Investigational drugs opaganib and RHB-107 (upamostat)
demonstrate distinct synergistic effect when combined individually
with remdesivir, significantly improving potency while maintaining
cell viability, in a new U.S. Army-funded and conducted in vitro
Ebola virus study
Opaganib and RHB-107 are both novel, oral, host-directed,
small molecule investigational drugs that are easy to administer
and distribute, with demonstrated activity against multiple viral
targets, including COVID-19, and are expected to be effective
against emerging viral variants
Opaganib is believed to be the first host-directed molecule
to show activity in Ebola virus disease, having recently delivered
a statistically significant increase in survival time in a separate
U.S. Army-funded in vivo Ebola virus study. RHB-107 was
recently accepted for inclusion in the ACESO PROTECT adaptive
platform trial for early COVID-19 outpatient treatment
TEL-AVIV, Israel and RALEIGH, N.C., Dec. 20,
2023 /PRNewswire/ -- RedHill Biopharma Ltd. (Nasdaq:
RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical
company, today announced that its two novel, oral host-directed
investigational drugs, opaganib[1] and RHB-107
(upamostat)[2], demonstrated robust synergistic effect
when combined individually with remdesivir
(Veklury®)[3], significantly improving viral
inhibition while maintaining cell viability, in a new U.S.
Army-funded and conducted Ebola virus in vitro study.
"These encouraging in vitro results for opaganib and
RHB-107 show a distinct synergy in terms of viral inhibition while
maintaining cell viability (i.e., not increasing toxicity), when
either is added to remdesivir, with opaganib showing the greatest
synergistic effect in combination with remdesivir," said
Jeffrey Kugelman, Ph.D.,
Major(P), US Army MSC, Branch Chief Synthetic Biology &
Surveillance, Molecular Biology Division, U.S. Army Medical
Research Institute of Infectious Diseases (USAMRIID), who led
the bioinformatics analysis of the study. "The results suggest that
opaganib and upamostat may have potential or use in combination
with direct antiviral agents, such as remdesivir, to improve
treatment outcome, increasing efficacy while maintaining
safety."
"Opaganib is believed to be the first host-directed molecule to
show activity in Ebola virus disease, and these results add to a
recent U.S. Army Ebola virus study in which opaganib delivered a
statistically significant increase in mice survival time in
vivo," said Reza Fathi,
Ph.D., RedHill's SVP R&D. "Opaganib and RHB-107 are both
novel, oral, host-directed, small molecule investigational drugs
with demonstrated activity against multiple viral targets,
including COVID-19, and are expected to be effective against
emerging viral variants. This, together with their growing safety
and tolerability databases, presents a compelling hypothesis for
further study of their potential in treating Ebola virus."
Utilizing a checkerboard design to test the study compounds in
combination, the study cell lines were pretreated and then infected
with Ebola virus. The cells were fixed, washed and subjected to
immunofluorescence staining using a virus-specific antibody. The
raw data for the combination was analyzed to determine synergistic,
additivity or antagonistic effects on viral inhibition while taking
into account cell viability.
Twice daily administered opaganib has previously demonstrated
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.
RHB-107 successfully met its U.S. Phase 2 study primary endpoint
of safety and tolerability and delivered promising efficacy
results, including marked reduction in hospitalization due to
COVID-19. RHB-107 was recently accepted for inclusion in the ACESO
PROTECT adaptive platform trial for early COVID-19 outpatient
treatment. The 300-patient PROTECT Phase 2 RHB-107 arm, fully
funded by non-dilutive external funding sources including the U.S.
government[4], has received FDA clearance to start, with
the first patient expected to be enrolled in the coming weeks. The
study is being conducted in the U.S., Thailand, Ivory
Coast, South Africa and
Uganda, and is estimated to be
completed by end of 2024.
About Ebola virus disease:
According to the Centers
for Disease Control and Prevention, 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 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).
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 RHB-107 (upamostat)
RHB-107 is a proprietary,
first-in-class, once-daily orally administered investigational
antiviral, that targets human serine proteases involved in
preparing the spike protein for viral entry into target cells.
Because it is host-cell targeted, RHB-107 is expected to also be
effective against emerging viral variants with mutations in the
spike protein. RHB-107 is well tolerated; in the initial COVID-19
study, among 41 patients only one reported a drug-related adverse
reaction (a mild, self-limited, rash).
In addition, RHB-107 inhibits several proteases targeting cancer
and inflammatory gastrointestinal disease. RHB-107 has undergone
several Phase 1 studies and two Phase 2 studies, demonstrating its
clinical safety profile in approximately 200
patients[5].
RedHill acquired the exclusive worldwide rights to RHB-107,
excluding China, Hong Kong, Taiwan and Macao, from Germany's Heidelberg Pharmaceuticals (FSE:
HPHA) (formerly WILEX AG) for all indications.
About USAMRIID
Since 1969, USAMRIID has served as the
U.S. Department of Defense's 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[6], and Aemcolo®,
for the treatment of travelers' diarrhea in
adults[7]. 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, with
non-dilutive external funding covering the entirety of the RHB-107
arm of the 300-patient Phase 2 adaptive platform trial, 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
compliance with the listing requirements of the Nasdaq Capital
Market ("Nasdaq"), 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 Company will not
comply with the listing requirements of Nasdaq to remain listed for
trading on Nasdaq, 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 the Phase 2/3 COVID-19 study for
RHB-107 and/or the Phase 2 ACESO PROTECT study for RHB-107 may not
be completed or, if completed, may not be successful or, even if
successful, may not be sufficient support for regulatory
applications, including emergency use or marketing applications,
the risk that RHB-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, 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.
Company contact:
Adi Frish
Chief Corporate & Business Development Officer
RedHill Biopharma
+972-54-6543-112
adi@redhillbio.com
Category: R&D
[1] Opaganib is an investigational new drug, not
available for commercial distribution.
[2] RHB-107 is an investigational new drug, not
available for commercial distribution.
[3] Remdesivir, a leading COVID-19 therapy, is sold
under the brand name Veklury® by Gilead Sciences, Inc.
(Nasdaq: GILD)
[4]
https://www.redhillbio.com/news/news-details/2023/RedHill-Announces-New-Non-Dilutive-External-Funding-of-Entire-RHB-107-COVID-19-300-Patient-Phase-2-Study/default.aspx
[5]
https://www.ijidonline.com/article/S1201-9712(22)00638-5/fulltext
[6] 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.
[7] 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.
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