Gemin X, a clinical stage biopharmaceutical company developing novel, targeted cancer therapeutics, today announced that one of its lead oncology candidates, obatoclax, has demonstrated biological and anti-cancer activity in heavily pre-treated patients with advanced chronic lymphocytic leukemia (CLL). The results are from a Phase 1 study, and have been published in the online version of Blood, the Journal of the American Society of Hematology. Full trial results are expected to be published in the upcoming print version of the journal.
Obatoclax is a potential first-in-class pan Bcl-2 inhibitor that initiates programmed cell death, or apoptosis, by targeting multiple Bcl-2 related proteins and is currently in Phase 2 clinical trials as both a single agent and combination therapy for the treatment of elderly acute myeloid leukemia (AML) and small cell lung cancer (SCLC), respectively.
“The activity we observed with obatoclax in this heavily pre-treated patient population with advanced disease is particularly encouraging when one considers how difficult it is to effectively treat CLL,” said Susan M. O’Brien, M.D., Professor of Medicine at the University of Texas M.D. Anderson Cancer Center, and a co-author of the Blood paper. “The medical and patient communities are in dire need of new, potent options to address life-threatening hematologic cancers, and we look forward to further evaluating obatoclax in a number of different settings as both a single and combination therapy.”
In the study, obatoclax was administered to 26 patients with advanced CLL at doses ranging from 3.5 to 14 mg/m2 as a one-hour infusion and from 20 to 40-mg/m2 as a three-hour infusion every three weeks. One (4%) of the 26 patients achieved a partial response, and patients with anemia (3 out of 11) or thrombocytopenia (4 out of 14) experienced improvements in hemoglobin and platelet counts. Two patients who had been red blood cell transfusion dependent had significant hemoglobin increases, and achieved sustained independence from transfusions. The majority of patients had lymphocyte reductions, with a mean reduction of 24%.
The maximum tolerated dose (MTD) was 28 mg/m2 over three hours every three weeks. Dose limiting reactions were associated with the infusion and composed of transient neurological events (somnolence, euphoria, ataxia) which were reduced by prolonging the rate of infusion.
“There currently exists a significant unmet medical need among physicians treating life-threatening cancers, and we believe that the safety and potent activity seen with obatoclax in early research efforts clearly differentiate this pan Bcl-2 inhibitor,” said Glenn J. Gormley, M.D., Ph.D., President and CEO of Gemin X. “We are enthusiastic about the potential of obatoclax to treat a broad range of hematologic and solid tumor cancers, and we look forward to aggressively pursuing our clinical development program.”
About Bcl-2 Antagonists and Obatoclax
Bcl-2 derives its name from B-cell lymphoma 2; the Bcl-2 family is a group of proteins that are involved in a number of cancers, including melanoma, breast, prostate and lung carcinomas, and are also thought to be involved in resistance to conventional cancer treatment. The Bcl-2 family is involved in the regulation of apoptosis, a form of cell death.
Obatoclax, Gemin X’s small molecule pan Bcl-2 antagonist, is specifically designed to inhibit all relevant members of the Bcl-2 family, a validated cancer target, thus restoring the process of apoptosis. Obatoclax is currently in multiple Phase 1 and 2 trials.
About Gemin X Pharmaceuticals
Gemin X Pharmaceuticals is dedicated to the discovery, development and commercialization of novel, targeted cancer therapeutics to improve the lives of patients. Gemin X is developing first-in-class cancer therapeutics based on reinitiating programmed cell death, or apoptosis, and the inhibition of metabolism in cancerous cells. Gemin X currently has three clinical development programs underway, ranging from Phase 2 clinical trials for its lead product candidates obatoclax (GX15-070), an innovative pan Bcl-2 inhibitor, and GMX1777, a novel inhibitor of NAD+ synthesis, to preclinical studies for its Telomere Capping program. Potential treatment indications for the full scope of pipeline programs span a broad range of hematological and solid tumors, including elderly acute myeloid leukemia (AML), mantle cell lymphoma (MCL), melanoma, glioblastoma, small cell lung cancer (SCLC), refractory acute lymphoblastic leukemia (ALL) and mastocytosis. Founded in 1998, Gemin X is privately held with drug development and executive headquarters in Malvern, Pennsylvania and drug discovery operations in Montréal, Canada. For more information, please visit geminx.