PR87377

TEL AVIV, Israel and RALEIGH, N.C., Dec. 22, 2020 /PRNewswire=KYODO JBN/ --

Independent DSMB unanimously recommends continuation of the global Phase 2/3

study of orally-administered opaganib in severe COVID-19 based on review of

unblinded safety data from 155 treated patients

Top-line data from the 270-patient global Phase 2/3 COVID-19 study expected Q1/2021

Top-line data from the 40-patient U.S. Phase 2 study of opaganib in severe

COVID-19 expected in the coming days; this non-powered study was designed to

evaluate safety and potential identification of preliminary efficacy signals in

support of the global Phase 2/3 study of opaganib

Opaganib potentially minimizes likelihood of resistance due to viral mutations

by targeting a human cell component involved in viral replication

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

("RedHill" or the "Company"), a specialty biopharmaceutical company, today

announced that the global Phase 2/3 study with orally-administered opaganib

(Yeliva®, ABC294640)[1] in patients hospitalized with severe COVID-19 pneumonia

has received a second unanimous recommendation to continue, following a second

independent Data Safety Monitoring Board (DSMB) safety review. The DSMB's

recommendation is based on an analysis of unblinded safety data from the first

155 patients treated for 14 days.

"This second unanimous independent DSMB recommendation to continue the global

Phase 2/3 study of opaganib in patients with severe COVID-19 confirms the

safety of opaganib and means we can continue to focus on completing enrollment

for this study as rapidly as possible, with a view to having top-line data in

the first quarter of 2021. If successful, we expect to make subsequent global

emergency use applications the same quarter," said Mark L. Levitt, M.D., Ph.D.,

Medical Director at RedHill.

Enrollment in the 270-patient global Phase 2/3 study of orally-administered

opaganib in hospitalized patients with severe COVID-19 pneumonia (NCT04467840)

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

  is more than 60% complete, and is on track to deliver top-line data in the

first quarter of 2021. This study is focused on and powered for efficacy

evaluation. A pre-scheduled, unblinded futility interim analysis will be

conducted by the DSMB in the coming weeks, evaluating data from the first 135

subjects that have reached the primary endpoint.

The parallel U.S. Phase 2 study with opaganib (NCT04414618)

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

has completed enrollment of all 40 subjects, with top-line data expected by

year's end. This study is not powered for efficacy and is focused on safety

evaluation and potential identification of preliminary efficacy signals.

Opaganib is a novel, orally-administered, sphingosine kinase-2 (SK2) selective

inhibitor with a preclinically demonstrated triple-action mechanism that

inhibits viral replication, reduces hyper-immune inflammatory response and

diminishes ARDS-related thrombosis (blood clots) – a dangerous complication of

COVID-19 disease – in effect acting on the cause and effect of COVID-19

disease. Opaganib's target is a human host cell component involved in viral

replication, potentially minimizing the likelihood of resistance due to viral mutations.

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[2]

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[3]  

[https://www.medrxiv.org/content/10.1101/2020.06.20.20099010v1]. 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(R) for opioid-induced constipation in

adults[4], Talicia(R) for the treatment of Helicobacter pylori (H. pylori)

infection in adults[5], and Aemcolo(R) 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 (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 / 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 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] Opaganib is an investigational new drug, not available for commercial distribution.

[2] 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.

[3] 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

[4] Full prescribing information for Movantik(R) (naloxegol) is available at: www.Movantik.com.  

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

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

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

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Source:  RedHill Biopharma Ltd.