PR92098

RedHill Biopharma Reports Further Analysis of Phase 2/3 Data Including a 62% Reduction in Mortality with Oral Opaganib in Moderately Severe COVID-19 Patients

TEL AVIV, Israel and RALEIGH, N.C., Oct. 4, 2021 /PRNewswire=KYODO JBN/ --

62% statistically significant reduction in mortality shown for moderately

severe COVID-19 patients group treated with opaganib vs. the placebo-controlled

arm (7 deaths in the 117-patient opaganib arm vs. 21 deaths in the 134-patient

placebo arm; nominal p-value=0.019)

21% statistically significant efficacy benefit with opaganib in reaching room

air by Day 14, the study primary endpoint (77% of opaganib patients vs 63.5% on

placebo; nominal p-value=0.033)

A median four days earlier hospital discharge for opaganib-treated patients vs.

placebo (10 days for opaganib arm vs. 14 days for placebo) a cumulative saving

of 524 days of hospitalization across the group by Day 42 (nominal

p-value=0.0195)  

The moderately severe group comprised 53% of study participants requiring a

Fraction of inspired Oxygen (FiO2) up to 60% at baseline (inhaled supplemental

oxygen via nasal cannula or face mask)

Data indicates a potential meaningful benefit with opaganib for these

hospitalized, moderately severe COVID-19 patients - a group at high risk of

disease progression, morbidity and mortality; the data also supports opaganib's

potential use in earlier stages of COVID-19 disease, consistent with opaganib's

U.S Phase 2 study results and the demonstrated potent antiviral inhibition of

SARS-CoV-2 variants

RedHill will hold a webcast on Thursday, October 7, 2021, at 08:30 am EDT to

further discuss these additional analyses

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

biopharmaceutical company, today reported new data from the opaganib global

Phase 2/3 study in hospitalized patients with severe COVID-19 pneumonia showing

that treatment with oral opaganib (ABC294640)[1] vs. the placebo-controlled arm

resulted in a 62% statistically significant reduction in mortality as well as

statistically significant improved outcomes in time to room air and median time

to hospital discharge in a group of 251 hospitalized, moderately severe

COVID-19 patients, comprising 53% of the 475 study participants.  

These important new results are from a post-hoc analysis of data from the 251

study participants requiring a Fraction of inspired Oxygen (FiO2) up to 60% at

baseline. Patients with FiO2 ¡Ü 60% are still considered to be severely

affected and typically require oxygen supplementation via a nasal cannula or

face mask.

"These new findings support the potential for opaganib's use in hospitalized,

moderately severe COVID-19 patients - a key group of patients that are at high

risk of disease progression, morbidity and mortality, and who may benefit from

opaganib's combined antiviral and anti-inflammatory activities," said Mark L.

Levitt, MD, Ph.D., Medical Director at RedHill. "The results provide a strong

rationale for opaganib's potential efficacy in hospitalized patients in need of

oxygen supplementation up to 60% FiO2, a large proportion of hospitalized

COVID-19 patients. The Phase 2/3 study results are also consistent with

opaganib's earlier U.S Phase 2 study results and the demonstrated potent

antiviral inhibition of SARS-CoV-2 variants in human bronchial epithelial

cells, providing further support for its potential in earlier stages of disease

where viral load is higher."

"We are excited about this promising and robust dataset. We are not aware of

any other novel oral pill-based therapy that has shown a similar magnitude of

difference in the mortality outcomes of hospitalized patients who are at this

moderately severe stage of disease. The data indicates opaganib's potential to

provide an effective option, in an easy to take and distribute pill-form, to

help prevent patient deterioration and mortality," said Dror Ben-Asher,

RedHill's CEO. "Pinpointing the most relevant target patient population is

particularly challenging with novel drugs, novel mechanisms of action and a

previously unknown disease. This trial and these data have given us a clear

indication of which groups of patients are likely to benefit the most from

opaganib."

Analyses of the FiO2 up to 60% patient subset from the opaganib Phase 2/3 study

(n=251), the approximate median for FiO2 levels in the study, who were treated

with either opaganib or placebo in addition to standard-of-care (including

dexamethasone and/or remdesivir) demonstrate consistent benefit across

endpoints, in this subset of hospitalized moderately severe patients. Given the

post-hoc characteristics of this subset, statistical inferences of significance

cannot be formally attributed (nominal values presented). The Company also

conducted a Sensitivity Analysis to account for missing data

interpretability[2]:

- Mortality: Opaganib treatment resulted in a statistically significant 62%

reduction in mortality (7/117 patients treated with opaganib vs. 21/134 for

placebo; nominal p-value=0.019, Relative Risk 2.6) (Sensitivity Analysis: 5/117

vs. 16/134, 64% efficacy benefit; nominal p-value=0.033, Relative Risk - 2.8).

A detailed analysis of baseline risk factors and their potential impact on the

mortality outcome in the sensitivity analysis group has also been undertaken,

showing that the benefit is robustly maintained irrespective of the

subgroups/risk factors, confirming that the positive outcome observed is due to

opaganib.

- Reaching Room Air by Day 14 (primary endpoint of the study): 77% of

opaganib-treated patients reached room air by Day 14 vs. 63.5% for placebo ¨C

an efficacy benefit of 21% with opaganib (nominal p-value= 0.033).

- Median time to discharge: Patients treated with opaganib showed median time

of 10 days to discharge vs. 14 days for the placebo arm, resulting in a saving

of four days hospitalization per opaganib patient and saving a total of 524

cumulative days of hospitalization across the group by Day 42, nominal

p-value=0.0195

- Safety: Overall adverse events were balanced between the opaganib and placebo

groups, suggesting good safety, with no new safety signals emerging, further

supporting potential use in this patient population and earlier stage

populations. [3]

The multi-center, randomized, double-blind, parallel-arm, placebo-controlled

global Phase 2/3 study enrolled 475 subjects with severe COVID-19 pneumonia

requiring hospitalization and treatment with supplemental oxygen. Subjects were

randomized at a 1:1 ratio to receive either opaganib or placebo, on top of

standard-of-care therapy.

The new data of the sub-group analysis follows the Company's previously

announced top-line results of the Phase 2/3 study. Analysis of the top-line

data is still ongoing, including further analysis of the potential for

increased benefit of treatment with opaganib in patients at earlier stages of

disease. RedHill intends to discuss the study outcomes with regulators,

including U.S. FDA and U.S. government agencies, as well as other regulators

and governments and international agencies, to help determine next steps.

Opaganib is a novel small molecule investigational drug in oral pill form.

Opaganib has a unique dual antiviral and anti-inflammatory mechanism of action

that acts on the viral cause and inflammatory effect of COVID-19. It is

believed to exert its antiviral effect by selectively inhibiting SK2, a key

enzyme produced in human cells that may be recruited by the virus to support

its replication and is expected to be effective against emerging viral

variants, having already preclinically demonstrated strong inhibition against

variants of concern, including Delta.

Webcast and Conference Call Information:

The Company will host a webcast on Thursday, October 7, 2021, at 8:30 a.m. EDT,

during which it will present the additional analysis of the Phase 2/3 study

results and answer questions.

The webcast including slides will be broadcast live on the Company's website,

https://www.redhillbio.com/investors/events-and-presentations/default.aspx, and

will be available for replay for 30 days.

To participate in the conference call, please dial one of the following numbers

15 minutes prior to the start of the call: United States: +1-877-870-9135;

International: +1 646-741-3167 and Israel: +972-3-530-8845; the access code for

the call is: 4785122.

About Opaganib (ABC294640)

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

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

anti-inflammatory and antiviral activity. Opaganib is host-targeted and is

expected to be effective against emerging viral variants, having already

demonstrated strong inhibition against variants of concern, including Delta.

Opaganib has also shown anticancer activity and positive preclinical results in

renal fibrosis, and also has the potential to target multiple oncology, viral,

inflammatory, and gastrointestinal indications.

Opaganib previously delivered positive U.S. Phase 2 data in patients with

severe COVID-19, submitted for peer review and recently published in medRxiv.

Opaganib has 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. Based on

a preliminary review of partial unaudited data, the ongoing study in prostate

cancer has met its primary endpoint. Patient accrual, treatment and analysis in

this study are ongoing.

Opaganib demonstrated potent antiviral activity against SARS-CoV-2, the virus

that causes COVID-19, inhibiting viral replication of all SARS-CoV-2 variants

tested to date in an in vitro model of human lung bronchial tissue.

Additionally, preclinical in vivo studies have demonstrated opaganib's

potential to ameliorate inflammatory lung disorders, such as pneumonia, have

demonstrated opaganib's potential to decrease renal fibrosis and have shown

decreased fatality rates from influenza virus infection and amelioration of

Pseudomonas aeruginosa-induced lung injury by reducing the levels of IL-6 and

TNF-alpha in bronchoalveolar lavage fluids[4].

The ongoing clinical 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.  

The top-line results from the Company's Phase 2/3 study with opaganib are

preliminary in nature. The Company intends to further examine the data from

this study in greater detail, along with all the information gathered during

this study, including all safety, and secondary outcome measures. Such analysis

may result in findings which are new or inconsistent with the top-line data

disclosed in this release. As such, investors should not rely on the analyses

reported in this release as the final definitive results of the study.

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

infection in adults[6], and Aemcolo(R) for the treatment of travelers' diarrhea

in adults[7]. 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 (ABC294640), a first-in-class oral

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), an oral serine protease inhibitor in a U.S.

Phase 2/3 study as treatment for 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 ,

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. 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 the risk that further analysis of the top-line

results of the Phase 2/3 COVID-19 study for opaganib results in findings

inconsistent with the data disclosed in this release; that no further COVID-19

studies for opaganib will be commenced, and if commenced, may not be

successful, including with respect to moderately severe COVID-19  and patients

in earlier stages of COVID-19 on low flow oxygen support; that any additional

studies for opaganib in COVID-19 patients, even if successful, will not be

sufficient for regulatory applications, including emergency use or marketing

applications, and that additional COVID-19 studies for opaganib and RHB-107

will be required by regulatory authorities to support such potential

applications and the use or marketing of opaganib or RHB-107 for COVID-19

patients, that opaganib and RHB-107 will not be effective against emerging

viral variants, 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 18, 2021. 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 contacts:

U.S.: Bryan Gibbs, Finn Partners

+1 212 529 2236

bryan.gibbs@finnpartners.com

UK: Amber Fennell, Consilium

+44 (0) 7739 658 783  

fennell@consilium-comms.com

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

distribution.

[2] While the overall risk factors are balanced, we are evaluating each

individually for potential effects on endpoints.

[3] A detailed safety analysis is still ongoing.

[4] 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.

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

www.Movantik.com.  

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

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

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

www.Aemcolo.com.

Source: RedHill Biopharma Ltd.