Gemin X Presents Mechanism of Action of GMX1778 and Preclinical Data of its Prodrug GMX1777
The study on the mechanism of action of GMX1777 was highlighted yesterday, October 23, 2007, in a poster presentation of an abstract titled, "GMX1777: A novel inhibitor of NAD+ biosynthesis via inhibition of nicotinamide phosphoribosyl transferase." The mechanism of action of the compound was initially believed to involve inhibition of NF-(kappa)B, a transcriptional factor that plays a role in cancer cell survival. Gemin X has discovered that GMX1778 functions by inhibiting nicotinamide phosphoribosyl transferase (NAMPRT), an enzyme involved in the biosynthesis of oxidized nicotinamide adenine dinucleotide (NAD+), and that NF-(kappa)B inhibition occurs as a consequence of NAMPRT inhibition and NAD+ decline.
"We are encouraged by the key discovery of the mechanism of action of our second compound to enter the clinic. Rationally targeting a key metabolic pathway essential for cancer cell growth, resulting in cancer cell death independently of the status of the p53 tumor suppressor, opens new opportunities for clinical development both as a single agent and in combination with other cancer therapeutics, " stated Dr. Gordon Shore, Chief Scientific Officer of Gemin X.
At a simultaneous poster session, the preclinical data were presented from an abstract titled, "Preclinical evaluation of the NAMPRT inhibitor prodrug GMX1777." NAMPRT, a recognized anti-cancer target, is an essential enzyme for the synthesis of NAD+ and is up-regulated in cancers. In this study, researchers evaluated several models of tumors in mice administered intramuscularly with GMX1777 and, consistent with the GMX1778 mechanism of action, observed that NAD+ levels decreased significantly prior to tumor regression. The data derived from the in vitro and in vivo studies suggest that GMX1777 exhibits mechanism-based efficacy against a wide range of human tumors and support the design of the first Phase 1 open-label, dose-escalation clinical trial on GMX1777 in patients with refractory solid tumors and lymphomas.
About Gemin X
Gemin X Pharmaceuticals, Inc., through its wholly-owned 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: October 2007