RedHill Biopharma Expands U.S.-Based Manufacturing Capacity of Opaganib for COVID-19

RedHill Biopharma Ltd., a specialty biopharmaceutical company, today announced partnerships with two leading, U.S.-based manufacturers for large-scale manufacturing of opaganib. These collaborations further advance ongoing preparations to support potential emergency use applications for opaganib to treat severe COVID-19 pneumonia, expected as early as the first quarter of 2021. The new collaborations follow recently announced collaborations with European and Canadian manufacturers. 

"We are expanding our U.S.-based manufacturing capacity for orally administered opaganib, ahead of potential emergency use applications as early as Q1/2021," said Reza Fathi, PhD., RedHill's Senior VP, R&D. "Together with our recently announced similar partnerships in Europe and Canada and in light of our rapidly progressing Phase 2/3 opaganib COVID-19 program, these new U.S. partnerships better place RedHill to meet potential demand for opaganib, if approved."

Opaganib is a novel, orally administered, sphingosine kinase-2 (SK2) selective inhibitor with demonstrated dual anti-inflammatory and antiviral activity that acts on the cause and effect of  COVID-19 disease, targeting a host cell component involved in viral replication, potentially minimizing likelihood of resistance due to viral mutations.

Enrollment in the 270-patient global Phase 2/3 study with opaganib in patients with severe  COVID-19 pneumonia (NCT04467840) is more than 50% complete. The study is approved in six countries and is on track to deliver top-line data in the first quarter of 2021. This study is focused on and powered for efficacy evaluation, and recently received a unanimous recommendation to continue by an independent Data and Safety Monitoring Board (DSMB), following a pre-scheduled safety review of the first 70 patients to have been treated for 14 days. A prescheduled, unblinded futility interim analysis will also be conducted by the DSMB in the coming weeks, evaluating data from the first 135 subjects that have reached the primary endpoint.

The parallel U.S. Phase 2 study with opaganib (NCT04414618) has completed enrollment of all 40 subjects, with topline data expected in the coming weeks. This study is not powered for efficacy and is focused on safety evaluation and identification of efficacy signals. 

About Opaganib (ABC294640, Yeliva®)

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, potentially minimizing the likelihood for resistance due to viral mutations. Opaganib has also shown anticancer activity and has the potential to target multiple oncology, viral, inflammatory and gastrointestinal indications.

Opaganib is being evaluated in a global Phase 2/3 study and a U.S. Phase 2 study for the treatment of severe COVID-19 pneumonia. Opaganib also 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.

Preclinical data have demonstrated both anti-inflammatory and antiviral activities of opaganib, with the potential to reduce inflammatory lung disorders, such as pneumonia, and mitigate pulmonary fibrotic damage. 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 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 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.

Under a compassionate use program, patients with severe COVID-19 (as classified by the WHO ordinal scale) were treated with opaganib in a leading hospital in Israel. Data from the treatment of these first patients with severe COVID-19 with opaganib have been published. Analysis of treatment outcomes suggest 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 on room air without requiring intubation and mechanical ventilation, whereas 33% of the matched case-control group required intubation and 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.

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.

The ongoing studies with opaganib are registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health, which provides public access to information on publicly and privately supported clinical studies.

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, Talicia® for the treatment of Helicobacter pylori (H. pylori) infection in adults, and Aemcolo® for the treatment of travelers' diarrhea in adults[6]. 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®), a first-in-class SK2 selective inhibitor targeting multiple indications with a Phase 2/3 program for COVID-19 and Phase 2 studies for prostate cancer and cholangiocarcinoma ongoing; (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-107 (upamostat), a Phase 2-stage serine protease inhibitor with a planned Phase 2/3 study in symptomatic COVID-19 and targeting multiple other cancer and inflammatory gastrointestinal diseases;  and (vi) RHB-106, an encapsulated bowel preparation.