Arbutus提供HBV发展计划的最新信息

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https://investor.arbutusbio.com/ ... grams-and-announces

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Arbutus Provides Update on HBV Development Programs and Announces Appointment of Dr. Gaston Picchio as Chief Development Officer
PDF Version
Oct 09,2018
Dr. Mark Murray, Arbutus President & Chief Executive Officer, to participate in a fireside chat at Chardan’s Genetic Medicines Conference at 2:45 pm ET today
WARMINSTER, Pa., Oct. 09, 2018 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS), an industry-leading Hepatitis B Virus (HBV) therapeutic solutions company, today announced a change to its executive leadership team and provided an update on its key HBV development programs.  These updates include:            
The progression of AB-506, the Company’s second-generation capsid inhibitor, which is poised to be dosed in HBV patients this month, following successful execution of the healthy volunteer portion of the ongoing phase 1 clinical study;
The decision to delay the initiation of the Phase 1 clinical trial for AB-452, its novel HBV RNA de-stabilizer that was planned in Q4;
An update on the status of ARB-1467, an RNAi agent targeting HBV, currently in a Phase 2 combination study;
An update on AB-729, a second-generation subcutaneously administered RNAi agent, expected to enter clinical studies in Q2 2019; and
The addition of Dr. Picchio, formerly Janssen’s Infectious Diseases & Vaccines VP Hepatitis Disease Area Leader, adds Antiviral Drug Development Expertise to Executive Leadership
Small Molecule Programs
AB-506
AB-506, the Company’s second generation capsid inhibitor, has progressed through the healthy volunteer portion of a multi-component phase 1a/1b study in which it was demonstrated to be generally safe and well-tolerated after 10 days of dosing. This month, AB-506 will enter the 28-day HBV patient portion of the trial, where it will be evaluated both with and without a nucleoside analog. The Company expects to complete this segment of the trial in Q2 2019. AB-506 exhibits dual anti-HBV activities, both inhibiting HBV DNA replication and preventing the establishment and replenishment of cccDNA through inhibition of capsid uncoating.
AB-452
AB-452 is a novel, orally available RNA-destabilizer that has shown compelling anti-viral effects in multiple preclinical models. AB-452 is a new chemical entity acting via a novel mechanism and the Company is taking the time needed to further characterize the compound following emerging nonclinical safety findings before initiating clinical studies. At present, this is expected to delay the initiation of the phase 1 program while the Company completes the ongoing nonclinical studies.
RNA Interference Programs
ARB-1467
ARB-1467, an RNAi agent targeting HBV replication and antigen production, is currently in a 30-week study in HBV patients, in combination with tenofovir and PEG-IFN. To date, six HBV patients have enrolled and been treated. Three patients did not meet the predetermined response criteria at week 6 to proceed to PEG-IFN treatment as per protocol. Two patients have not yet progressed to the six-week analysis point to determine if the addition of PEG-IFN is warranted. One patient has responded strongly, with a 3.17 log reduction in HBsAg level at treatment week 14 of under 4 IU/mL having started with a baseline level of greater than 6000 IU/mL, indicating that this regimen may drive HBsAg levels to undetectable in some patients. The study remains open to enrollment and the Company will provide periodic updates.
AB-729
Arbutus is developing a second-generation RNAi agent, AB-729, a subcutaneously-administered GalNAc conjugate, targeting HBV. In preclinical models AB-729 exhibits potent and durable reductions in HBsAg. This agent is expected to enter clinical studies in Q2 2019 and may be combined with AB-506 in a clinical study in 2H 2019.
New Chief Development Officer Dr. Gaston Picchio
Dr. Picchio has joined Arbutus from Janssen R&D, bringing with him over thirty years of basic and clinical experience in the field of human virology, and sixteen years of industry experience dedicated to the development of antiviral drugs including drug approvals for the treatment of HIV (etravirine and rilpivirine) and HCV (telaprevir and simeprevir).
“I am thrilled to be joining the Arbutus team after working on the development and approval of transformational therapies for chronic HCV infection. Chronic HBV remains a major unmet need globally. I believe Arbutus is uniquely positioned to lead this effort and it is a privilege to have the opportunity to take on this challenge as part of a remarkably talented and accomplished team,” said Dr. Picchio.
Prior to joining Arbutus, Dr. Picchio served in various senior management positions at Janssen R&D, including Vice President – Scientific Innovation Infectious Diseases & Vaccines, Vice President – Hepatitis Disease Area Leader and Vice President – Clinical Virology Infectious Diseases & Vaccines. Dr. Picchio received a Masters in Molecular Biology from University Centro de Altos Estudios en Ciencias Exactas, Buenos Aires, and a PhD degree from University of Buenos Aires, Argentina.

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ARB-1467, an RNAi agent targeting HBV replication and antigen production, is currently in a 30-week study in HBV patients, in combination with tenofovir and PEG-IFN. To date, six HBV patients have enrolled and been treated. Three patients did not meet the predetermined response criteria at week 6 to proceed to PEG-IFN treatment as per protocol. Two patients have not yet progressed to the six-week analysis point to determine if the addition of PEG-IFN is warranted. One patient has responded strongly, with a 3.17 log reduction in HBsAg level at treatment week 14 of under 4 IU/mL having started with a baseline level of greater than 6000 IU/mL, indicating that this regimen may drive HBsAg levels to undetectable in some patients. The study remains open to enrollment and the Company will provide periodic updates.

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ARB-1467是一种靶向HBV复制和抗原生成的RNAi制剂，目前正在HBV患者中与替诺福韦和PEG-IFN联合进行为期30周的研究。到目前为止，已有6名乙肝患者登记并接受治疗。3例患者在第6周没有达到预定的反应标准，按照治疗方案进行PEG-IFN治疗。两名患者尚未进展到6周的分析点，以确定是否需要添加PEG-IFN。一名患者反应强烈，在治疗第14周时HBsAg水平在4 IU/mL以下的患者中，HBsAg水平降低了3.17 log

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已有6名乙肝患者登记并接受治疗。3例患者在第6周没有达到预定的反应标准，按照治疗方案进行PEG-IFN治疗

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多剂量单用Rnai药实在效果不佳

，按照治疗方案进行加PEG-IFN治疗

春景

在当今所有乙肝药物研发企业中，Arbutus 和 Jassen 是进度领先企业，还有Contravir，进度也不落后。
接下来，最先上市的乙肝新药，预计是核衣壳抑制类药，和RNAI类药。
从进度来看，即使顺利，最早的上市新药，至少在后年2020年以后了。
基因编辑技术治疗乙肝的药物，目前看不到进度，远水不解近渴。

windu

有可能失败

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回复 春景 的帖子

2020年那还是对于美国来讲，虽然中国上市现在进度加快了，但得在此时间上加两年。另外核衣壳抑制剂+激活免疫药才是完美

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Janssen前副总裁加盟Arbutus任CDO专攻HBV项目开发
2018-10-10来源：一诺医学作者：略晓薛

业界领先的乙型肝炎病毒（HBV）治疗解决方案公司 Arbutus Biopharma（纳斯达克股票代码：ABUS）9号宣布将对其执行领导团队进行更换，并提供其关键HBV发展项目的最新信息更新。这些更新包括：

AB-506 是公司的第二代衣壳抑制剂（capsid inhibitor），在成功的执行仍在持续进行的 phase 1 期临床试验的健康志愿者的研究后，将在本月开始在慢乙肝患者中开始用药；

决定延迟启动 AB-452 的 phase 1 期临床试验，AB-452 是公司第四季度计划启动的新型HBV RNA去稳定剂;

对目前正在进行 phase 2 期联合研究的 ARB-1467（一种针对HBV的RNAi药物）的状态更新;

第二代皮下注射 RNAi 药物 AB-729 的更新，预计将于2019年第二季度进入临床研究；

Picchio 博士，前身为 Janssen 的传染病和疫苗副总裁，肝炎疾病领域领导者，他的加盟为公司领导增加了抗病毒药物开发专业知识；

公司的小分子项目

AB-506

AB-506 是公司的第二代衣壳抑制剂（capsid inhibitor），多组份 phase 1a / 1b 期研究中的健康志愿者在用药 10 天后证实该药安全并且耐受性良好。本月，AB-506 将进入该试验的 28天 HBV 患者部分，在此部分将联合/不联合核苷（酸）类似物进行评估。公司预计将在2019年第二季度完成该部分试验。AB-506表现出双重抗HBV活性，既抑制HBV DNA复制又通过抑制衣壳脱壳来阻止cccDNA的建立和补充。

AB-452

AB-452 是一种新型的口服 RNA 降解稳定剂，已在多种临床前模型中显示出引人注目的抗病毒作用。AB-452 是一种通过新机制起作用的新化学实体，在启动临床研究前，出现非临床安全性新发现后，公司正在花费时间进一步表征化合物。目前，预计在公司完成正在进行的非临床研究时，将推迟启动phase 1期临床试验计划。

RNA干扰项目

ARB-1467

ARB-1467 是一种靶向 HBV 复制和抗原产生的 RNAi 制剂，目前正在HBV患者中进行为期30周的研究，与替诺福韦和 PEG-IFN 联合使用。迄今为止，已有6名HBV患者入组并接受了治疗。根据方案，3名患者在第6周未达到预定的应答标准以进行PEG-IFN治疗。2 名患者尚未进展至 6 周分析点以确定是否需要添加PEG-IFN。1名患者的反应强烈，治疗第14周时HBsAg水平降低3.17 log，低于4 IU / mL，基线水平高于6000 IU / mL，表明该方案可能导致某些患者的 HBsAg 水平可达到未能检测水平。该研究仍然开放招募患者，公司将定期提供更新。

AB-729

AB-729 是一种靶向HBV的皮下注射GalNAc结合物，是Arbutus 正在开发的第二代RNAi制剂 。在临床前模型中，AB-729 显示出有效且持久的HBsAg降低。该药物预计将于2019年第二季度进入临床研究，并可能在2019年下半年的临床研究中与AB-506联合使用。

新任首席开发官 Gaston Picchio 博士

Picchio 博士从 Janssen R＆D 离职加入了 Arbutus，带来了他在人类病毒学领域30多年的基础和临床研究以及16年的行业经验，他致力于开发抗病毒药物，包括获得批准用于治疗HIV（ etravirine 和 rilpivirine）和 HCV（telaprevir 和 simeprevir）药物。

“在为慢性HCV感染转化疗法（transformational therapies）开发和批准工作之后，我很高兴能够加入 Arbutus 团队。慢性HBV治疗仍然是全球主要的未满足需求。我相信 Arbutus 在领导这项工作方面具有独特的优势，我很荣幸有机会接受这一挑战，成为一支非常有才华和成就卓着的团队的一员，“Picchio 博士说。

在加入 Arbutus 之前，Picchio 博士曾在 Janssen R＆D 担任过多个高级管理职位，包括科学创新传染病和疫苗事业部副总裁 -肝炎疾病领域 - 临床病毒学传染病和疫苗负责人和副总裁。 Picchio 博士在布宜诺斯艾利斯的Centro de Altos Estudios en Ciencias Exactas 获得分子生物学硕士学位，并在阿根廷布宜诺斯艾利斯大学获得博士学位。