PR91509

TEL AVIV, Israel and RALEIGH, N.C., Sept. 7, 2021 /PRNewswire=KYODO JBN/ --

- COVID-19 and long COVID patients are at increased risk of developing kidney

damage

- Opaganib significantly decreased kidney fibrosis in a preclinical in vivo

model

- Renal fibrosis is a progressive process which occurs in patients with chronic

kidney disease (CKD) and can ultimately lead to end-stage renal failure

- Opaganib is a novel, late clinical-stage oral pill drug candidate with dual

anti-inflammatory and antiviral activity and has already demonstrated strong

inhibition against variants of concern, including Delta

- The global 475-patient Phase 2/3 study with opaganib oral pill in

hospitalized COVID-19 patients has completed treatment and follow up phase,

with top-line results upcoming

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

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

announced results of a new preclinical study demonstrating opaganib's

(ABC294640)[1] efficacy in significantly decreasing renal fibrosis in a

unilateral ureteral obstruction-induced renal interstitial fibrosis model.

Reports suggest that over 20% of hospitalized COVID-19 patients experience

acute renal failure[2].

Kidney fibrosis generally leads to loss of tissue function and subsequent organ

failure, with high mortality rate. New therapeutic small molecules to modulate

fibrosis are urgently needed. The aim of the in vivo efficacy study was to

verify the effect of opaganib on kidney inflammation and fibrosis in a

unilateral ureteral obstruction (UUO) model – a well characterized model for

renal fibrosis. Results from the study showed that opaganib significantly

decreased renal fibrosis.

"A final, common pathway in chronic kidney disease is fibrosis, the formation

of internal scar tissue, which can cause devastating effects and can ultimately

lead to end-stage kidney failure. This new preclinical data, demonstrating

opaganib's ability to decrease kidney fibrosis, along with its observed

anti-inflammatory properties, positions opaganib as a potential novel therapy

for the millions of patients suffering from chronic kidney disease and

potentially extends to COVID-19 patients with Acute Kidney Injury (AKI) who are

at risk of developing renal fibrosis," said Reza Fathi, PhD., RedHill's Senior

VP, R&D. "Kidney injury and its associated progression to fibrosis is an

important facet in both the acute phase of COVID-19 and in long COVID. Recent

research has shown that after acute kidney injury, which we know can be a

result of COVID-19 infection, the kidneys often fail to repair themselves

properly and that sphingosine kinase-2 (SK2), which is inhibited by opaganib,

is part of this process. These findings provide further support for the

extensive work we are doing with opaganib in COVID-19. With the upcoming

readout, we expect to learn more about kidney outcomes from hospitalized

COVID-19 patients treated with opaganib in our global Phase 2/3 study."

Renal fibrosis, a common outcome of chronic kidney disease (CKD), is

characterized by an excessive accumulation and deposition of extracellular

matrix (ECM) components and fibrous tissue. Renal fibrosis may ultimately lead

to end-stage renal failure, a devastating disorder that requires dialysis or

kidney transplantation. CKD is a very common disease, affecting 15% of U.S.

adults[3].

Recent studies have found that patients infected with SARS-CoV-2 are at

increased risk of developing kidney damage, as well as chronic and end-stage

kidney disease., associated with morbidity and mortality in these patients.

Findings have suggested that beyond the acute phase of the disease, COVID-19

survivors, even those who did not require hospitalization, exhibit an increased

risk of developing major adverse kidney disease such as CKD. In addition, data

suggests that approximately 10% of people infected with COVID-19 may experience

long COVID (post-acute sequalae), potentially involving acute kidney-related

outcomes[4].

Opaganib, a leading novel small molecule investigational oral pill in

development for the treatment of COVID-19, is a unique host targeted, dual

antiviral and anti-inflammatory drug that acts on the cause and 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. Opaganib's global 475-patient Phase 2/3

study in hospitalized patients with COVID-19 has completed its treatment and

follow up phase, and study top-line results are upcoming.

Evaluations of blinded blended intubation and mortality rates from the Phase

2/3 study have been encouraging compared to reported rates of mortality from

large platform studies such as RECOVERY, and other studies in similar patient

populations[5]. Furthermore, the opaganib Phase 2/3 study has also passed four

Data Safety Monitoring Board reviews, as well as a futility review, extending

the total opaganib safety database to more than 460 patients and healthy

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

with severe COVID-19, has been recently published in medRxiv [

https://www.medrxiv.org/content/10.1101/2021.08.23.21262464v1 ]. Additionally,

encouraging use of opaganib under compassionate use exemption has been

experienced in Israel and Switzerland.

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 is being evaluated as a treatment for COVID-19 pneumonia in a global

Phase 2/3 study that has completed patient treatment and follow-up, with

top-line results upcoming. Opaganib previously delivered positive U.S. Phase 2

data in patients with severe COVID-19, recently published in medRxiv [

https://www.medrxiv.org/content/10.1101/2021.08.23.21262464v1 ].

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 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, 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[6].

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.  

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

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

adults. 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 in the next studies opaganib will not

be found effective in decreasing renal fibrosis, the delay in top-line data

from the Phase 2/3 COVID-19 study for opaganib, that the Phase 2/3 COVID-19

study for opaganib may not be successful and, even if successful, such study

and results may not be sufficient for regulatory applications, including

emergency use or marketing applications, and that additional COVID-19 studies

for opaganib are likely to be required by regulatory authorities to support

such potential applications and the use or marketing of opaganib for COVID-19

patients, that opaganib 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] Nadim, M.K., Forni, L.G., Mehta, R.L. et al. COVID-19-associated acute

kidney injury: consensus report of the 25th Acute Disease Quality Initiative

(ADQI) Workgroup. Nat Rev Nephrol 16, 747–764 (2020).

[3] Centers for Disease Control and Prevention – Chronic Kidney Disease in the

United States, 2021

[4] Bowe B, Xie Y, Xu E, Al-Aly Z, Kidney Outcomes in Long COVID. JASN Sep 2021

[5] Based on preliminary blinded blended data from 463 patients. The Company

did not conduct a head-to-head comparison study in the same patient population.

The theoretical comparison between the global Phase 2/3 study with opaganib and

reported rates of mortality from large platform studies such as RECOVERY, and

other studies in similar patient populations, serves as a general benchmark and

should not be construed as a direct and/or applicable comparison as if the

Company conducted a head-to-head comparison study.

[6] 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.

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Source:  RedHill Biopharma Ltd.