Publication of Data from Severe COVID-19 Patients Shows Substantial Benefit to Patients Treated with RedHill’s Opaganib Compared to Matched Case-Control Group

Analysis of treatment outcomes in five severe COVID-19 patients showed substantial benefit to patients treated with opaganib under compassionate use in both clinical outcomes and inflammatory markers as compared to a matched case-control group from the same hospital
--
All patients in the opaganib-treated group were discharged from hospital without requiring mechanical ventilation whereas 33% of the matched case-control group required 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
--
Phase 2/3 Clinical Trial Applications submitted for a multi-center, randomized, double-blind, parallel-arm, placebo-controlled study with opaganib in 270 patients with severe COVID-19 to be conducted in up to 40 clinical sites across Russia, Italy, the UK and additional countries
--
A randomized, double-blind, placebo-controlled study with opaganib in up to 40 patients with  severe COVID-19 initiated at leading medical centers across the U.S.

TEL-AVIV, Israel and RALEIGH, N.C., June 24, 2020 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, today announced that results from the treatment of the first severe COVID-19 patients with its investigational drug, opaganib (Yeliva^®, ABC294640)¹, have been published in medRxiv.

The article², entitled ‘Compassionate Use of Opaganib For Patients with Severe COVID-19’ was published under an expedited process and is available publicly.

Mark L. Levitt, M.D., Ph.D., Medical Director at RedHill, stated: “We are very encouraged by the analysis from severe COVID-19 patients treated with opaganib to date, demonstrating substantial benefit to patients in both clinical outcomes and inflammatory markers as compared to a matched case-control group. This data further supports our intensive efforts to rapidly advance the development of opaganib via the recently initiated Phase 2a clinical study under IND with the FDA and the Phase 2/3 study in European and other countries which we expect to initiate shortly, as well as through ongoing and planned compassionate use programs.”

Seven patients with severe³ COVID-19 were treated with opaganib under compassionate use in a leading hospital in Israel. Prior to treatment initiation, these patients were hospitalized and required treatment with supplemental oxygen via high-flow nasal cannula while being treated with standard-of-care. Opaganib was given on top of standard-of-care therapy. Five patients were included in the final published analysis⁴ of the active arm. An investigator-selected matched case-control group of patients with similar baseline characteristics at the same hospital was identified for comparison (n=18).

A comparison of outcomes between patients treated with opaganib and the matched case-controls treated with standard-of-care alone for both clinical and inflammatory measures revealed:

• All patients in the opaganib-treated group were discharged from hospital on room air, without having required mechanical ventilation, whereas 33% of patients in the control group required 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 control group.
   
• Improvement in lymphocyte counts was faster in opaganib-treated patients as compared to patients in the control group.
   
• C-reactive protein (an inflammatory marker) showed faster improvement in the opaganib treated group as compared to the control group.
   
• In this cohort of severe COVID-19 patients, opaganib was found safe and well tolerated and improvement in clinical and laboratory parameters was demonstrated for opaganib-treated patients compared to matched case-controls.  

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

A randomized, double-blind, placebo-controlled Phase 2a clinical study with opaganib in the U.S. is open for recruitment (NCT04414618). This study is set to enroll up to 40 patients with severe COVID-19 pneumonia requiring hospitalization and supplemental oxygen. This clinical trial is not powered for statistical significance. 

In parallel, the Company has submitted Clinical Trial Applications (CTA) in Russia, Italy and the UK for a multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 study with opaganib in patients hospitalized with severe COVID-19. This study is planned to commence shortly and enroll up to 270 subjects across up to 40 clinical sites in these European and other countries.

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-inflammatory and anti-viral 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.

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 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 studies⁵ 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 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). 

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 adults⁶, Talicia^® for the treatment of Helicobacter pylori (H. pylori) infection in adults⁷ and Aemcolo^® for the treatment of travelers’ diarrhea in adults⁸. RedHill’s key clinical late-stage development programs include: (i) RHB-204, with a planned pivotal Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) infections; (ii) Opaganib (Yeliva^®), a first-in-class SK2 selective inhibitor, targeting multiple indications, with a Phase 2/3 program for COVID-19 and ongoing Phase 2 studies for prostate cancer and cholangiocarcinoma; (iii) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; (iv) 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; (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.