肝胆相照论坛

标题: ArrowHead计划于8月4号发布第三季度财报 [打印本页]

作者: crystalandtiger 时间: 2015-7-29 04:57 标题: ArrowHead计划于8月4号发布第三季度财报

订阅了ArrowHead公司的event邮件提醒，刚刚收到邮件，官网上已经公布说预计8月4号公布第三季度财报。按照之前的公告，这次应该是要公布3mg，4mg还有大猩猩的数据吧。大家一起来祈祷并谨慎乐观的希望有好的结果吧。珍惜健康，快乐生活。链接http://ir.arrowheadresearch.com/releasedetail.cfm?ReleaseID=924312
Arrowhead to Report Fiscal 2015 Third Quarter Financial Results
[p=18, null, center]- Conference Call Scheduled for Tuesday, August 4, 2015

[p=18, null, left]PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that it will report its financial results for the fiscal 2015 third quarter ended June 30, 2015, on Tuesday, August 4, 2015, at 4:30 p.m. EDT. Investors may access a live audio webcast on the Company's website at http://ir.arrowheadresearch.com/events.cfm. For analysts that wish to participate in the conference call, please dial 315-625-6887 and enter Conference ID 97375077.

[p=18, null, left]A replay of the webcast will be available on the company's website approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 3 days. To access the audio replay, dial 404-537-3406 and enter Conference ID 97375077.

翻译： ArrowHead将于2015年8月4日召开2015年第三季度（于2015年6月30日截止）财务报告
时间是2015年8月4日周二下午4：30 EDT. 现场Webcast地址：http://ir.arrowheadresearch.com/events.cfm.
会议录音在会议结束后两个小时也可以在公司官网上公布。听力好的战友可以积极参与。

作者: disan 时间: 2015-7-29 05:51

don't get too excited. i don't believe it's going to be AD day.

作者: crystalandtiger 时间: 2015-7-29 06:09

回复 disan 的帖子

哦，原来不是同一天呀，好吧

作者: disan 时间: 2015-7-29 06:33

回复 crystalandtiger 的帖子

You are too much concerned about the new drugs. Even they would got approved by FDA someday, it would be far far away.

Just enjoy life, and don't look back to this board; or just simply don't concern too much about them.

作者: Zongguoyiren 时间: 2015-8-4 15:27

今天的会议呢

作者: qixianwhz 时间: 2015-8-4 18:41

消息呢

作者: 战天斗hbv 时间: 2015-8-4 19:16

本帖最后由战天斗hbv 于 2015-8-4 19:17 编辑

qixianwhz 发表于 2015-8-4 18:41
消息呢

人家还没天亮
2015年8月4日周二下午4：30 EDT

作者: newchinabok 时间: 2015-8-4 21:18

战哥好久没来了，难道又去写论文去了？还是要经常来检查，指导我们这里工作，我们还指望你的推给我们推点好消息，你不来推，老王最近也没来搞破坏了，论坛有点冷清

作者: 战天斗hbv 时间: 2015-8-4 22:16

newchinabok 发表于 2015-8-4 21:18
战哥好久没来了，难道又去写论文去了？还是要经常来检查，指导我们这里工作，我们还指望你的推给我们推点好 ...

最近在准备课题项目论证、头很大、、、、、、birinapant最近有HIV治疗的方向

作者: 战天斗hbv 时间: 2015-8-4 22:19

本帖最后由战天斗hbv 于 2015-8-4 22:23 编辑

突然想问SW一个问题、澳洲人一般说的CI和PI是指什么？具体来说在一个项目中干嘛的？是Principal Investigator吗？另RF，research fellow就是指干活的吧？RF是项目中的博士研究生吗？

作者: 战天斗hbv 时间: 2015-8-4 22:20

澳洲人说的这两个缩写和欧美似乎不是一个意思、我不能很深刻的理解这两个职位的具体含义

作者: StephenW 时间: 2015-8-4 22:31

回复战天斗hbv 的帖子

CI, PI, RF - context?

作者: 战天斗hbv 时间: 2015-8-4 23:33

StephenW 发表于 2015-8-4 22:31
回复战天斗hbv 的帖子

CI, PI, RF - context?

research proposal

作者: 42年才知道 时间: 2015-8-5 00:27

做到三期了，不成功则成仁，药物研发就是这么残酷。

作者: StephenW 时间: 2015-8-5 04:08

回复战天斗hbv 的帖子

PI - Principal Investigator
CI - (CO-PI) Co-Investigator
or
CI- Chief Investigator
PI - Partner Investigator

作者: disan 时间: 2015-8-5 04:08

AD day Sept 24

作者: StephenW 时间: 2015-8-5 04:16

Arrowhead Reports Fiscal 2015 Third Quarter Financial Results

- Conference Call and Webcast Today at 4:30 p.m. EDT

PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Research Corporation (NASDAQ: ARWR) today announced financial results for its fiscal 2015 third quarter ended June 30, 2015. The company is hosting a conference call at 4:30 p.m. EDT to discuss results.

Conference Call and Webcast Details

Investors may access a live audio webcast on the Company's website at http://ir.arrowheadresearch.com/events.cfm. For analysts that wish to participate in the conference call, please dial 315-625-6887 and enter Conference ID 97375077.

A replay of the webcast will be available on the company's website approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 3 days. To access the audio replay, dial 404-537-3406 and enter Conference ID 97375077.

Fiscal 2015 Third Quarter and Recent Company Highlights

ARC-520

Received regulatory permission to initiate three multiple-dose Phase 2b studies in the United States (Heparc-2004) and in Germany and Hong Kong (Heparc-2002 and 2003)
Completed dosing of four cohorts in a single-dose Phase 2a study (Heparc-2001) and expanded the study to include three additional cohorts
Completed dosing in a non-clinical study in chronically infected chimpanzees that spanned more than a year
Highlights of the Phase 2a and chimpanzee studies to be presented at an analyst day planned for September 24, 2015

ARC-AAT

Met the dosing target for Part A of the ARC-AAT Phase 1 study in healthy volunteers, and transitioned the study into Part B which is designed to enroll patients with PiZZ genotype alpha-1 antitrypsin deficiency
Began dosing Part B of the Phase 1 study at one site in Australia
Gained regulatory clearance to expand Part B of the Phase 1 study to allow additional sites in the United Kingdom and New Zealand
Gained Orphan Drug Designation from the United States Food and Drug Administration

Platform and Early Pipeline

Published data on advances being made in a subcutaneously administered formulation of the Dynamic Polyconjugate (DPC) delivery system
Presented preclinical data on ARC-F12, a potential new candidate targeting coagulation factor 12 for the potential treatment of hereditary angioedema and thromboembolic diseases

Selected Fiscal 2015 Third Quarter Financial Results
ARROWHEAD RESEARCH CORPORATION
CONSOLIDATED CONDENSED FINANCIAL INFORMATION (unaudited)

Three Months Ended June 30, Nine Months Ended June 30,

OPERATING SUMMARY
      2015             2014             2015             2014

REVENUE $ 123,750

$

43,750
$ 338,250 $ $131,250
OPERATING EXPENSES
Research and development 7,490,400 6,392,200 36,877,925 14,719,739
Acquired in-process research and development - - 10,142,786 -
Salaries and payroll-related costs 3,570,531 2,454,449 10,262,799 7,634,142
General and administrative expenses 1,829,393 1,582,465 5,612,219 3,865,845
Stock-based compensation 2,486,074 2,038,682 6,706,009 3,758,264
Depreciation and amortization       741,058             276,054             1,480,656             1,075,238
TOTAL OPERATING EXPENSES 16,117,456 12,743,850 71,082,394 31,053,228
OPERATING LOSS       (15,993,706 )       (12,700,100 )       (70,744,144 )       (30,921,978 )
OTHER INCOME/(EXPENSE)       57,653             1,073,649

      3,546,398             (5,372,902 )
NET LOSS $ (15,936,053 ) $ (11,626,451 ) $ (67,197,746 ) $ (36,294,880 )

EARNINGS PER SHARE (BASIC AND DILUTED): $ (0.27 ) $ (0.22 ) $ (1.19 ) $ (0.81 )
WEIGHTED AVERAGE SHARES OUTSTANDING       59,492,867             51,931,989             56,631,297             44,565,008


FINANCIAL POSITION SUMMARY
June 30, March 31,
      2015             2015
CASH AND CASH EQUIVALENTS $ 87,252,813 $ 96,447,301
SHORT AND LONG-TERM INVESTMENTS       24,365,922             31,922,240
TOTAL CASH RESOURCES (CASH, CASH EQUIVALENTS, INVESTMENTS) 111,618,735 128,369,541
OTHER ASSETS       33,571,590             34,008,917
TOTAL ASSETS $ 145,190,325       $ 162,378,458
TOTAL LIABILITIES $ 14,445,931 $ 18,182,104
TOTAL STOCKHOLDERS' EQUITY       130,744,394             144,196,354
TOTAL LIABILITIES AND STOCKHOLDERS' EQUITY $ 145,190,325       $ 162,378,458

SHARES OUTSTANDING 59,498,362 59,435,862
PROFORMA SHARES OUTSTANDING (INCLUDING CONVERSION OF PREFERRED SHARES) 62,169,352 62,106,852

About ARC-520

Arrowhead's RNAi-based candidate ARC-520 is being investigated in the treatment of chronic HBV infection. The small interfering RNAs (siRNAs) in ARC-520 intervene at the mRNA level, upstream of the reverse transcription process where current standard of care nucleotide and nucleoside analogues act. Arrowhead is investigating ARC-520 specifically, to determine if it can be used to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without sero-conversion. Arrowhead has completed a Phase 1 single ascending dose study in normal volunteers and the company is conducting single dose Phase 2a studies and multiple dose Phase 2b studies in chronic HBV patients. Approximately 350-400 million people worldwide are chronically infected with the hepatitis B virus, which can lead to cirrhosis of the liver and is responsible for 80% of primary liver cancers globally.

About ARC-AAT

Arrowhead's ARC-AAT is being investigated for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease that severely damages the liver and lungs of affected individuals. The mean estimated prevalence of AATD in the U.S. is 1 per 3000-5000, or approximately 100,000 patients. AATD is also an important cause of pediatric liver disease with an estimated prevalence in children of approximately 20,000 patients, and 50-80% likely to manifest liver disease during childhood. It is a rare disease that appears to be frequently misdiagnosed or undiagnosed. ARC-AAT, which was granted orphan drug designation, employs a novel unlocked nucleobase analog (UNA) containing RNAi trigger molecule designed for systemic delivery using the Dynamic Polyconjugate™ delivery system. ARC-AAT is highly effective at knocking down the Alpha-1 antitrypsin (AAT) gene transcript and reducing the hepatic production of the mutant AAT (Z-AAT) protein in animal models. Reduction of liver production of the inflammatory Z-AAT protein, which is believed to be the cause of progressive liver disease in AATD patients, is important as it is expected to halt the progression of liver disease and potentially allow fibrotic tissue repair. Arrowhead is conducting a single dose Phase 1 clinical study of ARC-AAT, with part A in healthy volunteers and part B in AATD patients

作者: StephenW 时间: 2015-8-5 04:17

箭头报告财政2015年第三季度财务业绩

- 电话会议和网络直播今天在4:30 pm EDT

加利福尼亚州帕萨迪纳 - （BUSINESS WIRE） - 箭头研究公司（纳斯达克股票代码：ARWR）今天公布的财务业绩。截至6月30日的2015年财政年度第三季度，2015年该公司被托管在4:30 pm EDT到电话会议讨论的结果。

电话会议和网络直播详情

投资者可访问本公司网站现场录音网络直播在http://ir.arrowheadresearch.com/events.cfm。对于那些希望参加本次电话会议的分析师，请拨打315-625-6887，并输入会议ID 97375077。

该网络广播的重播将在该公司的网站上的通话结束后大约两小时，将保持可用90天。音频重播也将是可利用的呼叫结束后约两小时，将可为3天。要访问音频重播，请拨打404-537-3406，并输入会议ID 97375077。

2015年财政年度第三季度及近期公司亮点

ARC-520

获得监管部门批准启动三个单项剂量阶段2b研究在美国（Heparc-2004）在德国和香港（Heparc，2002年和2003年）
四个同伙在单剂量2a期研究（Heparc-2001）完成计量，并扩大了研究，包括另外三个同伙
完成加药在非临床研究慢性感染的黑猩猩跨过了一年多
2a期和黑猩猩研究的亮点在分析师日计划于2015年9月24日提交

ARC-AAT

达到了定量目标在健康志愿者的ARC-AAT 1期研究的一部分，并在过渡到研究B部分，其目的是招收患者的基因型PiZZ组α-1抗胰蛋白酶缺乏症
开始给药的1期研究的B部分在澳大利亚一个网站
获得监管部门的批准，以扩大第一阶段研究的B部分，允许在英国和新西兰的其他网站
从美国食品和药物管理局获得孤儿药

平台和早期流水线

正在取得动态Polyconjugate（DPC）递送系统的皮下给药制剂上的进步已发布数据
上的ARC-F12呈现临床前数据，一个潜在的新的候选靶向凝血因子12，用于遗传性血管水肿和血栓栓塞性疾病的潜在治疗

选择2015年财年第三季度财务业绩
箭头研究有限公司
简明综合财务资料（未经审计）

三个月截至6月30日，九个月截至6月30日，

操作总结
2015年2014年2015年2014年

收入123750美元

$

43,750
338250美元$131250美元
营业费用
研发7490400 6392200 36877925 14719739
收购过程中的研究开发 - - 10142786 -
工资和工资有关的费用3570531 2454449 10262799 7634142
总务和行政支出1829393 1582465 5612219 3865845
基于股票的补偿2486074 2038682 6706009 3758264
折旧和摊销741058 276054 1480656 1075238
总经营费用16117456 12743850 71082394 31053228
经营亏损（15993706）（12700100）（70744144）（30921978）
其他收入/（费用）57653 1073649

3546398（5372902）
净亏损$（15936053）$（11626451）$（67197746）$（36294880）

每股收益（基本及摊薄）：$（0.27）$（0.22）$（1.19）$（0.81）
加权平均流通股59492867 51931989 56631297 44565008

财务状况摘要
6月30日，3月31日，
2015年2015年
现金及现金等价物87252813美元96447301美元
短期和长期投资24365922 31922240
现金资源总额（现金，现金等价物，投资）111618735 128369541
其他资产33571590 34008917
总资产145190325美元162378458美元
总负债14445931美元18182104美元
股东权益合计130744394 144196354
负债和股东权益145190325美元162378458美元

流通股59498362 59435862
PROFORMA流通股（优先股转换包括）62169352 62106852

关于ARC-520

箭头的基于RNAi的候选人ARC-520正在调查慢性HBV感染的治疗。小干扰RNA（siRNA）的ARC-520介入在mRNA水平，反转录过程，其中护理核苷酸的目前标准和核苷类似物起作用的上游。箭头正在调查的ARC-520具体地，以确定它是否可用于实现一个功能的治疗，这是其特征在于由乙肝表面抗原阴性血清或无血清转化的免疫clearant状态。箭头已经完成了正常的志愿者一期单剂量递增研究，该公司正进行单剂量2a期研究和多次给药阶段2b研究慢性乙肝患者。全世界大约350-400百万人慢性感染了乙肝病毒，其可以导致肝硬化，并负责全球80％的原发性肝癌。

关于ARC-AAT

箭头的ARC-AAT正在调查与α-1抗胰蛋白酶缺乏症（AATD），一种罕见的遗传性疾病，严重损害肝脏和受影响的个人相关的肺部肝脏疾病的治疗。 AATD在美国的平均估计流行是1元3000-5000，或约100,000名患者。 AATD也是儿科肝脏疾病具有在大约20,000例儿童估计流行的重要原因，而50-80％可能在儿童时期体现肝病。这是似乎经常被误诊或未确诊的一种罕见的疾病。 ARC-AAT，这是理所当然的孤儿药，含员工触发的RNAi分子设计为使用动态Polyconjugate™输送系统的全身交付一个新的解锁碱基类似物（UNA）。 ARC-AAT是在撞倒的α-1抗胰蛋白酶（AAT）基因转录物和降低肝生产突变的AAT（Z-AAT）蛋白在动物模型中非常有效。减少肝脏产生的炎症的Z-AAT旦白，这被认为是进行性肝脏疾病中AATD患者的原因的，是非常重要的，因为它是预期阻止肝脏疾病的进展，并且可能允许纤维化组织修复。箭头正在进行ARC-AAT单剂量期临床研究中，A部分在健康的志愿者和部分B AATD患者

作者: qixianwhz 时间: 2015-8-5 08:28

啥意思，有没有戏？

作者: Zongguoyiren 时间: 2015-8-5 09:00

9月24日公布2a期和黑猩猩数据？

作者: Zongguoyiren 时间: 2015-8-5 09:01

时间又推移了

作者: disan 时间: 2015-8-5 09:01

本帖最后由 disan 于 2015-8-5 09:20 编辑

回复 Zongguoyiren 的帖子
时间又推移？这话从何说起？

作者: 战天斗hbv 时间: 2015-8-5 09:48

能否解读一下

作者: disan 时间: 2015-8-5 10:36

Conference Call Transcript 可以下载了，有心的人可以去下载看看。
基本就是解释几个实验都怎么设计的，确认AD日9月24。
回答问题时间很短，没几个问题CEO就主动结束，AD日见。

作者: disan 时间: 2015-8-5 10:41

忘了说，这次CC又拽词了，这次有个实验是什么Monarch，就好像打游戏最后阶段打大Boss阶段，反正现在还在讨论Function Cure。

作者: jaylongli 时间: 2015-8-5 12:27

感觉又是忽悠投资人的把戏，没有结果

作者: jaylongli 时间: 2015-8-5 12:29

回复 StephenW 的帖子

辛苦了，这么早来更新信息，感谢

作者: tonychant 时间: 2015-8-5 12:34

jaylongli 发表于 2015-8-5 12:27
感觉又是忽悠投资人的把戏，没有结果

同意，可以明确这个药物黄了，不能根治。可笑的是Benitec Co. Ltd和Tekmira Pharmaceuticals还在接着忽悠圈钱。

作者: 相信会幸福 时间: 2015-8-5 12:47

不能根治没什么啊
关键是会不会降低S抗原，能降低多少，降低后能保持否

作者: crystalandtiger 时间: 2015-8-5 13:48

回复 disan 的帖子

Some of what we have learned was rather surprising to us and our advisors. We believe that our work represents a real advance for the HBV field and has helped us move our program forward. We have lined up a panel of international experts to talk about the HBV field and how our new data may challenge some widely accepted theories.
发现了一些很意外的数据....挑战被广泛接受的观点。感觉好像不乐观，是不是咱们之前讨论的那个关于转阴的理论假设被实验推翻了呀。

作者: mingbai 时间: 2015-8-5 17:22

公布结果的时间一再推迟，到了9月4日，会不会又是一些含糊的说辞，让人还是不清楚它成功了没有？怎么感觉像中国的研究报告，给人不踏实的感觉。请大神们解读一下。

作者: StephenW 时间: 2015-8-5 18:30

"We think the format of an analyst day will allow us to provide a more
comprehensive overview of what we are learning than if we simply provided top
line results in a press release. Some of what we have learned was rather surprising
to us and our advisors. We believe that our work represents a real advance for the
HBV field and has helped us move our program forward. We have lined up a panel
of international experts to talk about the HBV field and how our new data may
challenge some widely accepted theories. These panelists include Dr. Robert Gish,
Dr. Stephen Locarnini, and Dr. Robert Lanford. The live event for institutional
investors and analysts will be held in New York City. In addition, it will be
webcast live and available on the Arrowhead website. We will provide more
information about the event as the date approaches. We are also happy to
announce that reports from the chimp study will be presented at AASLD in
November."

我们认为，一个分析师日的格式将使我们能够提供更
我们正在学习，如果我们只是提供了比前全面概述
线导致的新闻稿。一些我们所学是相当令人吃惊
我们和我们的顾问。我们相信，我们的工作是一个真正的提前为
HBV领域，帮助我们推动我们前进的程序。我们已经列队面板
国际专家来谈谈乙肝病毒领域以及如何我们的新的数据可
挑战一些被广泛接受的理论。这些小组成员包括罗伯特·吉什博士，
斯蒂芬博士Locarnini，和罗伯特·兰福德博士。本次现场活动的机构
投资者和分析师将在纽约市举行。此外，这将是
网络直播和可用的箭头网站上。我们将提供更多
有关事件的最新方法的信息。我们也很高兴
宣布从黑猩猩的研究报告将在AASLD在提交
十一月。

作者: StephenW 时间: 2015-8-5 18:35

Dr Stephen Locarnini - 一个非常著名的澳大利亚HBV科学家
Dr Robert Gish - 一个非常著名的美国HBV医生，乙型肝炎基金会顾问
Dr Robert Lanford - 他做了GS9620黑猩猩研究.

作者: disan 时间: 2015-8-5 23:13

本帖最后由 disan 于 2015-8-6 01:29 编辑

回复 crystalandtiger 的帖子

我也很是有点怀疑。我感觉他们还没在人身上找到功能性治愈。但是也有希望
设计了2001到2008不同的实验。

具体还要看黑猩猩的数据，只要有黑星星有FC或者接近FC就好。

题外话。这是第一次确定AD日发布黑猩猩数据，何来又推迟一说？

在别的版乱说也就够了，在学术版乱传一气，我是够了。。。不能认真我只能这么跟自己说。

有认真的事讨论你私信我吧。。。

作者: StephenW 时间: 2015-8-6 21:09

德克Haussecker（作者）是一个投资者，而不是乙肝病毒专家，他是RNAi专家

Thursday, August 6, 2015
Arrowhead Research Believes ARC520 Ready to Shine

On Tuesday, Arrowhead Research announced further pipeline expansion with ARC-F12 chosen to become its third DPC-based clinical RNAi candidate, this time for the treatment of hereditary angioedema.

Although this could have been used by the company as an opportunity to distract investor attention from the mechanistically riskier lead HBV program for which a much-anticipated Analyst Day is coming up on September 24, Arrowheadd chose to spend most of its earnings call on HBV-targeting ARC520.

To sum it up, the company said that it now believes that it has gathered sufficient insights into HBV biology and ARC520 action that it is ready to take on the functional cure challenge to be tested in a key upcoming phase IIb (multi-dose!) combination study of ARC520 with other HBV-agents, dubbed the MONARC(H) study.

Knockdown at low doses below expectations

To wit, early results from ARC520 in HBV patients late last year has caused much investor angst and anger triggering a couple of 'I-don't-take-reponsbility-for-my-investment-decisions' lawsuits alleging the company of having set expectations too high

Well, they accuse management of 'over-promising', but since when is this illegal anyway; would recommend paying attention to the forward-looking statement safe harbor once in while).

Accordingly, at 2mg/kg, there was ‘only’ a, albeit rapid and prolonged ~50% knockdown of the HBV surface antigen (HBsAg) following a single dose of ARC520.

This was also below my expectations not only based on the preclinical data, including data from a single chimpanzee in 2013, but also data from its other DPC-based development programs in what should otherwise be highly predictive monkey models.

Hepatitis e-antigen coming into focus

HBV biology is complex, and one of the attractions of an RNAi approach for HBV is that it can target the expression of not just one gene, but all of the gene products.  This raises the hope that as more recent interferon-nuke combination studies show that HBV might be more vulnerable than previously thought when tackled in the proper sequence and in right combination that a pan-mRNA targeting agent might mess up HBV enough so that an effective T-cell response can be mounted against it.

Arrowhead has thus started to emphasize that it is not just targeting immune suppressive HBsAg, but also other HBV gene products.  At the same time, the clinical development program has strongly shifted from e-antigen negative chronic HBV patients in the single-dose Hong Kong study (Heparc 2002 1-4mg/kg) to e-antigen positive HBV patients in the imminent multi-dose studies in the US, Europe, and Asia.

Since you would expect single-dose data in e-antigen positive patients to be desirable before multi-dose studies from a regulatory/safety and scientific point-of-view, it is my expectation that at least some of the newly added 3 cohorts in the HK 2002 study involve e-antigen positive patients (most likely single-dose).

Is it possible that the e-antigen is playing a more prominent role in immune evasion than previously thought and that the e-antigen positive state of the one chimpanzee (which also did not receive concomitant nukes) facilitated the chimpanzee apparently mount a desired immune response?

E-antigen a natural candidate for being immune suppressive

When considering the natural history of HBV infection, HBeAg stands out as the natural candidate for serving an immune suppressive role.

First of all, unlike HBsAg, HBeAg is not required for HBV replication and spread per se.  In fact, most people lose it during the course of their infection and continued viral replication.  Since immune evasion is the 3rd most important task of a successful virus next to replication and spread, this would be the expected task of HBeAg.

Also remember that the HBV population can be broadly divided into two buckets.  In the first, young (typically Asian) people are infected around birth or early childhood.  It is highly interesting that they are in an immune tolerant state for a number of years, meaning that the virus can replicate to high titers yet is not seen by the immune system.

They also happen to be e-antigen positive during this period.

As they, however, enter adulthood, most develop chronic hepatitis reflected by flares in liver enzymes.  This is also the time when some of them either clear the virus or enter the e-antigen negative state.

This is consistent with e-antigen serving an immune suppressive role, yet when it disappears or it becomes ineffective in serving such a role due to changes in the state of the ageing immune system, it becomes a liability and those viruses without it (e-antigen negative) take over (and HBsAg takes over in serving the main immune suppressive function).

It is interesting to speculate that an agent like ARC520 might be most successful in this young population.

In the Western world meanwhile it is in adulthood that people become infected with HBV.  Although this is a surprisingly understudied area, it is my understanding from the literature that it is only HBeAg positive strains that can establish an infection.  Although the vast majority (~90%) of those exposed to HBV in adulthood go through an acute (some fulminant) hepatitis episode and clear the virus, successful chronic infection persists in ~10%.  Many of these will go on to seroconvert to e-antigen and become e-antigen negative.

The strict requirement for HBeAg in establishing an infection also in adulthood further strongly supports a key immune suppressive role for this protein.

Expectations for Analyst Day and beyond

With the above in mind, let’s speculate what might play out at Analyst Day and beyond.

On September 24, the company wants to present more or less complete data from the Heparc2002 HK study, including the unblinded results from the single-dose 3-4mg/kg cohorts and from 2 if not 3 of the newly added cohorts (note: one cohort is blinded so I am not sure whether there is enough time to gather the results for this event- hence two cohorts that are open-label).

As indicated above, I expect the new cohorts to involve e-antigen positive patients and to be single-dose.

For the 3-4mg/kg cohort, my hope is that they will reach an HBsAg knockdown of around 80%.  Keep in mind, this is single-dose.

The much more important data, however, should come from the yearlong study in 8 chimpanzees the existence of which the company disclosed a quarter ago.  Arrowhead Research is now saying that it has learned a lot from these to guide them in their crucial upcoming combination studies.

While I hate to set overly ambitious expectations for the chimpanzee results, also in light of the fact that functional cures (=s-antigen negative/seroconversion) are known to often occur long after interferon treatment (the only agent known to facilitate meaningful functional cure rates), it is my hope that they provide strong indications as to which treatment strategy, including combinations (nukes, interferons) e-antigen positive/negative state, immune tolerant/silent/active, will lead to functional cures.

It is worth keeping in mind that with 8 chimpanzees this is an ambitious task considering the potentially many variables, but when do you get the chance to test your drug in 8 chimpanzees anyway?

The tremendous upside, of course, is that if these studies indeed provide a clear path forward, the ‘theory risk’ of the ARC520 program will have been reduced tremendously given that HBV infection is essentially the same in chimpanzees and humans.

The final validation would then come from the multi-dose MONARC(H) study which should get underway in early 2016.  Here, Arrowhead Research will test ARC520 (taking foot off immune brake) in combination with likely first either nukes or (immune booster) interferon.  Arrowhead has also noted in the conference call that it has given ‘a lot of thought’ to combining ARC520 with other, likely investigational agents, but that given the early-stage nature of those, these might be few and far between.

The kicker is that these studies are open-label and flexible in their design so that the company can learn and adjust in real-time just as Pharmasset had done in developing fabled HCV blockbuster Sovaldi.

From a stock perspective, Arrowhead Research might be a year or so away from where comparable companies in the HCV space before (Vertex, Pharmasset) had been valued considerably higher before.

Disclosure: long ARWR. Here's why.

Market cap: $400M,

Growing pipeline (ARC520, ARC-AAT, ARC-F12)

RNAi delivery platform with broadest potential

Strong platform technology safety profile, including 6-9 month rat/monkey

Strong knockdown efficacy in non-human primates and apparently humans (à AAT)

Strong platform IP, including assets from Roche, Novartis, and others (àlow royalty
payments)

HBV and AAT first-mover (IP, including regarding combinations, and natural combo partner).

Hungry and capable management and scientific teams.

Invest at your own risk.
Posted by Dirk Haussecker at 4:12 AM Email

作者: StephenW 时间: 2015-8-6 21:09

周四2015年8月6日
箭头研究认为ARC520准备闪耀

周二，箭头研究进一步宣布扩大管道与ARC-F12选择成为其第三DPC为基础的临床候选的RNAi，这次遗传性血管性水肿的治疗。

虽然这可能已被用于该公司为契机，以分散投资者的注意力从机制上风险较高的铅HBV程序，其中一个万众瞩目的分析师日是9月24日即将到来，Arrowheadd选择如何度过最HBV-在其财报电话会议中针对ARC520。

概括起来，该公司表示，它现在认为它已经聚集足够的见解乙肝病毒生物学和ARC520的行动，这是准备采取功能性治愈挑战的关键即将到来的IIb期进行测试（多剂量！） ARC520的组合研究与其他乙肝病毒药物，被称为MONARC（H）的研究。

击倒在低剂量低于预期

要机智，从早期的ARC520结果乙肝患者去年年底已经引起了很多投资者的焦虑和愤怒引发了几个“我 - 不要通吃reponsbility换我的投资，决定”的诉讼，指控该公司具有集期望值过高

那么，他们指责“过度看好”的管理，但由于当反正这是非法的;建议在同时注意前瞻性陈述避风港一次）。

因此，在为2mg / kg时，出现了“仅”一，尽管HBV表面抗原（HBsAg）以下ARC520单剂量的快速和长期的〜50％击倒。

这也低于我的预期不仅是基于临床前数据，包括在2013年从单一的黑猩猩的数据，而且在什么原本应该是高度预测模型猴从其他DPC发展方案的数据。

乙型肝炎e抗原成为焦点

HBV的生物学是复杂的，并且对的RNA干扰方法的HBV景点之一是它可以针对不只是一个基因的表达，但所有的基因产物。这就提出了一个希望，因为最近的干扰素结合核弹研究表明，乙肝病毒可能是当一个泛基因靶向代理可能搞砸了HBV足以使一个有效的T在正确的顺序和正确的组合解决比以前认为的更加脆弱胰岛β细胞的反应可以安装反对。

箭头就此开始强调，它不只是针对免疫抑制的HBsAg，而且其他的HBV基因产物。与此同时，临床开发计划已经从强e抗原阴性的慢性乙肝患者在转移单剂量香港研究（Heparc 2002 1-4mg /公斤），以e抗原阳性乙肝患者在即将多剂量研究在美国，欧洲和亚洲。

因为你会期望在e抗原阳性患者单剂量的数据是从视点调节/安全和科学的多剂量研究之前可取的，这是我的期望，至少有一些新加入的3同伙2002年香港的研究涉及到e抗原阳性患者（最有可能的单剂量）。

是否有可能在e抗原是打在免疫逃避更突出的作用比以前认为的那一个黑猩猩的e抗原阳性的状态（其中还没有收到伴随核武器）促进了黑猩猩显然安装所需的免疫反应？

e抗原为是免疫抑制一个自然的候选

当考虑HBV感染的自然史，大三阳脱颖而出，成为天然的候选服务的免疫抑制的作用。

首先，不像的HBsAg，HBeAg的不需要HBV复制和传播本身。事实上，大多数人的感染和病毒的不断复制的过程中失去它。由于免疫逃避是复制和传播旁边一个成功的病毒本周最重要的任务，这将是大三阳的预期任务。

还记得那乙肝人群大致可分为两个水桶。在第一阶段，年轻的（通常是亚洲）人感染出生时或儿童早期周围。这是非常有趣的是，它们在免疫耐受状态的数年，这意味着该病毒可以复制到高滴度还是没有看到由免疫系统。

他们也正好是e抗原，在此期间积极。

因为他们，但是，进入成年，大部分发展成慢性肝炎在肝酶耀斑体现。这也是当他们中的一些或者清除病毒或者进入e抗原阴性状态的时间。

这是符合e抗原服务的免疫抑制的作用，然而，当它消失或变得无效服务这样的角色变化引起的老化免疫系统的状态时，它变成负担和这些病毒没有它（电子抗原阴性）接管（与HBsAg接管在服务的主要免疫抑制功能）。

有趣的是猜测，像ARC520的代理可能是最成功的在这个年轻的群体。

在西方世界，同时它是在成年的人感染乙肝病毒。虽然这是一个令人惊讶的充分研究区域，它是从文献，这是唯一的HBeAg阳性菌株可建立一个感染我的理解。虽然这些在成年期暴露于乙肝病毒的绝大多数（〜90％），通过一种急性（暴发型一些）肝炎发作和清除病毒，成功的慢性感染坚持〜10％。许多这些将前往血清转化为e抗原，成为e抗原阴性。

在成年后建立感染也严格要求大三阳进一步强烈支持这种蛋白质的主要免疫抑制的作用。

预期分析师日及以后

随着上述考虑，我们推测可能是什么发挥出在分析师日及以后。

9月24日，该公司希望从目前的Heparc2002香港研究或多或少完整的数据，包括从单剂量的非盲结果3-4mg / kg的同伙，并从2，如果新加入的同伙不是3（注：一种队列被蒙蔽，所以我不知道是否有足够的时间来收集结果该事件 - 因此两个队列打开的标签）。

正如上面所指出的，我希望新的同伙涉及e抗原阳性患者，并为单剂量。

为3-4mg / kg群组，我的希望是，他们将达到约80％的乙肝表面抗原击倒。请记住，这是单剂量。

在更为重要的数据，但是，应该来自为期一年的研究中黑猩猩8其中公司披露季度前的存在。现在箭头研究是说，它已经学会了很多从这些来指导他们在即将到来的关键组合研究。

虽然我讨厌设置过于雄心勃勃期望黑猩猩的结果，也是在光的事实，即功能性治愈（= S-抗原阴性/血清转换）是已知的干扰素治疗（称为促进有意义的功能治愈的唯一代理后，经常出现长率），这是我的希望，他们提供了强有力的迹象表明哪个治疗策略，包括组合（核武器，干扰素）e抗原阳性/阴性状态，免疫耐受/静音/主动，会导致功能治愈。

这是值得铭记，与8黑猩猩，这是一个雄心勃勃的任务，考虑到潜在的诸多变数，但是当你有机会反正来测试你的药在8黑猩猩？

当然的巨大上攻，是，如果这些研究确实提供了一个清晰的路径前进，所述ARC520程序的“理论风险”将减少大大鉴于HBV感染是基本上在黑猩猩和人类相同。

最终验证然后将来自多剂量MONARC（H）研究，应该进行在2016年年初在这里，箭头研究将测试ARC520（以脚离开刹车免疫）联合可能首先无论是核武器或（免疫助推器）干扰素。箭头还注意到在电话会议中，它已经给'了不少心思“来ARC520与其他可能的研究性药物结合，但鉴于这些早期阶段的性质，这可能是寥寥可数。

最厉害的是，这些研究是开放性和灵活的设计，使公司可以学习和调整实时就像Pharmasset开发传说中HCV大片Sovaldi做了。

从股票的角度来看，箭头研究可能是一年左右的车程从那里可比公司（顶点，Pharmasset）前HCV空间已被估价相当高了。

披露：长ARWR。这里的原因。

市值：4亿美元，

越来越多的管道（ARC520，ARC-AAT，ARC-F12）

RNA干扰交付平台与广泛的潜力

强大的平台技术的安全性，其中包括6-9个月的大鼠/猴

在非人灵长类强击倒效力和明显人类（单AAT）

强大的平台IP，包括罗氏，诺华公司的资产，和其他人（àlow版税
金）

HBV和AAT先发（IP，包括有关的组合，和自然组合的合作伙伴）。

饥饿和精干的管理和科学的团队。

在投资风险自负。
发贴者德克Haussecker在上午04时12分通过电子邮件

作者: 155190384 时间: 2015-8-6 22:14

有看，没懂!

作者: 中国先生ws 时间: 2015-8-6 23:23

回复 StephenW 的帖子

您觉得这算好消息还是坏消息？我看不太懂

作者: StephenW 时间: 2015-8-6 23:32

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德克推测arc520可能用于治疗大三阳患者

作者: 中国先生ws 时间: 2015-8-7 00:11

回复 StephenW 的帖子

520不是作用于基因沉默吗？为什么会区分大三阳和小三阳？

作者: 战天斗hbv 时间: 2015-8-7 00:20

中国先生ws 发表于 2015-8-7 00:11
回复 StephenW 的帖子

520不是作用于基因沉默吗？为什么会区分大三阳和小三阳？ ...

同问

作者: disan 时间: 2015-8-7 01:07

520作用于基因沉默，但是最终依靠免疫唤醒达到功能性治愈。
e+被认为有可能免疫唤醒。

作者: disan 时间: 2015-8-7 05:13

１）假设德克的猜想是正确的，说５２０可能治愈大三阳。
２）财报会议记录的说法也解释过去：We have lined up a panel of international experts to talk about the HBV field and how our new data may challenge some widely accepted theories.
发现了一些很意外的数据....挑战被广泛接受的观点。

就是说过去小三阳被认为好事，对比大三阳来说；现在根据５２０的数据，其实大三阳才表明免疫系统还有救？

拭目以待吧。

作者: 相信会幸福 时间: 2015-8-7 09:45

520是降s抗原的，会不会因为大三阳一般S抗原高，所以降得效果才显著
而小三阳很低，所以效果就不明显了…

作者: disan 时间: 2015-8-7 09:50

相信会幸福发表于 2015-8-7 09:45
520是降s抗原的，会不会因为大三阳一般S抗原高，所以降得效果才显著
而小三阳很低，所以效果就不明显了… ...

520全降。。。不仅是S抗原。E抗原DNA都降。只是已发布数据的实验设计目的是S抗原的降幅，没强调其它。事实上，全降。

作者: 相信会幸福 时间: 2015-8-7 09:55

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其实对这个药期待蛮大的
不期望完全治愈，比现在的药更先进一点，就可以
当然，如果能实现FC，我就是倾家荡产也是要治疗的

作者: disan 时间: 2015-8-7 10:40

相信会幸福发表于 2015-8-7 09:55
回复 disan 的帖子

其实对这个药期待蛮大的

有没有想过终极目的？
不管怎样，如果治疗可以达到和非乙人肝硬化肝癌期望值一样，FC不FC又有什么不一样？
反过来，如果FC了，肝硬化肝癌的几率和治愈前一样，FC又有什么用呢？

作者: qixianwhz 时间: 2015-8-7 10:56

只要和正常人一样就可以了主要得了乙肝对未知的恐惧压力很大

作者: jaylongli 时间: 2015-8-7 12:31

qixianwhz 发表于 2015-8-7 10:56
只要和正常人一样就可以了主要得了乙肝对未知的恐惧压力很大

实话，不知道将来发生什么，恐惧害怕

作者: tonychant 时间: 2015-8-7 13:01

既然e抗原与免疫抑制有关，为何临床上治疗后e抗原转换了停药了也没看到病毒根治啊？停药了还反弹？

作者: 相信会幸福 时间: 2015-8-7 14:35

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怎么可能没想过完全治愈呢
可是一次次…已经没那么贪心了
能和正常人一样，就好
这个病压力太大了

作者: StephenW 时间: 2015-8-7 17:17

回复中国先生ws 的帖子

520不是作用于基因沉默吗？为什么会区分大三阳和小三阳？

箭头相信ARC520可以沉默 s(surface)-基因, c(core)-基因, pgRNA-基因(?).
此前强调减少表面抗原,导致治愈.
但减少e抗原, 一些科学家认为应导致e转阴(大三阳变小三阳) - 所以这也许一可能性, 新的临床试验的患者包括大三阳患者.

但我的意见，也存在一些问题:
1.大三阳患者可以自然成为小三阳, 必须证明只由于arc520;
2.小三阳患者, ARC520沉默 c(core)-基因, 可以导致HBeAg阴性肝炎吗?!
3. 此前选择小三阳患者, 加ETV - 任何ALT升高(表面抗原减少,免疫作用), 可以归因于ARC520.

作者: 重韧 时间: 2015-8-16 17:20

大家9月24号晚间就应该能得到消息了，一个多月的时间没办法。也只能等了。

作者: 重韧 时间: 2015-8-16 17:27

回复 tonychant 的帖子

前面查了一下 Benitec Co. Ltd 是真的没什么戏，2009年就说用RNAI 技术来研究乙肝，结果也是屁都没有。 Tekmira Pharmaceuticals 到是我觉得能看好的公司，因为不仅仅是RNAI的技术，重要的吸收了ONCORE 的生物制药，这个比较的重要。。所以现在就看。9月24号，520能公布什么样的数据，在到美肝年会的时候就完全知道这个药还有没有戏。

作者: jaylongli 时间: 2015-8-16 23:59

回复重韧的帖子

美肝年会什么时候

作者: jaylongli 时间: 2015-8-17 00:01

回复重韧的帖子

美肝年会什么时候

作者: newchinabok 时间: 2015-8-17 08:28

arc520最新临床试验要到年底，2016初有结果，nvr3-778也要年底有结果

作者: 重韧 时间: 2015-8-17 09:19

回复 jaylongli 的帖子

2015年的11月13-17日在旧金山召开

作者: 咬牙硬挺 时间: 2015-8-18 12:07

感谢分享

作者: jaylongli 时间: 2015-8-18 16:29

回复 newchinabok 的帖子

nvr3-778 是哪个公司的？TEK?

作者: 相信会幸福 时间: 2015-8-19 12:37

期待～～～希望能有所成果

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