条条大路通罗马？

shiweibuyi

为了了解REP 9AC的近况，我直接联系REPLICor公司的CEO，Dr. Michel Bazinet。他的回答、翻译和有关文献如下：

REPLICor公司正在开发一种新的药物，可以彻底改变治疗慢性乙型肝炎患者的方式。我们的药物相互作用于表面抗原（HBsAg）、防止其从受感染的肝细胞释放。这样血液中的表面抗原达到逐步减少、消除的结果。许多科学论文都认为，表面抗原抑制免疫反应的病毒感染，并允许其长期维持在肝脏中。通过从血液中消除表面抗原，我们可以让免疫系统对病毒安装有效的应答，这可能会导致病毒从肝里被清除。换句话说，通过从血液中清除表面抗原，我们给病人予能力，让病人自己和B型肝炎感染战斗。

最近的数据在20年会在北京的APASL，中国（http://www.apasl2010beijing.org/en/index.aspx）颁发表明，REP 9AC治疗在12周内在乙肝病人身上迅速导致HBsAB的产生和血清内的HBsAg减少和/或清除。这些结果显示血清中的乙肝病毒滴度可以大量地和持久地被减少，可能是由于改进了对感染的免疫反应。第一个病人是一个很好的例子，他的病毒有200万拷贝/毫升，治疗了23周，至今（6个月了）保持着持续的病毒应答（<70的病毒拷贝/毫升）。停止治疗6个月后这名患者在血液中保持着在表面抗原检测不到的水平。

我们药物和表面抗原相互作用是大面积的，因此，耐药将是非常不易的。副作用现在还不好评论，因为我们只治疗了少数患者。但相信本药会比干扰素更容易容忍。

我们正在努力尽可能快地让病人使用这种药物，但它可能会需要数年才能获得批准，并在全球范围内使用。目前，我们正在设法筹集资金，加快我们的临床试验患者的招募工作。我们筹集资金的能力是最重要的限制我们进步的因素，限制我们尽快地将药物用于病人。 REPLICor公司总是在寻找私人投资者可能愿意资助我们的研究项目。由于REPLICor公司是一家私营公司，并没有投资说明书（费用昂贵），故只能接受认可的投资者的钱。在加拿大，认可的投资者是指净价值100万加元的（净值包括房子，股票，债券等）或年收入20万加元的收入（其中可以包括：配偶的收入）或最低15万加元的投资能力。如果投资者适合投资者的认可准则，最低投资2.5万加元。

在医疗或制药领域的具有专业知识的人不必受限以上标准，因为他们的经验或专业知识让他们能够评估在我们公司投资的风险。

我们目前在全球有75个投资人，共投资1,000万加元，其中25个有博士学位或医师学位，这些人投资是因为他们了解本投资，懂得我们技术的潜力。

我们相信我们的药品比现用的受批准的对付慢性乙型肝的药品要好许多，只是目前我们的经验只限于极少数病人。我们计划筹集4至5百万加元以增加患者受试来证明我们的药在更多的患者上有效且耐受性好。

我们相信，我们的药品要发展到不可置疑的阶段，需用最好的专业知识，最好的管理和大型制药公司才有的财政能力。因此，目前管理是从发现阶段进行该药物的发展，在人身上做功效的证明。我们期望一个大型制药公司的收购将是我们的投资者的最有可能的撤出战略。另一条路是开发股，但在目前的金融环境下，这是不太可能的。我们相信，新的投资者有一个良好的机会，对他们在未来的18至24个月的投资得到非常大的回报。

如果您是一个合格的投资者，并希望进一步了解本公司，我们会寄给您本公司的其它信息。投资可用电汇方式，一两个星期内会收到他们的股票。不幸的是，法律规定禁止接受不合格的投资者的投资。

有兴趣者可以联络：

Michel Bazinet, MD
公司董事长兼首席执行官
REPLICor公司公司
电话514 496 9016
[email protected]
http://www.replicor.com

原文：

Replicor is developing a new drug that could revolutionize the way patients with chronic hepatitis B are treated. Our drug interacts with surface antigen (HBsAg) and prevents its release from infected hepatocytes. This results in a gradual reduction and elimination of surface antigen in the blood. Many scientific papers have suggested that surface antigen suppresses the immune response to the virus and allow the infection to be chronically maintained in the liver. By eliminating the surface antigen from the blood, it appears that we allow the immune system to mount an effective response against the virus and this can result in clearance of the viral infection from the liver. In other words, by removing the surface antigen from the blood, we give the patient the ability to fight his hepatitis B infection on his own.

Recent data presented during the 20th annual meeting of the APASL in Beijing, China ( http://www.apasl2010beijing.org/en/index.aspx ) showed that treatment with REP 9AC rapidly leads to the detection of anti-HBsAg antibodies and the reduction and or clearance of serum HBsAg within the first 12 weeks of treatment in human patients. These findings are associated with substantial and sustained reductions in serum HBV titers which may be due to an improved immune response to the infection. This is exemplified by the first patient who had 2,000,000 copies of the virus / ml in his blood, was then treated for a total of 23 weeks and who has so far maintained a sustained virologic response (<70 copies of the virus / ml in his blood) for a period of 6 months off treatment. This patient has also maintained an undetectable level of surface antigen in his blood for the last 6 months off therapy.

The interaction between our drug and surface antigen occurs over a large surface area, therefore, resistance to the drug will be very unlikely. It is too early to comment on side effects since we have treated only a few patients but it appears that the drug will be much easier to tolerate than interferon.

We are trying to go as fast as possible to bring this drug to patients but it will likely take a few years before it is approved and available for use globally. We are currently trying to raise funds to accelerate the recruitment of patients in our clinical trial. Our ability to raise funds is the most important limiting factor in our progress to bring the drug to patients. Replicor is always on the lookout for private investors that might be willing to fund its research program. Because Replicor is a private company and does not issue a prospectus (because of the significant costs involved), Replicor can only accept money from accredited investors. In Canada, the conditions to be considered an accredited investor is a net value of $1 million dollars CAD (which include the value of your house, stocks, bonds, etc) or an income of $ 200,000 CAD dollars per year (which can include the salary of a spouse) or the ability to invest a minimum of $ 150,000 CAD. If an investor fit the criteria of an accredited investor, the minimum investment is $ 25,000 CAD.

People with specific expertise in the medical or pharmaceutical fields would be exempt from these criterias since they presumably have experience or expertise allowing them to assess the risk of an investment in our Company.

We have a total of 75 investors who globally have invested a total of $ 10 million dollars CAD so far. 25 of them have either a Ph.D. or a M.D. These people have invested because they understand and see the potential of our technology.

We believe that our drug is much better than the approved drugs against chronic hepatitis B currently on the market but our experience is still limited to very few patients. We plan to raise an additional amount of $ 4 to 5 million dollars CAD in the near future to increase the number of patients on trial and show that the drug is well tolerated and effective in a larger number of patients.

We believe that the development of our drug beyond the proof of principle stage, will best be achieved with the expertise, regulatory know-how and financial capability of a large pharmaceutical company.  Therefore, the role of the current management is to carry the development of the drug from the discovery phase to a proof of efficacy in humans. We expect that an acquisition by a large pharmaceutical company will be the most likely exit strategy for our investors. An alternative would be to do an IPO but in the current financial climate, this is a less likely event. We believe that new investors have a good chance to make a very large return on their investment within the next 18 to 24 months.

If you are an accredited investor and wish to learn more about the company, we will send you additional information on the Company. People that invest typically send money via wire transfer and receive their shares within a week or two. Unfortunately, regulations forbid us from accepting investment from people who do not fit the criterias for an accredited investor.

Potential investor with an interest should contact:

Michel Bazinet, MD
Chairman and CEO
REPLICor Inc.
514 496 9016 Tel
[email protected]
http://www.replicor.com

[ 本帖最后由 shiweibuyi 于 2010-4-7 02:56 编辑 ]

shiweibuyi

文献：

Brunetto, M.R., Morioconi, F., Bonino, F., Lau, G.K., Farci, P., Yurdaydin, C., Piratvisuth, T., Luo,K., Wang, Y., Hadziyannis, S., Wolf, E., McCloud, P., Batrla, R., Marcellin, P. 2009 Hepatitis Bvirus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAgnegative chronic hepatitis B. Hepatology 49: 1141-1150.

Cai, W., Xie, Q., Zhou, W., An, B., Zhao, G., Wang, H., Guo, Q., Gu, R. On - treatment SerumHBsAg Level at 2 Years: Strong Predictor of Sustained Virologic Response to Telbivudine for up to2 Years Off - treatment in Chronic Hepatitis B Patients. AASLD 2009, Boston U.S.A., abstract 424.

Chen, Z., Cheng, Y., Xu, Y., Liao, J., Zhang, X., Hu, Y., Zhang, Q., Wang, J., Zhang, Z., Shen, F.,Yuan, Z. 2008 Expression profiles and function of Toll-like receptors 2 and 4 in peripheral blood mononuclear cells of chronic hepatitis B patients. Clin. Immunol. 128: 400-408.

Cheng, J., Imanishi, H., Morisaki, H., Liu, W., Nakamura, H., Morisaki, T., Hada, T. 2005. Recombinant HBsAg inhibits LPS-induced COX-2 expression and IL-18 production by interfering with the NF-KB pathway in a human monocyte cell line, THP-1. J. Hepatol. 43: 465-471.

Chu, C.M., Liaw, Y.F. 2007. HBsAg seroclearance in asymptomatic carriers of high endemic areas: appreciably high rates during a long-term follow-up. Hepatology: 45: 1187-1192.

Gish, R.G., Chang, T.T., Lai, C.L., deMan, R., Gadano, A., Poordad, F., Yang, J., Brett-Smith, H., Tamez, R. 2009 Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B. J. Viral Hepatitis Jul 19 (Epub ahead of print).

Hadziyannis, E., Sevastianos, V., Georgiou, A., Hadziyannis, S.J., Treatment- Related Compared to Spontaneously – Occurring HBsAg Loss In HBeAg - Negative Chronic Hepatitis B. AASLD 2009a, Boston. U.S.A., abstract 431.

Hou, J., Sun, J., Xie, Q., Li, X., Zhang, J., Wang, Y., Wang, H., Lai, J., Chen, S., Jia, J., Sheng, J., Chan, H., Wang, J., Li, M., Jiang, M., Popescu, M., Sung, J. On - treatment quantification of HBsAg in difficult - to - treat patients with lamivudine resistance can help identify those most likely to achieve sustained post – treatment response to peginterferon alfa - 2a rescue therapy. AASLD 2009, Boston, U.S.A., abstract 392.

Liu, C., Chuang, W., Lee, C., Yu, M., Lu, S., Dai, C., Huang, J., Hu, T., Chen, C., Hung, C., Wang, J.H., Wu, S., Liao, L.Y., Kuo, H.T., Chao, Y., Tung, S.Y., Yang, S, Su, W.W., Lin, C., Kao, J., Liu, C., Chen, P., Chen, D. HBsAg clearance continues to increase post - treatment in patients with HCV/HBV coinfection treated with peginterferon alfa - 2a plus ribavirin: 1.5 year follow – up. AASLD 2009, Boston, U.S.A., abstract 419.

Manesis, E.K., Hadziyannis, E.S., Angelopoulou, O.P., Hadziyannis, S.J., 2007 Predicition of treatment-related HBsAg loss in HBeAg-negative chronic hepatitis B: a clue from serum HBsAg levels. Antiviral Ther. 12: 73-82.

Moucari, R., Korevaar, A., Lada, O., Martinot-Peignoux, M., Boyer, N., Mackiewicz, V.,
Dauvergne, A., Cardoso, A.C., Asselah, T., Nicolas-Chanoine, M.H., Vidaid, M., Valla, D., Bedossa, P., Marcellin, P. 2009a High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long term follow-up study. Hepatology 50: 1084-1092.

Op den Brouw, M.L., Binda, R.S., van Roosmalen, M.H., Protzer, U., Janssen, H.L.A., van der Molen, R.G., Woltman, A.M. 2008. Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a possible immune escape mechanism of hepatitis B virus. Immunology: 280-289.

Takkenberg, B., Zaaijer, H.L., de Niet, A., Weegink, C.J., Terpstra, V., Koot, M., Dijkgraaf, M., Jansen, P.L., Janssen, H.L., Beld, M., Reesink, H.W. Baseline HBsAg levels predict HBsAg loss in HBeAg negative but not in HBeAg positive chronic hepatitis B patients treated with Peginterferon alfa - 2a ( Pegasys® ) and Adefovir ( Hepsera ) : an interim analysis. AASLD 2009a, Boston, U.S.A., abstract 488.

Takkenberg, B., Zaaijer, H.L., de Niet, A., Weegink, C.J., Terpstra, V., Koot, M., Dijkgraaf, M., Jansen, P.L., Janssen, H.L., Beld, M., Reesink, H.W. Baseline HBsAg level and on – treatment HBsAg and HBV DNA decline predict sustained virological response in HBeAg negative chronic hepatitis B patients treated with Peginterferon alfa - 2a ( Pegasys® ) and Adefovir ( Hepsera ) ; an interim analysis. AASLD 2009b, Boston, U.S.A., abstract 491.

Takkenberg, B., Zaaijer, H.L., de Niet, A., Weegink, C.J., Terpstra, V., Koot, M., Dijkgraaf, M., Jansen, P.L., Janssen, H.L., Beld, M., Reesink, H.W. High levels of HBsAg and HBV DNA during treatment predict failure for HBeAg seroconversion in HBeAg positive chronic hepatitis B patients treated with Peginterferon alfa - 2a ( Pegasys® ) and Adefovir ( Hepsera ) ; an interim analysis. AASLD 2009c, Boston, U.S.A., abstract 495.

Vanlandschoot, P., Van Houtte, F., Roobrouck, A., Farhoudi, A., Leroux-Roels, G. 2002. Hepatitis B virus surface antigen suppresses the activation of monocytes through interaction with serum protein and a monocyte-specific receptor. J. Gen. Virol. 83: 1281-1289.

Wu, J., Meng, Z., Jiang, M., Pei, R., Tippler, M., Broering, R., Bucchi, A., Sowa, J.P., Dittmer, U., Yang, D., Roggendorf, M., Gerken, G., Lu, M., Schlaak, J.F. 2009 Hepatitis B virus suppresses tolllike receptor-mediated innate immune responses in murine parenchymal and nonparencyhmal liver cells. Hepatology 49: 1132-1140.

Wursthorn, K., Jung, M., Manns, M.P., Lopez, P.M., Wedemeyer, H., Naoumov, N.V. Different Kinetics of Serum HBsAg Decline in HBeAg - Positive vs HBeAg - Negative Patients During 3 Years of Telbivudine Treatment in Chronic Hepatitis B ( CHB ). AASLD 2009, Boston, U.S.A., abstract 487.

Xu, X., Hu, Y., Shi, B., Zhang, X., Wang, J., Zhang, Z., Shen, F., Zhang, Q., Sun, S., Yuan, Y. 2009. HBsAg inhibits TLR-9-mediated activation and INFalpha production in plasmacytoid dendritic cells. Mol. Immunol. 46: 2640-2646.

Yuen, M.F., Wong, D.K., Yuan, H.J., Sum, S.M. and Lai, C.L. 2004. HBsAg seroclearance in Chinese patients receiving lamivudine therapy for chronic hepatitis B virus infection. J. Clin. Microbiol. 42: 4882-4884.

Zheng, B.J., Zhou, J., Qu, D., Siu, K.L., Lam, T.W., Lo, H.Y., Lee, S.S., Wen, Y.M. 2004. Selective functional deficit in dendritic cell-T cell interaction is a crucial mechanism in chronic hepatitis B virus infection. J. Viral Hepatitis: 217-224.

佛光普照L

个人觉得有点骗钱的嫌疑，紧代表个人意见。还是等蔡荣的药吧！

走遍四方

我们这个组织可以影响并加速REPLICor的进程吗，如此可谓功德无量。前无古人了。。。

孤鸿落日

期盼中

fromdesert34

楼主之前不是在帖子中说REPLICor是加拿大十大生化公司之一吗？怎么这封信中不像是大公司的样子。。

走遍四方

原帖由 fromdesert34 于 2010-4-7 11:38 发表
楼主之前不是在帖子中说REPLICor是加拿大十大生化公司之一吗？怎么这封信中不像是大公司的样子。。

网站说的很清楚

http://www.replicor.com/debut_anglais2.htm

REPLICor was nominated as one of Canada’s Top 10 Life Sciences Companies for the years 2004/2005 and for 2007/2008 by the Ottawa Centre for Research and Innovation.

http://www.topcanadiancompanies.ca/winners/alumni.pdf

[ 本帖最后由 走遍四方 于 2010-4-7 11:56 编辑 ]

肝胆相照009

Our drug interacts with surface antigen (HBsAg) and prevents its release from infected hepatocytes. This results in a gradual reduction and elimination of surface antigen in the blood. Many scientific papers have suggested that surface antigen suppresses the immune response to the virus and allow the infection to be chronically maintained in the liver. By eliminating the surface antigen from the blood, it appears that we allow the immune system to mount an effective response against the virus and this can result in clearance of the viral infection from the liver. In other words, by removing the surface antigen from the blood, we give the patient the ability to fight his hepatitis B infection on his own.

也许是全新的思路！1！

齐欢畅2

富贵数字

原帖由 齐欢畅2 于 2010-4-7 17:14 发表

齐大笑那么开心 ？
你有空联系蔡老师的时候  问下 他的药 为什么要住院一个月?