Myrexis releases MPC-9528 cancer metabolism inhibitor preclinical study results

Sep 20 2010

Myrexis, Inc. (Nasdaq:MYRX), a biotechnology company focused on discovering, developing, and commercializing novel treatments for cancer, today announced key findings from preclinical studies of the Company's novel cancer metabolism inhibitor (CMI), MPC-9528, at the Cancer and Metabolism: Pathways to the Future Symposium in Edinburgh, Scotland. Compelling preclinical evidence demonstrates that treatment with MPC-9528 results in significant tumor growth inhibition and that the co-administration of niacin improves the therapeutic index of MPC-9528.  Additional data, from a large panel of tumor cell lines and primary human tumor tissue indicate that approximately 40% of all cancers may carry a biochemical defect making them respond well to the combination of niacin and MPC-9528 treatment.  A simple companion diagnostic could be used to identify patients with such tumors.

Key Findings:

MPC-9528 is a potent and selective inhibitor

In biochemical and cellular assays, MPC-9528 demonstrated picomolar potency for its target, Nampt (nicotinamide phosphoribosyltransferase).  Tumoricidal activity is on target and effective against a wide rage of tumor cells.   

Co-administration of niacin (vitamin B3) improves MPC-9528's therapeutic index

Myrexis demonstrated that co-administration of niacin (vitamin B3) could protect healthy cells from MPC-9528 activity, and that this protective effect was dependent on expression of the enzyme Naprt1.  Niacin could not prevent MPC-9528-induced cell death in cancer cells that express little or no Naprt1. 

Expression of Naprt1 is deficient in approximately 40% of all cancers

The Company evaluated 145 tumor cell lines across diverse cancer types and found Naprt1 deficiency to be common, affecting about 40% of the cell lines. 

MPC-9528 causes dramatic tumor regressions across multiple tumor types. 

In animal models, both Naprt1-proficient and Naprt1-deficient tumors responded to MPC-9528, demonstrating potent tumoricidal activity.  However, greater tumor growth inhibition could be achieved in Naprt1-deficient tumors by adding niacin, which allowed MPC-9528 to be tolerated at doses greater than twice the typical maximum tolerated dose (MTD). 

"MPC-9528 is a unique IND candidate.  The compound has highly selective, potent on-target anti-cancer activity.  It is possible to use a simple and straightforward companion diagnostic to identify tumors which are dependent upon the biochemical pathway inhibited by MPC-9528.  It should be possible to treat these tumors safely and even more aggressively and effectively with the co-administration of niacin," commented Robert Carlson, Ph.D., Vice President and Head of Research at Myrexis.  "Use of a companion diagnostic and niacin in our clinical program has the potential to increase the efficiency of patient enrollment and enrich for patients likely to be responsive to MPC-9528."

A copy of the Poster, "MPC-9528, a cancer metabolism inhibitor, demonstrates greater therapeutic index in a Naprt1 deficient cancer xenograft model with co-administration of nicotinic acid," which was presented at Cancer and Metabolism: Pathways to the Future Symposium in Edinburgh, Scotland earlier today is available on-line at the Company's website, www.myrexis.com.

Source : Myrexis, Inc.