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标题: [Press Release]Arrowhead:RANi based Hepatitis B Treatment [打印本页]

作者: StephenW 时间: 2012-5-4 08:21 标题: [Press Release]Arrowhead:RANi based Hepatitis B Treatment

本帖最后由 StephenW 于 2012-5-4 08:28 编辑

press release

May 3, 2012, 7:00 a.m. EDT

Arrowhead to Present at Series of Upcoming Scientific Conferences Data Highlights Results Demonstrating Effectiveness of DPC siRNA Delivery System and Path to the Clinic for siRNA-based Hepatitis B Treatment

PASADENA, Calif., May 03, 2012 (BUSINESS WIRE) --Arrowhead Research Corporation today announced that senior management will present data for its Dynamic PolyConjugate(TM) (DPC) delivery platform for siRNA delivery including its RNAi therapeutic candidate for the treatment of hepatitis B virus (HBV) at several upcoming scientific conferences.

"Arrowhead's DPC delivery system and the associated HBV program have been under development for several years at our Madison site, first as Mirus Bio and then as a subsidiary of Roche. It's been several years since data regarding the programs have been presented to the scientific community at large. We are looking forward to unveiling advanced and exciting results in these forums and to related publications later this year," said Dr. Christopher Anzalone, Arrowhead's CEO & President.

Scheduled conference presentations are as follows:

European Foundation for Clinical Nanomedicine (CLINAM) Basel, Switzerland An oral presentation titled, "DPC Technology for Safe and Effective siRNA Delivery," will be presented by Dr. David Lewis, Vice President, Biology and Site Head on May 9, 2012 at 8:35 AM CEST TIDES:Oligonucleotide & Peptide(R) Research, Technology & Product Development Las Vegas, NV, May 20-23 A poster titled, "Liver-targeted and reversibly masked-polycation co-delivery improves cholesterol-conjugated siRNA efficacy," will be presented by Dr. Darren Wakefield, Senior Scientist RNA Society Annual Meeting Ann Arbor, MI A poster titled, "Effective RNAi Therapeutic to Treat Chronic Hepatitis B Virus Infection," will be presented by Dr. Christine Wooddell, Senior Scientist RNAi Research & Therapeutics Conference Boston, MA, May 29-June 3 An oral presentation titled, "The Development of Dynamic Poly Conjugates," will be presented by Dr. David Rozema, Vice President, Chemistry, on May 30, 2012 at 10:30 AM ET RNAi & Nanotechnology Conference London, UK An oral presentation titled, "DPC Technology for siRNA Delivery: from rodents to primates," will be presented by Dr. David Lewis on June 11, 2012, 11:40 AM GMT International Congress on Infectious Diseases Bangkok, Thailand An oral presentation in the session New Developments in Viral Diseases: "RNAi therapeutics for the treatment of chronic hepatitis B virus infection" will be presented by Dr. David Lewis on Friday, June 15, 2012, 3:45 PMICT

Arrowhead published a white paper providing an overview of its proprietary DPC technology for safe and effective delivery of siRNA. This white paper can be found on the Arrowhead website at http://www.arrowheadresearch.com ... er-November2011.pdf

Arrowhead has also released a white paper describing the health problem posed by the hepatitis B virus (HBV), the substantial unmet need for chronic HBV infected patients, and how Arrowhead's Dynamic Polyconjugate (DPC) enabled RNAi therapeutic in development could potentially address deficiencies of current treatment options. This white paper can be found on the Arrowhead website at http://www.arrowheadresearch.com/pdf/whitepaper-hbv-3-7-12.pdf

About Arrowhead Research Corporation

Arrowhead Research Corporation is a clinical stage nanomedicine company developing innovative therapies at the interface of biology and nanoengineering. Arrowhead's world-class capabilities and intellectual property covering nucleic acid delivery, siRNA chemistry, and tissue targeting allow it to design and develop therapeutic agents for a wide range of diseases. The company's lead products include CALAA-01, an oncology drug candidate based on the gene silencing RNA interference (RNAi) mechanism, and Adipotide(TM), an anti-obesity peptide that targets and kills the blood vessels that feed white adipose tissue. Arrowhead is leveraging its proprietary Dynamic PolyConjugate (DPC), Liposomal Nanoparticle (LNP), and RONDEL(TM) delivery platforms to support its own pipeline of preclinical and clinical candidates and to secure external partnerships and collaborations with biotech and pharmaceutical companies.

For more information please visit http://www.arrowheadresearch.com , or follow us on Twitter @ArrowRes. To be added to the Company's emaillist to receive news directly, please send an email to [email protected].

SOURCE: Arrowhead Research Corporation

作者: StephenW 时间: 2012-5-4 08:28

新闻稿

2012年5月3日，美东时间上午7:00
箭头以出席即将举行的科学会议系列
数据聚焦结果显示siRNA为基础的B型肝炎治疗的诊所DPC siRNA传递系统和路径的有效性

加利福尼亚州帕萨迪纳的箭头研究公司ARWR 0.00％，2012年5月03，（美国商业资讯） - 今天宣布，高级管理人员将介绍其的动态PolyConjugate（TM）的（DPC）的siRNA运送交付平台，包括RNAi治疗候选人的资料治疗B型肝炎病毒（HBV）在即将到来的几个科学会议。

“箭头的DPC的交付系统和的相关乙肝病毒程序已经正在开发几年我们的麦迪逊网站，首先Mirus生物和然后作为罗氏集团的子公司。它是被几年来，因为有关方案的数据已被提交给科学界大。我们期待着在这些论坛上推出先进的和令人兴奋的结果和相关出版物，今年晚些时候，博士说：“克里斯托弗Anzalone，箭头的首席执行官兼总裁。

会议介绍如下：

欧洲临床纳米医学基金会（CLINAM），瑞士巴塞尔的一个口头报告，题目是“DPC的安全和有效的siRNA传递技术，”将提交由大卫·刘易斯博士，副总裁，生物学和网站负责人于5月9日，2012年8 ：上午35欧夏令时潮汐：寡核苷酸与肽（R）的研究，技术及产品开发内华达州拉斯维加斯，5月20-23日海报名为“肝针对性和可逆屏蔽阳离子共交付提高胆固醇结合的siRNA疗效， “将由达伦·韦克菲尔德博士，资深科学家RNA学会年度会议安阿伯，MI海报，题目是”有效的RNAi治疗治疗慢性乙型肝炎病毒感染“，将通过的恭Wooddell博士，资深科学家提出的RNAi研究治疗会议马萨诸塞州的波士顿5月29日6月3日口头报告题为“动态聚缀合物的发展，”将提交于2012年5月30日，由大卫Rozema博士，副总裁，化学，上午10时30分ET RNAi技术及纳米技术会议，英国伦敦的口头报告，题目是“DPC的siRNA传递技术：从啮齿动物到灵长类动物，”将会由大卫·刘易斯博士，2012年6月11日，11:40 GMT国际大会上传染病泰国曼谷，在会议的口头报告，在病毒病的新进展：“RNAi疗法治疗慢性乙型肝炎病毒感染”将由大卫·刘易斯博士，2012年6月15日，星期五，3:45 PMICT

箭头发表了一份白皮书提供了DPC的安全和有效的siRNA交付其专有技术的概述。本白皮书箭头的网站上可以找到

箭头已公布的1白色纸张描述的健康问题，肝炎乙病毒（HBV）的，的大量慢性乙肝病毒感染的患者未满足的需要所造成的，如何箭头的动态Polyconjugate（DPC）的启用在开发RNAi治疗可能潜在的解决目前的不足之处治疗方案。本白皮书箭头的网站上可以找到http://www.arrowheadresearch.com/pdf/whitepaper-hbv-3-7-12.pdf

关于箭头研究公司

箭头研究公司是一个临床阶段，纳米公司开发创新疗法在生物学和纳米工程学的界面。箭头的世界一流的能力和知识产权，涵盖核酸交付的siRNA化学，和组织的目标，使其能够设计和开发的多种疾病的治疗药物。公司的主导产品包括CALAA-01，肿瘤候选药物的基因沉默RNA干扰（RNAi）机制为基础，Adipotide（TM），肽，针对杀死养活白色脂肪组织的血管，抗肥胖。慈姑利用其专有的动态PolyConjugate（DPC），脂质体纳米粒子（的LNP），罗德尔（TM）的交付平台，以支持其自己的管道，临床前和临床的候选人和外部伙伴关系和合作，以确保与生物技术和制药公司。

欲了解更多信息，请，参观http://www.arrowheadresearch.com，或者按照我们对Twitter的@ ArrowRes。被添加到本公司的电子邮件列表，直接接收消息，请发送电子邮件[email protected]。

来源：箭头研究公司Xīnwén gǎo

作者: 咬牙硬挺 时间: 2012-5-4 23:24

似乎是好消息

作者: MP4 时间: 2012-5-6 11:18

本帖最后由 MP4 于 2012-5-6 11:19 编辑

作者: StephenW 时间: 2012-5-9 21:02

本帖最后由 StephenW 于 2012-5-9 21:10 编辑

回复 MP4 的帖子
press release

May 9, 2012, 7:00 a.m. EDT

Arrowhead Presents Data on DPC System and Hepatitis B Program at CLINAM 2012          Preclinical Studies Show Substantial Reduction of Serum HBsAg, HBV DNA and Dramatically Decreased HBV RNA and DNA in Liver

PASADENA, Calif., May 09, 2012 (BUSINESS WIRE) --Arrowhead Research Corporation today announced that David Lewis, Ph.D., Vice President Biology and Site Head of its Madison, WI research and development facility presented data at the European Foundation for Clinical Medicine Conference in Basel, Switzerland. Dr.Lewis' presentation, "DPC Technology for Safe and Effective siRNA Delivery" described the development and capabilities of Arrowhead's Dynamic Polyconjugate (DPC) siRNA delivery platform, as well as the system's deployment in the development of a new treatment for chronic Hepatitis B.

Dr. Lewis reported data from Arrowhead's preclinical HBV program that support Arrowhead's clinical strategy for the development of an effective siRNA-based therapeutic for the treatment of patients with chronic HBV infection. Single-dose injections of hepatocyte-targeted anti-HBV siRNA DPCs in a replication-competent, transiently transgenic HBV mouse model resulted in a multi-log reduction of serum HBsAg and serum HBV DNA. Using a transgenic mouse model of chronic HBV infection in collaboration with Dr. Alan McLachlan at the University of Illinois-Chicago, dramatic reductions in viral transcripts, viral replicative DNA intermediates, and intracellular HBV core antigen were observed in the liver after two weekly doses. In multi-dose studies in mice carrying a hepatocyte-specific reporter gene fused to HBV sequences, four biweekly injections of anti-HBV siRNA DPCs resulted in a multi-log reduction in gene expression over 2 months without changes in toxicity markers. Safety studies performed in non-human primates have shown DPCs to be highly effective and well tolerated.

导致多log减少了血清HBsAg和血清HBV DNA单剂量注射抗乙肝病毒复制的主管，瞬时乙肝转基因小鼠模型肝靶向siRNA的DPC的。利用转基因小鼠模型的慢性乙肝病毒感染在伊利诺伊州芝加哥大学的艾伦·克兰博士，大幅减少病毒的转录，病毒复制DNA中间体，和细胞内的HBV核心抗原在肝脏中经过两个星期的剂量观察协作。在小鼠携带肝细胞特异性报告基因融合到乙型肝炎病毒序列的多剂量研究中，抗乙肝病毒的siRNA DPC的双周注射多log超过2个月，在基因表达减少，无毒性标志物的变化。在非人类灵长类动物进行的安全性研究表明DPC的是高效和良好的耐受性。

According to the World Health Organization, about 2 billion people worldwide have been infected with the virus and about 350 million live with chronic infection. An estimated 600,000 persons die each year due to the acute or chronic consequences of hepatitis B.

"Current treatments for HBV are poorly tolerated and fail to adequately reduce circulating Hepatitis B Surface Antigen (HBsAG), which is thought to hinder the immune system's ability to eradicate the virus," said Dr. Lewis. "RNAi has the potential to be much more effective through its ability to not only knock down the replication of the virus but crucially reduce the expression of viral proteins as well, including HBsAG. It is believed this will clear the way for the patient's immune system to mount an effective response to the infection."

Full data from these experiments will be submitted for publication.

About the Dynamic PolyConjugate siRNA Delivery Platform

Achieving safe and effective in vivo delivery of siRNA to the appropriate tissue and cell type is the primary barrier to development f RNAi as a therapeutic modality. Dynamic PolyConjugate (DPC) technology overcomes this barrier. Key features of the DPC technology include:

-- New classes of membrane-active and biodegradable polymers,

-- Reversible chemical masking of the polymers so that membrane-lytic activity is revealed only in the acidic environment of endosomes, and

-- The ability to attach ligands to guide the polymer and the siRNA cargo to specific cell types in vivo.

The utility of this technology has been demonstrated by ligand-mediated delivery of siRNA to liver hepatocytes in mice, rats, and non-humanprimates resulting in high-level knockdown of the targeted gene.Importantly, DPCs display a low toxicity profile enabling siRNA redosing and long-term target gene knockdown.

About Arrowhead Research Corporation

Arrowhead Research Corporation is a clinical stage nanomedicine company developing innovative therapies at the interface of biology and nanoengineering. Arrowhead's world-class capabilities and intellectual property covering nucleic acid delivery, siRNA chemistry, and tissue targeting allow it to design and develop therapeutic agents for a wide range of diseases. The company's lead products include CALAA-01, an oncology drug candidate based on the gene silencing RNA interference (RNAi) mechanism, and Adipotide(TM), an anti-obesity peptide that targets and kills the blood vessels that feed white adipose tissue. Arrowhead is leveraging its proprietary Dynamic PolyConjugate (DPC),Liposomal Nanoparticle (LNP), and RONDEL(TM) delivery platforms to support its own pipeline of preclinical and clinical candidates and to secure external partnerships and collaborations with biotech and pharmaceutical companies.

For more information please visit http://www.arrowheadresearch.com , or follow us on Twitter @ArrowRes. To be added to the Company's email list to receive news directly, please send an email to [email protected]

SOURCE: Arrowhead Research Corporation

作者: 咬牙硬挺 时间: 2012-5-10 08:15

好消息

作者: MP4 时间: 2012-5-18 00:38

http://v.youku.com/v_show/id_XMjQ5MTQ1NjQ=.html
不要胎死腹中就好了。

作者: StephenW 时间: 2012-5-18 07:14

本帖最后由 StephenW 于 2012-5-18 07:15 编辑

回复 MP4 的帖子

是的，没有保证。Nucleonics公司破产，因为知识产权纠纷。报告说，Arrowhead会
向FDA申请IND（新药的指示）在2013年.这意味着他们将开始临床试验在2013年.
希望。

作者: MP4 时间: 2012-5-18 10:02

StephenW 发表于 2012-5-18 07:14
回复 MP4 的帖子

是的，没有保证。Nucleonics公司破产，因为知识产权纠纷。报告说，Arrowhead会

Nucleonics据闻都IND了·还是破产了,那Sirna Therapeutics呢？默克收了就没声音了。
FDA应该采取快速的方法，比如一期通过就许可自愿自费使用。不然即使顺利按进度可能要2023年。

作者: 咬牙硬挺 时间: 2012-5-18 10:37

哎呀呀，祈祷研发顺利

作者: StephenW 时间: 2012-5-18 12:17

本帖最后由 StephenW 于 2012-5-18 12:17 编辑

回复 MP4 的帖子

那Sirna Therapeutics呢？默克收了就没声音了 - 默克支付十亿美元，根据维基百科.如果一种药物是好的，FDA将会开快车.

作者: cwy121 时间: 2012-5-18 12:45

快点出来新药吧，要不然我在中国充满歧视的环境中都没发活了，上了一二十年的学，再有两年研究生都毕业了，工作可咋办啊?????

作者: StephenW 时间: 2012-6-7 10:34

PASADENA, Calif., Jun 06, 2012 (BUSINESS WIRE) -- Arrowhead Research Corporation ARWR -4.78% , a targeted therapeutics company, today announced that its hepatitis B virus (HBV) program has completed all internal preclinical requirements and has named a clinical candidate. As such, the Company has initiated the final IND-enabling steps, including GMP manufacturing, GLP toxicology, and preparation of a pre-IND data package for the US FDA and foreign counterparts. The candidate, named ARC-520, is an RNAi therapeutic actively targeted to the liver using the company's Dynamic Polyconjugate (DPC) delivery system and includes two siRNA sequences targeting two different regions of the HBV genome.

加利福尼亚州帕萨迪纳，2012年6月06，（美国商业资讯） - 箭头研究公司ARWR-4.78％，
专门
的治疗公司今天宣布，其B型肝炎病毒（HBV）的方案已完成所有内部的临床要求，并已命名的临床候选人。正因为如此，该公司已开始IND支持的最后步骤，包括GMP生产，GLP毒理学，编制预实业美国FDA和外国同行的数据包。候选人，命名的ARC-520，是积极有针对性地使用该公司的，动态Polyconjugate（DPC）的输送系统，肝脏的RNAi治疗，包括针对HBV基因组的两个不同地区的两个siRNA序列。

作者: cwy121 时间: 2012-6-7 12:16

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这代表着什么。。。

作者: StephenW 时间: 2012-6-7 12:31

本帖最后由 StephenW 于 2012-6-7 12:32 编辑

回复 cwy121 的帖子

如果要进行临床试验, 必须向FDA申请。IND (Indication for New Drug)新药物指示。所以ARC520是上轨道，开始第一期临床试验.

作者: 希望奇迹 时间: 2012-6-7 12:46

期待

作者: cwy121 时间: 2012-6-7 13:30

ARC520是属于什么药物，其研究中展现出来的预期疗效谁什么样的？

作者: StephenW 时间: 2012-6-7 14:21

回复 cwy121 的帖子

RNAi

作者: 才易的生活 时间: 2012-6-7 14:58

回复 StephenW 的帖子

您辛苦了，请问这个帖子说的是什么新药，疗效如何，已进入临床试验了吗！

作者: StephenW 时间: 2012-6-7 15:43

本帖最后由 StephenW 于 2012-6-7 15:44 编辑

回复才易的生活的帖子

RNA干扰                                                                                                                   维基百科，自由的百科全书

RNAi示意图

RNA干扰（RNA interference，缩写为RNAi）是指一种分子生物学上由双链RNA诱发的基因沉默现象，其机制是通过阻碍特定基因的翻译或转录来抑制基因表达。当细胞中导入与内源性mRNA编码区同源的双链RNA时，该mRNA发生降解而导致基因表达沉默[1] 。与其它基因沉默现象不同的是，在植物和線蟲中，RNAi具有传递性，可在细胞之间传播，此現象被稱作系統性RNA干擾(systemic RNAi)[2][3]。在秀丽隐杆线虫上实验时还可使子一代产生基因突变，甚到於可用喂食細菌給線蟲的方式讓線蟲得以產生RNA干擾現象。RNAi现象在生物中普遍存在。
RNAi与转录后基因沉默(post-transcriptional gene silencing and transgene silencing)在分子層次上被证实是同一种现象[來源請求]

应用RNAi在基因沉默(silent gene)方面具有高效性和简单性，所以是基因功能研究的重要工具。
大多数药物属于標靶基因（或疾病基因）的抑制剂，因此RNAi 模拟了药物的作用，这功能丢失（LOF)的研究方法比传统的功能获得（GOF)方法更具优势。因此, RNAi 在今天的制药产业中是药物靶标确认的一个重要工具。同时，那些在靶标实验中证明有效的siRNA/shRNA本身还可以被进一步开发成为RNAi药物。
在药物標靶发现和确认方面，RNAi技术已获得了广泛的应用。生物技术公司或制药公司通常利用建立好的RNAi文库来引入细胞，然后通过观察细胞的表型变化来发现具有功能的基因。如可通过RNAi文库介导的肿瘤细胞生长来发现能抑制肿瘤的基因[來源請求]。一旦所发现的基因属于可用药的靶标（如表达的蛋白在细胞膜上或被分泌出细胞外），就可以针对此靶标进行大规模的药物筛选。此外，被发现的靶标还可用RNAi技术在细胞水平或动物体内进一步确认[來源請求]。
在疾病治疗方面，双链小分子RNA或siRNA已被用于临床测试用于几种疾病治疗，如老年视黄斑退化、肌肉萎縮性側索硬化症、类风湿性关节炎、肥胖症等。在抗病毒治疗方面，帕金森病等神经系统疾病已经开始初步采用RNA干扰疗法。肿瘤治疗方面也已经取得了一些成果[17]。

RNAi是一种非常有前途的技术。难的是：
1。如何传送小块的RNA
到靶细胞（肝细胞）
2。副作用

ARC520旨在干扰乙肝病毒感染在肝细胞内复制。
计划在2013年开始第一期临床试验.

作者: cwy121 时间: 2012-6-7 18:50

回复 StephenW 的帖子

等到他弄成，咱们还有木有都难说。关键是歧视啊，先让我找个活干干啊，要不我等不到那一天啊

作者: 才易的生活 时间: 2012-6-7 19:05

回复 StephenW 的帖子

谢了，要是在中国临床能让我们报上名多好啊！

作者: cwy121 时间: 2012-6-7 22:49

这东西也是打针的，只要进入临床试验，那需要的时间不会很长。

作者: MP4 时间: 2012-8-11 01:03

http://www.arrowres.com/sites/de ... aper-hbv-3-7-12.pdf

作者: kaorusai 时间: 2012-8-26 13:21

回复 StephenW 的帖子

这种药物也是抑制病毒复制啊，有可能像核苷类药物那样耐药吗？

作者: StephenW 时间: 2012-8-26 13:35

本帖最后由 StephenW 于 2012-8-26 13:35 编辑

回复 kaorusai 的帖子

这种药物也是抑制病毒复制啊，有可能像核苷类药物那样耐药吗？是的，可以耐药.

我不是专家，我认为它可以针对RNA在几个地点，因此可以减少耐药性。最重要的是，它声称它也可以抑制乙肝表面抗原的生产.

RNAi最重要的问题是安全性.

作者: kaorusai 时间: 2012-8-28 08:46

回复 StephenW 的帖子

如果说治疗周期短，效力强，也不失为一个好的治疗方法

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