性脂肪性肝炎

标题：ALG-055009 的临床前药代动力学分析，一种治疗非酒精性脂肪性肝炎的强效选择性甲状腺激素受体 β 激动剂，及其人体药代动力学预测
出版号：1932
会议名称：NAFLD 和 NASH：治疗学
主讲人：库苏姆·古普塔
总结：ALG-055009 在几种动物模型物种中的非临床药代动力学特性表明，临床上的有效剂量可能是亚至低毫克范围内的每日一次剂量，并且药物相互作用的风险可能很低。

标题：开发一种新的 7 天给药小鼠疗效模型来评估甲状腺激素受体激动剂治疗 NASH
出版号：1907
会议名称：NAFLD 和 NASH：治疗学
主讲人：宣龙
摘要：作者开发了一种高胆固醇饮食 (HCD) 小鼠模型，用于在体内有效筛选 THR-β 激动剂作为非酒精性脂肪性肝炎 (NASH) 的潜在治疗剂。该模型似乎可以预测患者在临床相关暴露下的反应，并为通过高脂肪饮食管理开发的耗时的标准功效模型提供快速替代方案。

关于阿里哥斯
Aligos Therapeutics, Inc. 是一家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领域的全球领导者。 Aligos 专注于发现和开发针对慢性乙型肝炎 (CHB) 和冠状病毒的靶向抗病毒疗法，并利用其在肝脏疾病方面的专业知识开发针对非酒精性脂肪性肝炎 (NASH) 的靶向疗法。 Aligos 的战略是利用其团队在肝病，尤其是病毒性肝炎方面的深厚专业知识和数十年的药物开发经验，快速推进其产品线

StephenW

Aligos Therapeutics Presents Data for its Chronic Hepatitis B (CHB) and Nonalcoholic Steatohepatitis (NASH) Portfolio at The Liver Meeting® 2021
Aligos Therapeutics
Sat, November 13, 2021, 12:00 AM·9 min read

Several clinical and nonclinical posters to be presented at the conference

Aligos’ capsid assembly modulator (CAM) candidate, ALG-000184, achieved rapid, substantial reductions in hepatitis B virus DNA and RNA in CHB patients after 28 daily doses

SOUTH SAN FRANCISCO, Calif., Nov. 12, 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, will present several poster presentations at The Liver Meeting® 2021, hosted by the American Association for the Study of Liver Diseases (AASLD). All of these posters will also be available on the Aligos website at Scientific Presentations & Conferences as of today and following the conclusion of the conference.

“As we continue to progress our pipeline with a multifaceted approach to addressing chronic liver diseases, we are pleased to showcase our progress with posters covering our CHB drugs, including STOPS™, CAM, ASO, and siRNA drug candidates, as well as encouraging results from a preclinical study showing additive to synergistic activity when several of these modalities are combined,” said Lawrence Blatt, Ph.D., MBA, Chairman and Chief Executive Officer of Aligos. “We believe that combining multiple modalities that reduce hepatitis B virus S-antigen together with drugs that inhibit viral replication will be the key to achieving enhanced functional cure rates in people living with CHB.”

Dr. Blatt continued, “We are especially pleased to present preclinical data further elucidating the molecular mechanism of action for our STOPS molecules as well as clinical data for our CAM drug candidate, ALG-000184, demonstrating good tolerability and significant reductions in HBV DNA and RNA after 28 days of oral dosing. We are also excited to present our THR-β agonist drug candidate, ALG-055009, that has a favorable preclinical pharmacokinetic profile that is supportive of once-daily dosing in humans and appears to have a low risk of drug-drug interactions.”

Chronic Hepatitis B

S-antigen Transport-inhibiting Oligonucleotide Polymers (STOPS™)

Title: S-antigen Transport-inhibiting Oligonucleotide Polymers, (STOPS™) Sequester Cellular Proteins to Reduce Hepatitis B Virus S-Antigen Expression and Increase Its Proteasomal Degradation
Publication Number: 845
Session Title: Hepatitis B: Therapeutics: New Agents
Presenter: C. Cheng Kao
Summary: As part of an in vitro study to elucidate STOPS’ mechanism of action in the context of hepatitis B virus (HBV) infection, five host proteins were identified as binding to STOPS. The proteins are known to be involved in RNA processing, translation, and protein folding and degradation, supporting the premise that STOPS molecules likely inhibit HBV infection and hepatitis B virus surface antigen (HBsAg) production by sequestering host proteins needed to express and properly fold the antigen.

STOPS are Aligos’ proprietary single-stranded oligonucleotides that are designed to improve functional cure rates by reducing HBsAg, which is thought to suppress antiviral immune responses in CHB subjects.

Capsid Assembly Modulator (CAM)

Title: Safety, Pharmacokinetics (PK), and Antiviral Activity of the Capsid Assembly Modulator (CAM) ALG-000184 in Subjects with Chronic Hepatitis B (CHB)
Publication Number: 843
Session Title: Hepatitis B: Therapeutics: New Agents
Presenter: Ed Gane
Summary: ALG-000184 is Aligos’ class II CAM candidate in development to inhibit HBV infection by interfering with HBV capsid assembly and viral replication by causing the formation of non-infectious empty viral particles.

As part of the ongoing, three-part, multicenter, double-blind, randomized, placebo-controlled study (NCT04536337), Cohorts 1 and 2 (n=10/cohort; 8 active:2 placebo) of E-antigen (HBeAg)-negative, currently not treated (CNT)/treatment naïve (TN) CHB subjects received 50-mg or 100-mg daily oral doses of ALG-000184 or placebo for 28 days. In both cohorts, ALG-000184 administration was associated with similar rapid, substantial reductions in HBV DNA and RNA through the 28-day period, with ≥75% and 100% of evaluable subjects achieving HBV DNA and RNA reductions below the lower limit of quantitation (LLOQ), respectively.
Antisense Oligonucleotide (ASO)

Title: Best-in-Class Antisense Oligonucleotides Against Hepatitis B Virus: Next Generation Bridged Nucleic Acid Chemistries Significantly Increase In Vivo Efficacy and Reduce Hepatotoxicity in Mice
Publication Number: 820
Session Title: Hepatitis B: Therapeutics: New Agents
Presenter: Dinah Misner
Summary: Aligos’ application of next-generation Bridged Nucleic Acid (BNA) chemistries to ASO candidates already using Locked Nucleic Acid (LNA) technology stands to yield a best-in-class ASO candidate in terms of efficacy relative to hepatotoxicity.

Aligos is advancing ASO drug candidates as part of a combination approach to reducing HBsAg, which suppresses the patient’s antiviral immune response in CHB. Historically, hepatotoxicity has been a major side effect of ASOs; however, next-generation BNA chemistries, when used in ASOs that contain LNA components, can reduce hepatotoxicity while maintaining efficacy.

Title: ALG-020572, a GalNAc-Conjugated Antisense Oligonucleotide, Demonstrates In Vivo Efficacy and Favorable Preclinical Profile for the Treatment of Chronic Hepatitis B
Publication Number: 819
Session Title: Hepatitis B: Therapeutics: New Agents
Presenter: Kusum Gupta
Summary: Aligos’ ASO therapeutic candidate ALG-020572 was shown to potently inhibit HBsAg in vitro and in vivo. The antiviral activity, hepatocyte targeting and a favorable PK profile of ALG-020572 following SC administration warrants its advancement into clinical development as a potential treatment for CHB.

siRNA

Title: Incorporation of Novel siRNA Chemistries Significantly Improves the Potency and Durability of HBV siRNAs in the AAV-HBV Mouse Model
Publication Number: 831
Session Title: Hepatitis B: Therapeutics: New Agents
Presenter: Jin Hong
Summary: Aligos’ nonclinical small interfering RNA (siRNA) therapeutic candidates in development for CHB demonstrated improved potency and/or durability in vitro and in vivo when modified with novel siRNA chemistries.

Combinations

Title: Triple Combination of Anti-Hepatitis B Virus Drugs Demonstrates Synergistic Activity In Vitro
Publication Number: 852
Session Title: Hepatitis B: Therapeutics: New Agents
Presenter: Hua Tan
Summary: Aligos’ siRNA compound in development against hepatitis B virus, ALG-125755, in combination with the company’s ASO, ALG-020572, and STOPS™ molecule, ALG-010133, demonstrated synergistic activity in cell culture with respect to reducing HBsAg when added to various triple-combination groupings with nucleos(t)ide analogs (NA), CAM or interferon.

Triple combinations of the siRNA ALG-125755 and STOPS ALG-010133 with the ASO ALG-020572 showed additive activity in reducing HBsAg and demonstrated a dose-dependent response with respect to the ASO. When interferon or STOPS were added to the ASO-siRNA combination, the effect was enhanced, indicating the possibility of lowering doses needed to treat HBV when combined with other HBV therapies. Additionally, when tested in pairwise combinations with a NA or CAM, the compounds demonstrated additive to synergistic interactions on inhibition of HBV DNA.

NASH

Title: Preclinical Pharmacokinetic Profiling of ALG-055009, a Potent and Selective Thyroid Hormone Receptor Beta Agonist for the Treatment of Nonalcoholic Steatohepatitis, and Prediction of its Human Pharmacokinetics
Publication Number: 1932
Session Title: NAFLD and NASH: Therapeutics
Presenter: Kusum Gupta
Summary: The nonclinical pharmacokinetic properties of ALG-055009 in several animal model species indicate efficacious doses in the clinic are likely to be once daily doses in the sub- to low milligram range and there is likely a with low risk of drug-drug interactions.

Title: Development of a Novel Seven-Day Dosing Mouse Efficacy Model to Evaluate Thyroid Hormone Receptor Agonists for the Treatment of NASH
Publication Number: 1907
Session Title: NAFLD and NASH: Therapeutics
Presenter: Xuan Luong
Summary: Authors developed a high-cholesterol diet (HCD) mouse model for efficient in vivo screening of THR-β agonists as potential therapeutic agents in nonalcoholic steatohepatitis (NASH). The model appears to be predictive of patient response at clinically relevant exposures and provides a rapid alternative to the time-consuming standard efficacy models developed through high-fat diet administration.

About Aligos
Aligos Therapeutics, Inc. is a 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 discovery and 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’s strategy is to harness the deep expertise and decades of drug development experience its team has in liver disease, particularly viral hepatitis, to rapidly advance its pipeline