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
sp@contravir.com; (732) 902-4028
Tiberend Strategic Advisors, Inc.
Joshua Drumm, Ph.D. (investors)
jdrumm@tiberend.com; (212) 375-2664
Claire LaCagnina (media)
clacagnina@tiberend.com; (212) 375-2686
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SOURCE ContraVir Pharmaceuticals, Inc.