RedHill Biopharma Accelerates Phase 2/3 COVID-19 Program with Addition of Brazil and Mexico

• Phase 2/3 study process initiated in Brazil and Mexico 

• The global Phase 2/3 study with opaganib in patients with severe COVID-19 has already been approved in the UK and Russia
   
• Enrollment planned to be initiated this month - 270 subjects to be enrolled in up to 40 clinical sites
   
• Potential submission of emergency use applications planned for Q4/2020
   
• Enrollment in parallel U.S. Phase 2 study in severe COVID-19 patients expected to be completed in August

TEL-AVIV, Israel and RALEIGH, N.C., July 22, 2020 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, today announced that it has submitted a Clinical Trial Application (CTA) with the Mexican Federal Committee for the Protection against Sanitary Risks (COFEPRIS) and initiated CTA submission with the Brazilian Health Regulatory Agency (ANVISA) for the Phase 2/3 clinical study evaluating opaganib (Yeliva^®, ABC294640)¹ in patients hospitalized with severe SARS-CoV-2 infection (the cause of COVID-19) and pneumonia.

RedHill’s CTA applications for this study have already been approved in the UK and Russia and a similar application is under review in Italy, with plans to expand the study to additional countries.

“We are advancing rapidly with our Phase 2/3 program for COVID-19 and continue to expand the study to additional countries where there is substantial growth in diagnosed cases. With the study now approved in the UK and Russia, and additional approvals expected in the coming weeks, patient enrollment is planned to commence later this month,” said Aida Bibliowicz, RedHill’s Vice President of Clinical Affairs. “In parallel, good progress has been made with the ongoing Phase 2 study with opaganib in the U.S. If successful, our goal is for the compiled clinical data set to support potential applications for emergency use authorization in the fourth quarter of this year.”

The multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 study (NCT04467840) is set to enroll up to 270 patients with severe COVID-19 pneumonia requiring hospitalization and treatment with supplemental oxygen. Subjects will be randomized at a 1:1 ratio to receive either opaganib or placebo, along with standard-of-care therapy. The primary endpoint of the study is to evaluate the proportion of patients requiring intubation and mechanical ventilation by Day 14. An unblinded futility interim analysis will be conducted by an independent data safety monitoring board (DSMB), when approximately 100 subjects have been evaluated for the primary endpoint.

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

RedHill recently announced that results from the treatment of the first patients with severe COVID-19 with opaganib have been published². Analysis of treatment outcomes in five patients with severe COVID-19 showed substantial benefit to patients treated with opaganib under compassionate use in both clinical outcomes and inflammatory markers as compared to a retrospective 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.

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, viral, inflammatory and gastrointestinal indications. By inhibiting SK2, opaganib impacts multiple cellular pathways which are associated with cancer growth, viral replication 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 2a study in advanced cholangiocarcinoma and in a Phase 2 study in prostate cancer. Opaganib is also being evaluated for the treatment of coronavirus (COVID-19). 

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-sense 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.

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-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 and is also being evaluated for COVID-19. More information about the Company is available at www.redhillbio.com.