APASL2012 REP9AC'诱导表面抗原转阴后短期免疫诱导持久免疫控

StephenW

Abstract
     
Short Term Immunotherapy Following REP 9AC'-induced HBsAg Seroclearance Induces Durable Immunological Control of Chronic HBV Infection    Move back Print add this item to your Itinerary
     
Mamun Al-Mahtab1, Michel Bazinet2, Andrew Vaillant2
1Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, 2REPLICor Inc., Montreal, QC, Canada

Background: REP 9AC' is a nucleic acid-based polymer (NAP) that clears serum HBsAg by blocking HBV subviral particle formation and release. The effect of add on immunotherapy after HBsAg clearance in chronically infected patients receiving REP 9AC' was examined.
Methods: Add on immunotherapy to existing REP 9AC' therapy was initiated in patients who had cleared their serum HBsAg but with persistent serum HBV DNA. Immmunotherapy consisted of thymosin α1 (Zadaxin™) or pegylated interferon α-2a (Pegasys™). Virologic responses were monitored by measuring serum HBV DNA (Roche Cobas™), serum HBsAg and serum anti-HBs (Abbott Architect™).
Results: REP 9AC'-induced HBsAg seroclearance is accompanied by the appearance of anti-HBs and reductions in serum HBV DNA. However, the continued production of anti-HBs in most patients never exceeded 50 mIU/ml and serum HBV DNA levels in most patients persisted in the range of 1000-3000 cpm. Addition of either Zadaxin™ or Pegasys™ to REP 9AC' therapy resulted in dramatic increases in anti-HBs titers with as little as 5 weeks of immunotherapy to levels comparable to or greater than titers observed in healthy patients with a strong vaccine response. Combination treatment was halted in 6 patients after 13 weeks of immunotherapy. In these patients, anti HBs levels are persistently > 100mIU/ml (2 of 6 patients) and > 1000mIU (4 of 6 patients) 4-12 weeks off treatment. HBV DNA levels are also declining off treatment in these patients. Currently, serum HBV DNA levels have reached < 300 cpm (1 patient), < 200 cpm (1 patient) or < 116 cpm (LLOQ) in the remaining 4 patients.
Conclusions: REP 9AC'-induced HBsAg seroclearance appears to potentiate the immunostimulatory effects of either Zadaxin™ or Pegasys ™ in all patients. Short term exposure to immunotherapy in the absence of HBsAg may induce permanent immunological control of HBV infection in most patients.


Assigned speakers:
Dr. Andrew Vaillant, REPLICor Inc. , Montreal , Canada

Assigned in sessions:
07.06.2013, 08:30-17:30, PT-4, HEP B Clinical, Exhibition Hall

StephenW

背景：REP 9AC'是基于核酸的聚合物（NAP），通过阻断HBV的亚病毒颗粒的形成和释放，清除血清HBsAg。添加免疫在慢性感染的患者接受REP 9AC HBsAg清除后的效果进行了检查。
方法：添加免疫现有的REP 9AC治疗患者清除血清HBsAg，但血清HBV DNA持续发起。 Immmunotherapy包括胸腺肽α1（日达仙™）或聚乙二醇干扰素α-2a干扰素（派罗欣™）。病毒学反应监测通过测量血清HBV DNA（罗氏COBAS™），血清HBsAg和血清抗-HBs（雅培建筑师™）。
结果：的REP 9AC'引起的乙肝表面抗原转阴同时抗-HBs和降低血清HBV DNA的外观。然而，在大多数患者中抗-HBs继续生产永远不会超出，50庙/毫升，在大多数患者中的血清HBV DNA水平持续在每分钟1000〜3000的范围内。此外，日达仙™或派罗欣™REP 9AC治疗导致的急剧增加，在短短的5个星期的免疫水平相媲美或更高的抗-HBs滴度比观察到患者的健康具有较强的疫苗反应滴度。 13周后，免疫治疗，联合治疗6例被叫停。在这些患者中，抗HBs水平持续> 100mIU/ml（6例）和> 1000mIU 6例（4）治疗4-12周关闭。 HBV DNA水平也在不断下降在这些患者的治疗。目前，血清HBV DNA水平已经达到了每分钟300（1例），200次（1例）或<116 CPM（LLOQ）在剩下的4名患者。
结论：的REP 9AC'引起的乙肝表面抗原转阴出现在所有患者中，日达仙™或派罗欣™的能够增强免疫效果。在没有对HBsAg的免疫治疗的短期暴露可能会引起在大多数患者中HBV感染的永久的免疫控制。

咬牙硬挺

这是去年的消息吧，今年的呢

StephenW

回复 咬牙硬挺 的帖子

去新加坡 问？

咬牙硬挺

回复 StephenW 的帖子

REPLICor presents clinical efficacy and toxicology results in patients with chronic hepatitis B with shortterm exposure to immunotherapy after REP 9AC’ induced clearance of serum HBsAg.
14 May 2013, Boston, U.S.A.
Montreal, Quebec – Tuesday , May14th, 2013 – REPLICor has previously undertaken a proof of concept trial to examine the efficacy of REP 9AC monotherapy in patients with chronic HBV infection.  A second proof of concept trial is currently underway in patients with chronic hepatitis B (HBV)undergoing treatment with REP 9AC’in combination with Zadaxin™ or Pegasys™.
Efficacy and toxicology results in REPLICor’s proof of concept trials from monotherapy exposure to REP 9AC or REP 9AC’ were disclosed on Tuesday May 14th, 2013 at the 15 th annual TIDES meeting held in Boston, U.S.A.
Both REP 9AC and REP 9AC’ were shown to rapidly and effectively remove HBsAg from the blood of patients with HBV infection.  While REP9AC monotherapy led to the establishment of control of infection off treatment in 2/7 patients, the addition of immunotherapy (either Pegasys™ or Zadaxin™) after REP 9AC’ mediated HBsAg clearance led to profound increases in immune function in all patients and in 8 out of 9 patients, control their viral infection has been maintained for 12 – 24 weeks after all treatment is stopped.
Toxicology results from weekly monotherapy exposure to REP 9AC or REP 9AC’ in many cases > 1 year resulted in no observable drug relatedeffects on liver and kidney function or in lipid or hematological function.  Major reported symptoms were shown to be related to the development of mineral deficiency likely due to the mineral chelation properties of these compounds and were controlled or prevented with proper mineral supplementation during treatment.
These results show the well tolerated nature of long term treatment with the nucleic acid polymer compounds REP 9AC and REP 9AC’ and further show the promise of achieving well tolerated control of HBV infection withcombination treatments using these agents.
For the 15th annual TIDES meeting:
http://www.ibclifesciences.com/TIDES/overview.xml

StephenW

回复 咬牙硬挺 的帖子

TIDES 2013 - 涵蓋藥物研發，新藥開發及製造的首屈一指的活動2013年5月12日 - 2013年5月15日Boston, USA                                        寡核苷酸的製造，技術，及產品開發                胜肽的製造，技術及產品開發                寡核苷酸治療藥物研發                胜肽藥物研發與開發                分子診斷的核酸技術       
                                                                專題簡報                               

Mipomersen相關臨床實驗最新趨勢	抗原表位標靶PCC劑	球狀核酸(SNAS)	寡核苷酸及胜肽的 風險投資資金	胜肽的給藥及設備策略
Mary P. McGowan, M.D.Senior Medical Director, Clinical Research, Genzyme, A Sanofi Company	James R. Heath, Ph.D.Professor, Chemistry and Chemical Engineering, California Institute Of Technology	Chad A. Mirkin, Ph.D.Professor, Chemistry, Northwestern University	Bruce Booth, D.Phil.Partner, Life Sciences, Atlas Venture	William J. Lambert, Ph.D.Fellow, Drug Delivery and Device Development, Medimmune, Inc.

               
                                                                                                        Special Discounted Hotel Rate
               

                Special Discounted Hotel Rate Available Until April 13, 2013. To book your room, call 1-888-627-7054 or 617-236-6148 and mention that you are an IBC attendee at this event.                       

               
       
        寡核苷酸的製造，技術，及產品開發       

• 可以直接聽取法規及產業的領導者們，關於品質和純度的規格相關見解，解決貴公司的雜質規格相關迫在眉睫的疑問。
• 實施產業聯盟的最新資訊，以及持續性流程檢驗。
• 在新的化學製程會議中，提供最新報告與化學製程的最新資訊。
  

                胜肽的製造，技術及產品開發       

• 胜肽疫苗相關FDA的展望和規模化報告
• 新的合成技術的未來計劃(附加Lonza，Bachem，EMD的新資料)
• 學習避免在可能延誤產品發布的後期階段問題的解決方法與防止凝集方法。
  

                寡核苷酸治療藥物研發       

• 驗證單鏈RNA，與非編碼RNA，及非肝細胞組織標靶化的新發展趨勢。
• 考量為了寡核苷酸劑市場投入的必要事項是什麼，學習各階段應該預先實施的策略。
• 探究寡核苷酸的給藥相關問題的新解決辦法，有利貴公司的寡核苷酸治療藥物企劃的最新前臨床及臨床資料。
  

                胜肽藥物研發與開發       

• 說明促進肽類支架與結構，及藥物研發的蛋白質間相互作用調節因子的胜肽相關最新趨勢。
• 可以獲得貴公司針對自身企劃的教訓經驗，正在開發的多個胜肽藥物相關的新前臨床及臨床資料。
• 學習胜肽改良的新合成方法及改善分子藥物特性的細胞內胜肽輸送策略。
  

                分子診斷的核酸技術       

• 學習未來的試樣製備和診斷的新技術。
• 確保避免流通中斷的顯示及修正相關供應鏈。
  

                產業首位的科學，商務，及網路活動                與超過750名的參加者和超過90名的技術供應商及服務供應商互相學習，交流，合作。
       

• 提供在簡報和分科委員會中可以直接聽取CBER，FDA及瑞士的 Medical Products Agency等國際法規當局的機會。
• 從全部的大企業及最新的新興生物科技企業，獲得CMC製造，共軛策略，製劑及給藥，最新的劃時代藥物研發趨勢相關最新資料。
  

               

                "TIDES is THE venue for oligonucleotides and peptides together. The complete package only exists in one setting and that's TIDES. There is no forum that has the same level of expertise in one place at one time other than TIDES." - Scott Petersen, Ph.D., Chief Scientific Officer, Liposciences, Inc.       

StephenW

9:30
                                                Nucleic Acid Polymers and Their Application in Hepatitis B Infection (HBV): Efficacy and Safety (9:40)
                        Nucleic acid polymers (NAPs) utilize the sequence independent interaction of PS-ONs with apolipoproteins to block HBsAg-release into the blood. A second generation NAP (REP 9AC') clears the blood of HBsAg in HBV-infected patients which dramatically improves the efficacy of immunotherapy to establish durable immunological control of HBV infection off treatment in most patients. The safety profile of NAPs are presented to demonstrate the toxicological properties of PS-ONs which do not target protein expression.
                        Andrew Vaillant, Ph.D., Vice President and Chief Scientific Officer, REPLICor Inc., Canada
9时30分
乙肝感染（HBV）核酸聚合物及其应用的疗效和安全（9点40）
核酸聚合物（NAPS）的利用独立的序列PS-ONS互动与载脂蛋白阻止乙肝表面抗原释放入血。第二代的NAP（REP9AC“的）清除血中HBsAg HBV感染患者免疫治疗的有效性极大地提高了治疗，大多数患者HBV感染关，建立持久的免疫控制。国家行动方案的安全性，以示PS插件，不针对蛋白表达的毒理学性质。
安德鲁威能，博士，副总裁兼首席科学官，REPLICor公司，加拿大
                       

齐欢畅2

个人对replicor持怀疑态度，去了他们的网站，感觉很山寨，虽说是广谱抗病毒的药物，首页却写了专门对付hbv，总之很假，而且该公司成立的时间也没写，网上流传了六七年，也无法证伪，全凭他们说了算。八成是假的吧，但我不完全否定。

StephenW

回复 齐欢畅2 的帖子


你读他们的 法文/英文版网站? REPLICor公司于1999年开始经营.
"网上流传了六七年" - 这是不真实的. 不是"网上流传", 是在国际会议上发表了六七年!

齐欢畅2

不知为什么一直没有出产品呢，搜索了一些资料，好像药物对多种病毒都有效果，但就是没产品，这不得不引起怀疑啊，可能国外研发周期长吧。