Aligos Therapeutics 将提供其慢性乙型肝炎和...的非临床和临床数

StephenW

Aligos Therapeutics 将提供其慢性乙型肝炎和...的非临床和临床数据

    Aligos Therapeutics - (GLOBE NEWSWIRE) 13 小时前

    0

Facebook
推特

    电子邮件

Facebook
推特
电子邮件
打印

    节省

加利福尼亚州南旧金山，2022 年 10 月 21 日 (GLOBE NEWSWIRE) -- Aligos Therapeutics, Inc. (Nasdaq: ALGS) 是一家临床阶段的生物制药公司，专注于开发新的疗法来解决病毒和肝脏疾病中未满足的医疗需求，今天宣布了即将在美国肝病研究协会 (AASLD) 主办的 The Liver Meeting®（2022 年 11 月 4 日至 8 日）上的七个海报展示。

所有海报，涵盖针对慢性乙型肝炎 (CHB) 和非酒精性脂肪性肝炎 (NASH) 的候选药物，将在会议结束后在 Aligos 网站上的 Scientific Presentations & Conferences 上提供。

“Liver Meeting® 2022 将展示 Aligos 潜在 CHB 治疗组合的广度和深度，以及我们 NASH 计划的持续进展，”Aligos 首席执行官兼董事会主席 Lawrence Blatt 博士说. “我们很高兴在会议上提供有关我们临床阶段候选药物的最新信息，特别是我们用于 CHB 的 2 类衣壳组装调节剂 (CAM)，ALG-000184，它在各种病毒标记。我们还将提供 ALG-125755 的临床前数据，这是我们的 siRNA 候选药物，旨在降低 HBsAg，目前正在第一阶段的健康志愿者中给药。最后，我们很高兴分享出色的药代动力学 (PK) 特性，耐受性良好我们在高脂血症受试者接受多剂我们的甲状腺激素β激动剂 ALG-055009 后观察到的安全性和各种血脂水平的降低。”

Blatt 博士继续说道，“我们也很高兴分享两个早期慢性乙型肝炎项目的临床前发现，包括第二类小分子 CAM 和两种 PD-L1 抑制剂模式。”

慢性乙型肝炎

衣壳组装调制器-2 (CAM-2)

标题：衣壳组装调节剂 (CAM) ALG-000184 在 HBeAg 阳性慢性乙型肝炎 (CHB) 受试者中的安全性、药代动力学 (PK) 和抗病毒活性

海报编号：33693

主讲人：侯金林，医学博士

总结：在 HBeAg 阳性的目前未治疗或初治 CHB 受试者中，给予 100 和 300 毫克 ALG-000184 长达 28 天的耐受性良好。两种剂量水平也表现出可预测的 PK 特性，并导致多种病毒标志物的快速和显着下降。海报中讨论了显示 ALG-000184 对 HBV DNA、RNA 和 HBsAg 水平影响的数据。

CAM-1

标题：非 HAP I 类衣壳组装调节剂具有不同的特征和不同的作用机制

海报编号：37007

主持人：Yannick Debing，博士

摘要：非 HAP（杂芳基二氢嘧啶）CAM-1 化合物 ALG-005398 和 ALG-006162 具有明显不同于已知 HAP CAM-1 的特征。由于优化的非 HAP CAM-1 具有合适的 ADME/毒性特征，它们代表了一类具有吸引力的分子，可作为 CHB 潜在功能性治愈方案的一部分进一步开发。

标题：HAP I 类衣壳组装调节剂通过核心依赖性肝细胞死亡和随后的增殖清除乙型肝炎病毒感染的肝细胞

海报编号：36810

主讲人： Dieudoneé Buh Kum 博士

总结：HAP CAM-1 被证明通过两种机制发挥作用，可能由免疫反应补充，导致 HBV 阳性细胞持续丢失。首先，HAP CAM-1 被证明在 HBc 表达细胞中诱导乙型肝炎病毒 (HBV) 核心蛋白 (HBc) 聚集和肝细胞凋亡。其次，代偿性肝细胞增殖被证明导致 AAV-HBV 附加体的额外损失。

siRNA

标题： ALG-125755（一种 GaINAc 偶联 siRNA，用于慢性乙型肝炎的功能性治愈）的非临床疗效、药代动力学特征和药代动力学/药效学 (PK/PD) 相关性

海报编号：35097

主持人：库苏姆·古普塔

总结：ALG-125755 展示了令人鼓舞的临床前药理学、PK 特性和在肝脏中的长半衰期，这预示着在人类受试者中每月或更少的给药频率。

PD-L1抑制剂：siRNA

标题：一种新型肝靶向 siRNA 抑制 PD-L1 表达可恢复针对 HBV 的免疫反应

海报编号：36189

主讲人：蔡大伟，博士

摘要：肝脏靶向 PD-L1 siRNA 疗法可能会导致针对 HBV 的免疫反应的恢复和随之而来的 HBV 感染清除，这被认为是慢性乙型肝炎治愈的关键。已鉴定出多种具有亚纳摩尔 PD-L1 mRNA 抑制 EC50 值的 siRNA。鉴定具有更高 PD-L1 表达敲低效率以及更高抗 HBV 活性的 siRNA 的努力正在进行中。
PD-L1抑制剂：小分子

标题：发现肝脏靶向口服PD-L1小分子抑制剂治疗慢性乙型肝炎和肝癌

海报编号：34890

会议标题：针对乙型和丁型肝炎功能性治愈的新型治疗方法

主讲人：吴彤飞，博士

总结：作者合理设计了肝脏靶向口服 PD-L1 小分子抑制剂，以定位肝脏中的 T 细胞活化，从而潜在地减轻全身毒性，努力为慢性乙型肝炎患者开发耐受性更好的 PD1/PD-L1 抑制剂。迄今为止开发的先导分子显示出与批准的抗体相似的体内功效，但在肝转移性肿瘤模型中比抗体更有效。

纳什

THR-β激动剂

标题：高脂血症受试者多次口服 ALG-055009（一种甲状腺激素受体 β 激动剂）的安全性、药代动力学和药效学

海报编号：2354

主讲人：Hakim Charfi，医学博士

摘要：甲状腺激素受体-β (THR-β) 激动剂药物已被证明可快速降低致动脉粥样硬化的脂质、降低肝脏脂肪含量并改善肝脏组织学，因此是治疗脂肪肝患者的一种有前途的方法。 ALG-055009 是一种新型 THR-β 激动剂，具有高 THR-β 选择性和效力。作为正在进行的 1 期研究（ALG-055009-301，或 NCT05090111）的一部分，在患有高脂血症的受试者中，连续 14 天每天多次服用 ALG-055009 的耐受性良好，具有良好的 PK 曲线和降脂活性的证据。

关于阿里戈斯

Aligos Therapeutics, Inc. 是一家临床阶段的生物制药公司，成立于 2018 年，其使命是成为治疗病毒感染和肝病的世界领导者。 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来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，特别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，以迅速推进其潜在一流分子的管道。

StephenW

Aligos Therapeutics to Present Nonclinical and Clinical Data for its Chronic Hepatitis B and ...

    Aligos Therapeutics - (GLOBE NEWSWIRE) 13 hrs ago

    0

Facebook
Twitter

    Email

Facebook
Twitter
Email
Print

    Save

SOUTH SAN FRANCISCO, Calif., Oct. 21, 2022 (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 seven upcoming poster presentations at The Liver Meeting® (November 4-8, 2022), hosted by the American Association for the Study of Liver Diseases (AASLD).

All posters, which cover drug candidates targeting chronic hepatitis B (CHB) and nonalcoholic steatohepatitis (NASH), will be available on the Aligos website at Scientific Presentations & Conferences following the conclusion of the conference.

“The Liver Meeting® 2022 will showcase the breadth and depth of Aligos’ portfolio of potential treatments for CHB and the continued progress in our NASH program,” said Lawrence Blatt, Ph.D., MBA, CEO and Chairman of the Board at Aligos. “We are excited to provide an update at the conference on our clinical-stage drug candidates, particularly our Class 2 capsid assembly modulator (CAM) for CHB, ALG-000184, which continues to show best-in-class declines in a variety of viral markers. We will also present preclinical data for ALG-125755, our siRNA drug candidate which is designed to reduce HBsAg and is currently being dosed in healthy volunteers in Phase 1. Finally, we are excited to share the excellent pharmacokinetic (PK) properties, well tolerated safety profile and reductions in various lipid levels we have observed after hyperlipidemic subjects received multiple doses of our thyroid hormone beta agonist, ALG-055009.”

Dr. Blatt continued, “We are also pleased to share preclinical findings for two early-stage CHB programs, including a second class of small molecule CAMs and two modalities of PD-L1 inhibitors.”

Chronic Hepatitis B

Capsid Assembly Modulator-2 (CAM-2)

Title: Safety, pharmacokinetics (PK), and antiviral activity of the capsid assembly modulator (CAM) ALG-000184 in subjects with HBeAg positive chronic hepatitis B (CHB)

Poster Number: 33693

Presenter: JinLin Hou, M.D.

Summary: In currently not treated or treatment-naïve CHB subjects who were HBeAg positive, 100 and 300 mg of ALG-000184 given for up to 28 days was well tolerated. Both dose levels also exhibited predictable PK properties and resulted in rapid and substantial declines in multiple viral markers.   Data showing the effects of ALG-000184 on HBV DNA, RNA and HBsAg levels are discussed in the poster.  

CAM-1

Title: Non-HAP class I capsid assembly modulators have distinct profiles and a differentiated mechanism of action

Poster Number: 37007

Presenter: Yannick Debing, Ph.D.

Summary: Non-HAP (heteroaryldihydropyrimidine) CAM-1 compounds ALG-005398 and ALG-006162 have a profile that is clearly distinct from known HAP CAM-1s. As optimized non-HAP CAM-1s have suitable ADME/toxicity profiles, they represent an attractive class of molecules for further development as a part of potential functional cure regimens for CHB.

Title: HAP Class I capsid assembly modulators clear hepatitis B virus-infected hepatocytes through core-dependent hepatocyte death and subsequent proliferation

Poster Number: 36810

Presenter: Dieudoneé Buh Kum, Ph.D.

Summary: HAP CAM-1s were shown to act through two mechanisms, possibly complemented by an immune response, that result in a sustained loss of HBV-positive cells. First, HAP CAM-1s were shown to induce hepatitis B virus (HBV) core protein (HBc) aggregation and hepatocyte apoptosis in HBc-expressing cells. Second, compensatory hepatocyte proliferation was shown to lead to an additional loss of AAV-HBV episomes.

siRNA

Title: Nonclinical efficacy, pharmacokinetic profile and pharmacokinetic/pharmacodynamic (PK/PD) correlation of ALG-125755, a GaINAc-conjugated siRNA, for functional cure of chronic hepatitis B

Poster Number: 35097

Presenter: Kusum Gupta

Summary: ALG-125755 demonstrates encouraging preclinical pharmacology, PK properties, and a long half-life in the liver, which predicts monthly or less frequent dosing in human subjects.

PD-L1 inhibitor: siRNA

Title: Suppression of PD-L1 expression by a novel liver-targeted siRNA leads to potential restoration of immune responses against HBV

Poster Number: 36189

Presenter: Dawei Cai, Ph.D.

Summary: Liver-targeted PD-L1 siRNA therapy may lead to restoration of immune responses against HBV and consequent clearance of HBV infection, which is considered critical for CHB cure. Multiple siRNAs with sub-nanomolar PD-L1 mRNA inhibition EC50 values have been identified. Efforts to identify siRNAs with greater PD-L1 expression knockdown efficiency as well as greater anti-HBV activity are ongoing.

PD-L1 inhibitor: small molecule

Title: Discovery of liver-targeted oral PD-L1 small molecule inhibitors for the treatment of chronic hepatitis B and liver cancers

Poster Number: 34890

Session Title: Novel Therapeutic Approaches Aimed at Functional Cure of Hepatitis B and D

Presenter: Tongfei Wu, Ph.D.

Summary: The authors rationally designed liver-targeted oral PD-L1 small molecule inhibitors to localize T cell activation in the liver and thereby potentially mitigate systemic toxicity, toward an effort to develop better tolerated PD1/PD-L1 inhibitors for CHB patients. Lead molecules developed to date show similar in vivo efficacy to approved antibodies but were more efficacious than antibodies in a liver metastatic tumor model.

NASH

THR-β agonist

Title: Safety, Pharmacokinetics, and Pharmacodynamics of multiple ascending oral doses of ALG-055009, a thyroid hormone receptor beta agonist, in hyperlipidaemic subjects

Poster Number: 2354

Presenter: Hakim Charfi, M.D.

Summary: Thyroid hormone receptor-beta (THR-β) agonist drugs have been shown to rapidly reduce atherogenic lipids, decrease hepatic fat content and improve liver histology, and thus represent a promising approach to treat patients with fatty liver disease. ALG-055009 is a novel THR-β agonist with high THR-β selectivity and potency. As part of an ongoing Phase 1 study (ALG-055009-301, or NCT05090111), in subjects with hyperlipidemia, multiple daily doses of ALG-055009 given for 14 days were well tolerated with a favorable PK profile and evidence of lipid lowering activity.

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’ 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 of potentially best-in-class molecules.