Xanthus Pharmaceuticals, Inc. presented preclinical results from the Company’s FLT3 autoimmune program that describe a novel mechanism of action for achieving prolonged disease attenuation in an animal model for multiple sclerosis (MS). The experiments showed that Symadex™, the lead compound from Xanthus’ FLT3 autoimmune program, directly targets macrophages and monocytes, key cells responsible for driving the autoimmune response. Stephen J. Karlik, Ph.D., Professor of Diagnostic Radiology at the University of Western Ontario, London, Ontario, described these findings in an oral presentation at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Prague, Czech Republic.
Dr. Karlik, together with researchers from Xanthus, conducted several studies to investigate the immunomodulatory effects and kinase activity of Symadex using a model of experimental autoimmune encephalomyelitis (EAE) that is designed to represent multiple sclerosis. Researchers examined Symadex-treated versus control animals for changes in several circulating biomarkers known to be relevant to autoimmune disease. Symadex was found to bring elevated levels of monocyte- and macrophage-related biomarkers associated with disease back to normal. MRI imaging showed that macrophage function was inhibited in areas of inflammation. In vitro studies supporting this mode of action show that Symadex is an inhibitor of FLT3, a receptor tyrosine kinase known to regulate dendritic cells, as well as CSF-1R, a related receptor expressed particularly on macrophages.
"We observed that Symadex exhibits a distinctive targeted effect on macrophage and monocyte function. These cell types play a key role in driving the autoimmune response, and the ability of Symadex to specifically interfere with their function makes this candidate a potentially unique therapeutic opportunity for MS and other autoimmune diseases," said Dr. Karlik.
"We believe that the targeted mechanism of action observed with Symadex in these studies has opened the door for Xanthus to explore multiple autoimmune and oncology indications for this compound and our series of related agents. We are preparing to initiate a human proof-of-principle trial with Symadex in autoimmune disease in 2008 to support our partnering objective for the FLT3 autoimmune program, and we are exploring the potential of additional oncology studies that may leverage Symadex’s targeted kinase activity," stated Richard T. Dean, Ph.D., Xanthus' Chief Executive Officer.
Symadex (formerly C-1311) is the lead compound in clinical development from a new series of agents, the imidazoacridinones, which have shown in vitro to be potent and selective FLT3 receptor tyrosine kinase inhibitors. Symadex is currently in a Phase 2 study for women with metastatic breast cancer, and has the potential to be active in hematological malignancies. Xanthus is also exploring the use of Symadex and follow-on compounds for the treatment of a number of autoimmune diseases, such as multiple sclerosis and inflammatory bowel disease. Early preclinical data has shown encouraging signs of activity in models of autoimmune disease. Given the compound's safety profile and oral availability, Xanthus believes Symadex represents the potential for a large-scale drug opportunity. Further preclinical studies are currently being conducted, after which the Company expects to enter clinical development.
Source: Xanthus Pharmaceuticals, Inc. (15/10/07)