AsiaNet  87845

TEL AVIV, Israel and RALEIGH, N.C., Jan. 29, 2021, /PRNewswire=KYODO JBN/ --

Following interim review of unblinded safety and efficacy data, independent

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

orally-administered opaganib for severe COVID-19

Opaganib targets a human cell component involved in viral replication and is

therefore expected to be effective against emerging viral variants with

mutations in the spike protein

Preliminary data from the non-powered U.S. Phase 2 study of opaganib

demonstrated safety and positive efficacy data across key primary and secondary

endpoints

RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a

specialty biopharmaceutical company, today announced that the independent Data

Safety Monitoring Board (DSMB) for the global Phase 2/3 study of opaganib[1] in

patients with severe COVID-19, unanimously recommended to continue the study

following a pre-scheduled futility review of unblinded efficacy data from the

first 135 patients treated in the study and safety data from the first 175

patients.

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

with demonstrated antiviral, anti-inflammatory, and anti-thrombotic activity.

The positive and unanimous DSMB recommendation is a significant milestone in

the progress of our development program for COVID-19 disease. Taken together

with the positive results from the Phase 2 study, this unanimous DSMB

recommendation to continue the global Phase 2/3 study suggests we are heading

in the right direction from both a safety and efficacy perspective," said Mark

L. Levitt, M.D., Ph.D., Medical Director at RedHill. "This is a particularly

difficult time in the fight against the pandemic, with viral mutations

increasing infection rates and impacting many aspects of society's response to

the pandemic. The need for effective therapeutics is clear. Opaganib's

mechanism of action targets the human host cell component SK2, which is

involved in both viral replication inside the cell and downstream

inflammatory/immune responses. This means that opaganib is expected to maintain

its activity irrespective of the worrisome mutations in SARS-CoV-2 spike

protein. These mutations underscore the potential of SARS-CoV-2 to develop

resistance to direct anti-viral mAbs, and to potentially impact vaccine

effectiveness. This is an important advantage of opaganib in the face of the

growing multitude of viral strains and provides the promise of a much-needed

treatment option to help get patients off oxygen and out of hospital."

This positive DSMB futility review, which is suggestive that the global Phase

2/3 study is progressing as expected, adds to positive top-line safety and

efficacy data from the U.S. Phase 2 study, in which opaganib demonstrated

greater improvement in reducing oxygen requirement by end of treatment on Day

14 across key primary and secondary efficacy outcomes, correlating with

clinical improvement as defined by the World Health Organization (WHO) ordinal

scale. The Phase 2 data also showed no material safety differences between the

opaganib and placebo treatment arms - further adding to the growing safety

database for opaganib. Full analysis of the Phase 2 data, including viral and

inflammatory biomarker analyses, baseline risk factors and standard-of-care

background therapy stratification, is expected in the coming weeks and is

planned to be provided for peer review.

In-line with rapidly evolving clinical practice and guidelines for treatment of

hospitalized COVID-19 patients, which aim to minimize patient intubation and

mechanical ventilation, the primary endpoint of the global Phase 2/3 study is

now the proportion of patients reaching room air (no longer requiring oxygen

supplementation) by Day 14, previously a key secondary endpoint. Intubation and

mechanical ventilation remains as a secondary endpoint. Correspondingly, a

blind resizing of the study is planned, to approximately 460 patients. There

are approximately 30 study sites in 7 countries with additional sites and

countries being added in the coming days and weeks. Top-line data, and

potential global emergency use authorization applications are expected in the

second quarter of 2021.

About Opaganib (Yeliva(R), ABC294640)

Opaganib, a new chemical entity, is a proprietary, first-in-class,

orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with

demonstrated dual anti-inflammatory and antiviral activity that targets a host

cell component of viral replication, potentially minimizing the likelihood of

viral resistance. Opaganib has also shown anticancer activity and has the

potential to target multiple oncology, viral, inflammatory, and

gastrointestinal indications.

Opaganib 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. Opaganib is also

being evaluated as a treatment for COVID-19 pneumonia in a global Phase 2/3

study and has demonstrated positive safety and efficacy signals in preliminary

top-line data from a U.S. Phase 2 study.

Preclinical data have demonstrated anti-inflammatory, antiviral and

anti-thrombotic activities of opaganib, with the potential to ameliorate

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. Opaganib also demonstrated reduced

blood clot length, weight and total thrombus score in a preclinical model of

Acquired Respiratory Distress Syndrome. 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.

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

infection in adults[4], and Aemcolo(R) 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 (Yeliva(R), ABC294640), 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-107 (upamostat), a serine protease

inhibitor with a planned Phase 2/3 study in 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 (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; 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 includes statements regarding the

timing of the reporting of a full analysis of the data from the U.S. Phase 2

trial evaluating opaganib, the timing of potential emergency use applications

for opaganib and the timing of reporting of top-line data for 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 successful; the risk of a delay

in receiving top-line data from the Phase 2/3 study and in receiving data to

support emergency use applications or in making such emergency use

applications, if at all; the risk that the full analysis of data from the U.S.

Phase 2 clinical study evaluating opaganib will be delayed or will differ from

the preliminary data; the risk that the Company will not initiate the Phase 2/3

study for opaganib in certain geographies, will not expand this study to

additional countries and that it will not be successful and that enrollment

will be delayed; the risk that other COVID-19 patients treated with opaganib

will not show any 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, 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(R);

(v) the Company's ability to successfully commercialize and promote

Movantik(R), Talicia(R) and Aemcolo(R); (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 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] Full prescribing information for Movantik(R) (naloxegol) is available at:

www.Movantik.com.  

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

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

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

www.Aemcolo.com.

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