PR87444

TEL AVIV, Israel and RALEIGH, N.C., Dec. 31, 2020 /PRNewswire=KYODO JBN/ --

- Preliminary data from the non-powered U.S. Phase 2 study of 40 hospitalized

patients shows that orally-administered opaganib was safe, with no material

safety differences between opaganib and control arms

- Consistent trends demonstrate greater improvement in reducing oxygen

requirement by end of treatment at Day 14 in the opaganib-treated arm across

key primary and secondary efficacy outcomes, correlating with clinical

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

- The opaganib-treated arm demonstrated a greater improvement in reaching room

air within 14 days (52.6% vs. 22.2%); greater improvement in reduction to 50%

supplemental oxygen by Day 14 (89.5% vs. 66.7%); a higher proportion of

patients discharged by Day 14 (73.7% vs. 55.6%) and a greater reduction in the

median total oxygen requirement (AUC) over 14 days (68.0% vs. 46.7%)

- Top-line data from the global Phase 2/3 COVID-19 study in 270 hospitalized

patients expected Q1/2021 and an interim DSMB futility analysis is expected in

the coming weeks

- Opaganib targets a human cell component involved in viral replication,

potentially minimizing the likelihood for resistance due to viral mutations

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

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

announced that preliminary top-line data from its U.S. Phase 2 study with

orally-administered opaganib (Yeliva(R), ABC294640)[1] in patients hospitalized

with COVID-19 pneumonia demonstrated positive safety and efficacy signals.

The randomized, double-blind, placebo-controlled U.S. Phase 2 proof-of-concept

study with opaganib (NCT04414618

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

) enrolled 40 patients requiring oxygen support. The study was not powered for

statistical significance and aimed to evaluate safety and identify preliminary

signs of activity. Patients in the study were randomized at a 1:1 ratio to

receive either opaganib or placebo on top of standard-of-care (SoC) and were

followed up for up to 42 days post treatment initiation.

- Top-line results from the study found opaganib to be safe, with no material

safety differences between the opaganib and placebo treatment arms. Overall,

fewer patients suffered from serious adverse events (SAEs) in the opaganib

treatment arm than in the placebo arm. In this small sample size, there were

few events of intubation or fatality and these were balanced between the two

arms.

- The opaganib-treated arm demonstrated a consistent trend of 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:

- A greater improvement in the proportion of patients reaching room air and no

longer requiring oxygen support by Day 14 vs. the control arm (52.6% vs. 22.2%).

- A greater improvement in the proportion of patients with 50% reduction in

supplemental oxygen by day 14 vs. the control arm (89.5% vs. 66.7%).

- A higher proportion of patients discharged by Day 14 vs. the control arm

(73.7% vs. 55.6%).

- A greater reduction from baseline of the median total oxygen requirement

(AUC) over 14 days vs. the control arm (68.0% vs. 46.7%).

Full analysis of the data, including viral and inflammatory biomarker analyses,

baseline risk factors and SoC background therapy stratifications, is expected

in the coming weeks. The Company will provide the data for peer review when

available.

"We are pleased with these encouraging top-line results from our exploratory

Phase 2 study which confirm opaganib's safety and demonstrate promising signals

of activity when treating patients with COVID-19 and who require oxygen

support. These preliminary results support our ongoing global Phase 2/3 study

in severe COVID-19 pneumonia, which is expected to read out in Q1/2021. We

continue to work diligently to compile a robust data set to support potential

filing of global emergency use applications," said Mark L. Levitt, MD, Ph.D.,

Medical Director at RedHill.

Gilead Raday, RedHill's Chief Operating Officer, added: "Opaganib has a unique

dual mode of action that is both anti-inflammatory and antiviral – acting on

both the cause and the effects of COVID-19. Opaganib targets sphingosine

kinase-2, a human cell component involved in viral replication and not the

virus itself. The mounting evidence of new SARS-CoV-2 mutations emerging

globally underscores the importance of this unique mechanism, which potentially

minimizes the risk of viral resistance to therapy. The trends of patient

improvement shown by the preliminary top-line data support the ongoing Phase

2/3 study with opaganib, which will provide a more in-depth understanding of

opaganib's activity."

The efficacy of opaganib in severe COVID-19 pneumonia is being further explored

in an ongoing global Phase 2/3 study and is expected to report top-line data in

the first quarter of 2021. This study (NCT04467840

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

) is being conducted across approximately 30 clinical sites in several

countries and is on track to enroll up to 270 patients. The study has undergone

two unblinded reviews of safety data by an independent Data and Safety

Monitoring Board (DSMB), with unanimous recommendations to continue the study.

An interim DSMB futility analysis will be conducted in the coming weeks,

evaluating data from the first 135 subjects that have reached the primary

endpoint.

The top-line results from the U.S. Phase 2 study of opaganib in patients

hospitalized with COVID-19 pneumonia 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 studies.

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

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 both anti-inflammatory and antiviral

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. 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

[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 with non-cancer pain[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 investigational development programs include: (i) RHB-204,

with an ongoing Phase 3 study for pulmonary nontuberculous mycobacteria (NTM)

infections; (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, a Phase 2-stage first-in-class, serine protease inhibitor,

targeting cancer and inflammatory gastrointestinal diseases and is also being

evaluated for COVID-19 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 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, safety analysis and

of unblinded futility interim analysis 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 2/2 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, reporting of

top-line data, safety analysis and/or unblinded futility interim analysis 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®; (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.

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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.

Source: RedHill Biopharma Ltd.