US National Cancer Institute awards grant to Apogee for YELIVA prostate cancer research

In March 2015, RedHill Biopharma acquired from Apogee the exclusive worldwide rights to YELIVA (ABC294640), a first-in-class, orally-administered sphingosine kinase-2 ("SK2") selective inhibitor.

Following prior pre-clinical studies in early-stage and advanced prostate cancer models, the NCI grant is intended to support additional studies with YELIVA (ABC294640) to determine its therapeutic efficacy in in vitro and in vivo models of prostate cancer in combination with radiotherapy.

These pre-clinical studies could potentially support future clinical studies with YELIVA (ABC294640) for this important indication with over 200,000 estimated new cases of prostate cancer in the U.S. in 20151.

The previous prostate cancer pre-clinical study, supported by a grant from the Pennsylvania Department of Health, a Prostate Cancer Foundation Young Investigator award, and a Prostate Cancer Foundation Mazzone Challenge award, is described in an article authored by scientists from Apogee and from the Kimmel Cancer Center at Thomas Jefferson University, and was initially published online in Molecular Cancer Research. The article, entitled "Downregulation of Critical Oncogenes by the Selective SK2 Inhibitor ABC294640 Hinders Prostate Cancer Progression" 2, describes the findings of the pre-clinical study, suggesting that oral administration of YELIVA (ABC294640) disrupts multiple oncogenic signaling pathways that are deregulated in prostate cancer, including significant inhibition of tumor growth, proliferation and cell cycle progression.

In particular, the article noted that YELIVA (ABC294640) inhibited, in vitro, several very resistant types of prostate cancer. The authors of the article conclude that their pre-clinical findings support the hypotheses that SK2 activity is required for prostate cancer growth and that YELIVA (ABC294640) could represent a new pharmacological agent for the treatment of aggressive prostate cancer.

A Phase I/II clinical study was recently initiated in the U.S. evaluating YELIVA (ABC294640) in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL), primarily in patients with HIV-related DLBCL.

The study is being conducted at the Louisiana State University Health Sciences Center (LSUHSC) in New Orleans and is supported by a grant awarded to Apogee from the NCI Small Business Technology Transfer (STTR) program.

A Phase II study of YELIVA (ABC294640) for the treatment of refractory or relapsed multiple myeloma is planned to be initiated by early 2016.

The study will be conducted at Duke University Medical Center and has received Institutional Review Board (IRB) approval from Duke University (DUHS IRB). The study is supported by a $2m grant awarded to Apogee, in conjunction with Duke University, from the NCI SBIR Program.

A third Phase II clinical study is planned to evaluate YELIVA (ABC294640) as a radioprotectant to prevent mucositis in cancer patients undergoing therapeutic radiotherapy. This study is planned to be funded directly by RedHill, which is also funding the data management and providing the drug for the NCI-supported studies.

The ongoing and planned Phase II studies follow numerous successful pre-clinical studies conducted with YELIVA (ABC294640) in GI, inflammation, radioprotection and oncology models, as well as a Phase Ib study in patients with advanced solid tumors, supported by grants awarded to Apogee from the National Cancer Institute (NCI) and the FDA’s Office of Orphan Products Development (OOPD).