RedHill Biopharma Initiates Phase I/II Study of ABC294640 for Refractory Lymphoma

RedHill Biopharma Ltd.

("RedHill" or the "Company"), an Israeli biopharmaceutical company focused on late clinical-stage, proprietary, orally-administered, small molecule drugs for inflammatory and gastrointestinal diseases, including gastrointestinal cancers, today announced that it has initiated a Phase I/II clinical study in the U.S. evaluating ABC294640 in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL). ABC294640 is a proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor, with anti-inflammatory and anti-cancer activities, targeting multiple inflammatory, gastrointestinal (GI) and oncology indications. SK2 is an innovative molecular target for anti-cancer therapy because of its critical role in catalyzing the formation of the lipid-signaling molecule sphingosine 1-phosphate (S1P), which is known to regulate cell proliferation and activation of inflammatory pathways. By inhibiting SK2, ABC294640 could potentially be effective in treating multiple inflammatory, oncologic and gastrointestinal diseases. The Phase I/II study is intended to evaluate the safety and tolerability of ABC294640, as well as provide a preliminary evaluation of efficacy of the drug in patients with refractory/relapsed DLBCL, primarily patients with HIV-related DLBCL. Up to 33 patients are expected to be enrolled in the study, which will be conducted at the Louisiana State University Health Sciences Center (LSUHSC) in New Orleans. The study is funded primarily by a grant awarded by the National Cancer Institute (NCI) Small Business Technology Transfer (STTR) program. Dr. Chris Parsons, MD, an associate professor in the Departments of Medicine and Microbiology, Immunology & Parasitology at LSUHSC, is the lead investigator for the study. Dr. Terry Plasse, MD, RedHill's Medical Director, said: "We are excited to initiate this translational study with ABC294640, carrying Dr. Parson's laboratory evaluations into an important clinical population of patients with refractory/relapsed diffuse large B-cell lymphoma, primarily patients with HIV-related DLBCL, a group of patients with substantial unmet medical needs. RedHill continues to advance towards additional Phase II clinical studies with ABC294640 as a radioprotectant in cancer patients undergoing therapeutic radiotherapy and, subject to a pending NCI/SBIR grant, multiple myeloma." DLBCL is the most common subtype of non-Hodgkin's lymphoma, accounting for an estimated 30% of the 70,000 projected non-Hodgkin's lymphoma cases diagnosed in the U.S. in 20151. Many DLBCLs are etiologically linked to the human viruses which encode unique oncogenes contributing to tumor onset and progression. Standard treatments for DLBCL exhibit limited efficacy and incur significant toxicities. The Phase I/II study was initiated following positive pre-clinical studies, led by Dr. Parsons, indicating the therapeutic activity of ABC294640 for virus-associated DLBCL, in an established xenograft model for Kaposi's sarcoma-associated herpesvirus-associated DLBCL, including reversal of disease progression for established tumors. The pre-clinical studies were performed in parallel with a successful Phase I study that demonstrated the drug's safety and assessed its pharmacokinetics and pharmacodynamics in cancer patients with advanced solid tumors. RedHill acquired the rights to ABC294640 in March 2015 from U.S.-based Apogee Biotechnology Corporation ("Apogee"). Prior to the acquisition, Apogee completed numerous successful pre-clinical studies with ABC294640 in GI, inflammation, radioprotection and oncology models, as well as a successful Phase I clinical study in cancer patients with advanced solid tumors. The open-label, dose-escalation, Phase I clinical study demonstrated the drug's safety and assessed its pharmacokinetics and pharmacodynamics in cancer patients with advanced solid tumors. The development of ABC294640 was funded to date primarily through grants and contracts in excess of $14 million from U.S. federal and state government agencies, such as the FDA, Department of Defense (DoD) and the National Institutes of Health (NIH), including the National Cancer Institute and BARDA. A second Phase II study of ABC294640 is planned to evaluate ABC294640 as a radioprotectant to prevent mucositis in cancer patients undergoing therapeutic radiotherapy. RedHill also plans a third Phase II clinical study for the treatment of multiple myeloma, subject to funding by a pending grant from the National Cancer Institute. The Phase I/II study with ABC294640 for refractory/relapsed diffuse large B-cell lymphoma is 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: https://www.clinicaltrials.gov/ct2/show/NCT02229981?term=abc294640&rank=2. About ABC294640: ABC294640 is a first-in-class, proprietary sphingosine kinase-2 (SK2) selective inhibitor, administered orally, with anti-cancer and anti-inflammatory activities, targeting multiple potential inflammatory, oncology and gastrointestinal indications. By inhibiting the SK2 enzyme, ABC294640 blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid that promotes cancer growth and pathological inflammation. ABC294640 was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in inflammatory, GI, radioprotection and oncology models, as well as a Phase I clinical study in cancer patients with advanced solid tumors. A Phase I/II clinical study evaluating ABC294640 in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL) has been initiated in the U.S. The development of ABC294640 was funded to date primarily through grants and contracts in excess of $14 million from U.S. federal and state government agencies.