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 / RALEIGH, NC, December 20, 2023, RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, today announced that its two novel, oral host-directed investigational drugs, opaganib¹ 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. 

GIE MEDICAL ANNOUNCES FIRST PATIENT ENROLLED IN PATENT-E BENIGN ESOPHAGEAL STRICTURE TREATMENT STUDY 

The large, multicenter randomized controlled clinical trial is evaluating the safety and efficacy of the ProTractX3™ TTS drug coated balloon for the treatment of benign esophageal strictures 

MINNEAPOLIS – December 7, 2023. GIE Medical, a clinical stage company developing solutions for patients suffering from benign stricture(s) of the esophagus or bowel, announced today that enrollment has begun in its Paclitaxel Coated Balloon for the Treatment of Chronic Benign Stricture – Esophagus (PATENT-E) study. The study is evaluating the safety and efficacy of the first of its kind ProTractX3™ TTS drug coated balloon (DCB) and the first patient was enrolled at the University of North Carolina School of Medicine. 

“We are excited to be testing this promising new technology,” said Nicholas J. Shaheen, MD, MPH, Chief, Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine. “Our patients with difficult-to-treat strictures need treatment options that are effective and safe. We hope to show that this innovative approach provides a new direction for them.” 

Earlier this year, the Food and Drug Administration Center for Devices and Radiological Health (CDRH) granted GIE Medical the Breakthrough Device Designation to expedite development of its ProTractX3™ TTS DCB for patient access because it has a reasonable chance of providing more effective treatment of life-threatening or irreversibly debilitating human disease or conditions than the current standard of care. 

“We are pleased to be enrolling the randomized cohorts in PATENT-E, our treatment for esophageal stricture IDE study, and look forward to the results,” said GIE Medical Vice President Drew McClure. “We sincerely thank our clinical partners and internal GIE Medical team for achieving this significant milestone.” 

• People who may qualify to participate in the PATENT-E study: 
• Are 22 years of age or older 
• Are failing to respond to conventional dilation (have had at least one previous dilation in the past 12 months with diagnosis of stricture recurrence) 

GIE Medical’s ProTractX3™ 3-Stage TTS DCB is a balloon coated with the anti-restenotic agent paclitaxel. It is an investigational device in the U.S. 

ABOUT GIE MEDICAL 

GIE Medical is a clinical stage company conducting trials in the U.S. to help patients suffering from benign stricture(s) of the esophagus or bowel (small intestine, colon, and rectum). 

The ProTractX3™ Through the Scope Drug Coated Balloon could offer a new solution for treating GI strictures, potentially creating sustained long-term patency and reducing the number of treatments.

For more information, visit: GIEMedical.com 

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