Opaganib (ABC294640), a proprietary investigational drug, is a first-in-class, orally administered sphingosine kinase-2 (SPHK2) selective inhibitor with anticancer, anti-inflammatory and antiviral activity, targeting multiple potential diseases, including gastrointestinal acute radiation syndrome (GI-ARS), COVID-19 and cholangiocarcinoma (bile duct cancer). 

Opaganib's suggested mechanism of action, which was published in the journal Drug Design, Development and Therapy, is host-directed and potentially broad-acting and is expected to maintain effect against emerging viral variants.

Opaganib is thought to work through the inhibition of multiple pathways, the induction of autophagy and apoptosis, and disruption of viral replication, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS).

RedHill announced that opaganib was selected by the U.S. Government's Radiation and Nuclear Countermeasures Program (RNCP), led by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, for the nuclear medical countermeasures product development pipeline as a potential treatment for ARS. Additionally, RedHill announced that opaganib was selected for evaluation as a potential chemical medical countermeasure against Sulfur Mustard exposure by BARDA and NIH countermeasures programs.  

Opaganib has completed a 463-patient global Phase 2/3 study in hospitalized patients with severe COVID-19 pneumonia (NCT04467840). Despite not meeting the study’s primary endpoint, several efficacy trends in key patient sub-groups were achieved.

RedHill announced data from the prespecified analyses of all Phase 2/3 study patients, which showed improvements compared to the control arm with respect to median time to viral RNA clearance. In addition, RedHill announced positive data, which was also published in medRxiv, from a post-hoc analysis in a subset of moderately severe COVID-19 patients evaluating clinical parameters including mortality, time to discharge and time to recovery. Overall adverse events were balanced between the opaganib and placebo groups. 

More recently, RedHill announced data from a U.S. Army-funded in vivo study that investigated the effects of opaganib on Ebola virus disease. Additionally, RedHill reported results from its in vitro study investigating the effects of opaganib and RHB-107 combined individually with remdesivir in a U.S. Army-funded and conducted Ebola virus study.

Opaganib has undergone a U.S. Phase 2a clinical study in patients with advanced, unresectable cholangiocarcinoma and was granted FDA Orphan Drug designation for the treatment of cholangiocarcinoma.

An investigator-sponsored Phase 2 study with opaganib in prostate cancer has completed enrollment and patient follow up is ongoing at MUSC Hollings Cancer Center and Emory University (NCT04207255).

Opaganib has completed a Phase 1 clinical study in cancer patients with advanced solid tumors and an investigator-sponsored Phase 1b clinical study in the treatment of multiple myeloma undertaken at Duke University Medical Center.

The 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.

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* Yeliva® is a proposed tradename for the drug product containing opaganib, which is subject to review by the FDA at the time of NDA filing