On March 31, 2015 RedHill Biopharma reported that they have entered into an exclusive worldwide license agreement under which RedHill has acquired the rights to the Phase II drug candidate ABC294640 and additional intellectual property rights (Press release, RedHill Biopharma, MAR 31, 2015, View Source [SID:1234502885]). ABC294640 is a proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) inhibitor, with anti-inflammatory and anti-cancer activities, targeting multiple inflammatory, gastrointestinal (GI) and oncology indications. Schedule your 30 min Free 1stOncology Demo! Under the terms of the agreement, RedHill has acquired the exclusive worldwide development and commercialization rights to ABC294640 and additional intellectual property for all indications. RedHill will pay Apogee an upfront payment of $1.5 million, as well as an additional $4 million in potential milestone payments, and potential tiered royalties starting in the low double-digits.
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ABC294640 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, ABC294640 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, ABC294640 may have a better therapeutic ratio than nonspecific sphingosine kinase inhibitors or those targeting only SK1.
Apogee received cumulative funding exceeding $14 million to support the development of ABC294640, primarily through grants and contracts from U.S. federal and state government agencies such as the NIH Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) program, including funding from the National Cancer Institute (NCI), the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), the Department of Defense (DoD), the FDA Office of Orphan Products Development and the Pennsylvania Department of Health.
With this funding Apogee has 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.
A Phase Ib/II clinical study with ABC294640 for refractory/relapsed diffuse large B cell lymphoma (DLBCL) is planned to commence in the second quarter of 2015 and will be funded by a $1.5 million grant awarded by the National Cancer Institute under the NIH SBIR/STTR program to Apogee in conjunction with the Louisiana State University Health Science Center. The study will include approximately 30 patients and is intended to assess the tolerability of ABC294640 within the DLBCL population, as well as provide a preliminary evaluation of efficacy. A second Phase II clinical study of ABC294640 for the treatment of multiple myeloma is planned, subject to funding by a pending grant from the National Cancer Institute. A third Phase II clinical study is being planned by RedHill in order to evaluate ABC294640 as a radio-protectant and radiation enhancer in cancer patients undergoing radiotherapy.
Furthermore, multiple pre-clinical studies funded by the NIH (BARDA) and the DoD have demonstrated activity of ABC294640 against gastrointestinal injury from accidental acute radiation exposure. Therefore, a possible additional indication of protection against accidental radiation exposure may qualify as a medical countermeasure under the Animal Rule, under which no human efficacy studies would be required for FDA approval.
"With a unique mechanism of action, ABC294640 is a novel potential treatment for multiple inflammatory and oncology diseases with strong unmet medical needs. In particular, the drug may be a unique and important treatment for prevention of severe toxicity and inflammation induced in many cancer patients by radiotherapy, while at the same time potentially enhancing the effectiveness of the radiotherapy treatment," said Dr. Terry Plasse, Medical Director at RedHill. "We are looking forward to further advancing this promising program into clinical studies, and plan a Phase II study to evaluate the ability of ABC294640 to decrease radiotherapy-induced toxicity."
Adi Frish, Senior VP Business Development and Licensing at RedHill added: "With the acquisition of ABC294640 we adhere to RedHill’s multiple-shots-on-goal strategy. The acquisition of this potential blockbuster further expands our late clinical-stage pipeline, reflecting RedHill’s solid commitment to patients suffering from inflammatory and gastrointestinal diseases, including cancer, who are in need of new treatment options. Thanks to the thorough development work conducted by Apogee, ABC294640 is supported by extensive pre-clinical, clinical and CMC package, as well as strong intellectual property protection, and we believe in its potential to become a leading treatment for multiple inflammatory, gastrointestinal and oncology indications. We are excited to continue advancing this important novel drug candidate, and would like to thank our new partners at Apogee for entrusting us with the development and commercialization of ABC294640."
Dr. Charles Smith, President and CEO at Apogee stated: "We are very pleased to be collaborating with RedHill to advance the clinical development of ABC294640 for the potential benefit of cancer patients. We view RedHill as an outstanding partner for this effort, and are particularly impressed by their demonstrated commitment to tackling the difficult problem of improving therapeutic outcomes and the quality of life for cancer patients. Additionally, RedHill’s expertise with gastrointestinal inflammatory diseases provides a very strong foundation for clinical testing of this drug candidate, and we are looking forward to a successful outcome of this collaboration."
In addition to the three ongoing Phase III studies in GI indications (RHB-105 for H. pylori infection, BEKINDA (RHB-102) for gastroenteritis, and RHB-104 for Crohn’s disease), RedHill’s pipeline now includes three proprietary, Phase II-stage, orally-administered, first-in-class small molecule drug candidates intended to treat gastrointestinal and other solid tumor cancers, as well as other potential indications: Mesupron, a urokinase-type plasminogen activator (uPA) inhibitor, RP101 (under an option-to-acquire), a heat shock protein 27 (Hsp27) inhibitor, and the newly-acquired SK2 inhibitor, ABC294640.
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 a number of 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 has 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.