-Paper Confirms that Obatoclax Defeats Cancer Cell Survival Mechanisms -
MALVERN, PA. & MONTREAL, November 27 /CNW/ - 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
For further information:
For further information: MacDougall Biomedical Communications Jennifer
Greenleaf, 508-647-0209 or Gemin X Biotechnologies Inc. Diane Viens,
514-281-8989 ext.387 email@example.com