PR87278

TEL AVIV, Israel and RALEIGH, N.C., December 15, 2020, /PRNewswire=KYODO JBN/--

RedHill Biopharma Ltd. [https://www.redhillbio.com/RedHill/  ] (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)

[https://clinicaltrials.gov/ct2/show/NCT04414618?term=NCT04414618&draw=2&rank=1

] 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)

[https://clinicaltrials.gov/ct2/show/NCT04467840?term=NCT04467840&draw=2&rank=1

] 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(R))

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)

[https://finance.yahoo.com/quote/RDHL?p=RDHL&.tsrc=fin-srch ] is a specialty

biopharmaceutical company primarily focused on gastrointestinal and infectious

diseases. RedHill promotes the gastrointestinal drugs, Movantik(R) for

opioid-induced constipation in adults[5], Talicia(R) for the treatment of

Helicobacter pylori (H. pylori) infection in adults[6], and Aemcolo(R) 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(R)), 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(R)), 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(R); (vi) the Company's ability to successfully

commercialize and promote Movantik(R), Talicia(R) and Aemcolo(R); (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(R) (naloxegol) is available at:

www.Movantik.com.  

[6] Full prescribing information for Talicia(R) (omeprazole magnesium,

amoxicillin and rifabutin) is available at: www.Talicia.com.      

[7] Full prescribing information for Aemcolo(R) (rifamycin) is available at:

www.Aemcolo.com.

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SOURCE: RedHill Biopharma Ltd.