RedHill and U.S. Army Announce Opaganib and RHB-107 Combinations with Remdesivir Show Distinct Synergistic Effect Against Ebola

Investigational drugs opaganib and RHB-107 (upamostat) demonstrate distinct synergistic effect when combined individually with remdesivir, significantly improving potency while maintaining cell viability, in a new U.S. Army-funded and conducted in vitro Ebola virus study

Opaganib and RHB-107 are both novel, oral, host-directed, small molecule investigational drugs that are easy to administer and distribute, with demonstrated activity against multiple viral targets, including COVID-19, and are expected to be effective against emerging viral variants

Opaganib is believed to be the first host-directed molecule to show activity in Ebola virus disease, having recently delivered a statistically significant increase in survival time in a separate U.S. Army-funded in vivo Ebola virus study. RHB-107 was recently accepted for inclusion in the ACESO PROTECT adaptive platform trial for early COVID-19 outpatient treatment

TEL-AVIV, Israel and RALEIGH, N.C., Dec. 20, 2023 /PRNewswire/ — RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, today announced that its two novel, oral host-directed investigational drugs, opaganib^[1] and RHB-107 (upamostat)^[2], demonstrated robust synergistic effect when combined individually with remdesivir (Veklury^®)^[3], significantly improving viral inhibition while maintaining cell viability, in a new U.S. Army-funded and conducted Ebola virus in vitro study.

“These encouraging in vitro results for opaganib and RHB-107 show a distinct synergy in terms of viral inhibition while maintaining cell viability (i.e., not increasing toxicity), when either is added to remdesivir, with opaganib showing the greatest synergistic effect in combination with remdesivir,” said Jeffrey Kugelman, Ph.D., Major(P), US Army MSC, Branch Chief Synthetic Biology & Surveillance, Molecular Biology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), who led the bioinformatics analysis of the study. “The results suggest that opaganib and upamostat may have potential or use in combination with direct antiviral agents, such as remdesivir, to improve treatment outcome, increasing efficacy while maintaining safety.”

“Opaganib is believed to be the first host-directed molecule to show activity in Ebola virus disease, and these results add to a recent U.S. Army Ebola virus study in which opaganib delivered a statistically significant increase in mice survival time in vivo,” said Reza Fathi, Ph.D., RedHill’s SVP R&D. “Opaganib and RHB-107 are both novel, oral, host-directed, small molecule investigational drugs with demonstrated activity against multiple viral targets, including COVID-19, and are expected to be effective against emerging viral variants. This, together with their growing safety and tolerability databases, presents a compelling hypothesis for further study of their potential in treating Ebola virus.”

Utilizing a checkerboard design to test the study compounds in combination, the study cell lines were pretreated and then infected with Ebola virus. The cells were fixed, washed and subjected to immunofluorescence staining using a virus-specific antibody. The raw data for the combination was analyzed to determine synergistic, additivity or antagonistic effects on viral inhibition while taking into account cell viability.

Twice daily administered opaganib has previously demonstrated benefit in late-stage clinical studies of patients hospitalized with moderate to severe COVID-19 and was selected by the NIH Radiation and Nuclear Countermeasures Program (RNCP) for Acute Radiation Syndrome development.

RHB-107 successfully met its U.S. Phase 2 study primary endpoint of safety and tolerability and delivered promising efficacy results, including marked reduction in hospitalization due to COVID-19. RHB-107 was recently accepted for inclusion in the ACESO PROTECT adaptive platform trial for early COVID-19 outpatient treatment. The 300-patient PROTECT Phase 2 RHB-107 arm, fully funded by non-dilutive external funding sources including the U.S. government^[4], has received FDA clearance to start, with the first patient expected to be enrolled in the coming weeks. The study is being conducted in the U.S., Thailand, Ivory Coast, South Africa and Uganda, and is estimated to be completed by end of 2024.