The study, which appears in the May 15 print edition of Blood, is titled, "The BH3-mimetic GX15-070 synergizes with Bortezomib in Mantle Cell Lymphoma by enhancing Noxa-mediated activation of Bak." It was led by Patricia Perez-Galan et al., from the Hematopathology Unit, Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
According to the report, GX15-070 was active in cells bearing defective DNA damage sensor genes or cell cycle regulators. Additionally, the compound synergized with bortezomib (Velcade(R)), a proteasome inhibitor, such that MCL cells became sensitized to low doses of bortezomib. Bortezomib was shown to induce the pro-survival Bcl member, Mcl-1, which causes resistance to the drug. Inhibition of Mcl-1 by GX15-070, in contrast, overcame this resistance. This positive preclinical activity of GX15-070 led to an increased activation of the apoptotic pathway, while showing no significant cytotoxic effect in normal cells from healthy donors when used both alone and in combination with bortezomib.
"The results of this study show that a small molecule inhibitor, such as obatoclax (GX15-070) that modulates the Bcl-2 pathway, is a rational approach for the treatment of MCL," said Gordon Shore, Chief Scientific Officer of Gemin X. "Its ability to enhance the effects of bortezomib by overcomi ng resistance mediated by Mcl-1 also reveals the breadth of the compound's therapeutic potential. These findings suggest that Gemin X's obatoclax (GX15-070) in combination with bortezomib may prove to be an attractive new approach in the treatment of MCL, and further support our recent initiation of this combination in a Phase 1b trial in MCL."
Gemin X is currently conducting several clinical trials of obatoclax (GX15-070) in multiple cancer types as a combination therapy and as a single agent. In addition to the Phase 1b trial in MCL, Gemin X recently initiated a Phase 1/2 clinical trial in combination with docetaxel in patients with non-small cell lung cancer. Obatoclax (GX15-070) is also in Phase 2 clinical trials in patients with Hodgkin's Lymphoma, myelofibrosis with myeloid metaplasia, myelodysplastic syndrome, and follicular lymphoma both as single agent and in combination with rituximab. In multiple Phase 1 studies, obatoclax (GX15-070) was well-tolerated and resulted in clinical and biological activity.
About Mantle Cell Lymphoma (MCL)
Mantle cell lymphoma (MCL) belongs to a group of diseases known as non-Hodgkin's lymphomas, which are related cancers that affect the lymphatic system. Mantle cell lymphoma is an aggressive B-cell lymphoma that historically has been resistant to current standard chemotherapeutic approaches, making it a difficult cancer to treat. The median survival time is three years and the ten-year survival rate is only 5-10%.
Gemin X Biotechnologies Inc. specializes in the discovery and development of novel small molecule cancer therapeutics based on the regulation of apoptosis, the body's natural ability to destroy injured or damaged cells. Gemin X's lead product, obatoclax (GX15-070), is a small molecule, pan-inhibitor of Bcl-2 pro-survival proteins and is currently in Phase 2 clinical trials. Gemin X is also developing a small molecule that induces apoptosis in p53-defective cancers. Gemin X is privately hel d and is located in Montreal, Quebec and Malvern, Pennsylvania. For additional information please visit Gemin X at www.geminx.com
Velcade(R) is a registered trademark of Millenium Pharmaceuticals.