Positive in vivo results from a new study of opaganib in
radiation-induced hematologic and renal toxicity reaffirms
opaganib's potential protective impact on hematological and kidney
function following total body irradiation (TBI)
These new preclinical results are consistent with recently
published, U.S. government funded, in vivo efficacy data suggestive
of opaganib's potential as a nuclear radiation injury therapeutic
for homeland security medical countermeasures (MCM)
Opaganib is an oral, highly stable, novel small molecule pill
potentially suitable, if approved, for central stockpiling by
governments against mass casualty nuclear radiation
incidents
Following prior FDA guidance specific to opaganib, and
subject to further FDA guidance, development of opaganib as a
homeland security nuclear medical countermeasure is expected to
follow the Animal Rule under which human efficacy studies may not
be required
Opaganib, if approved, may be eligible for a medical
countermeasure Priority Review Voucher
Discussions regarding further support and pathway to
potential approval have been initiated with U.S. and other
governments
Development continues for COVID-19, other pandemic
preparedness antiviral indications and oncology, strongly
positioning opaganib as a pipeline-in-a-product
TEL
AVIV, Israel and RALEIGH,
NC, Nov. 17, 2022 /PRNewswire/ -- RedHill
Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a
specialty biopharmaceutical company, today announced positive in
vivo results from a new pre-clinical study evaluating the
effects of opaganib[1] on radiation-induced hematologic and renal
toxicity, undertaken by RedHill and its partner Apogee
Biotechnology Corporation ("Apogee"). The results, suggesting that
opaganib exerts a protective impact on key hematological and kidney
function parameters following total body irradiation (TBI), are
consistent with recently published U.S. government-funded in
vivo opaganib data[2] and are further supportive of opaganib's
planned development under the Animal Rule for nuclear radiation
protection.
Lynn W. Maines, PhD., Apogee's
VP of Research, said: "These results, as well as the
established scientific understanding that disruption of S1P
production reduces damaging pathologic inflammation, further
support the hypothesis that opaganib's inhibition of SK2, and
subsequent reduction S1P production, suppresses Heme-ARS and kidney
damage by lethal total body irradiation, and may play a key role in
protecting against generalized radiation injury."
"These new results add to, and are consistent with, the positive
indications towards opaganib's radioprotective capabilities
reported in the recent peer-reviewed International Journal of
Molecular Sciences (IJMS) publication and support further studies
of opaganib in this indication," said Dr Mark Levitt, MD, PhD, Chief Scientific Officer
at RedHill. "Our assessment of the pathway towards approval,
and following recent discussions with key government agencies,
gives us an understanding of the progress already made, and of the
areas of ongoing work still to be completed, which we believe can
be done in an expedited manner given the prevailing need for new
radioprotective treatment options."
Recently published, U.S. government funded results, from eight
preclinical studies and additional experiments, indicate opaganib's
potential as a nuclear radiation injury therapeutic for homeland
security material threat medical countermeasures (MCM) and for
antitumor radiotherapy. These results indicate that opaganib may
protect normal tissue from damage due to ionizing radiation
exposure or cancer radiotherapy, improve antitumor activity and
response to chemoradiation, and enhance tolerability and
survival.
Opaganib is a novel oral small molecule sphingosine kinase 2
(SK2) inhibitor that is potentially suitable to current government
research priorities for material threat medical countermeasures
suitable for central stockpiling for use in mass casualty nuclear
radiation incidents. Opaganib can be administered 24 hours or later
after radiation exposure, is highly stable with a more than
five-year shelf-life, easy to administer and distribute, and
demonstrated its clinical safety profile in various human clinical
studies and expanded access uses in other indications.
Multiple discussions with government agencies in the U.S. and
internationally are ongoing regarding funding and medical
countermeasure development pathways.
Sponsors of approved medical countermeasures product
applications may be eligible for a medical countermeasure Priority
Review Voucher.
About Opaganib (ABC294640)
Opaganib a new chemical entity, is an orally administered,
first-in-class proprietary selective inhibitor of sphingosine
kinase-2 (SK2) with suggested anti-inflammatory, anticancer,
radioprotective and antiviral activity.
Opaganib 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 (SK2, DES1 and
GCS).
In an oncology & radiological setting, opaganib has been
observed to elevate certain ceramides and reduces sphingosine
1-phosphate (S1P) in cells, conditions that increase the antitumor
efficacy of radiation while concomitantly suppressing inflammatory
damage to normal tissue, leading to the potential to suppress
toxicity from unintended ionizing radiation (IR) exposure and
improve patient response to chemoradiation. Opaganib has
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. Patient accrual, treatment
and analysis in a prostate cancer study is ongoing. Opaganib has a
Phase 1 chemoradiotherapy study protocol ready for IND
submission.
Opaganib has demonstrated broad-acting, host-directed, 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 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[3], Talicia® for the treatment
of Helicobacter pylori (H. pylori) infection in
adults[4], and Aemcolo® for the
treatment of travelers' diarrhea in adults[5]. 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
(ABC294640), a first-in-class oral broad-acting,
host-directed, SK2 selective inhibitor targeting multiple
indications, including for pandemic preparedness, with a Phase 2/3
program for hospitalized COVID-19 and a Phase 2 program in oncology
and a radiation protection program ongoing; (iii) RHB-107
(upamostat), an oral broad-acting, host-directed serine
protease inhibitor with potential for pandemic preparedness and is
in Phase 3-stage development as treatment for non-hospitalized
symptomatic COVID-19, and targeting multiple other cancer and
inflammatory gastrointestinal diseases; (iv) RHB-104, with
positive results from a first Phase 3 study for Crohn's disease;
and (v) RHB-102, with positive results from a Phase 3 study
for acute gastroenteritis and gastritis and positive results from a
Phase 2 study for IBS-D. More information about the Company is
available at www.redhillbio.com/ twitter.com/RedHillBio.
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. 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
the risk that opaganib will not be shown to elevate ceramide and
reduce sphingosine 1-phosphate (S1P) in cells, increasing the
antitumor efficacy of radiation while concomitantly suppressing
inflammatory damage to normal tissue, leading to the potential to
suppress toxicity from unintended ionizing radiation (IR) exposure
and improve patient response to chemoradiation in an oncology &
radiological setting, 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 opaganib will not be shown to be broad acting,
host-directed candidate therapies for pandemic preparedness, the
risk that a pivotal Phase 3 trial for opaganib will not be
initiated or that such trial be successful and, even if successful,
such study and results may not be sufficient for regulatory
applications, including emergency use or marketing applications,
and that additional COVID-19 studies for opaganib are required by
regulatory authorities to support such potential applications and
the use or marketing of opaganib for COVID-19 patients, that
opaganib will not be effective against emerging viral variants, 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 Company's ability to
advance its therapeutic candidates into clinical trials or to
successfully complete its preclinical studies or clinical trials
(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 Movantik®, 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 and sustain 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, preclinical 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 commercial products 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 events using investigative drugs under the
Company's Expanded Access Program; and (xiv) 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 17,
2022, and the Company's Report on Form 6-K filed with the
SEC on November 10, 2022. 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] Maines LW, Schrecengost RS, Zhuang Y, Keller SN, Smith RA,
Green CL, Smith CD. Opaganib Protects against Radiation Toxicity:
Implications for Homeland Security and Antitumor Radiotherapy.
International Journal of Molecular Sciences. 2022; 23(21):13191.
https://doi.org/10.3390/ijms232113191.
[3] Movantik® (naloxegol) is indicated for opioid-induced
constipation (OIC). Full prescribing information see:
www.movantik.com
[4] 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.
[5] 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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SOURCE RedHill Biopharma Ltd.