Aligos 在 HEP DART 2021 上展示了慢性乙型肝炎管道产品组合的更

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Aligos 在 HEP DART 2021 上展示了慢性乙型肝炎管道产品组合的更新

2021 年 12 月 7 日 08:00 ET |资料来源：Aligos Therapeutics

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接受 100 mg ALG-000184 的 HBeAg 阳性患者的新数据表明与先前报道的 HBeAg 阴性患者数据相似的 PK 和有效的抗病毒活性

新型口服小分子 PD-1/PD-L1 拮抗剂的新临床前数据显示出诱导免疫反应的潜力，结合 HBsAg 减少和病毒复制的抑制，可以提供多因素联合方法来实现 CHB 患者的功能性治愈

加利福尼亚州南旧金山，2021 年 12 月 7 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，今天宣布，公司管理层将在 2021 年 12 月 5 日至 9 日在墨西哥卡波圣卢卡斯举行的 2021 年 HEP DART 会议上发表受邀的口头报告。

该演讲题为“慢性乙型肝炎功能性治疗的联合方法”，提供了新的临床和临床前数据，以及有关 Aligos 开发多种疗法组合组合的战略方法的详细信息，这些疗法旨在为慢性乙型肝炎提供功能性治愈。 CHB）。 Aligos 的产品组合包括多种寡核苷酸模式（ALG-010133，一种专有的 STOPSTM 分子，ALG-020572，一种反义寡核苷酸 (ASO) 和 ALG-125755，一种 siRNA）、一种小分子衣壳组装调节剂 (CAM) 和一种新宣布的该计划旨在发现一种可口服的小分子 PD-1/PD-L1 拮抗剂。

“自 2019 年上一次 HEP DART 会议以来，Aligos 在构建一系列针对 CHB 感染和持续性临床验证机制的专用治疗候选药物组合方面取得的进展让我们感到非常自豪，”Lawrence M. Blatt 博士说。 D.，MBA，Aligos 董事长兼首席执行官。 “目前 CHB 的护理标准有效地阻止了病毒复制，但它无法提供功能性治愈，因为它必须终生服用。我们相信，通过靶向减少 HBV 抗原、抑制病毒复制和增强免疫反应，我们可以找到一种或多种可以在 CHB 患者中产生高功能治愈率的内部候选药物组合。”

HEP DART 展示了来自 Aligos 公司 CAM 候选 ALG-000184 的 1b 期研究（ALG-000184-201，NCT04536337）的新数据。队列 4 招募了 10 名乙型肝炎 E 抗原阳性慢性乙型肝炎患者（8 名 ALG-000184：2 名安慰剂）。 HBeAg 阳性 CHB 病例的典型特征是乙型肝炎病毒复制活跃，基线时病毒载量高。每天口服一次 100 mg ALG-000184 28 天后，HBV DNA 平均减少 4 log10 IU/mL，HBV RNA 平均减少 >3 log10 拷贝/mL。这类似于最近在两个接受 50 毫克或 100 毫克 ALG-000184 剂量的 HBeAg 阴性患者队列中观察到的反应。无论 HBeAg 状态如何，ALG-000184 在 CHB 受试者中均具有良好的耐受性。正在对 HBeAg 阴性受试者的 10 mg 剂量进行评估。

此外，演讲重点介绍了源自公司内部发现引擎的口服小分子 PD-1/PD-L1 拮抗剂的初步临床前数据，以将这种免疫增强机制潜在地添加到 Aligos 的 CHB 产品组合中。先前已在已发表文献的多项临床研究中建立了抗 PD1 或 PD-1 抗体的 CHB 患者的概念验证，这些研究证明 HBsAg 减少。除了其他候选产品对 HBsAg 减少和病毒复制抑制的影响外，Aligos 新宣布的计划旨在促进内源性 T 细胞对 HBV 的活性，以提高病毒清除率。早期先导化合物 ALG-093453 是一种小分子 PD-1/PD-L1 拮抗剂，具有出色的体外生化和细胞效力，已被选中用于进一步的临床前分析和优化。

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Aligos Presents Update of Chronic Hepatitis B Pipeline Portfolio at HEP DART 2021

December 07, 2021 08:00 ET | Source: Aligos Therapeutics

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New data from HBeAg-positive patients receiving 100 mg of ALG-000184 demonstrates similar PK and potent antiviral activity to previously reported data for HBeAg-negative patients

New preclinical data with a novel oral small molecule PD-1/PD-L1 antagonist shows potential to induce immune responses that together with HBsAg reduction and inhibition of viral replication could provide a multifactorial combination approach to achieve functional cure in CHB patients

SOUTH SAN FRANCISCO, Calif., Dec. 07, 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 company management, will deliver an invited oral presentation at the 2021 HEP DART meeting, being held December 5 – 9, 2021 in Cabo San Lucas, Mexico.

Titled “Combination Approaches Towards a Functional Cure for Chronic Hepatitis B”, the presentation provides new clinical and preclinical data as well as details on Aligos’ strategic approach in developing a combination portfolio of multiple therapeutics designed to provide a functional cure for chronic hepatitis B (CHB). Aligos’ portfolio includes several oligonucleotide modalities (ALG-010133, a proprietary STOPSTM molecule, ALG-020572, an antisense oligonucleotide (ASO), and ALG-125755, a siRNA), a small molecule capsid assembly modulator (CAM) and a newly announced program to discover an orally available small molecule PD-1/PD-L1 antagonist.

“We’re very proud of the progress Aligos has made since the last HEP DART meeting in 2019 toward building a portfolio of purpose-built therapeutic candidates that target clinically validated mechanisms of CHB infection and persistence,” said Lawrence M. Blatt, Ph.D., MBA, Chairman and CEO of Aligos. “The current standard of care in CHB effectively blocks viral replication, but it falls short of providing a functional cure as it must be administered for life. We believe that by targeting HBV antigen reduction, inhibiting viral replication and boosting immune responses, we can find one or more combinations of in-house candidates that can produce high rates of functional cure in CHB patients.”

New data were shown at HEP DART from Aligos’ Phase 1b study (ALG-000184-201, NCT04536337) of the company’s CAM candidate ALG-000184. Cohort 4 enrolled 10 hepatitis B E-antigen positive chronic hepatitis B patients (8 ALG-000184: 2 placebo). HBeAg-positive cases of CHB are typically marked by active hepatitis B virus replication with high viral loads at baseline. After once daily oral dosing for 28 days with 100 mg of ALG-000184, there was an average reduction of 4 log10 IU/mL of HBV DNA and >3 log10 copies/mL of HBV RNA. This is similar to the responses recently observed in two cohorts of HBeAg-negative patient who received 50 mg or 100 mg doses of ALG-000184. ALG-000184 was well tolerated in CHB subjects regardless of HBeAg status. Evaluation of a 10 mg dose in HBeAg-negative subjects is ongoing.

Additionally, the presentation highlighted initial preclinical data on an oral small molecule PD-1/PD-L1 antagonist derived from the company’s internal discovery engine, for potential addition of this immune boosting mechanism to Aligos’ CHB portfolio. Proof-of-concept in CHB patients with anti-PD1 or PD-1 antibodies has been previously established in multiple clinical studies in the published literature where they demonstrated reductions in HBsAg. In addition to the other portfolio candidates’ effects on HBsAg reduction and viral replication inhibition, Aligos’ newly announced program is designed to promote endogenous T-cell activity against HBV to enhance viral clearance. An early lead compound, ALG-093453, is a small molecule PD-1/PD-L1 antagonist with excellent in vitro biochemical and cell-based potency and has been selected for further preclinical profiling and optimization.