Opaganib demonstrated strong inhibition of COVID-19 Delta variant in a human bronchial epithelial cells model, adding to prior data demonstrating potent inhibition of all COVID-19 variants tested to date
Opaganib's unique, host-targeted, dual antiviral and anti-inflammatory approach to combatting COVID-19 is expected to maintain effect against other emerging variants
The global 475-patient Phase 2/3 study with opaganib oral pill in hospitalized COVID-19 patients has completed treatment and follow up phase, with top-line results upcoming
RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced preliminary results of a new preclinical study showing strong inhibition by opaganib (ABC294640)[i] of Delta variant replication while maintaining cell viability at relevant concentrations.
Working with the University of Louisville Center for Predictive Medicine, opaganib was studied in a 3D tissue model of human bronchial epithelial cells (EpiAirway(TM)) to evaluate the in vitro efficacy of opaganib in inhibiting the Delta (Indian) variant. This work adds to the previously reported work that showed opaganib also inhibits Alpha (Washington), Beta (South African) and Gamma (Brazilian) SARS-CoV-2 variants.
"There is growing evidence in support of the possible key role played by sphingosine kinase-2 in the replication of RNA viruses such as SARS-CoV-2, irrespective of mutations at the spike protein. This makes inhibition of this intra-cellular enzyme a promising therapeutic target for treating COVID-19 disease," said Reza Fathi, PhD., RedHill's Senior VP, R&D. "We have now accumulated extensive evidence from our preclinical work of opaganib's potent ability to inhibit SARS-CoV-2 variants of concern, such as Delta, and expect that to extend to new emerging variants. The strong antiviral and anti-inflammatory activities of oral opaganib potentially address both the viral cause and inflammatory effects of COVID-19."
Opaganib, a leading novel small molecule investigational oral pill in development for the treatment of COVID-19, is a unique host targeted, dual antiviral and anti-inflammatory drug that acts on the cause and effect of COVID-19. It is believed to exert its antiviral effect by selectively inhibiting sphingosine kinase-2 (SK2), a key enzyme produced in human cells that may be recruited by the virus to support its replication. Opaganib's global 475-patient Phase 2/3 study in hospitalized patients with COVID-19 has completed its treatment and follow up phase, and study top-line results are upcoming.
Evaluations of blinded blended intubation and mortality rates from the Phase 2/3 study have been encouraging compared to reported rates of mortality from large platform studies such as RECOVERY, and other studies in similar patient populations[ii]. Furthermore, the opaganib Phase 2/3 study has also passed four Data Safety Monitoring Board reviews, including a futility review, and extends the total opaganib safety database to more than 460 patients. Opaganib previously delivered positive U.S. Phase 2 data in patients with severe COVID-19, presented in June at the World Microbe Forum (WMF) 2021. Additionally, encouraging use of opaganib under compassionate use exemption has been experienced in Israel and Switzerland.
About Opaganib (ABC294640)
Opaganib, a new chemical entity, is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor, with dual anti-inflammatory and antiviral activity. Opaganib is host-targeted and is expected to be effective against emerging viral variants, having already demonstrated strong inhibition against variants of concern, including Delta. Opaganib has also shown anticancer activity and has the potential to target multiple oncology, viral, inflammatory, and gastrointestinal indications.
Opaganib is being evaluated as a treatment for COVID-19 pneumonia in a global Phase 2/3 study that has completed patient treatment and follow-up, with top-line results upcoming. Opaganib previously delivered positive U.S. Phase 2 data in patients with severe COVID-19, presented in June at the World Microbe Forum (WMF) 2021.
Opaganib has 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.
Opaganib demonstrated potent antiviral activity against SARS-CoV-2, the virus that causes COVID-19, 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 have shown decreased fatality rates from influenza virus infection and amelioration of Pseudomonas aeruginosa-induced lung injury by reducing the levels of IL-6 and TNF-alpha in bronchoalveolar lavage fluids[iii].
The ongoing clinical 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(R) for opioid-induced constipation in adults[iv], Talicia(R) for the treatment of Helicobacter pylori (H. pylori) infection in adults[v], and Aemcolo(R) for the treatment of travelers' diarrhea in adults[vi]. 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 (ABC294640), a first-in-class oral 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-107 (upamostat), an oral 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 , 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. More information about the Company is available at www.redhillbio.com / https://twitter.com/RedHillBio.
| Company contact: Adi Frish Chief Corporate & Business Development Officer RedHill Biopharma +972-54-6543-112 adi@redhillbio.com | Media contacts: U.S.: Bryan Gibbs, Finn Partners +1 212 529 2236 bryan.gibbs@finnpartners.com UK: Amber Fennell, Consilium +44 (0) 7739 658 783 fennell@consilium-comms.com |
[i] Opaganib is an investigational new drug, not available for commercial distribution.
[ii] Based on preliminary blinded blended data from 463 patients. The Company did not conduct a head-to-head comparison study in the same patient population. The theoretical comparison between the global Phase 2/3 study with opaganib and reported rates of mortality from large platform studies such as RECOVERY, and other studies in similar patient populations, serves as a general benchmark and should not be construed as a direct and/or applicable comparison as if the Company conducted a head-to-head comparison study.
[iii] 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.
[iv] Full prescribing information for Movantik(R) (naloxegol) is available at: www.Movantik.com.
[v] Full prescribing information for Talicia(R) (omeprazole magnesium, amoxicillin and rifabutin) is available at: www.Talicia.com.
[vi] Full prescribing information for Aemcolo(R) (rifamycin) is available at: www.Aemcolo.com.
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