RedHill Biopharma Ltd (RDHL)

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RedHill Biopharma’s Opaganib Demonstrates Complete Inhibition of SARS-CoV-2

Opaganib completely inhibited SARS-CoV-2 viral replication as measured after three days incubation in an in vitro model of human bronchial tissue, comparing favorably with remdesivir, the positive control in the study
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Opaganib is uniquely positioned as an orally-administered potential COVID-19 treatment combining potent antiviral and anti-inflammatory mechanisms of action, targeting a host cell component and minimizing likelihood of resistance
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Global Phase 2/3 and U.S. Phase 2 clinical studies ongoing with opaganib for severe COVID-19 pneumonia
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RedHill’s second COVID-19 drug candidate, RHB-107 (upamostat), a novel serine protease inhibitor, strongly inhibited SARS-CoV-2 viral replication in the same model, further supporting planned initiation of a Phase 2/3 U.S. outpatient study later this year

TEL AVIV, Israel and RALEIGH, N.C., Sept. 08, 2020 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, today announced that opaganib1 demonstrated potent inhibition of SARS-CoV-2, the virus that causes COVID-19, achieving complete blockage of viral replication in an in vitro model of human lung bronchial tissue. Opaganib is a first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with dual anti-inflammatory and anti-viral activity that targets a host cell component, unaffected by viral mutation, thus minimizing the likelihood of resistance. Opaganib is currently being evaluated in global Phase 2/3 and U.S. Phase 2 clinical studies for the treatment of severe COVID-19 pneumonia.

Working in collaboration with the University of Louisville Center for Predictive Medicine, opaganib was studied in a 3D tissue model of human bronchial epithelial cells (EpiAirway™) which morphologically and functionally resembles the human airway and is similar to the model used to discover SARS-CoV-22. This study was designed to evaluate the in vitro efficacy of opaganib in inhibiting SARS-CoV-2 infection and included a positive control of remdesivir, a drug with known antiviral activity.

Results from this study showed a clear and compelling antiviral effect of opaganib against SARS-CoV-2. Opaganib demonstrated the most potent activity compared to all compounds tested, including the positive control, remdesivir. Treatment of cells infected with SARS-CoV-2 resulted in a dose-dependent inhibition of virus production without compromising cell membrane integrity, a measure of cell viability and drug safety, further demonstrating opaganib’s promising potential for treating patients with COVID-19.

A graphic accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/e60ced55-ca9d-4648-81cb-907be7571136

Opaganib at 1mg/ml (a pharmacologically relevant concentration) completely inhibited viral replication as measured after three days of incubation. This potent opaganib activity compares favorably with remdesivir data as the active control in the RedHill study which is consistent with published remdesivir data3. Data from the study is planned to be submitted to a peer-reviewed journal.

“Opaganib’s previously demonstrated anti-inflammatory activity, combined with our now proven specific anti-SARS-CoV-2 viral activity, provides a unique dual mechanism of action with the potential to greatly benefit COVID-19 patients by inhibiting the key drivers of disease progression - viral replication and lung inflammation,” said Mark L. Levitt, M.D., Ph.D., Medical Director at RedHill. “These compelling data, using a physiologically relevant human respiratory tissue model, demonstrate opaganib’s potential to strongly inhibit SARS-CoV-2 viral replication, validating the hypotheses underlying our ongoing global Phase 2/3 and U.S. Phase 2 clinical studies and further supporting their rationale. Accordingly, we are accelerating progress toward our goal of generating a robust data package to potentially support emergency use authorizations for COVID-19.”

The ongoing global multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 study (NCT04467840) evaluating opaganib for the treatment of patients with severe COVID-19 pneumonia continues to enroll with a target of up to 270 patients requiring hospitalization and treatment with supplemental oxygen. The study recently received approval in Israel and has been approved in the United Kingdom, Italy, Russia and Mexico, with further expansion progressing.

In parallel, the randomized, double-blind, placebo-controlled U.S. Phase 2 study (NCT04414618) with opaganib in patients with severe COVID-19 pneumonia is more than 50% enrolled, with enrollment set to be completed in the coming weeks. Recently, a pre-scheduled independent Safety Monitoring Committee recommended that the study continue without change. The study, which is not powered for statistical significance, is set to enroll up to 40 patients requiring hospitalization and supplemental oxygen.

The Company is in discussions with U.S. government agencies around potential funding to support the rapid advancement of opaganib toward potential emergency use approval.

In addition to opaganib, RedHill’s in-vitro study evaluated the antiviral activity of its Phase-2 stage investigational drug, RHB-107 (upamostat), a serine protease inhibitor active against a number of human serine proteases, with results demonstrating potent inhibition of SARS-CoV-2 viral replication. A U.S. Phase 2/3 study with RHB-107 in an outpatient setting is planned to be initiated later this year.

“Host cellular proteases play a critical role in the process of SARS-CoV-2 entry into cells, specifically responsible for activating the SARS-CoV-2 spike (S) protein, which is a prerequisite for the fusion of viral and host cell membranes during viral entry,” said Terry F. Plasse MD, Medical Director at RedHill. “RHB-107 demonstrated excellent antiviral activity, with viral replication being strongly inhibited in a dose-dependent manner at pharmacologically relevant concentrations. As with opaganib, RHB-107 (upamostat) is orally bioavailable and therefore potentially suitable for both inpatient and out-patient settings.”

The results from the preclinical studies of opaganib and RHB-107 are preliminary and were provided to the Company by an independent third-party following an initial independent analysis and remain subject to additional review and analysis of the data and potentially supportive experiments.