RedHill Biopharma Ltd., a specialty biopharmaceutical company, announced that the global Phase 2/3 study with orally-administered opaganib (Yeliva?, ABC294640)[1] in patients hospitalized with severe COVID-19 pneumonia has received a unanimous recommendation to continue, following a fourth independent Data Safety Monitoring Board (DSMB) safety review. The DSMB's recommendation is based on an analysis of unblinded safety data from the first 255 patients treated for 14 days, extending the total opaganib safety database to approximately 380 patients.

Mark L. Levitt, M.D., Ph.D., Medical Director at RedHill, said: "With approximately 380 patients in the opaganib safety database following this positive fourth DSMB review, we are building a clear picture of the safety profile of opaganib." Dr. Levitt continued: "Moreover, adding together the positive Phase 2 data, the successful DSMB futility reviews and the outcomes from compassionate use of opaganib, we look forward with optimism to the reporting of top-line data from the Phase 2/3 study, which will provide the clearest indication to date of opaganib's promise in treating COVID-19."

The global Phase 2/3 randomized, double-blind, parallel-arm, placebo-controlled study of opaganib in patients with severe COVID-19 pneumonia requiring hospitalization and treatment with supplemental oxygen (NCT04467840), is over 75% enrolled in approximately 40 recruiting sites.

RedHill recently announced positive top-line safety and efficacy data from the non-powered U.S. Phase 2 study with opaganib in 40 patients with COVID-19 pneumonia, in which opaganib demonstrated greater improvement in reducing oxygen requirement by end of treatment on Day 14, on top of standard-of-care. The Phase 2 data also showed no material safety differences between the opaganib and placebo on top of standard-of-care treatment arms - further adding to the growing safety database for opaganib.

About Opaganib (Yeliva?, ABC294640)

Opaganib, a new chemical entity, is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with demonstrated dual anti-inflammatory and antiviral activity that targets a host cell component of viral replication, potentially minimizing the likelihood of viral resistance. Opaganib has also shown anticancer activity and has the potential to target multiple oncology, viral, inflammatory, and gastrointestinal indications.

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 as a treatment for COVID-19 pneumonia in a global Phase 2/3 study and has demonstrated positive safety and efficacy signals in preliminary top-line data from a 40-patient U.S. Phase 2 study.

Opaganib demonstrated potent antiviral activity against SARS-CoV-2, the virus that causes COVID-19, completely 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 mitigate pulmonary fibrotic damage, and has shown 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[2].

Opaganib was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful preclinical studies in oncology, inflammation, GI, and radioprotection models, as well as a Phase 1 clinical study in cancer patients with advanced solid tumors and an additional Phase 1 study in multiple myeloma.

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 and infectious diseases. RedHill promotes the gastrointestinal drugs, Movantik? for opioid-induced constipation in adults[3], Talicia? for the treatment of Helicobacter pylori (H. pylori) infection in adults[4], and Aemcolo? for the treatment of travelers' diarrhea in adults[5]. 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 (Yeliva?, ABC294640), a first-in-class SK2 selective inhibitor targeting multiple indications with positive Phase 2 COVID-19 data and an ongoing Phase 2/3 program for COVID-19 and Phase 2 studies for prostate cancer and cholangiocarcinoma ongoing; (iii) RHB-107 (upamostat), a 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 (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; and (vi) RHB-106, an encapsulated bowel preparation. 

[1] Opaganib is an investigational new drug, not available for commercial distribution.

[2] 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.

[3] Full prescribing information for Movantik? (naloxegol) is available at: www.Movantik.com.  

[4] Full prescribing information for Talicia? (omeprazole magnesium, amoxicillin and rifabutin) is available at: www.Talicia.com.       

[5] Full prescribing information for Aemcolo? (rifamycin) is available at: www.Aemcolo.com.