Replicor提出关于REP的安全性和有效性基于2139ca合治疗慢性

guilin2013

史帝份，我真的好尊敬你的，是你为我们广大HCV\HBV带来了医学的前沿，但就这个公司来说，真的够奇啪的了，因为若果是做生意的话，在现在这个医学快速发展的年代，这么好的一个药，应走最快速度让它上市（只要是它的10年药效太好了，这是现今在研药物最好的一个，但它就是不按正规流程快速走完实验，好的药绝对不差钱进行实验的，但关键是到现在还在修正做一个3年的二期实验，关键还没见到三期和上市时间表，再关键已经有很多在研药物快走到功能性治愈边上了，难道这个公司就不怕市场给别人先占了吗，难道它真的在玩笑吗，难道它再来个10年大忽悠吗，到时还能忽悠吗，很多很多的？？但这个公司都没对外界说明他们具体计划，也不对公众来个交代，不懂得怎样吐槽这个公司），10年时想到最多5年后15、16上市了吧（这是因为这个药效率太好了，所以那进才有这个预估，），但到现在，它还是.......,没完没了的结果，没完没了的参加各种会议，难道这个公司又是以参加会议为目标的吗，唉，好多想说的，好多想吐槽的，不一一说了

ivanich

大神不是说了么，a car without engine

StephenW

回复 HBVCURER 的帖子

“没有REP9AC，也不会有ARC520/1”，你这么说ARC的科学家肯定不乐意的

I think you missed the point completely! We are not talking about RNAi, as you know very well, it was a technology looking for a solution and was abandoned by many. Arrowhead initially developed RNAi for HBV with the aim to effect hbvdna reduction, by knocking down some of the viral proteins needed in hbv replication , as in NUCs. Of course they soon realized that ARC520, targeting various viral proteins, will never be as effective as existing NUCs in reducing hbvdna. But then they noticed ARC520 can lower HBsAg, and according to research literature, they know serum HBsAg is an immune suppressor, and maybe from the results of REP9AC,  therefore they can sell ARC520 as a drug to lower serum HBsAg, thereby providing a functional cure for HBV. Up to now, there is not a single piece of evidence to show from ARC520 data alone, not even from the chimps, that it can cure HBV. The only evidence that reduction in HBsAg can cure HBV came from REP9AC. So this is the point you missed or refused to acknowledge.

Even now Arrowhead discovered that their knockdown of HBsAg is nowhere deep enough, so attention is turning to HHBeAg, a reduction in theory may lead to e-seroconversion. Other people had pointed this out to them.

siRNA治疗HBV的策略远在siRNA技术诞生之初就有了，ARC520/1也不仅仅靶向HBsAg而是所有的HBV mRNA/antigen。至于说通过降低HBsAg的策略来消除免疫耐受实现血清学转换，也并非是Replicor的原创。

REP9AC在2010年最初报道的时候，就号称仅通过短短数月的单药治疗使60%以上的患者实现了HBsAb的阳转！5年过去了，Replicor的药物候选换了又换，名字改了又改，可是实际效果似乎却没跟上，HBsAb的高阳转率没了，反而要开始和干扰素联合治疗了.

Again, I don't know how closely you followed REP9AC's clinical trials results (BTW the Dr who conducted the clinical trial for Replicor in Bangladesh is the very same Dr who conducted the Phase II/III for ABX203), in 2009 they did announce patients had lost HBsAg and developed HBsAb (easily deduced, HBsAb was always there, but it was neutralized by the excessive HBsAg, with no or minimal HBsAg, HBsAab becomes excessive). You are right, at follow-up, the results were not durable. So they experimented with Interferon and Zadaxin, and now they conclude:
"The second discovery has been to understand the role of surface antigen. Replicor’s hypothesis, which has now been proven in four separate human clinical trials, is that by reducing and eliminating surface antigen with NAPs, the immune system is allowed to recover and regain control of the infection. More importantly, in those patients where removing HBsAg was not enough to restore immune control, the elimination of HBsAg greatly improved their response to immunotherapy compared to patients receiving immunotherapy without the benefit of HBsAg removal. This combination treatment of NAP-based HBsAg removal and concomitant immunotherapy results in high rates of restoration of immune control over HBV infection off treatment. "

最后说点内幕吧。有几家公司（名字不说了，都是大牌），曾经私下合成过Replicor的NAPs（结构本身不是秘密），然后在细胞及动物模型上测试过，都没看到相应的效果（当然，也可能是他们合成的不对）。所以Replicor至今没有大公司提出收购，也没有其他公司跟随他家的策略。

Well, we have to take your words for it. If you read the recent research literature, REP9AC results in test tube and animal models have been verified by well known scientists from research institutes from Europe. Hard to conclude they are part of the conspiracy, after all, they put their names as authors of the studies. BTW, the pre-clinical studies of REP9AC were done in Australia by a PHD student, her thesis is in the public domain. So this is as transparent and factual as you can get. This student is now a PHD and researcher in her home country.

Yes, the components of REP9AC are well known. Studyforhope from Medhelp can even find you labs that can make up the compound for you.


这在药物研发领域还是比较少见的。任何研发策略，比如核衣壳抑制剂，比如siRNA，再比如治疗型疫苗，任何一种策略，都可以看到两家甚至更多家研发团队的跟进和竞争，即便有技术上的专利保护也不大可能一家垄断。

This are rather unsophisticated reasons. REP9AC has potential hurdles. It is now administered by infusion only, hardly convenient as a drug candidate without further development. And maybe big companies cannot agree on a reasonable price and cannot see profit in a short time.

当然，如果Replicor最终能用公开透明的临床实验的结果打翻所有质疑，让这个领域所有的大公司大跌眼镜俯首称臣，也是一段传奇。我个人很希望看到这样的结果，这也是所有HBV患者的大福音。

According to you, their results are not "transparent". This is strange, considering that they have published abstracts and given oral presentations, at all the leading HBV conferences!, some even by invitation! I think it was Dr Locarnini who gave an introduction to REP9AC in its first international conference. Dr Locarnini of course now consults for Arrowhead and you seem to have no complaint about his transparency when he suggests hbvdna integration in chimps model can be extended to humans.

I understand you had rejected REP9AC because you said "they wanted only money". Why talk money if you don't believe in their claims?  If you really have any evidence that REP9Ac does not reduce serum HBsAg, please show them, this is what I would wish to see and really appreciate!

guilin2013

唉，这就是生活，你猜得开始，猜不到结果，从此不谈这药了，因为用到它的可能性已经没有了，因为他肯定迟过ABX203、ARC-520等药上市，到时都医好了，它上市也用不到它了

StephenW

guilin2013 发表于 2015-11-6 17:07
史帝份，我真的好尊敬你的，是你为我们广大HCV\HBV带来了医学的前沿，但就这个公司来说，真的够奇啪的了， ...

为什么他们要忽悠? 难道他们问你要钱?  

guilin2013

是的，发邮件问它时，都问我没有没有中国的投资者

StephenW

guilin2013 发表于 2015-11-6 18:00
是的，发邮件问它时，都问我没有没有中国的投资者

那么你为什么不投资? 他们需要投资者支持他们的研究, 没有研究，怎么能证明他们的药可以治愈?  所以你要别人承担全部风险?

guilin2013

为什么史蒂分对这药情有独钟呢，难道你没怀疑过它吗，一直不出来

HBVCURER

StephenW 发表于 2015-11-6 16:49
回复 HBVCURER 的帖子

我老板对其CEO（Michel Bazinet）的评价是：“Michel can easily sell you a car wi ...

如果你见过他现场做报告，或者目睹他和其他公司的人打交道，也许可能有不同的感受。事实上，见人说人话见鬼说鬼话，可能是作为一个私营企业CEO的必要素质之一吧。能让不同的人有不同的感受，也是他厉害的地方。

当然了，对同一个人，不同人也会有不同的判断，这没啥可奇怪的，非说说话的不是同一个人，才有点奇怪。

HBVCURER

StephenW 发表于 2015-11-6 18:06
那么你为什么不投资? 他们需要投资者支持他们的研究, 没有研究，怎么能证明他们的药可以治愈?  所以你要 ...

投资从来都不是盲目的，并不是看到一个大饼看起来很好吃就一定要投资，因为投资是有风险的，很可能血本无归。这种风险自然不应该由普通患者来承担，而是由对该公司该产品有巨大信心并希望从中获益的人来承担，如果你非常看好，我觉得你应该投资才对。

私营企业（投资人）当然要自己承担风险，为什么要转嫁给患者？因为一旦成功，巨大的利益也是他们获得，别人不会分一杯羹。患者需要做的，是在药物上市之后，付出购买药物的价格，作为回报开发人员和投资人的最基本方式。