- Novel, oral opaganib, delivered a statistically
significant increase in survival time (at 150 mg/kg BID) in a U.S.
Army-funded in vivo Ebola virus study
- Opaganib is believed to be the first host-directed molecule
to show activity in Ebola virus disease, having previously shown in
vitro benefit in several strains of Ebola virus disease
models
- Twice daily administered opaganib has previously
demonstrated antiviral benefit in late-stage clinical studies of
patients hospitalized with moderate to severe COVID-19; opaganib
was also selected by the NIH Radiation and Nuclear Countermeasures
Program (RNCP) for Acute Radiation Syndrome development
TEL
AVIV, Israel and RALEIGH,
NC, Oct. 3, 2023 /PRNewswire/ -- RedHill
Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a
specialty biopharmaceutical company, today announced that novel,
twice daily, oral opaganib[1], delivered a statistically
significant increase in survival time when given at 150 mg/kg twice
a day (BID) in a United States Army Medical Research Institute of
Infectious Diseases (USAMRIID) in vivo Ebola virus study,
making it the first host-directed molecule to show activity in
Ebola virus disease.
Rekha Panchal, Ph. D of
USAMRIID, who led the study, said: "These results represent an
alternative strategy of using a host-directed therapeutic with
activity in Ebola virus disease in-vivo. Given the unmet medical
need and the untapped potential of host-directed antivirals, these
results with opaganib, an easy to distribute and administer oral
small molecule drug, support its further investigation for use in
treating Ebola."
The U.S. Army study tested three doses of opaganib (50, 100 and
150 mg/kg BID), against an inactive vehicle control arm. The in
vivo study results showed a statistically significant survival
increase in mean (SE) survival time of 11.2 (2.6) days in the 150
mg/kg opaganib group (p=0.0279) compared to a mean (SE) survival
time of 5.5 (0.4) days in the inactive vehicle control group. A 30%
mice survival was observed in the 150 mg/kg treated group compared
to the vehicle control.
"We believe opaganib is the most advanced sphingosine kinase-2
(SPHK2) selective inhibitor in clinical development, and the more
we learn about this molecule, its novel host-directed mechanism of
action, and its growing safety and tolerability database, the more
promising it appears," said Reza
Fathi, PhD, RedHill's SVP R&D. "Opaganib has shown
its host-directed antiviral potential in clinical and non-clinical
studies, warranting further investigation in Ebola and other
infectious viral diseases. Working through the inhibition of
multiple pathways, anti-inflammatory properties, the induction of
autophagy and apoptosis, and disruption of viral replication and
potential inhibition of cell entry via simultaneous inhibition of
three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1
and GCS), we believe opaganib offers a potential breakthrough for
fighting a virus capable of causing devastating outbreaks of
disease in the countries least equipped to cope with them."
Twice daily administered opaganib has previously demonstrated
antiviral benefit in late-stage clinical studies of patients
hospitalized with moderate to severe COVID-19 and was selected by
the NIH Radiation and Nuclear Countermeasures Program (RNCP) for
Acute Radiation Syndrome development.
About Ebola virus disease:
According to the Centers for Disease Control and Prevention
(CDC), Ebola disease is a rare and often deadly illness, caused by
infection by one of a group of four viruses, known as ebolaviruses,
that are found primarily in sub-Saharan Africa and are known as:
Zaire, Sudan, Taï Forest (formerly Côte d'Ivoire) and
Bundibugyo. Transmission of the disease is mostly through contact
with an infected animal (bat or nonhuman primate) or a sick or dead
person infected with an ebolavirus. The course of the illness
typically progresses from "dry" symptoms initially (such as fever,
aches and pains, and fatigue), and then progresses to "wet"
symptoms (such as diarrhea, vomiting and unexplained hemorrhaging,
bleeding or bruising) as the person becomes sicker. There are
currently only two FDA-approved therapies to treat EVD caused by
the Ebola virus, species Zaire
ebolavirus, in adults and children; Inmazeb™, a combination of
three monoclonal antibodies and Ebanga™, a single monoclonal
antibody. Both are intravenously infused direct acting monoclonal
antibody antivirals that bind to glycoproteins on the Ebola virus's
surface to prevent the virus from entering a person's cells. There
is an urgent need for host-directed small molecule therapies that
may be effective against multiple strains of ebolavirus, less
likely to be impacted by viral mutation, and that are easy to
store, distribute and administer, especially in areas where
healthcare services and infrastructures may be
sub-optimal.
About Opaganib (ABC294640)
Opaganib, a proprietary investigational host-directed and
potentially broad-acting drug, is a first-in-class, orally
administered sphingosine kinase-2 (SPHK2) selective inhibitor with
anticancer, anti-inflammatory and antiviral activity, targeting
multiple potential diseases, including gastrointestinal acute
radiation syndrome (GI-ARS), COVID-19, other viruses as part of
pandemic preparedness, and cholangiocarcinoma (bile duct
cancer).
Opaganib's host-directed action is thought to work through the
inhibition of multiple pathways, the induction of autophagy and
apoptosis, and disruption of viral replication, through
simultaneous inhibition of three sphingolipid-metabolizing enzymes
in human cells (SPHK2, DES1 and GCS).
Opaganib was recently selected by the U.S. Government's
Radiation and Nuclear Countermeasures Program (RNCP), led by the
National Institute of Allergy and Infectious Diseases, part of the
National Institutes of Health, for the nuclear medical
countermeasures product development pipeline as a potential
treatment for Acute Radiation Syndrome (ARS). As part of this
collaboration, contractors directed and supported by the RNCP will
undertake studies, designed in collaboration with RedHill, to test
opaganib in established ARS models. In an ARS setting, opaganib is
thought to exert its protective effects via an anti-inflammatory
mechanism of action involving ceramide elevation and reduction of
sphingosine 1-phosphate (S1P) in human cells - suppressing
inflammatory damage to normal tissue and thus suppressing toxicity
from unintended ionizing radiation exposure. It has also been
reported in the literature that inhibition of sphingosine kinase 2
promotes the viability and robustness of hematopoietic stem cells,
even in the face of radiation damage, supporting increased
survival.
Opaganib has received Orphan Drug designation from the FDA for
the treatment of cholangiocarcinoma and has undergone studies in
advanced cholangiocarcinoma (Phase 2a) and prostate cancer.
Opaganib also has a Phase 1 chemoradiotherapy study protocol ready
for FDA-IND submission.
Opaganib has demonstrated antiviral activity against SARS-CoV-2,
multiple variants, and several other viruses, such as Influenza A.
Being host-targeted, and based on data accumulated to date,
opaganib is expected to maintain effect against emerging viral
variants. In prespecified analyses of Phase 2/3 clinical data in
hospitalized patients with moderate to severe COVID-19, oral
opaganib demonstrated improved viral RNA clearance, faster time to
recovery and significant mortality reduction in key patient
subpopulations versus placebo on top of standard of care. Data from
the opaganib global Phase 2/3 study has been submitted for peer
review and recently published in medRxiv.
Opaganib has also shown positive preclinical results in renal
fibrosis, and has the potential to target multiple oncology,
radioprotection, viral, inflammatory, and gastrointestinal
indications.
About USAMRIID
Since 1969, USAMRIID has served as the Department of Defense's
(DoD) lead laboratory for medical biological defense research. The
core mission is to protect the warfighter from biological threats,
while also investigating disease outbreaks and threats to public
health. Research conducted at USAMRIID leads to medical
solutions—therapeutics, vaccines, diagnostics, and information—that
benefit both military personnel and civilians. USAMRIID is a
subordinate laboratory of the U.S. Army Medical Research and
Development Command.
About RedHill Biopharma
RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty
biopharmaceutical company primarily focused on gastrointestinal and
infectious diseases. RedHill promotes the gastrointestinal drugs
Talicia®, for the treatment of Helicobacter
pylori (H. pylori) infection in
adults[2], and Aemcolo®,
for the treatment of travelers' diarrhea in
adults[3]. RedHill's key clinical late-stage
development programs include: (i) opaganib (ABC294640),
a first-in-class oral broad-acting, host-directed
SPHK2 selective inhibitor with potential for pandemic preparedness,
targeting multiple indications with a U.S. Government collaboration
for development for Acute Radiation Syndrome (ARS), a Phase 2/3
program for hospitalized COVID-19, and a Phase 2 program in
oncology; (ii) RHB-107 (upamostat), an oral
broad-acting, host-directed, serine protease inhibitor with
potential for pandemic preparedness is in late-stage development as
a treatment for non-hospitalized symptomatic COVID-19, and is also
targeting multiple other cancer and inflammatory gastrointestinal
diseases; (iii) RHB-102, with potential UK submission
for chemotherapy and radiotherapy induced nausea and vomiting,
positive results from a Phase 3 study for acute gastroenteritis and
gastritis and positive results from a Phase 2 study for IBS-D;
(iv) RHB-104, with positive results from a first Phase
3 study for Crohn's disease; and (v) RHB-204, a
Phase 3-stage program for pulmonary nontuberculous mycobacteria
(NTM) disease.
More information about the Company is available at:
www.redhillbio.com / twitter.com/RedHillBio.
Forward Looking Statements
This press release contains "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Such statements, including, but not limited to, statements
regarding the intended use of net proceeds therefrom, may be
preceded by the words "intends," "may," "will," "plans," "expects,"
"anticipates," "projects," "predicts," "estimates," "aims,"
"believes," "hopes," "potential" or similar words and include
statements regarding anticipated the addition of new revenue
generating products, out-licensing of the Company's development
pipeline assets, timing of opaganib's development for Acute
Radiation Syndrome, non-dilutive development funding from RHB-107
and its inclusion in a key platform study. Forward-looking
statements are based on certain assumptions and are subject to
various known and unknown risks and uncertainties, many of which
are beyond the Company's control and cannot be predicted or
quantified, and consequently, actual results may differ materially
from those expressed or implied by such forward-looking statements.
Such risks and uncertainties include, without limitation, market
and other conditions, the risk that the addition of new revenue
generating products or out-licensing transactions will not occur;
the risk that acceptance onto the RNCP Product Development Pipeline
will not guarantee ongoing development or that any such development
will not be completed or successful; the risk that the FDA does not
agree with the Company's proposed development plans for opaganib
for any indication, the risk that observations from preclinical
studies are not indicative or predictive of results in clinical
trials; the risk that the FDA pre-study requirements will not be
met and/or that the Phase 3 study of RHB-107 in COVID-19
outpatients will not be approved to commence or if approved, will
not be completed or, should that be the case, that we will not be
successful in obtaining alternative non-dilutive development
funding for RHB-107, the risk that HB-107's late-stage development
for non-hospitalized COVID-19 will not benefit from the resources
redirected from the terminated RHB-204 Phase 3 study, that the
Phase 2/3 COVID-19 study for RHB-107 may not be successful and,
even if successful, such studies and results may not be sufficient
for regulatory applications, including emergency use or marketing
applications, and that additional COVID-19 studies for opaganib and
RHB-107 are likely to be required, as well as risks and
uncertainties associated with the risk that the Company will not
successfully commercialize its products; as well as risks and
uncertainties associated with (i) the initiation, timing, progress
and results of the Company's research, manufacturing, pre-clinical
studies, clinical trials, and other therapeutic candidate
development efforts, and the timing of the commercial launch of its
commercial products and ones it may acquire or develop in the
future; (ii) the Company's ability to advance its therapeutic
candidates into clinical trials or to successfully complete its
pre-clinical studies or clinical trials or the development of a
commercial companion diagnostic for the detection of MAP; (iii) the
extent and number and type of additional studies that the Company
may be required to conduct and the Company's receipt of regulatory
approvals for its therapeutic candidates, and the timing of other
regulatory filings, approvals and feedback; (iv) the manufacturing,
clinical development, commercialization, and market acceptance of
the Company's therapeutic candidates and Talicia®; (v) the
Company's ability to successfully commercialize and promote
Talicia® and Aemcolo®; (vi) the Company's ability to establish and
maintain corporate collaborations; (vii) the Company's ability to
acquire products approved for marketing in the U.S. that achieve
commercial success and build its own marketing and
commercialization capabilities; (viii) the interpretation of the
properties and characteristics of the Company's therapeutic
candidates and the results obtained with its therapeutic candidates
in research, pre-clinical studies or clinical trials; (ix) the
implementation of the Company's business model, strategic plans for
its business and therapeutic candidates; (x) the scope of
protection the Company is able to establish and maintain for
intellectual property rights covering its therapeutic candidates
and its ability to operate its business without infringing the
intellectual property rights of others; (xi) parties from whom the
Company licenses its intellectual property defaulting in their
obligations to the Company; (xii) estimates of the Company's
expenses, future revenues, capital requirements and needs for
additional financing; (xiii) the effect of patients suffering
adverse experiences using investigative drugs under the Company's
Expanded Access Program; (xiv) competition from other companies and
technologies within the Company's industry; and (xv) the hiring and
employment commencement date of executive managers. More detailed
information about the Company and the risk factors that may affect
the realization of forward-looking statements is set forth in the
Company's filings with the Securities and Exchange Commission
(SEC), including the Company's Annual Report on Form 20-F filed
with the SEC on April 28, 2023. All
forward-looking statements included in this press release are made
only as of the date of this press release. The Company assumes no
obligation to update any written or oral forward-looking statement,
whether as a result of new information, future events or otherwise
unless required by law.
1. Opaganib is an investigational new drug, not
available for commercial distribution.
2. Talicia® (omeprazole magnesium,
amoxicillin and rifabutin) is indicated for the treatment of H.
pylori infection in adults. For full prescribing information
see: www.Talicia.com.
3. Aemcolo® (rifamycin) is indicated for the
treatment of travelers' diarrhea caused by noninvasive strains of
Escherichia coli in adults. For full prescribing information
see: www.aemcolo.com.
Category: R&D
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Company contact:
Adi Frish
Chief Corporate & Business Development Officer
RedHill Biopharma
+972-54-6543-112
adi@redhillbio.com
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SOURCE RedHill Biopharma Ltd.