The data, published in the International Journal of Molecular
Sciences, demonstrate that opaganib significantly improved
long-term survival in an in vivo model of lung damage following
exposure to ionizing radiation
Opaganib is the first selective sphingosine kinase-2
(SPHK2) inhibitor investigational drug targeting
sphingolipid metabolism for the treatment of radiation-induced
inflammation
Opaganib, a novel oral, small molecule pill with a five-year
shelf-life, is easy to administer and distribute, supporting
potential central government stockpiling for use as radioprotection
therapy in mass casualty radiological or nuclear incidents, if
approved by the FDA
Opaganib is being tested as a potential treatment for Acute
Radiation Syndrome (ARS) following selection by the U.S government
National Institutes of Health's (NIH) Radiation and Nuclear
Countermeasures Program (RNCP) for its radiation medical
countermeasures Product Development Program
Opaganib is being developed for multiple additional
indications, including COVID-19, acute respiratory distress
syndrome (ARDS), filoviruses (including Ebola) and oncology
TEL
AVIV, Israel and RALEIGH,
N.C., Feb. 20, 2024 /PRNewswire/ -- RedHill
Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a
specialty biopharmaceutical company, today announced a new
publication of data from multiple experiments in the International
Journal of Molecular Sciences1. The published data shows
that opaganib2 protects against radiation-induced
lung inflammation and fibrosis in an in vivo mouse
model of lung damage following exposure to ionizing radiation,
demonstrating its potential use as a medical countermeasure against
nuclear irradiation and in cancer radiotherapy.
Radiation-induced inflammation is known to occur in two phases –
in an initial inflammatory response immediately after irradiation
and in a delayed response that can occur weeks later. As such, one
of the experiments looked specifically at longer-term survival with
two treatment windows: 1-3 days post-radiation and 31-45 days
post-radiation. The opaganib group treated both during the initial
and delayed phases of inflammation demonstrated a highly
statistically significant improvement in survival at Day 180 (60%
survival compared with 10% for controls, p=0.008). Thus, treating
with opaganib during both initial and delayed phases of
inflammation provided the greatest improvement in survival.
"The data, when looked at collectively across multiple
experiments, demonstrate that opaganib significantly improved
long-term survival associated with reduced lung fibrosis,
suppression of granulocyte infiltration, and reduced expression of
IL-6 and TNFα in an in vivo model of lung damage following
exposure to ionizing radiation," said Dr. Lynn W. Maines, lead author of the publication
and VP of Research at Apogee Biotechnology Corporation, RedHill's
development partner for opaganib. "These data further
demonstrate that sphingolipid metabolism is a critical regulator of
fibrogenesis, and specifically show that opaganib suppresses
radiation-induced pulmonary inflammation and fibrosis."
Opaganib is being tested as a potential treatment for Acute
Radiation Syndrome (ARS), following selection by the U.S government
National Institutes of Health's (NIH) Radiation and Nuclear
Countermeasures Program (RNCP) for its radiation medical
countermeasures Product Development Program. Opaganib was also
recently selected for inclusion into the BARDA/NIH Chemical
Countermeasures screening program for Sulfur Mustard exposure.
Opaganib, a novel, oral, small molecule pill with a five-year
shelf-life, is easy to administer and distribute, supporting
potential central government stockpiling for use as a medical
countermeasure in the event of mass casualty nuclear radiation
incidents or Sulfur Mustard attack, if approved by the U.S. Food
and Drug Administration (FDA).
About Lung Inflammation, Fibrosis and Acute Radiation
Syndrome (ARS)
ARS, sometimes known as radiation toxicity or radiation
sickness, is generally rare; however, public health emergencies,
such as a nuclear power plant accident or detonation of a nuclear
device, could affect large numbers of people. ARS is an acute
illness caused by irradiation of the body by a high dose of
penetrating radiation in a short period of time. Much of the damage
caused by ARS is caused by inflammation secondary to the direct
effects of ionizing radiation itself. The inflammation can occur
throughout the body, but specifically, inflammation in the lungs
can cause the tissue around the air sacs of the lungs (alveoli) to
become damaged, thickened, and scarred – this is known as pulmonary
fibrosis. As the lungs scar and stiffen, breathing becomes more
difficult, and the amount of oxygen entering the blood system
becomes reduced.
Current treatments for ARS are supportive care, including blood
transfusions, antibiotics, etc., as well as the availability of
four approved products (three growth factors to address neutropenia
and one to mitigate thrombocytopenia*). However, other
radiation-induced clinical manifestations that have been observed
in natural history studies and remain unaddressed with the current
treatments include GI-ARS, cutaneous injury, and late effects in
the lung, heart, and kidneys. Opaganib, an SPHK2 inhibitor, may
offer a new therapeutic approach to mitigate both hematopoietic-ARS
and GI-ARS. It has also been reported in the literature that
inhibition of SPHK2 promotes the viability and robustness of
hematopoietic stem cells, even in the face of radiation damage,
supporting increased survival.
* The agents are filgrastim, PEGylated filgrastim and
romiplostim (Neupogen®, Neulasta® and
Nplate®, all Amgen Inc., NasdaqGS: AMGN), sargramostim
(Leukine®, Partner Therapeutics Inc.).
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 demonstrated antiviral activity against SARS-CoV-2,
multiple variants, and several other viruses, such as Influenza A.
Opaganib also recently demonstrated a distinct synergistic effect
when combined individually with remdesivir (Veklury®, Gilead
Sciences Inc., Nasdaq: GILD), significantly improving potency while
maintaining cell viability, in a U.S. Army-funded and conducted
in vitro Ebola virus study.
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. Opaganib
has demonstrated its safety and tolerability profile in more than
470 people in multiple clinical studies and expanded access use.
Data from the opaganib global Phase 2/3 study was published in
medRxiv.
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 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
Talicia®, for the treatment of Helicobacter
pylori (H. pylori) infection in
adults[3], and Aemcolo®,
for the treatment of travelers' diarrhea in
adults[4]. 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.
RedHill is open to opportunities to acquire revenue generating
assets in various indications, aligned to our strategic direction.
Trading in RedHill's shares, ADSs and Warrants is regulated by the
Securities and Exchange Commission (SEC), and the Company is
committed to work in compliance with all relevant SEC and FDA
regulations and requirements.
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 and may discuss investment opportunities, stock analysis,
financial performance, investor relations, and market trends. Such
statements, including, but not limited to, statements regarding the
intended use of net proceeds from the offering, 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 risk that the Company will not comply with
the listing requirements of the Nasdaq Capital Market ("Nasdaq") to
remain listed for trading on Nasdaq, 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.
Company contact:
Adi Frish
Chief Corporate & Business Development Officer
RedHill Biopharma
+972-54-6543-112
adi@redhillbio.com
Category: Financials
[1] Maines LW, Keller SN, Smith RA, Green CL, Smith CD. The
Sphingolipid-Modulating Drug Opaganib Protects against
Radiation-Induced Lung Inflammation and Fibrosis: Potential Uses as
a Medical Countermeasure and in Cancer Radiotherapy. International
Journal of Molecular Sciences. 2024; 25(4):2322.
https://doi.org/10.3390/ijms25042322
[2] Opaganib is an investigational new drug, not available for
commercial distribution.
[3] 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.
[4] 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.
View original
content:https://www.prnewswire.com/news-releases/redhills-opaganib-protects-against-radiation-induced-lung-inflammation-and-fibrosis--new-publication-302065891.html
SOURCE RedHill Biopharma Ltd.