Gemin X Announces Publication of Unique Mechanism of Action of Obatoclax in Proceedings of the National Academy of SciencesMALVERN, Pa. & MONTREAL--(BUSINESS WIRE)--Nov 27, 2007 - Gemin X announced today that a report published in the online version of the journal Proceedings of the National Academy of Sciences (PNAS) confirmed the Bcl-2-mediated mechanism of action of its lead compound, obatoclax (GX15-070), demonstrating that it specifically disrupts the survival of cancer cells as a result of inhibiting the Bcl-2 pro-survival protein Mcl-1. This mechanism of action allows obatoclax to overcome Mcl-1-mediated cancer cell resistance to apoptosis, or programmed cell death. Obatoclax is a novel, small molecule candidate in Phase 2 trials in multiple cancer indications that is specifically designed to inhibit all relevant members of the Bcl-2 protein family, a validated cancer target, restoring the natural cell death process of apoptosis.
Elevated expression of members of the Bcl-2 pro-survival family of proteins can confer resistance to apoptosis in cancer cells. In prior studies, obatoclax has been shown to antagonize these members, thus inducing apoptosis. In this scientific paper, in vitro studies confirmed that obatoclax overcomes Bcl-2 pro-survival proteins' resistance to pro-apoptotic proteins BAX and BAK. The anti-apoptotic protein Mcl-1 plays a particularly central role in conferring cancer cell resistance in certain instances, and importantly, the study demonstrated that obatoclax potently interferes with the direct interaction between Mcl-1 and BAK in the intact mitochondrial outer membrane and inhibited the association between Mcl-1 and BAK in intact cells. It is thought that Mcl-1 regulates BAK within the mitochondrial outer membrane.
"These results build upon a body of data confirming the unique mechanism of action of obatoclax and further support our clinical development plans for the compound, particularly in cancer indications or treatments where Mcl-1 contributes to the resistance to apoptosis," stated Gordon Shore, Ph.D., Gemin X's Interim CEO and Chief Scientific Officer, and Professor of Biochemistry at McGill University "We are particularly encouraged that these data differentiate obatoclax from otherwise similar drugs in development and on the market that are affected by Mcl-1-mediated resistance, as obatoclax appears to overcome such resistance. This emerging profile of our lead compound provides the basis for rationally combining it with other targeted cancer agents hindered by this resistance mechanism."
The paper by Dr. Mai Nguyen et al., which appeared in yesterday's Early Edition of PNAS, is titled, "Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis," and was the result of collaborations between Gemin X, McGill University, the NRC Biotechnology Research Institute, and the Peter MacCallum Cancer Institute. The paper will also appear in the print edition of PNAS.
Obatoclax (GX15-070) is a small molecule indole bipyrrole drug compound that was discovered and is being developed at Gemin X. The attractive safety profile and mechanism of action of obatoclax offers the opportunity to treat many forms of cancer as both a single agent and in combination with current treatments. Obatoclax is currently being assessed in multiple Phase 2 company-sponsored clinical trials directed against multiple solid tumor and hematologic malignancies. In addition to clinical activity in multiple indications, obatoclax is generally well tolerated, and is without evidence of immuno- and myelosuppression.
About Gemin X
Gemin X Pharmaceuticals, Inc., through its subsidiary Gemin X Biotechnologies Inc., specializes in the discovery and development of target-based novel cancer therapeutics. Gemin X's lead product, obatoclax (GX15-070), is a small molecule, pan-inhibitor of Bcl-2 proteins and is currently in Phase 2 clinical trials. Gemin X is also developing GMX1777, a small molecule that targets cancer metabolism by a p53-independent mechanism. Gemin X is privately held and is located in Malvern, Pennsylvania and Montreal, Quebec. For additional information please visit Gemin X at www.geminx.com.
MacDougall Biomedical Communications
Jennifer Greenleaf, 508-647-0209
Gemin X Biotechnologies Inc.
Diane Viens, 514-281-8989 ext.387
Posted: November 2007