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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