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Opaganib (Yeliva®, ABC294640)

Opaganib (Yeliva®, ABC294640) is a first-in-class, proprietary sphingosine kinase-2 (SK2) selective inhibitor, administered orally, with anticancer, anti-inflammatory and anti-viral activities. Opaganib is an investigational drug targeting several potential oncology, inflammatory and gastrointestinal indications. Opaganib is also under development as a potential therapy for COVID-19.

Opaganib inhibits SK2, a lipid kinase that catalyzes formation of the lipid signaling molecule sphingosine 1-phosphate (S1P). S1P promotes cancer growth, and proliferation and pathological inflammation, including TNFα signaling and other inflammatory cytokine production. Specifically, by inhibiting the SK2 enzyme, opaganib blocks the synthesis of S1P which regulates fundamental biological processes such as cell proliferation, migration, immune cell trafficking and angiogenesis, and are also involved in immune-modulation and suppression of innate immune responses from T cells. Preliminary evidence suggests that because of its specificity for targeting SK2, rather than SK1, opaganib may have a better therapeutic ratio than nonspecific sphingosine kinase inhibitors or those targeting only SK1.

RedHill acquired opaganib from U.S.-based Apogee Biotechnology Corp. in March 2015. Apogee previously completed numerous successful pre-clinical studies with opaganib in oncology, GI-inflammation and radioprotection models, as well as a successful Phase 1 clinical study in cancer patients with advanced solid tumors.

A Phase 2a clinical study with opaganib in patients with advanced, unresectable, intrahepatic and extrahepatic cholangiocarcinoma is ongoing at Mayo Clinic and MD Anderson. Opaganib was granted FDA Orphan Drug designation for the treatment of cholangiocarcinoma.

An investigator-sponsored Phase 2 study with opaganib in prostate cancer is ongoing at MUSC Hollings Cancer Center.

Enrollment and treatment have been completed in an investigator sponsored Phase 1b clinical study of opaganib for the treatment of multiple myeloma at Duke University Medical Center. The study is supported by a $2 million grant from the NCI Small Business Innovation Research Program (SBIR) awarded to Apogee in conjunction with Duke University, with additional support from RedHill.

The final results from the Phase 1 study with opaganib in patients with advanced solid tumors confirmed that the study successfully met its primary and secondary endpoints, demonstrating that the drug is well tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity. The study included the first-ever longitudinal analyses of plasma sphingosine 1-phosphate (S1P) levels as a potential pharmacodynamic biomarker for activity of a sphingolipid-targeted drug; administration of opaganib resulted in a rapid and pronounced decrease in levels of S1P with several patients having prolonged stabilization of disease. 

The Phase 2 clinical studies, as well as the completed Phase 1 clinical study in cancer patients with advanced solid tumors, 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.