箭头提交申请书开始ARC- 520阶段2a试验

StephenW

咬牙硬挺 发表于 2013-11-26 20:49
感觉比rep靠谱，但愿进展顺利

也许，箭头筹集了6000万美元资金 (从股市).

相信医学

好消息。

boom413

科技在进步,这些真正做实事的公司,他们要赚钱,就给他们赚,只要能做一些事情!

相信医学

对，支持。

齐欢畅2

rep和arc520都值得关注

StephenW

Result: DPC delivery结果：DPC传递
Ligand mediated targeting of DPCs to Hepatocytes in Liver配体介导的DPCs靶向肝细胞
红色 - siRNA
蓝色 - 细胞核
绿色 - 细胞膜
图A - NAG配体
图B - 葡萄糖配体

StephenW

ARC-520 Results

In animal models of HBV infection, a single co-injection of the DPC delivery vehicle with cholesterol-conjugated siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect.
Treatment in mouse model of HBV infection
Treatment with ARC-520 in a non-transgenic mouse model for HBV infection resulted in strong reduction of serum viral markers, notably the following:

Decreased S-Antigen 3-4 log reduction with the most potent chol-siHBVs Greater than 2 log reduction for one month Decreased viral DNA Approximately 3 log reduction of HBV DNA for one month Decreased E-Antigen Knockdown to limit of detection for at least one month

ARC-520结果

在HBV感染，单个共注射与胆固醇偶联的靶的siRNA的DPC递送载体的动物模型中的HBV序列导致了HBV RNA，蛋白质和病毒DNA带的效果持续时间长的多记录击倒。

治疗小鼠HBV感染模型

治疗与ARC-520在非转基因小鼠模型的HBV感染后，强烈降低的血清病毒标记物，尤其是以下内容：

降低S-抗原

    3-4数减少最有力哲 -  siHBVs
    大于2的对数下降为一个月

减少病毒DNA

    HBV DNA的约3为一个月log减少

降低e抗原

    拦截到的检测极限为至少一个月

StephenW

Treatment in an HBV-infected Chimpanzee
A low dose of ARC-520 induced rapid and deep reductions in viral particles and key viral antigens in a chimpanzee chronically infected with hepatitis B virus. The treatment was well-tolerated and led to a 95% reduction in circulating viral DNA, and approximately 90% reductions in hepatitis e-antigen (HBeAg) and s-antigen (HBsAg). The chimp being treated had exceptionally high titers of circulating HBV DNA and HBsAg that measured 1,000 to 10,000-fold higher than the average chronic hepatitis B patient. The HBV infection has been chronic for over thirty years and has persisted despite prior therapy with multiple anti-viral drugs and therapeutic vaccine exposures. Notably, these results were achieved despite a mismatch in sequence between the viral DNA and one of the siRNAs included in ARC-520.

治疗在乙肝病毒感染的黑猩猩

的ARC-520诱导快速和大幅度削减病毒颗粒和关键病毒抗原在黑猩猩低剂量感染慢性B型肝炎病毒。治疗耐受性良好，并导致在循环的病毒DNA减少95％，约90％的减少，肝炎E-抗原（HBeAg）和s-抗原（HBsAg）。正在接受治疗的黑猩猩有循环HBV DNA和乙肝表面抗原的异常高滴度的测定1000〜10000倍比一般的慢性乙型肝炎患者高。在HBV感染已慢性超过三十年，并一直坚持，尽管之前的治疗有多种抗病毒的药物和治疗性疫苗的风险。值得注意的是，这些结果均达到尽管在序列的病毒DNA和siRNA的1之间的不匹配包括在ARC-520。

StephenW

为什么HBsAg的下降（图3）不是一样迅速，相比 HBVDNA下降（图1）或e抗原下降（图2）？

StephenW

灰色区域 - ALT
蓝线 - 乙肝表面抗原
X axis - 日
the data demonstrate that intravenous administration of two doses (2 mg/kg, 3 mg/kg) of ARC-520 in a chimpanzee chronically infected with HBV, resulted in substantial and sustained reductions in HBV DNA, HBeAg, and HBsAg, which did not return to baseline until study day 43, 43, and 71 respectively. In addition, an increase in serum alanine transaminase (ALT) occurred 4 weeks after the last dose, coincident with the nadir of circulating HBsAg. This is suggestive of a therapeutic immunological flare, which is thought to be part of a cascade that under chronic therapy may lead to HBsAg seroconversion and functional cure. Robert E. Lanford, Ph.D., of the Texas Biomedical Research Institute where the study was conducted, presented these data and the poster was selected as a Presidential Poster of Distinction indicating that it was in the top 10% of all abstracts selected for poster presentation.

“This study would have been important if ARC-520 just demonstrated safe and effective HBsAg reduction because this is thought to be a necessary step in achieving a functional cure,” said Dr. Lanford. “What is really exciting about these data, however, is that we appear to have seen immune de-repression, the next step toward HBsAg seroconversion and functional cure. The timing of the ALT rise and associated increases in key chemokine/cytokine mRNAs suggest that they were related to the therapy-induced reduction in circulating HBsAg and represented an immunological event.”
该数据表明的ARC- 520两种剂量（ 2毫克/公斤， 3毫克/公斤）的黑猩猩慢性HBV感染的静脉给药，导致大量和持续降低HBV DNA和HBeAg ，与HBsAg ，哪些没有回到基线，直到分别研究一天43 ， 43 ，和71 。此外，增加血清丙氨酸转氨酶（ ALT ）发生后4周的最后一剂，暗合循环HBsAg的最低点。这是暗示治疗免疫耀斑，这被认为是，在长期治疗可能导致HBsAg血清学转换和功能治愈级联的一部分。罗伯特·E·兰福德德州生物医学研究所在那里进行的研究，博士，发表上述研究资料和海报被选为优异的总统海报，表明它是在选定的所有论文摘要的前10％海报介绍。

“这项研究将是重要的，如果ARC- 520只是证明安全有效的乙肝表面抗原减少，因为这被认为是在实现一个功能治愈的必要步骤， ”兰福德博士说。 “什么是真正令人兴奋的关于这些数据，但是，我们似乎已经看到免疫力去压制，对HBsAg血清学转换和功能治愈下一步。的ALT升高和时间的关键趋化因子/细胞因子mRNA的增加相关联表明，它们均与循环中的乙肝表面抗原治疗引起的减少和代表的免疫活动。 “