Six COVID-19 Patients Treated with RedHill’s Opaganib Under Compassionate Use Show Objective Clinical Improvement

Preliminary data in moderate-to-severe COVID-19 patients treated with opaganib show measurable clinical improvement in all six patients analyzed, including decreased requirement for supplemental oxygenation, higher lymphocyte counts and decreased CRP 
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Five of the six patients have been weaned from oxygen altogether, the sixth patient continues to improve, and three out of the six were discharged from the hospital
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Opaganib has been well tolerated and no patient required mechanical ventilation following treatment with opaganib 
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Opaganib’s unique mechanism of action has both anti-inflammatory and anti-viral activities, targeting a critical host factor, potentially minimizing development of resistance  
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IND submitted to the FDA for a randomized clinical study in COVID-19 patients in the U.S.; Clinical studies also planned in Israel and Italy; discussions ongoing for compassionate use and clinical programs in additional countries

TEL-AVIV, Israel and RALEIGH, N.C., April 27, 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 (the cause of COVID-19) in Israel.

At the time of treatment initiation, all of the patients were hospitalized, suffered from moderate-to-severe acute respiratory symptoms related to SARS-CoV-2 infection and were treated with standard-of-care (mostly hydroxychloroquine). All patients required supplemental oxygenation and were hypoxic despite being treated with supplemental oxygen.  

Preliminary findings from all six patients analyzed have shown that all the patients demonstrated objective significant measurable clinical improvement within days following treatment initiation with opaganib, including a decrease in required supplemental oxygenation, higher lymphocyte counts, a sign of improvement from virus-induced lymphopenia, and decreased C-reactive protein (CRP) levels, an important inflammatory biomarker correlated with lung lesions which could reflect disease severity². Opaganib was well tolerated and showed clinical improvement both with and without hydroxychloroquine.

Five of the six patients analyzed were weaned from oxygen, and three were discharged from the hospital within days of treatment initiation. The 6^th patient, whose therapy was initiated more recently, is improving. To date, two patients have safely completed 14 days of opaganib therapy, which has been well tolerated.

A 7^th patient who was treated with hydroxychloroquine and azithromycin suffered from side effects of diarrhea, which resolved quickly following cessation of all therapies. This patient received only 1 day of opaganib dosing and therefore was not included in this analysis.

“These preliminary findings are highly encouraging, show clinical improvement in the first COVID-19 patients treated with opaganib and provide preliminary support for the tolerability of opaganib and its potential efficacy in COVID-19 patients,” said Mark L. Levitt, MD, Ph.D., Medical Director at RedHill. “We have submitted to the FDA an application to initiate a clinical study with opaganib in the U.S. and are also working on expanding access to opaganib through compassionate use and clinical programs in additional countries.”

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

RedHill recently announced that it has submitted an Investigational New Drug (IND) application to the FDA to evaluate the safety and efficacy of opaganib in a randomized, double-blind, placebo-controlled Phase 2a study in patients hospitalized with positive SARS-CoV-2 and pneumonia in the U.S. 

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 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-inflammatory and anti-viral 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 studies³ 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.

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 adults⁴, Talicia^® for the treatment of Helicobacter pylori (H. pylori) infection in adults⁵ and Aemcolo^® for the treatment of travelers’ diarrhea in adults⁶. 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.