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YELIVA® (Oncology)

YELIVA® (ABC294640) is a first-in-class, proprietary sphingosine kinase-2 (SK2) selective inhibitor, administered orally, with anti-cancer and anti-inflammatory activities, targeting a number of potential oncology, inflammatory and gastrointestinal indications.

YELIVA® 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, YELIVA® 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, YELIVA® may have a better therapeutic ratio than nonspecific sphingosine kinase inhibitors or those targeting only SK1.

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

The final results from the Phase I study with YELIVA® 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 YELIVA® resulted in a rapid and pronounced decrease in levels of S1P with several patients having prolonged stabilization of disease.

A Phase Ib/II clinical study of YELIVA® for the treatment of multiple myeloma was initiated 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.

A Phase II study with YELIVA® for the treatment of advanced hepatocellular carcinoma was initiated at  the MUSC Hollings Cancer Center. The study is supported by a $1.8 million grant from the NCI awarded to MUSC, intended to support a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, including the Phase II study with YELIVA®, and will be further supported by additional funding from RedHill.

A Phase I/IIa clinical study evaluating YELIVA® in patients with refractory/relapsed diffuse large B-cell lymphoma and Kaposi sarcoma was initiated at the Louisiana State University Health Sciences Center in New Orleans. The study is supported by a grant from the NCI awarded to Apogee, with additional support from RedHill.

A Phase IIa clinical study with YELIVA® in patients with advanced, unresectable, intrahepatic and extrahepatic cholangiocarcinoma is planned to be initiated. YELIVA® was granted FDA Orphan Drug designation for the treatment of cholangiocarcinoma.  

A Phase Ib clinical study to evaluate YELIVA® as a radioprotectant to prevent mucositis in cancer patients undergoing therapeutic radiotherapy is planned to be initiated.

A Phase II study to evaluate the efficacy of YELIVA® in patients with moderate to severe ulcerative colitis is planned to be initiated. 

The Phase I/II clinical studies, as well as the completed Phase I 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.