ContraVir Reports New CRV431 Data Highlighting Synergistic Activity with CMX157 Against Hepatitis B

EDISON, N.J., Sept. 12, 2016 /PRNewswire/ -- ContraVir Pharmaceuticals, Inc. (NASDAQ: CTRV), a biopharmaceutical company focused on the development and commercialization of targeted antiviral therapies, today announced that it has taken a major step forward in its pursuit of a potentially curative combination therapy for chronic hepatitis B (HBV).  The Company presented new preclinical data profiling the robust anti-HBV activity of its potentially best-in-class cyclophilin inhibitor CRV431, including evidence of synergy with CMX157, ContraVir's highly potent prodrug of tenofovir, when the two drugs are used together.  CMX157 is currently in Phase 2 clinical trials in Thailand.

The peer-reviewed findings were presented at a joint meeting sponsored by the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) called HBV Treatment Endpoints Workshop: From Discovery to Regulatory Approval, in a poster titled, "CRV431: An Optimized Cyclophilin Inhibitor with Multiple Anti-HBV Activities, High Selectivity Index, and Synergy with CMX157."

Human liver cells (AD38) treated in vitro with multiple combinations of CRV431 and CMX157 showed synergistic inhibition of HBV replication, as measured by a reduction in HBV DNA.  These data are the first to demonstrate synergistic activity of these drugs against HBV, confirming ContraVir's belief that a combination of CRV431 and CMX157 may be more effective at killing the virus by potently targeting multiple stages of the viral life cycle.

"This study validates our approach and the significant opportunity we have to leverage our two HBV assets to create a uniquely powerful combination therapy and potential functional cure for hepatitis B," said James Sapirstein, CEO of ContraVir. "On its own, CRV431 demonstrates the potential to address multiple key endpoints thought to be essential for curing HBV.  As we have seen with other successfully cured viral diseases, combination with a proven backbone therapy like tenofovir/CMX157 may unlock the full potential of these drugs and bring us closer to an HBV cure."

Data from the study also describe the in vitro anti-HBV activity of CRV431, as well as other clinically relevant findings.  Importantly, CRV431 was shown to have the widest selective index of any known cyclophilin inhibitor, calculated by CC₅₀/IC₅₀ ratio.  This optimized selective index may correlate with a best-in-class therapeutic index, and therefore, enhanced clinical utility against HBV.  Other key findings for CRV431 monotherapy in vitro include:

• Cyclophilin-independent inhibition of viral uptake by liver cells through its common route, the sodium taurocholate co-transporting polypeptide (NTCP) receptor;
• Significantly greater potency compared to a related cyclophilin inhibitor, alisporovir, as measured by inhibition of intracellular HBV DNA in AD38 cells; and
• Inhibition of production and/or secretion of HBV antigens HBeAg and HBsAg by infected or transfected Huh7 cells.  Reduction or elimination of these antigens is considered to be a key requirement for a curative HBV regimen.

In vivo studies in rats and mice highlighted additional characteristics of CRV431 that enhance its profile.  Dosing studies showed that CRV431 is suitable for oral dosing, demonstrating a significantly improved oral pharmacokinetic profile compared to cyclosporine A, the parent molecule from which CRV431 is derived.  Additionally, in a mouse model of liver fibrosis, orally-administered CRV431 was shown to reduce the area of fibrosis in a dose dependent manner.  This activity is independent of viral inhibition and instead may be a result of CRV431's interaction with host cyclophilins, which are implicated in multiple pro-fibrotic mechanisms.

Mr. Sapirstein concluded, "We are highly encouraged by these findings, which clearly support further development of CRV431 into IND-enabling studies and ultimately into clinical development in human combination studies with CMX157.  We expect to continue preclinical development of CRV431, with a potential IND filing in the last quarter of 2017."

About ContraVir Pharmaceuticals

ContraVir is a biopharmaceutical company focused on the development and commercialization of targeted antiviral therapies with a specific focus on developing a potentially curative therapy for hepatitis B virus (HBV). The Company is developing two novel anti-HBV compounds with complementary mechanisms of action: CMX157, a highly potent analog of the successful antiviral drug tenofovir currently in Phase 2a, which has demonstrated the potential for low, once a day dosing compared to Viread^® and decreased systemic exposure, thereby potentially reducing renal and bone side effects; and CRV431, a next generation cyclophilin inhibitor with a unique structure that increases its potency and selective index against HBV. ContraVir is also developing FV-100, an orally available nucleoside analogue prodrug for the treatment of herpes zoster, or shingles, in a Phase 3 clinical trial. In addition to direct antiviral activity, FV-100 has demonstrated the potential to reduce the incidence of debilitating shingles-associated pain known as post-herpetic neuralgia (PHN) in a Phase 2 clinical study. For more information visit www.contravir.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as "anticipate," "believe," "forecast," "estimated" and "intend," among others. These forward-looking statements are based on ContraVir's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. ContraVir does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in ContraVir's Form 10-K for the year ended June 30, 2015 and other periodic reports filed with the Securities and Exchange Commission.

For further information, please contact:

Sharen Pyatetskaya
Director of Investor Relations
[email protected]; (732) 902-4028

Tiberend Strategic Advisors, Inc. 
Joshua Drumm, Ph.D. (investors)
[email protected]; (212) 375-2664

Claire LaCagnina (media)
[email protected]; (212) 375-2686

SOURCE ContraVir Pharmaceuticals, Inc.

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