abus的 TLR-9 program, CYT-003

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TLR-9 agonists are a novel approach to immune reactivation in patients with chronic HBV. By stimulating cellular TLRs we expect to be able to elicit an innate immune response that leads to the production of cellular proteins that target viral infections.

Our lead TLR-9 program, CYT-003, was in-licensed from Cytos Biotechnology Ltd., where it was evaluated clinically in allergic asthma. We are currently evaluating the utility of CYT-003 in HBV. If positive, we may be able to utilize the existing safety database to expedite development.

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TLR-9激动剂是一种新型的免疫激活在慢性HBV。通过刺激细胞TLRs我们期望能够引起免疫反应，导致细胞的蛋白质，病毒感染的生产目标。
我国铅TLR-9程序，cyt-003，在Cytos生物技术有限公司授权，在过敏性哮喘的临床评价。我们目前正在评估cyt-003 HBV的效用。如果积极的话，我们可以利用现有的安全数据库加快发展。

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http://www.cytos.com/cyt003/mechanism-of-action.html

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CYT003 offers a differentiated approach for the treatment for asthma that acts upstream of most therapeutic agents currently in development.

It is a targeted therapy based on a biological carrier filled with an activating ligand (agonist) of Toll-like receptor 9 (TLR9), a key mediator of innate immunity. TLR9 is the receptor that detects the presence of microbial DNA and induces the immune system’s first line of defense against bacterial infection. The TLR9 agonist of CYT003 is a synthetically produced oligonucleotide containing non-methylated CpG motifs as found in bacterial DNA and belongs to the class of A-type CpGs.

Toll-like receptors are expressed in a subset of immune cells called antigen-presenting cells (APCs; e.g. dendritic cells, macrophages, B-cells).  APCs are typically found in tissues in contact with the external environment (skin, lining of the nose, lungs, stomach and intestines) and serve as an important element of the immune defense. APCs, and in particular dendritic cells, communicate with T-cells to orchestrate the immune response when challenged by bacteria or viruses.

TLR9 is predominantly expressed in plasmacytoid dendritic cells (pDCs) and B-cells in humans. CYT003 is actively taken up by pDCs, activates TLR9, and induces the production of type 1 helper T cell (Th1) cytokine IFN-alpha and the co-stimulatory molecule ICOS-Ligand. CYT003-activated pDCs are then postulated to inhibit type 2 helper T (Th2) cells, which are critically involved in the development of allergic asthma.

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提供了一种区分方法CYT003治疗哮喘的作用大多数治疗药物目前在发展上。它是一种基于生物载体的靶向治疗充满活化配体（激动剂）Toll样受体9（TLR9），先天免疫的重要介质。TLR9是检测微生物的DNA的存在，导致免疫系统的第一道防御细菌感染的受体。CYT003的TLR9激动剂是一种合成的寡核苷酸含有非甲基化CpG序列在细菌DNA的发现属于A型cpgs.toll-like受体类免疫细胞的一个子集称为抗原提呈细胞（APC的表达；如树突状细胞，巨噬细胞，B细胞）。APC通常是在与外界环境接触的组织（皮肤，李宁的鼻子，肺，胃和肠道）作为免疫防御的重要元素。APC，和特别是树突状细胞，与T细胞的免疫应答来编排时受到细菌或viruses.tlr9是浆细胞样树突状细胞（pDCs）和B细胞主要表达在人类。CYT003是积极向上的pDCs，激活TLR9，诱导1型辅助性T细胞（Th1）生产细胞因子IFN-α和共刺激分子ICOS配体。CYT003激活pDCs假设抑制2型辅助性T细胞（Th2），这是极为参与过敏性哮喘的发展。

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看官网，手机不好弄，或帮忙或自己看

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Arbutus Biopharma Announces Third Quarter 2015 Financial Results

VANCOUVER, British Columbia and DOYLESTOWN, Pa., Nov. 5, 2015 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading therapeutic solutions company focused on developing a cure for chronic hepatitis B virus infection (HBV), today announced its third quarter 2015 unaudited financial results and provided a corporate update.
"We are excited to advance the development of our lead HBV candidate, TKM-HBV, to a Phase II, multi-dosing, clinical trial that will measure hepatitis B surface antigen (HBsAg) reduction in HBV infected patients," said Dr. Mark J. Murray, Arbutus' President and CEO. "We are also accelerating the development of our other promising HBV candidates, in particular, those that target cccDNA formation and core protein/capsid assembly."
Recent Company Highlights

Arbutus announced progression of TKM-HBV to Phase II studies in HBV infected patients based on results from a Phase I single ascending dose study. The TKM-HBV product candidate that will be studied in Phase II will be referred to as ARB-1467.
Arbutus presented preclinical HBV data at the 2015 International Meeting on Molecular Biology of Hepatitis B Viruses, held on October 4-8, 2015. The presentations were titled: 1) "Profiling the Effects of TKM-HBV on cccDNA in Humanized Chimeric Mouse Model of HBV"; 2) "TKM-HBV, a Novel RNA Interference Treatment for Chronic Hepatitis B, Mediates Global Viral Antigen Reductions through a Well-Defined Mechanism of Action"; and 3) "Novel Inhibitors of HBV cccDNA Formation Exhibit Synergistic Effects with Nucleoside and Nucleotide Analog."
Arbutus announced plans to present at the 2015 American Association for the Study of Liver Diseases (AASLD) Liver Meeting held on November 13-17, 2015. The titles of Arbutus' accepted abstracts are: 1) "TKM-HBV, a Novel RNA Interference Treatment for Chronic Hepatitis B, Rapidly Reduces Surface Antigen and other Viral Proteins in Both Intrahepatic and Peripheral Compartments"; 2) "TKM-HBV, a Novel RNA Interference Treatment for Chronic Hepatitis B, has a Complementary Mode of Action to Current Standard of Care Nucleos(t)ide Analogs"; and 3) "Development of a Direct RNA Interference Therapy for Hepatitis Delta Virus Infection."
Upcoming Pipeline Milestones

4Q15: Initiate phase II, multi-dose efficacy study of TKM-HBV in chronically infected patients
2016: HBsAg reduction data from TKM-HBV Phase II trial (final data in 2H16)
2016: Initiate clinical immune biomarker study for CYT-003 in HBV chronically infected patients
2H16: File IND (or equivalent) for cccDNA formation inhibitor
2H16: File IND (or equivalent) for core protein/capsid assembly inhibitor
2017: Initiate combination studies including two or more Arbutus HBV product candidates

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杨梅生物制药宣布2015年第三季度的财务业绩
温哥华,不列颠哥伦比亚大学和美国多伊尔斯敦,Pa。2015年11月5日(全球通讯社)——杨梅生物制药公司(纳斯达克:离合器),一家行业领先的治疗解决方案公司专注于开发一种治疗慢性乙型肝炎病毒(HBV)感染,今天宣布其2015年第三季度未经审计的财务结果,提供了企业更新。
“我们兴奋地推进我们的发展导致乙肝病毒的候选人,TKM-HBV,第二阶段,多剂量,临床试验,测量乙型肝炎表面抗原(HBsAg)减少乙肝病毒感染患者,”马克·j·默里博士说,杨梅的总裁兼首席执行官。“我们也加速发展的其他承诺HBV候选人,特别是那些目标cccDNA的形成和核心蛋白质衣壳组装。”
最近公司强调
杨梅宣布TKM-HBV的第二阶段研究乙型肝炎病毒感染患者基于结果从一个阶段我单一剂量提升的研究。TKM-HBV产品候选人,将在第二阶段研究将称为arb - 1467。
杨梅提出临床乙肝病毒分子生物学数据在2015年的国际会议的乙肝病毒,2015年10月4 - 8,举行。演讲题目:1)”分析的影响TKM-HBV cccDNA的人性化嵌合小鼠模型的乙肝病毒”;2)”小说TKM-HBV RNA干扰治疗慢性乙型肝炎,协调全球病毒抗原减少通过一个定义良好的机制的行动”,和3)“小说HBV cccDNA形成的抑制剂表现出协同效应与核苷和核苷酸模拟。”
杨梅宣布参加2015年美国肝病研究协会(肝病)肝脏会议于11月13 - 17,2015。标题的杨梅的接受抽象是:1)”小说TKM-HBV RNA干扰治疗慢性乙型肝炎,迅速降低表面抗原和其他病毒蛋白在肝内和外围隔间”;2)”小说TKM-HBV RNA干扰治疗慢性乙型肝炎,有互补作用方式目前的标准治疗干扰素有ide(t)类似物”;3)“发展直接RNA干扰治疗δ型肝炎病毒感染。”
即将到来的管道的里程碑
4最喜欢:启动二期,多剂量TKM-HBV在慢性感染患者的疗效研究
2016:从TKM-HBV HBsAg减少数据二期试验(最终数据2 h16)
2016:启动临床免疫生物标志物研究cyt - 003乙肝病毒慢性感染患者
2 h16:文件印第安纳州(或同等)cccDNA形成抑制剂
2 h16:文件印第安纳州(或同等)核心蛋白/衣壳组装抑制剂
2017:启动组合的研究包括两个或两个以上的杨梅乙肝病毒产品候选人

fs2002

虽然看不太懂，但还是感谢这些药物研发人员；当然也要感谢楼主，使我们能够及时了解一些全球药物研发的最新进展情况，无疑增强了病友的信心！

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好懂，上面全是荷兰话，学好荷兰话，就会看懂了