Hepion Pharmaceuticals’ Rencofilstat, in Combination with an Immune Checkpoint Inhibitor, Demonstrates Synergistic Anti-Tumor Activity in a Nonclinical Liver Cancer Study
January 26 2022 - 8:00AM
Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage
biopharmaceutical company focused on Artificial Intelligence
(“AI”)-driven therapeutic drug development for the treatment of
non-alcoholic steatohepatitis (“NASH”) and hepatocellular carcinoma
(“HCC”), today announced the results of a nonclinical research
study showing that its clinical phase drug candidate, rencofilstat
(CRV431), synergistically decreased liver tumor growth and extended
mouse survival when combined with an anti-PD1 antibody, an immune
checkpoint inhibitor (“ICI”). The effects were observed in fatty
livers, which may be associated with lower anti-PD1 efficacy in
HCC, suggesting that rencofilstat may increase the treatment
potential of anti-PD1 treatment in human liver cancer.
The study was conducted by Fibrofind Ltd
(Newcastle, UK) in collaboration with Professor Derek Mann, Dean of
Research, and Innovation at Newcastle University. In this study,
mice were first fed a Western-type diet (high fat, cholesterol, and
sugar) for three months to generate fatty livers, followed by
surgical implantation of cancerous HCC cells (mouse hep53.4 cell
line) into the livers. Drug treatments began on Day 14 after HCC
cell implantation, when tumors were approximately 15% of their
final, end-of-study size. Mice received either once-daily, orally
administered rencofilstat; twice-weekly, intraperitoneally
administered anti-PD1 antibody; or a combination of both
rencofilstat and anti-PD1. In the first study arm, drugs were
administered from Day 14 to Day 28 post-tumor cell implantation,
followed by measurement of liver tumor size. In the second study
arm, drugs were administered from Day 14 post-tumor cell
implantation until ethical euthanasia or death of the mice
resulting from tumor growth.
Neither rencofilstat nor anti-PD1 administered alone altered the
size of tumors at Day 28, nor the survival of the mice compared to
vehicle treatment. In contrast, combination treatment of
rencofilstat plus anti-PD1 decreased tumor size by 69% at Day 28
(p=0.022) and increased median mouse survival time by 26% (vehicle
19.5 days; rencofilstat + anti-PD1 24.5 days; p=0.0011), compared
to vehicle treatment. A robust anti-tumor effect from the drug
combination, but not from monotherapy treatments, is an indication
of rencofilstat and anti-PD1 synergy.
“Anti-PD1 therapies that stimulate immune cell attack on cancer
cells are approved and effective in many types of cancer, but they
have had limited success in HCC clinical trials. The lack of
clinical outcomes success may be partly due to the occurrence of
HCC in individuals that also have non-alcoholic fatty liver disease
(NAFLD) or the more advanced form of the disease, NASH. NAFLD and
NASH are both highly prevalent across the globe, and recent reports
indicate that a fatty liver environment blocks the efficacy of
anti-PD1 drugs, and perhaps other checkpoint inhibitors. In
addition, as successful treatments for viral hepatitis have been
implemented, NASH has been quickly becoming the leading cause of
HCC,” said Daren Ure, PhD, Hepion’s Chief Scientific Officer.
Dr. Ure continued, “In agreement with this known limitation of
these drugs, our own studies found that treatment with either
anti-PD1 or rencofilstat alone in the hep53.4 HCC model decreased
tumor growth by 76% when tumorigenic cells were implanted into
non-fatty livers1 but were not effective as monotherapies in fatty
livers in the current study. It is also significant to note that
rencofilstat in combination with anti-PD1 not only decreased tumor
growth, but also extended the survival of the mice in this very
aggressive model of HCC. We are continuing to study the mechanisms
underlying the synergistic effect of rencofilstat and
anti-PD1.”
Robert Foster, PharmD, PhD, Hepion’s CEO, further commented,
“HCC is the most common type of liver cancer. It has a poor
prognosis compared to many other types of cancer, claiming
approximately 800,000 lives annually across the globe. Although a
few therapeutic compounds have been approved for non-resectable
HCC, response rates are still low and there remains an urgent need
for new, safe, and effective anti-HCC therapies. We were excited to
have received authorization from the U.S. Food and Drug
Administration last month to move directly into a Phase 2a study of
rencofilstat for the treatment of HCC, and have already begun
preparations to initiate that trial in parallel with our Phase 2b
NASH clinical program in H2-2022. As far as we are aware,
rencofilstat is the only drug in development that is being
clinically evaluated in these two severe, and often comorbid liver
indications.”
Reference
1
https://www.globenewswire.com/news-release/2021/11/16/2335363/0/en/Hepion-Pharmaceuticals-and-FibroFind-Announce-Anti-Cancer-Activity-of-CRV431-in-a-Nonclinical-Liver-Cancer-Study.html
About Hepion Pharmaceuticals
The Company's lead drug candidate, rencofilstat,
is a potent inhibitor of cyclophilins, which are involved in many
disease processes. Rencofilstat is currently in clinical-phase
development for the treatment of NASH, with the potential to play
an important role in the overall treatment of liver disease - from
triggering events through to end-stage disease. Rencofilstat has
been shown to reduce liver fibrosis and hepatocellular carcinoma
tumor burden in experimental models of NASH, and has demonstrated
antiviral activities towards HBV, HCV, and HDV through several
mechanisms, in nonclinical studies. In November 2021, the U.S. Food
and Drug Administration (“FDA”) granted Fast Track designation for
rencofilstat for the treatment of NASH. That was soon followed in
December 2021 by the FDA’s acceptance of Hepion’s investigational
new drug (IND) application for rencofilstat for the treatment of
hepatocellular carcinoma (HCC).
Hepion has created a proprietary AI platform, called AI-POWR™,
which stands for Artificial Intelligence -
Precision Medicine; Omics
(including genomics, proteomics, metabolomics, transcriptomics, and
lipidomics); World database access; and
Response and clinical outcomes. Hepion intends to
use AI-POWR™ to help identify which NASH patients will best respond
to rencofilstat, potentially shortening development timelines and
increasing the delta between placebo and treatment groups. In
addition to using AI-POWR™ to drive its ongoing NASH clinical
development program, Hepion intends to use the platform to identify
additional potential indications for rencofilstat to expand the
company's footprint in the cyclophilin inhibition therapeutic
space.
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 Hepion
Pharmaceuticals’ 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; risks associated with delays,
increased costs and funding shortages caused by the COVID-19
pandemic; 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. Hepion Pharmaceuticals does not undertake
an obligation to update or revise any forward-looking statement.
Investors should read the risk factors set forth in Hepion
Pharmaceuticals’ Form 10-K for the year ended December 31, 2020,
and other periodic reports filed with the Securities and Exchange
Commission.
For further information, please contact:
Stephen KilmerHepion Pharmaceuticals Investor RelationsDirect:
(646) 274-3580skilmer@hepionpharma.com
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