ContraVir说CMX157有资料报道，在HEPDART显示增强体外的安全性

StephenW

ContraVir (CTRV) Says CMX157 Data Reported at HEP DART Shows Enhanced in vitro Safety Profile vs Viread

ContraVir Pharmaceuticals, Inc. (NASDAQ: CTRV) reports positive results regarding CMX157's significantly enhanced potency against hepatitis B virus (HBV), now determined to be 97-fold compared to tenofovir (TFV), based on state-of-the-art in vitro studies. These results from head-to-head studies support CMX157's potential for an enhanced safety profile compared to Gilead's tenofovir DF (Viread®).

The data were presented at HEP DART 2015 by John Sullivan-Bolyai, MD, MPH, Chief Medical Officer of ContraVir, who stated, "These compelling results, derived from state-of-the-art in vitro studies, show that CMX157 potentially demonstrates equal, if not better, antiviral activity at low doses compared to Viread®. Furthermore, we've consistently shown that CMX157 not only has less cytotoxicity than Viread® in vitro along with a low potential for mitochondrial toxicity, but should significantly reduce the amount of TFV exposure outside the liver, further enhancing the safety profile of CMX157 compared to Viread®. These favorable results provide a solid foundation for advancing our Hepatitis B clinical program."

The presentation is available on the ContraVir website, www.contravir.com.

CMX157 demonstrates a potential enhanced safety profile compared to Viread® (Tenofovir DF, TDF)

    CMX157 exhibited a low potential for mitochondrial toxicity in a standard assay of mitochondrial integrity under glucose vs. galactose growth conditions, confirming previous in vitro results.
    CMX157 was less cytotoxic than TDF, based on IC50 concentrations that were consistently similar to or higher than TDF across a large panel of diverse cell lines.

CMX157 is 97-fold more active against HBV than TFV in vitro

    Final results, from a greater number of experiments, improved upon earlier estimates of 60-fold greater potency of CMX157 compared to TFV.
    The amount of drug required to inhibit HBV DNA in HepG2.2.15 liver cells was dramatically lower (EC50 = 15.03 +/- 4.31 nM) for CMX157 compared to TFV (EC50 1460 +/- 1127 nM).

CMX157 is highly liver targeted (rat model), limiting exposure of other tissues to TFV

    After a single, oral dose, 86% of absorbed CMX157 was rapidly extracted by the liver.
    Blood levels of CMX157 peaked at 1-3 hours and then declined rapidly, becoming undetectable after 6 hours; only low levels of TFV were detected in the peripheral circulation.
    There was no substantial accumulation or retention in the heart following oral or intravenous administration.

CMX157 is rapidly and efficiently converted to the active antiviral, TFV diphosphate by liver cells, consistent with its improved antiviral activity and potential for dose reduction

    CMX157 was efficiently metabolized by hepatocytes into active TFV diphosphate (TFV-PP).
    CMX157 metabolism in vitro was time- and dose-dependent, yielding proportional levels of TFV and TFV-PP over time, during which liver cells remained fully viable.
    CMX157 showed only minimal metabolism by cardiomyocytes in vitro compared to Viread®.

CMX157 exhibits low potential for drug-drug interactions

    CMX157 did not exhibit significant induction/inhibition of key metabolic enzymes or transporters in vitro.

StephenW

ContraVir（CTRV）说CMX157有资料报道，在高能物理DART显示增强体外的安全性VS Viread的

ContraVir制药公司（纳斯达克股票代码：CTRV）报告关于CMX157的显著增强抗乙型肝炎病毒的效力（HBV）阳性结果，现在确定为97倍相比，替诺福韦（TFV）的基础上，先进设备，先进的体外研究。这些结果来自头对头研究支持CMX157的潜力，增强的安全性相比，Gilead公司替诺福韦DF（Viread®）。

这些数据是由约翰·沙利文，波尔约，MD，MPH，ContraVir的首席医疗官，谁说，“这些令人瞩目的成果，从体外研究国家的最先进的来源提出了在高能物理DART 2015年，表明CMX157潜在演示相等的，如果不是更好，在低剂量的抗病毒活性相比Viread®。此外，我们已经一致表明CMX157不仅具有比Viread®细胞毒性较少体外连同低电位为线粒体毒性，但应显著减少的量肝外被害人信托基金接触，进一步增强CMX157的安全性相比，Viread®，这些有利的结果为推进我国乙型肝炎的临床方案的坚实基础“。

这次报告是可在ContraVir网站，www.contravir.com上。

CMX157演示相比，Viread®潜在的增强的安全性（替诺福韦，TDF）

    CMX157表现出低电位线粒体毒性的线粒体完整性的标准检测下，葡萄糖与半乳糖的生长条件，证实先前的体外研究结果。
    CMX157比TDF的细胞毒性更小，根据IC 50浓度分别是在不同的细胞系的一个大的面板始终如一相似或高于TDF。

CMX157是97倍更积极的抗HBV比TFV体外

    最终的结果，从更大数量的实验中，改善在早先的估计60倍CMX157的更大的效力相比TFV。
    在抑制HBV DNA中的HepG2.2.15肝细胞所需的药物量显着降低（EC 50 = 15.03 +/- 4.31海里）CMX157相比，被害人信托基金（EC50 1460 +/- 1127纳米）。

CMX157是高度肝靶向（大鼠模型），限制其他组织暴露于TFV

    后一个单一的，口服，吸收CMX157的86％由肝脏迅速萃取。
    CMX157的血液水平达到高峰，1〜3小时，然后迅速下降，成为检测不到6小时后，在末梢循环中检测到的TFV的只有低的水平。
    有是在心脏以下的口服或静脉给药没有丰厚的积累或保留。

CMX157迅速而有效地转化为具有活性的抗病毒，TFV二磷酸被肝细胞，与减少剂量的改进的抗病毒活性和潜在的一致

    CMX157是有效的肝细胞进入活跃TFV二磷酸（TFV-PP）代谢。
    CMX157代谢体外是时间和剂量依赖的，得到TFV和TFV-PP的比例水平随时间，在此期间，肝细胞仍然完全可行的。
    CMX157显示由心肌细胞在体外相比Viread®只有很少的新陈代谢。

CMX157出低潜力的药物相互作用

    CMX157没有表现出在体外关键代谢酶或转运的显著诱导/抑制。

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感谢sw  忙了一年，想念老王。最近老王怎么就哑了火了？