TEL AVIV, Israel—RedHill Biopharma Ltd. recently published a paper on ABC294640 in prostate cancer in Molecular Cancer Research. The paper, "Downregulation of Critical Oncogenes by the Selective SK2 Inhibitor ABC294640 Hinders Prostate Cancer Progression,” was authored by scientists from Apogee Biotechnology Corporation and the Kimmel Cancer Center at Thomas Jefferson University.
ABC294640 is a first-in-class, proprietary sphingosine kinase-2 (SK2) selective inhibitor with anti-cancer and anti- inflammatory activities. Through inhibition of the SK2 enzyme, it blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid that promotes cancer growth and pathological inflammation.
The article covers the results of a preclinical study of ABC294640 in early-stage and advanced prostate cancer models, and seem to indicate that oral administration of the drug candidate disrupts multiple oncogenic signaling pathways that are deregulated in prostate cancer, leading to significant inhibition of tumor growth, proliferation and cell cycle progression. When tested in vitro, ABC294640 inhibited several extremely resistant subtypes of prostate cancer. Based on these results, it is believed that SK2 activity is necessary for prostate cancer development, and that ABC294640 could offer a new treatment option for early-stage and aggressive prostate cancer.
"This paper provides further definition of the mechanism of the anticancer activities of ABC294640, including the first demonstration of inhibition of signaling through the androgen receptor pathway, which is critical for prostate cancer growth. The growing body of mechanistic and clinical data on ABC294640 suggests that this drug may be useful for the treatment of early-stage and castrate-resistant prostate cancer,” commented Dr. Charles Smith, president and CEO of Apogee Biotechnology Corporation and one of the authors of the article.
RedHill has also investigated ABC294640 in preclinical models of GI, inflammation, radioprotection and oncology, as well as a Phase 1 study in solid tumors that demonstrated the drug candidate's safety and determined its pharmacodynamics and pharmacokinetics.
The company recently began a Phase 1/2 clinical study of ABC294640 in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL) to determine its safety and tolerability as well as a preliminary evaluation of efficacy. A Phase 2 study will also be launched to evaluate the drug candidate as a radioprotectant to prevent mucositis in cancer patients receiving therapeutic radiotherapy, and should RedHill receive a pending grant from the National Cancer Institute, another Phase 2 clinical study will examine ABC294640 in multiple myeloma.
In addition, RedHill recently filed a trademark application with the U.S. Patent and Trademark Office for the brand name Yeliva should ABC294640 secure necessary regulatory approval.
Patricia Bandeira, RedHill's Product Manager for ABC294640, noted in a press release that, "We are pleased to have these important findings, suggesting that ABC294640 could be effective in treating prostate cancer, published in a peer-reviewed journal. ABC294640, under its new brand name YELIVA, is a novel and promising drug candidate with multiple potential oncology and inflammatory indications. RedHill recently initiated a Phase 1/2 study of YELIVA (ABC294640) in patients with refractory/relapsed diffuse large B-cell lymphoma, and is progressing towards a second Phase 2 study to evaluate YELIVA (ABC294640) as a radioprotectant in cancer patients undergoing therapeutic radiotherapy, and a third Phase 2 clinical study for the treatment of multiple myeloma."