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RCS - RedHill Biopharma - Opaganib MoA Not Impacted by Omicron Mutations

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RNS Number : 6707U  RedHill Biopharma Ltd  06 December 2021

 

 

 

 

 

 

Press Release

 

RedHill Biopharma Reports that Opaganib Mechanism Not Impacted by Viral
Spike-Protein Mutations, Including Omicron Mutations

 

Unique Mode of Action

Opaganib works by targeting the human host cell rather than the virus itself
and is therefore not expected to be impacted by spike protein mutations,
providing a strong rationale for its potential to address the Omicron
SARS-CoV-2 variant, as well as other variants of concern

--

Regulatory update

Opaganib global Phase 2/3 data packages submitted to European EMA, with
initial feedback expected by end of year, to the U.S. FDA with initial
feedback expected in January, and to the UK MHRA, with other countries lined
up

--

A number of pending grant applications in the U.S. and abroad with both
government bodies and non-government entities

--

Opaganib designed for underserved hospitalized patient population with
advanced disease; Opaganib treatment initiated a median of 11 days from
symptom onset in the Phase 2/3 global study, compared to the limited 3-5-day
from symptom onset scope of the Pfizer & Merck pills

--

RHB-107, RedHill's other oral COVID-19 drug candidate, expected to deliver
top-line data in Q1/2022 from Part A of its Phase 2/3 study in
non-hospitalized patients in the U.S. and South Africa; RHB-107 also not
expected to be impacted by spike protein mutations

 

TEL AVIV, Israel and RALEIGH, NC, December 6, 2021, RedHill Biopharma Ltd.
(https://www.redhillbio.com/home/default.aspx) (Nasdaq: RDHL) ("RedHill" or
the "Company"), a specialty biopharmaceutical company, today announced that
because opaganib's 1  proposed mechanism of action is not impacted by spike
protein mutations, opaganib is expected to be unaffected by mutations
associated with Omicron and other known variants of concern. The Company also
provided an update on the status of its regulatory submissions for opaganib.

 

Increased hospitalizations in South Africa due to Omicron highlight the urgent
need for drugs aimed at moderately severe COVID-19 patients with pneumonia
requiring hospital treatment. By focusing on this large group of patients,
opaganib, if approved, would target an entirely different and sicker patient
population than the Pfizer and Merck oral drug candidates, which showed
benefit only in non-hospitalized patients at the earliest stages of
symptomatic infection.

 

Opaganib acts independently of mutations to the viral spike protein. We
believe that its unique proposed mechanism of action - targeting a protein in
the human cell required by the virus for replication rather than the virus
itself - holds significant potential versus Omicron and other existing and
emerging variants with mutations to the spike protein. Extensive clinical and
non-clinical data support the rationale for accelerating this program,
including clinical data from Phase 2 and Phase 2/3 studies, compassionate use
experience and strong inhibition against variants of concern, including Delta.

 

"Omicron is just another reminder that COVID-19 is an endemic virus at this
point, and it is not going away. The evolution of this virus will continue as
long as it circulates, and we will need to continue to tweak our vaccines and
monoclonal antibodies in order to respond to new variants as they arise. Most
importantly, this underscores the need for safe and effective anti-viral
therapies that will continue to work no matter which variants present
themselves. It is vital that focus, time and resources are given to the
development of anti-viral therapies that can effectively treat those COVID-19
high risk patients, preferably without concern for variants and mutations,"
said Kevin Winthrop, MD, MPH, Professor of Infectious Diseases at Oregon
Health & Science University. "The post-hoc data from the opaganib Phase
2/3 study in moderate and severe COVID-19 patients is intriguing and suggests
the possibility that opaganib might prove itself as an effective anti-viral in
this setting. In a subpopulation of patients defined as moderately severe
based on their level of baseline oxygen supplementation, mortality was 62%
lower in those using opaganib (16% placebo Vs. 6% opaganib). The results
suggest a sub-group of patients who would likely benefit from this therapy,
and they highlight the need for additional studies in the development of this
therapy."

 

Regulatory & Development Update:

Given the promising clinical results to-date in the moderately severe
hospitalized patient population in a large subpopulation analysis of the
global Phase 2/3 study, RedHill is vigorously pursuing the development program
for opaganib:

 

·    Submitted data packages to the U.S. FDA, the European Medicines
Agency (EMA) and the UK (MHRA) actively seeking scientific advice on the
potential path towards approval of opaganib. The EMA has indicated a rapid
procedure timeline, and we expect their advice by end of the year, with
preliminary feedback from the FDA expected in January 2022.

·    Pursuing submission in other countries including South Africa,
Russia, Israel, Switzerland, India, Brazil and Colombia.

·    Discussions and preparation ongoing for a confirmatory study with
opaganib in the targeted moderately severe hospitalized patient group,
engaging with the FDA, other regulatory bodies as well as other government
agencies on the need to further accelerate development of much needed
therapeutics, such as opaganib and RHB-107, against Omicron and emerging
variants.

·    A number of pending grant applications in the U.S. and abroad with
both government bodies and non-government entities.

 

"Both opaganib and RHB-107 have unique human cell-targeted mechanisms of
action that act independently of mutations at the spike protein. Given the
gravity of the threat presented by Omicron, and the likely emergence of other
variants, RedHill is pursuing development of these two promising COVID-19
pills as quickly and diligently as possible. We have extensive safety data
and, in the case of opaganib, an apparent clinical benefit in reducing
mortality, getting patients back onto room air and getting them out of
hospital faster," said Gilead Raday, RedHill's Head of R&D "Importantly,
opaganib benefited a population of hospitalized patients in moderately severe
condition with treatment being initiated a median of 11 days from the onset of
symptoms in our Phase 2/3 global study. This distinguishes opaganib as a
potential game-changer for advanced COVID-19 patients who are at a significant
risk of dying from their condition and already well beyond the 3-5-day from
symptom onset scope offered by the Pfizer and Merck anti-viral pills."

 

Unique Opaganib Proposed Mechanism of Action:

Opaganib is a sphingosine kinase-2 (SK2) inhibitor, a promising and
differentiated approach that targets the SK2 human host cell factor rather
than the virus itself, working independently of spike protein mutations, such
as those associated with Omicron and emerging variants of concern. SARS-CoV-2,
the virus which causes COVID-19 disease, is a positive-sense single-stranded
RNA (+ssRNA) virus, which account for more than one-third of all known virus
genera. These viruses use host factors in various steps of viral infection,
such as cell entry and replication - SK2 is one such factor, potentially
making it a broad-spectrum antiviral target. SK2 is also active in the
modulation of certain pro-inflammatory cytokines, with in vivo studies
demonstrating opaganib's potential to ameliorate inflammatory lung disorders
and decrease renal fibrosis by reduction of IL-6 and TNF-alpha levels in
bronchoalveolar lavage fluids. Thus, inhibition of SK2 may deliver a 2-pronged
antiviral and anti-inflammatory effect - a highly desirable mechanism in the
case of COVID-19. Moreover, opaganib's targeting of SK2 and not the virus
itself, means it is expected to uphold antiviral activity irrespective of the
worrisome mutations in the SARS-CoV-2 spike protein and the emergence of new
strains, such as Omicron, which may be evasive of direct antiviral antibodies
and vaccines.

 

RHB-107 Mode of Action and Development Status

RHB-107 2 , RedHill's other oral COVID-19 drug candidate, is a once-daily oral
capsule, given early in the course of the disease, to outpatients. It targets
Serine Proteases, which are human enzymes that are involved in facilitating
the entry of SARS-CoV-2 into target cells. The cleaving of the spike protein
by these host human serine proteases, is a necessary step in viral attachment
and entry into the cells, which is independent of the mutations observed in
the Omicron variant that are altering the spike-protein antigenic properties.

 

RHB-107 is currently being evaluated in a Phase 2/3 study in non-hospitalized
COVID-19 patients in the U.S. and in South Africa. Recruitment for part A of
the study has been completed and top-line results are expected in the first
quarter of 2022.

 

About Opaganib (ABC294640)

Opaganib, a new chemical entity, is a proprietary, first-in-class,
orally-administered, sphingosine kinase-2 (SK2) selective inhibitor, with
proposed dual anti-inflammatory and antiviral activity. Opaganib is
host-targeted and is expected to be effective against emerging viral variants,
having already demonstrated strong inhibition against variants of concern,
including Delta. Opaganib has also shown anticancer activity and positive
preclinical results in renal fibrosis, and also has the potential to target
multiple oncology, viral, inflammatory, and gastrointestinal indications.

 

Opaganib previously delivered positive U.S. Phase 2 data in patients with
moderate to severe COVID-19, submitted for peer review and recently published
in medRxiv.

 

Opaganib has 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. Patient
accrual, treatment and analysis in this study are ongoing.

 

Opaganib demonstrated potent antiviral activity against SARS-CoV-2, the virus
that causes COVID-19, inhibiting viral replication of all SARS-CoV-2 variants
tested to date in an in vitro model of human lung bronchial tissue.
Additionally, preclinical in vivo studies have demonstrated opaganib's
potential to ameliorate inflammatory lung disorders, such as pneumonia, have
demonstrated opaganib's potential to decrease renal fibrosis and have shown
decreased fatality rates from influenza virus infection and amelioration of
Pseudomonas aeruginosa-induced lung injury by reducing the levels of IL-6 and
TNF-alpha in bronchoalveolar lavage fluids(( 3 )).

 

The ongoing clinical 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.

 

The top-line results from the Company's Phase 2/3 study with opaganib are
preliminary in nature. The Company intends to further examine the data from
this study in greater detail, along with all the information gathered during
this study, including all safety, and secondary outcome measures. Such
analysis may result in findings which are new or inconsistent with the
top-line data disclosed in this release. As such, investors should not rely on
the analyses reported in this release as the final definitive results of the
study.

 

About RHB-107 (upamostat)

RHB-107 is a proprietary, first-in-class, orally-administered antiviral, that
targets human serine proteases involved in preparing the spike protein for
viral entry into target cells. RHB-107 targets human cell factors involved in
preparing the spike protein for viral entry into target cells and is therefore
expected to be effective against emerging viral variants with mutations in the
spike protein. RHB-107 is being evaluated in a Phase 2/3 study, in the U.S.
and South Africa, for treatment of patients with symptomatic COVID-19 who do
not require inpatient care. 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. 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 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(( 4 )), Talicia(®) for the treatment of Helicobacter
pylori (H. pylori) infection in adults(( 5 )), and Aemcolo(®) for the
treatment of travelers' diarrhea in adults(( 6 )). 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 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-107 (upamostat), an
oral serine protease inhibitor in a U.S. Phase 2/3 study as treatment for
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; (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; and (vi) RHB-106, an encapsulated bowel
preparation. More information about the Company is available at
www.redhillbio.com (https://www.redhillbio.com/home/default.aspx) /
twitter.com/RedHillBio (https://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, without limitation, the risk of a
regulatory feedback regarding the Phase 2/3 data packages submitted to the
regulatory authorities, the risk of a delay in top-line data from Part A of
the Phase 2/3 study of once-daily oral RHB-107 in non-hospitalized patients
with symptomatic COVID-19, the risk that further analysis of the top-line
results of the Phase 2/3 COVID-19 study for opaganib results in findings
inconsistent with the data disclosed in this release; that no further COVID-19
studies for opaganib will be commenced, and if commenced, may not be
successful, including with respect to moderately severe COVID-19  and
patients in earlier stages of COVID-19 on low flow oxygen support; that any
additional studies for opaganib in COVID-19 patients, even if successful, will
not be sufficient for regulatory applications, including emergency use or
marketing applications, 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
will be required by regulatory authorities to support such potential
applications and the use or marketing of opaganib or RHB-107 for COVID-19
patients, that opaganib and RHB-107 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
18, 2021. 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:                                     Media contacts:

 Adi Frish                                            U.S.: Bryan Gibbs, Finn Partners

 Chief Corporate & Business Development Officer       +1 212 529 2236

 RedHill Biopharma                                    bryan.gibbs@finnpartners.com

 +972-54-6543-112                                     UK: Amber Fennell, Consilium

 adi@redhillbio.com                                   +44 (0) 7739 658 783

                                                      fennell@consilium-comms.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  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  Full prescribing information for Movantik(®) (naloxegol) is available at:
www.Movantik.com.

 5  Full prescribing information for Talicia(®) (omeprazole magnesium,
amoxicillin and rifabutin) is available at: www.Talicia.com.

 6  Full prescribing information for Aemcolo(®) (rifamycin) is available at:
www.Aemcolo.com.

 

 

 

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