Additional Update on COVID-19 Compassionate Use with Opaganib in Israel Provided by RedHill Biopharma

All five patients have shown an improved CRP, with four of the five patients also demonstrating measurable clinical improvement, including required supplemental oxygenation and higher lymphocyte counts
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Opaganib was administered to all five patients in addition to standard-of-care, including hydroxychloroquine background therapy, and was well tolerated
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Opaganib’s unique mechanism of action has both anti-viral and anti-inflammatory activities, targeting a critical host factor, minimizing potential development of resistance due to viral mutations
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Compassionate use plan in Italy to be converted to a clinical study, in line with the global shift to generate more robust data in a controlled setting for regulatory purposes

TEL-AVIV, Israel and RALEIGH, N.C., April 17, 2020 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, today provided an additional update on the compassionate use program with its investigational drug, opaganib (Yeliva^®, ABC294640)¹, in patients with confirmed SARS-CoV-2 infection (COVID-19) in Israel.

Following the recently announced preliminary findings of clinical improvement in the first two COVID-19 patients treated with opaganib at a leading hospital in Israel, three additional patients have been treated with opaganib, leading to a total of five patients, four of whom have demonstrated measurable improvement within days following treatment initiation.

At the time of treatment initiation, all five patients suffered from moderate to severe acute respiratory symptoms related to SARS-CoV-2 infection, required supplemental oxygenation and were hypoxic despite being treated with supplemental oxygen. The first patient has now completed 14 days of opaganib therapy, safely, with continuous improvement.

Preliminary findings from all five patients have shown an improved C-Reactive Protein (CRP) with four of the five patients also demonstrating measurable clinical improvement, including required supplemental oxygenation and higher lymphocyte counts within days following treatment initiation with opaganib. Two patients were entirely weaned from supplemental oxygenation, one of whom has been discharged from the hospital, and another patient was released from the intensive care unit (ICU) within a few days from treatment initiation with opaganib.

Opaganib was administered to the hospitalized patients in addition to standard-of-care, which included hydroxychloroquine (HCQ) as background therapy. Opaganib was well tolerated at the doses administered and no opaganib-related treatment emergent adverse events have been reported to date.

“We are very pleased with the continued clinical improvement in four of the first five COVID-19 patients treated thus far with opaganib,” said Mark L. Levitt, MD, Ph.D., Medical Director at RedHill. “We continue to work diligently to make opaganib available under compassionate use to additional hospitals and countries, and we hope to see similar clinical outcomes in additional COVID-19 patients planned to be treated with opaganib.”

To find out more about RedHill Biopharma's Expanded Access policy, please visit: www.redhillbio.com/expandedaccess.

In order to facilitate access to opaganib, various programs are currently under discussion in other countries. Following further communication with the Italian Medicines Agency (AIFA), and in line with the current global shift from compassionate use programs with COVID-19 therapeutic candidates to more rigorously-controlled studies, the compassionate use program in Italy is planned to be converted to a clinical study in order to generate more robust clinical data in a controlled setting for regulatory purposes.

A total of 131 subjects have been dosed with opaganib to date in ongoing and completed Phase 1 and Phase 2 clinical studies in oncology indications in the U.S., in pharmacokinetic studies in healthy volunteers in the U.S., and under the existing FDA-approved expanded access requests from physicians for individual oncology patients, establishing safety and tolerability in humans both in the U.S. and ex-U.S.

Pre-clinical data have demonstrated both anti-viral and anti-inflammatory activities of opaganib, with the potential to reduce lung inflammatory disorders, such as pneumonia, and mitigate pulmonary fibrotic damage. Several prior pre-clinical studies support the potential role of sphingosine kinase-2 (SK2) in the replication-transcription complex of positive-strand single-stranded RNA viruses, similar to coronavirus, and its inhibition may potentially inhibit viral replication. Pre-clinical in vivo studies² have demonstrated that opaganib decreased fatality rates from influenza-virus infection and ameliorated Pseudomonas aeruginosa-induced lung injury.

About Opaganib (ABC294640, Yeliva^®)
Opaganib, a new chemical entity, is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anticancer, anti-viral and anti-inflammatory activities, targeting multiple oncology, inflammatory and gastrointestinal indications. By inhibiting SK2, opaganib blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid-signaling molecule that promotes cancer growth and pathological inflammation. By inhibiting SK2, opaganib potentially blocks viral replication complex and pathological inflammation. Opaganib was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as a Phase 1 clinical study in cancer patients with advanced solid tumors. Opaganib received Orphan Drug designation from the U.S. FDA for the treatment of cholangiocarcinoma and is being evaluated in a Phase 1/2a in advanced cholangiocarcinoma and in a Phase 2 study in prostate cancer. Opaganib is also being evaluated for the treatment of coronavirus (COVID-19) in confirmed COVID-19 patients in Israel. 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.

About RedHill Biopharma  
RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on gastrointestinal diseases. RedHill promotes the gastrointestinal drugs Movantik^® for opioid-induced constipation in adults³, Talicia^® for the treatment of Helicobacter pylori (H. pylori) infection in adults⁴ and Aemcolo^® for the treatment of travelers’ diarrhea in adults⁵. RedHill’s key clinical late-stage development programs include: (i) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; (ii) RHB-204, with a planned pivotal Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) infections; (iii) RHB-102 (Bekinda^®), with positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (iv) Opaganib (Yeliva^®), a first-in-class SK2 selective inhibitor, targeting multiple oncology, inflammatory and gastrointestinal indications, with an ongoing Phase 1/2a study for cholangiocarcinoma; (v) RHB-106, an encapsulated bowel preparation, and (vi) RHB-107, a Phase 2-stage first-in-class, serine protease inhibitor, targeting cancer and inflammatory gastrointestinal diseases. More information about the Company is available at www.redhillbio.com.