PR86741

TEL AVIV, Israel and RALEIGH, NC, Nov. 20, 2020 /PRNewswire=KYDO JBN/ --

Enrollment completed in the U.S. Phase 2 study evaluating opaganib's safety and

initial efficacy signal in 40 hospitalized patients with severe COVID-19 pneumonia

A parallel global Phase 2/3 study with orally administered opaganib for severe

COVID-19 is approximately 50% enrolled - on track to enroll all 270 patients

and report topline data in Q1/2021

Potential emergency use applications expected as early as Q1/2021

Opaganib's unique dual anti-inflammatory and antiviral activity acts on the

cause and effect of COVID-19 disease with host cell targeting, minimizing

potential for resistance due to viral mutations  

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

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

announced that the U.S. Phase 2 study with opaganib (Yeliva(R), ABC294640)[1]

in patients hospitalized with severe COVID-19 pneumonia has completed

enrollment of the last patient in the study. The study is not powered for

statistical significance. Topline data is expected in the coming weeks.

"Completing enrollment in this U.S. Phase 2 study of orally administered

opaganib in severe COVID-19 is a key milestone, indicating that we are just

weeks away from important safety data and increased understanding of the

potential of opaganib. In parallel, our global Phase 2/3 study is approximately

50% enrolled and is expected to undergo its first pre-planned safety analysis

in the coming days and report topline data in the first quarter of 2021. We are

compiling a robust data set to support the planned emergency use applications,

expected as early as next quarter, subject to study success." said Mark L.

Levitt, MD, Ph.D., Medical Director at RedHill. "Opaganib has a demonstrated

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

acting on the cause and the effect of COVID-19. Moreover, opaganib acts on a

host cell component involved in viral replication and not the virus itself,

which could minimize issues of resistance due to emergence of viral mutations.

In light of the encouraging data from patients with severe COVID-19 treated

with opaganib under compassionate use[2] and the potent anti-SARS-CoV-2

activity that opaganib has demonstrated in vitro, we are excited to see the

data from the U.S. Phase 2 study and look to rapidly complete the global Phase

2/3 development program for opaganib toward potential emergency use

authorization applications."

The randomized, double-blind, placebo-controlled Phase 2 study with opaganib

(NCT04414618)

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

enrolled 40 patients in clinical sites across the U.S. The study is not

powered for statistical significance and is focused on safety evaluation and

identifying a signal of efficacy. Patients in the study were randomized at a

1:1 ratio to receive either opaganib or placebo on top of standard-of-care. The

primary objective of the study is to evaluate the reduction in total oxygen

requirement over the course of treatment for up to 14 days. Secondary endpoints

include time to 50% reduction in oxygen requirements, the proportion of patients

without fever at Day 14, and proportion with negative nasal swabs at Day 14.

In parallel, the 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 approximately 50% enrolled and is expected

to report topline data in the first quarter of 2021. The study is being conducted across 21

clinical sites and is on track to enroll up to 270 patients. A first unblinded review of

safety data from the first 70 patients enrolled in the study by an independent Data

and Safety Monitoring Board (DSMB) is expected in the coming days. An 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. This study is

focused on, and powered for, efficacy evaluation. The study has been approved in the UK,

Italy, Russia, Mexico, Brazil and Israel, with further expansion ongoing.

The clinical studies with opaganib are intended to support potential emergency

use applications as early as the first quarter of 2021, subject to positive results.

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 in a global Phase 2/3 study and a U.S. Phase 2 study for the

treatment of COVID-19.

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, COVID-19 patients (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[2]. Analysis of treatment outcomes suggested 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 with non-cancer pain[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

investigational development programs include: (i) RHB-204, with a planned 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 data from the U.S. Phase 2 trial evaluating

opaganib, the timing of potential emergency use applications of opaganib.

Reporting of topline 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 data to support emergency use applications or

in making such 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 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 topline 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(R);

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

Movantik(R), Talicia® 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.  

References:

[1] Opaganib is an investigational new drug, not available for commercial distribution.

[2] 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 

[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] Full prescribing information for Movantik(R) (naloxegol) is available at:

www.Movantik.com.  

[5] Full prescribing information for Talicia® (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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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

Source: RedHill Biopharma Ltd.