TEL AVIV, Israel and
RALEIGH, N.C., Dec. 15, 2020 /CNW/ -- RedHill Biopharma Ltd.
(Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty
biopharmaceutical company, today announced promising preliminary
results from a preclinical study within which opaganib, a novel,
orally administered sphingosine kinase 2 (SK2) selective inhibitor,
(administered at 250mg/kg,) demonstrating a reduction of thrombosis
(blood clotting) in an acute respiratory distress syndrome (ARDS) –
a preclinical animal model designed to measure thrombotic (blood
clot) risks.
This latest finding points towards another important potential
benefit of opaganib to COVID-19 patients – in addition to the
already established inhibition of SARS-CoV-2 replication and the
potential reduction in hyper immune-response by opaganib. Following
these preliminary findings, additional work is being planned to
evaluate the range of potential physiologically and
pharmacologically relevant opaganib doses with respect to
thrombosis reduction.
"Acute Respiratory Distress Syndrome (ARDS) is one of the most
dangerous outcomes of COVID-19 disease, putting severely ill
COVID-19 patients at an increased risk of potentially fatal venous
thrombosis and pulmonary embolism. There are currently very
limited options available to physicians that have been shown to be
effective against ARDS, and specifically against ARDS-induced
thrombosis," said Reza
Fathi, PhD., RedHill's Senior VP, R&D. "Results from
our study show opaganib 250 mg/kg reduced blood clot length, weight
and total thrombus score in a preclinical model of ARDS. This adds
to the known antiviral and anti-inflammatory activities of opaganib
and provides the potential for a unique triple-action effect on the
pathophysiological processes associated with COVID-19 disease.
Opaganib, which targets a host cell component, potentially
minimizes the likelihood for resistance due to viral mutations.
Before the end of this month, we expect topline clinical data
insights into the safety and potential efficacy signals of opaganib
from the non-powered U.S. Phase 2 study in which the last patient
has been given their last dose on November
26, followed in Q1/2021 by top-line data from the larger
global Phase 2/3 study, which is powered for efficacy and already
more than 60% enrolled."
"The ARDS thrombosis model we used to conduct this work is
validated and highly predictive, and the results we saw with
opaganib are impressive and provide reason for
promise," said Sebastien
Labbe, Ph.D., Director, Translational Research at IPS
Therapeutique Inc., who carried out the study. "The results
provide insight into a highly desirable potential effect of
opaganib for use in managing patients with severe COVID-19, whose
prognosis can be very poor."
ARDS-induced thrombosis may occur in up to one-third of COVID-19
patients requiring Intensive Care Unit (ICU) admission and up to 9%
of all hospitalized patients[1] and is associated
with a poor prognosis. The preclinical study was designed to assess
the efficacy of opaganib in reducing the incidence of adverse
thromboembolic events in situ in the lipopolysaccharide
(LPS)-induced model of pulmonary inflammation, a reliable model of
ARDS that can mimic COVID-19 inflammation[2].
The results from the preclinical study of opaganib are
preliminary and were provided to the Company by an independent
third-party following an initial independent analysis and remain
subject to additional review and analysis. Such review and analysis
may result in findings inconsistent with the results disclosed in
this release and may not be replicated in future preclinical or
clinical studies.
Opaganib is a novel, orally administered, sphingosine kinase-2
(SK2) selective inhibitor with demonstrated dual anti-inflammatory
and antiviral activity that acts on both the cause and the effects
of COVID-19 disease, targeting a host cell component involved in
viral replication, potentially minimizing likelihood of resistance
due to viral mutations.
A U.S. Phase 2 study with opaganib in patients with severe
COVID-19 pneumonia (NCT04414618) has completed enrollment of all 40
subjects, and the last patient has been given their last dose –
top-line data is expected later this month. This Phase 2 study is
not powered for efficacy and is focused on safety evaluation and
identification of efficacy signals.
In parallel, enrollment in the 270-patient global Phase 2/3
study with opaganib in patients with severe COVID-19 pneumonia
(NCT04467840) is over 60% complete. The study is approved in six
countries and is on track to deliver topline data in the first
quarter of 2021. This study is focused on and powered for efficacy
evaluation, and recently received a unanimous recommendation to
continue by an independent Data and Safety Monitoring Board (DSMB),
following a pre-scheduled safety review of the first 70 patients to
have been treated for 14 days. The DSMB is scheduled to conduct a
second pre-planned safety review this month of the first 135
patients who have reached the primary endpoint, and this will later
be followed by a prescheduled, unblinded futility interim analysis
of efficacy data from the same patients. The Company will remain
blinded to this data.
About Opaganib (ABC294640, Yeliva®)
Opaganib, a new chemical entity, is a proprietary,
first-in-class, orally administered, sphingosine kinase-2 (SK2)
selective inhibitor with a demonstrated unique triple-action effect
on the pathophysiological processes associated with COVID-19
disease, that targets a host cell component, potentially minimizing
the likelihood for resistance due to viral mutations. Opaganib has
also shown anticancer activity and has the potential to target
multiple oncology, viral, inflammatory and gastrointestinal
indications.
Opaganib is being evaluated in a global Phase 2/3 study and a
U.S. Phase 2 study for the treatment of severe COVID-19 pneumonia.
Opaganib also received Orphan Drug designation from the U.S.
FDA for the treatment of cholangiocarcinoma and is being evaluated
in a Phase 2a study in advanced cholangiocarcinoma and in a Phase 2
study in prostate cancer.
Preclinical data have demonstrated both anti-inflammatory and
antiviral activities of opaganib, with the potential to reduce
inflammatory lung disorders, such as pneumonia, and mitigate
pulmonary fibrotic damage. Opaganib demonstrated potent antiviral
activity against SARS-CoV-2, the virus that causes
COVID-19, completely inhibiting viral replication in an in
vitro model of human lung bronchial tissue. Additionally,
preclinical in vivo studies[3] have demonstrated that
opaganib decreased fatality rates from influenza virus infection
and ameliorated Pseudomonas aeruginosa-induced lung injury
by reducing the levels of IL-6 and TNF-alpha in bronchoalveolar
lavage fluids.
Opaganib was originally developed by U.S.-based Apogee
Biotechnology Corp. and completed multiple successful preclinical
studies in oncology, inflammation, GI, and radioprotection models,
as well as a Phase 1 clinical study in cancer patients with
advanced solid tumors and an additional Phase 1 study in multiple
myeloma.
Under a compassionate use program, patients with severe COVID-19
(as classified by the WHO ordinal scale) were treated with opaganib
in a leading hospital in Israel.
Data from the treatment of these first patients with severe
COVID-19 with opaganib have been published[4]. Analysis of
treatment outcomes suggests substantial benefit to patients treated
with opaganib under compassionate use in both clinical outcomes and
inflammatory markers as compared to a retrospective matched
case-control group from the same hospital. All patients in the
opaganib-treated group were discharged from hospital on room air
without requiring intubation and mechanical ventilation, whereas
33% of the matched case-control group required intubation and
mechanical ventilation. Median time to weaning from high-flow nasal
cannula was reduced to 10 days in the opaganib-treated group, as
compared to 15 days in the matched case-control group.
The development of opaganib has been supported by grants
and contracts from U.S. federal and state government agencies
awarded to Apogee Biotechnology Corp., including from the NCI,
BARDA, the U.S. Department of Defense and the FDA Office of Orphan
Products Development.
The ongoing studies with opaganib are registered
on www.ClinicalTrials.gov, a web-based service by the U.S.
National Institute of Health, which provides public access to
information on publicly and privately supported clinical
studies.
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,
Movantik® for opioid-induced constipation in
adults[5], 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) RHB-204, with an
ongoing Phase 3 study for pulmonary nontuberculous mycobacteria
(NTM) disease; (ii) opaganib (Yeliva®), a
first-in-class SK2 selective inhibitor targeting
multiple indications with a Phase 2/3 program for COVID-19 and
Phase 2 studies for prostate cancer and cholangiocarcinoma ongoing;
(iii) RHB-104, with positive results from a first Phase 3
study for Crohn's disease; (iv) RHB-102
(Bekinda®), with positive results from a Phase 3
study for acute gastroenteritis and gastritis and positive results
from a Phase 2 study for IBS-D; (v) RHB-107
(upamostat), a Phase 2-stage serine protease inhibitor with
a planned Phase 2/3 study in symptomatic COVID-19 and targeting
multiple other cancer and inflammatory gastrointestinal
diseases; and (vi) RHB-106, an encapsulated
bowel preparation. More information about the Company is available
at www.redhillbio.com.
This press release contains "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Such statements 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 the timing of the
reporting of data from the U.S. Phase 2 trial evaluating opaganib,
and the timing, if at all, of potential emergency use applications
of opaganib and reporting of data, from the global Phase 2/3 study
with opaganib. 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, the risk that the Company's Phase 2/3 study
evaluating opaganib will not be completed or successful; the risk
of a delay in receiving data from the Phase 2/3 study with opaganib
or delay in making emergency use applications, if at all; the risk
that the U.S. Phase 2 clinical study evaluating opaganib will not
be successful and the risk that the reporting of data from this
clinical study will be delayed, if at all; the risk that other
COVID-19 patients treated with opaganib will not show any or
insufficient clinical improvement; the development risks of
early-stage discovery efforts for a disease that is still little
understood, including difficulty in assessing the efficacy of
opaganib for the treatment of COVID-19, if at all; intense
competition from other companies developing potential treatments
and vaccines for COVID-19; the effect of a potential occurrence of
patients suffering serious adverse events using opaganib under
compassionate use programs; the risk that the ongoing Phase 3 study
for pulmonary nontuberculous mycobacteria (NTM) disease will be
delayed, not be completed, or will not be successful, as well as
risks and uncertainties associated with (i) the initiation, timing,
progress and results of the Company's research, manufacturing,
preclinical 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 lack of sufficient financial
resources which may result in material adverse impact on the
Company's research, manufacturing, preclinical studies, clinical
trials, and other therapeutic candidate development activities
including delay or termination of preclinical or clinical
activities or of any other such activities (iii) the Company's
ability to advance its therapeutic candidates into clinical trials
or to successfully complete its preclinical studies or clinical
trials (iv) 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; (v)
the manufacturing, clinical development, commercialization, and
market acceptance of the Company's therapeutic candidates and
Talicia®; (vi) the Company's ability to successfully
commercialize and promote Movantik®, Talicia®
and Aemcolo®; (vii) the Company's ability to establish
and maintain corporate collaborations; (viii) the Company's ability
to acquire products approved for marketing in the U.S. that achieve
commercial success and build and sustain its own marketing and
commercialization capabilities; (ix) the interpretation of the
properties and characteristics of the Company's therapeutic
candidates and the results obtained with its therapeutic candidates
in research, preclinical studies or clinical trials; (x) the
implementation of the Company's business model, strategic plans for
its business and therapeutic candidates; (xi) the scope of
protection the Company is able to establish and maintain for
intellectual property rights covering its therapeutic candidates
and commercial products and its ability to operate its business
without infringing the intellectual property rights of others;
(xii) parties from whom the Company licenses its intellectual
property defaulting in their obligations to the Company; (xiii)
estimates of the Company's expenses, future revenues, capital
requirements and needs for additional financing; (xiv) the effect
of patients suffering adverse events using investigative drugs
under the Company's Expanded Access Program; and (xv) competition
from other companies and technologies within the Company's
industry. 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 March 4, 2020. 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
|
Media contact
(U.S.):
Bryan
Gibbs
Vice
President
Finn
Partners
+1 212 529
2236
bryan.gibbs@finnpartners.com
|
[1] Sakr, Y., Giovini, M., Leone, M. et al. Pulmonary
embolism in patients with coronavirus disease-2019 (COVID-19)
pneumonia: a narrative review. Ann. Intensive Care 10, 124 (2020).
https://doi.org/10.1186/s13613-020-00741-0.
[2]
https://blog.covance.com/2020/08/using-acute-respiratory-disease-syndrome-ards-in-vivo-models-to-screen-for-coronavirus-inflammation-treatment/
[3] Xia C. et al. Transient inhibition of sphingosine
kinases confers protection to influenza A virus infected mice.
Antiviral Res. 2018 Oct; 158:171-177. Ebenezer DL et al.
Pseudomonas aeruginosa stimulates nuclear
sphingosine-1-phosphate generation and epigenetic regulation of
lung inflammatory injury. Thorax. 2019 Jun;74(6):579-591.
[4] Kurd R, Ben-Chetrit E, Karameh H, Bar-Meir M,
Compassionate Use of Opaganib For Patients with Severe COVID-19.
medRxiv 2020.06.20.20099010; doi:
https://doi.org/10.1101/2020.06.20.20099010
[5] Full prescribing information for
Movantik® (naloxegol) is available at:
www.Movantik.com.
[6] Full prescribing information for Talicia®
(omeprazole magnesium, amoxicillin and rifabutin) is available at:
www.Talicia.com.
[7] Full prescribing information for Aemcolo®
(rifamycin) is available at: www.Aemcolo.com.
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