Replicor announces publication of new study examining antiviral mechanisms of REP 2139
MONTREAL, February 18th, 2019 – Replicor Inc., a privately held biopharmaceutical company targeting a cure for patients with chronic hepatitis B virus (HBV) and chronic HBV and hepatitis delta virus (HDV) co-infection, announces the publication of new data examining the antiviral mechanism of REP 2139 in HBV infection in the journal of Antiviral Research.
The article is entitled “Inhibition of HBsAg secretion by nucleic acid polymers in HepG2.2.15 cells” and is the first publication from an ongoing collaboration between Replicor and Dr. Patrick Labonté at the Institute Armand Frappier, part of the Institut National de la Recherche Scientifique (IAF-INRS), located in Laval, Quebec, Canada. This new data firmly establishes not only the ability of REP 2139 to block the release of HBsAg but also its ability to reduce intracellular HBsAg.
Dr. Andrew Vaillant, CSO at Replicor commented, “This study is the first to provide tangible observation of the inhibition of HBsAg release and the simultaneous reduction of intracellular HBsAg in infected cells, consistent with the clearance of HBsAg from the blood and liver observed in several previously published pre-clinical and clinical studies.” The publication provides additional data suggesting that these antiviral effects are driven by inhibition of assembly of subviral particles, not by a direct inhibition of their secretion.
Dr. Vaillant added, “while additional work is underway in this model to identify potential host targets for REP 2139, these data provide an important bridge between antiviral mechanism of REP 2139 in HBV and the observed antiviral effects of REP 2139-based therapy in clinical studies.”
About Replicor
Replicor is a privately held biopharmaceutical company with the most advanced animal and human clinical data in the development of the cure for HBV and HDV. The company is dedicated to accelerating the development of an effective treatment for patients with HBV and HBV/HDV co-infection. For further information about Replicor please visit our website at www.replicor.com.作者: StephenW 时间: 2019-2-19 10:07
Replicor的CSO Andrew Vaillant博士评论说:“这项研究首次提供了对HBsAg释放抑制和感染细胞内HBsAg同时减少的切实观察,与血液和肝脏中HBsAg的清除一致。几个先前发表的临床前和临床研究。“该出版物提供了额外的数据,表明这些抗病毒作用是由抑制亚病毒颗粒的组装驱动的,而不是通过直接抑制其分泌。
Replicor 2017-2018 huìyì bàogào. Zìjǐ dú
Replicor personnel and collaborators attend and often present at all the major international scientific conferences where HBV or HDV is discussed. Selected presentations can be downloaded below.
Date Conference Location Topic Abstract/Poster
10.11.2018 Hepatitis Delta International Network Meeting
(AASLD 2018) San Francisco, USA REP 301-LTF update
REP 2139-Mg transition to SC HDIN AASLD 2018
9.11.2018 AASLD 2018 San Francisco, USA Achieving functional cure with REP 2139 REP 401 AASLD 2018
7.11.2018 HBV Cure Workshop 2018 Toronto, Canada REP 401 study interim follow-up update HBV Cure Workshop 2018
6.10.2018 2018 HBV International Meeting Taormina, Italy Achieving functional cure with REP 2139 REP 2139 clinical HBV INT 2018
5.10.2018 2018 HBV International Meeting Taormina, Italy REP 2139 mechanism of action in vitro REP 2139 vs HBsAg HBV INT 2018
4.10.2018 2018 HBV International Meeting Taormina, Italy Apolipoproteins in HBsAg secretion in vitro Apos vs HBsAg HBV INT 2018
25.09.2018 Discovery on Target 2018: Targeting HBV Boston, USA Achieving functional cure with REP 2139 CHT Targeting HBV 2018
15.06.2018
Global Hepatitis Summit 2018
(16th International Symposium of Viral Hepatitis and Liver Disease)
Toronto, Canada Updated follow-up analysis in the REP 401 protocol. GHS 2018 presentation
09.06.2018
Science of HBV Cure
(Singapore Hepatitis Conference)
Singapore, Singapore Achieving functional control of HBV and HDV infection with REP 2139-based combination therapy Combination therapy presentation
08.06.2018
Science of HBV Cure
(Singapore Hepatitis Conference)
Singapore, Singapore REP 2139 mechanistic insights and effects in monotherapy Monotherapy presentation
13.04.2018 EASL ILC 2018 Paris, France Modelling viral kinetics during REP 2139-Ca monotherapy Poster FRI-324
13.04.2018 EASL ILC 2018 Paris, France Updated follow-up data in the REP 301-LTF study (HBV/HDV). Poster FRI-326
13.04.2018 EASL ILC 2018 Paris, France Updated follow-ip data in the REP 401 study (HBV) Poster FRI-343
07.12.2017 HEPDART 2017 Kona, HI, U.S.A. REP 401 Interim follow-up update Presentation O-19
21.10.2017 AASLD 2017 Washington, DC, U.S.A REP 401 Interim follow-up update Poster LB-24
21.10.2017 AASLD 2017 Washington, DC, U.S.A Update on NAP mechanism of action in HBV Poster 957
21.10.2017 AASLD 2017 Washington, DC, U.S.A Update on NAP mechanism of action in HDV Poster 942
25.09.2017 CHT Discovery on Target:Targeting HBV Boston, U.S.A. Targeting HBsAg secretion with NAPs: Drug development update Presentation
05.09.2017 HBV International Meeting 2017 Washington DC, U.S.A. Modelling post-entry effects of NAPs against HBV infection in vitro. Poster P-146
05.09.2017 HBV International Meeting 2017 Washington DC, U.S.A. Activity of NAPs against HDV in vivo Poster P-144
05.09.2017 HBV International Meeting 2017 Washington DC, U.S.A. NAPs interact with small and large hepatitis delta antigen Poster P-145
05.09.2017 HBV International Meeting 2017 Washington DC, U.S.A. HBsAg Quasispecies evolution in the REP 102 trial. Poster P-127
05.09.2017 HBV International Meeting 2017 Washington DC, U.S.A. Mathematical modelling of viral dynamics in the REP 102 protocol. Poster P-148
05.09.2017 HBV International Meeting 2017 Washington DC, U.S.A. Clinical NAP Summary (critical role for HBsAg suppression in achieving functional cure. Poster P-147
07.09.2017 HBV International Meeting 2017 Satellite Symposium Washington DC, U.S.A. Clinical NAP Summary (critical role for HBsAg suppression in achieving functional cure. Presentation O-198.
20.04.2017 HDIN meeting (EASL 2017) Amsterdam, The Netherlands REP 301 / 301-LTF update HDIN (EASL 2017) Presentation HDIN (EASL 2017)
20.04.2017 EASL 2017 Amsterdam, The Netherlands REP 301 / 301-LTF update LBP-507 Poster LBP-507
20.04.2017 EASL 2017 Amsterdam, The Netherlands REP 401 update EASL 2017 THU-154 Poster THU-154
20.04.2017 EASL 2017 Amsterdam, The Netherlands REP 102 HBsAg deep sequencing EASL 2017 THU-155 Poster THU-155
20.04.2017 EASL 2017 Amsterdam, The Netherlands NAP post-entry activity modelling in vitro EASL 2017 THU-156 Poster THU-156
20.04.2017 EASL 2017 Amsterdam, The Netherlands Modeling HBsAg and HDV DNA kinetics EASL 2017 THU-173 Poster THU-173
18.02.2017 APASL 2017 Shanghai, China Update on Safety and Efficacy in the REP 401 protocol APASL 2017 oral presentation作者: StephenW 时间: 2019-2-26 20:26
Peer Reviewed同行评审 Publications on Replicor's NAP Technology: 2018-2017
Inhibition of HBsAg secretion by nucleic acid polymers in HepG2.2.15 cells.
Blanchet M, Sinnathamby V, Vaillant A, Labonté P. Antiviral Research 2019 epub Feb 13, 2019.
Read publication
Variants of hepatitis B virus surface antigen observed during therapy with nucleic acid polymer REP 2139-Ca have no influence on treatment outcome and its detection by diagnostic assays.
Mijočević H, Karimzadeh H, Seebach J, Usman Z, Mamun AM, Bazinet M, Vaillant A, Roggendorf M. Journal of Viral Hepatitis 2018 epub Nov 19, 2018.
Read publication
REP 2139: Antiviral Mechanisms and Applications in Achieving Functional Control of HBV and HDV Infection.
Vaillant A. ACS Infectious Diseases 2018 epub Oct 8, 2018.
Read publication
Nucleic acid polymer REP 2139 and nucleos(t)ide analogues act synergistically against chronic hepadnaviral infection in vivo.
Quinet J, Jamard C, Burtin M, Lemasson M, Guerret S, Sureau C, Vaillant A, Cova L. Hepatology 2017 epub Dec 18 2017.
Read publication
Nucleic acid polymers are active against Hepatitis Delta Virus infection in vitro.
Beilstein F, Blanchet M, Vaillant A, Sureau C. Journal of Virology 2017 epub Dec 6 2017.
Read publication
Activity of nucleic acid polymers in rodent models of HBV infection.
Schöneweis K, Motter N, Roppert PL, Lu M, Wang B, Roehl I, Glebe D, Yang D, Morrey JD, Roggendorf M, Vaillant A. Antiviral Research 2017 epub Nov 8, 2017.
Read publication
Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial
Bazinet M, Pântea V, Cebotarescu V, Cojuhari L, Jimbei P, Albrecht J, Schmid P, Le Gal F, Gordien E, Krawczyk A, Mijočević H, Karimzadeh H, Roggendorf M, Vaillant A. The Lancet Gastroenterology & Hepatology 2017 epub Sept 27, 2017.
Read publication
REP 301 study protocol
Read Publication
Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes
Guillot C, Martel N, Berby F, Bordes I, Hantz O, Blanchet M, Sureau C, Vaillant A, Chemin I. PLOS ONE 2017 12: e0179697.
Read Publication
Nucleic Acid Polymers with Accelerated Plasma and Tissue Clearance for Chronic Hepatitis B Therapy.
Roehl I, Seiffert S, Brikh C, Quinet Q, Jamard C, Dorfler N, Lockridge JA, Cova L, Andrew Vaillant A. Mol Ther Nuc Acids. 2017 8: 1-12.
Read Publication
Nucleic acid-based polymers effective against hepatitis B Virus infection in patients don’t harbor immunostimulatory properties in primary isolated liver cells.
Real CI, Werner M, Paul A, Gerken G, Schlaak JF, Vaillant A, Broering B, Sci. Reports. 2017 7: 43838.
在完成24周无治疗随访的患者中,功能性抑制(HBV DNA < 1000 IU/mL)的患者比例达到87%(其中79% HBsAg <10 IU / mL),功能性清除 (HBV DNA < LLOQ)的患者比例为 70%(其中66%未检测到 HBsAg [0.00 IU / mL])。92%的患者肝功能正常。
摘要由每个类别的至少四个评论者评分,并根据数字评分进行排名。 审稿人对作者的姓名和隶属关系不知情。 有冲突的审稿人不会对相关摘要进行评分。
AASLD Abstract Review and Selection Policy
Abstracts are scored by at least four reviewers for each category and ranked according to numerical score. Reviewers are blinded to the author's names and affiliations. Reviewers with conflicts do not score pertinent abstracts.作者: StephenW 时间: 2019-2-26 21:06
Peer Reviewed同行评审 Publications on Replicor's NAP Technology: 2018-2017
Inhibition of HBsAg secretion by nucleic acid polymers in HepG2.2.15 cells.
Blanchet M, Sinnathamby V, Vaillant A, Labonté P. Antiviral Research 2019 epub Feb 13, 2019.
Read publication
Variants of hepatitis B virus surface antigen observed during therapy with nucleic acid polymer REP 2139-Ca have no influence on treatment outcome and its detection by diagnostic assays.
Mijočević H, Karimzadeh H, Seebach J, Usman Z, Mamun AM, Bazinet M, Vaillant A, Roggendorf M. Journal of Viral Hepatitis 2018 epub Nov 19, 2018.
Read publication
REP 2139: Antiviral Mechanisms and Applications in Achieving Functional Control of HBV and HDV Infection.
Vaillant A. ACS Infectious Diseases 2018 epub Oct 8, 2018.
Read publication
Nucleic acid polymer REP 2139 and nucleos(t)ide analogues act synergistically against chronic hepadnaviral infection in vivo.
Quinet J, Jamard C, Burtin M, Lemasson M, Guerret S, Sureau C, Vaillant A, Cova L. Hepatology 2017 epub Dec 18 2017.
Read publication
Nucleic acid polymers are active against Hepatitis Delta Virus infection in vitro.
Beilstein F, Blanchet M, Vaillant A, Sureau C. Journal of Virology 2017 epub Dec 6 2017.
Read publication
Activity of nucleic acid polymers in rodent models of HBV infection.
Schöneweis K, Motter N, Roppert PL, Lu M, Wang B, Roehl I, Glebe D, Yang D, Morrey JD, Roggendorf M, Vaillant A. Antiviral Research 2017 epub Nov 8, 2017.
Read publication
Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial
Bazinet M, Pântea V, Cebotarescu V, Cojuhari L, Jimbei P, Albrecht J, Schmid P, Le Gal F, Gordien E, Krawczyk A, Mijočević H, Karimzadeh H, Roggendorf M, Vaillant A. The Lancet Gastroenterology & Hepatology 2017 epub Sept 27, 2017.
Read publication
REP 301 study protocol
Read Publication
Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes
Guillot C, Martel N, Berby F, Bordes I, Hantz O, Blanchet M, Sureau C, Vaillant A, Chemin I. PLOS ONE 2017 12: e0179697.
Read Publication
Nucleic Acid Polymers with Accelerated Plasma and Tissue Clearance for Chronic Hepatitis B Therapy.
Roehl I, Seiffert S, Brikh C, Quinet Q, Jamard C, Dorfler N, Lockridge JA, Cova L, Andrew Vaillant A. Mol Ther Nuc Acids. 2017 8: 1-12.
Read Publication
Nucleic acid-based polymers effective against hepatitis B Virus infection in patients don’t harbor immunostimulatory properties in primary isolated liver cells.
Real CI, Werner M, Paul A, Gerken G, Schlaak JF, Vaillant A, Broering B, Sci. Reports. 2017 7: 43838.
我们的 I / II 期临床研究的中期临床数据表明,我们的药物耐受性良好,对慢性乙肝病毒感染患者有强大的抗病毒活性。使用我们的药物后,大多数病人产生 HBsAg抗体,及血液中的病毒 DNA 滴度得到大幅度下降,这表明使用该药可消除血液中的表面抗原,恢复免疫功能。恢复免疫反应后,患者具有长期控制病毒感染的能力,使在疗程治疗后血液中病毒DNA的滴度不可检测。作者: newchinabok 时间: 2019-2-28 09:06
我们的 I / II 期临床研究的中期临床数据表明,我们的药物耐受性良好,对慢性乙肝病毒感染患者有强大的抗病毒活性。使用我们的药物后,大多数病人产生 HBsAg抗体,及血液中的病毒 DNA 滴度得到大幅度下降,这表明使用该药可消除血液中的表面抗原,恢复免疫功能。作者: newchinabok 时间: 2019-2-28 09:07
a) REP9AC通过输注(infusion)给予, 每次这需要几个小时;治疗期间对于患者非常不方便;
b) 输液(infusion)有副作用; REP9AC也有副作用;
c) 显然,与ETV / TDF不同,REP9AC不能用药多年 - 短期HBsAg已经为零,HBaAB已经呈阳性在初次几个输注后,通过继续实还能实现其他目标吗?
d) 最重要的是,在停止REP9AC后,HBsAg是否仍然为阴性,HBsAb仍为阳性,hbvdna仍然低?