Clinical Candidates

Aminopterin is an antifolate in the same class as the widely used drug, methotrexate.  The clinical use of Aminopterin was pioneered by Dr. Barton Kamen at the University of Medicine and Dentistry in New Jersey (UMDNJ).  Compared to methotrexate, Aminopterin is more bioavailable (90% in Phase I studies), and is 10- to 20-fold more potent.  Phase 2 trials are underway in pediatric leukemia and psoriasis.  The exclusive worldwide rights to Aminopterin were licensed from UMDNJ.  The Company has developed a proprietary position around novel stable Aminpterin formulations and methods of use and synthesis.

GST inhibitors are bivalent molecules that bind tightly and specifically to each active site of glutathione-S-transferase (GST) dimers, and were developed through a collaborative research program with Dr. William Atkins of the University of Washington, Department of Medicinal Chemistry.  GSTs are responsible for tumor resistance to standard chemotherapeutic drugs and are involved in cell signaling pathways that stimulate the bone marrow resulting in the release of white blood cells.  These inhibitors may therefore be used as either an adjuvant to standard chemotherapy, or as a bone marrow stimulant to increase the levels of circulating white blood cells.  Depression of white blood cell levels is a common, toxic effect of many standard chemotherapeutic drugs.

Chemotaxis inhibitors are small molecules that block the activity of neutrophil chemotaxis in vitro.  Clinical applications include disease where abnormal accumulations of neutrophils occur, such as in inflammatory bowel disease and bronchopulmonary dysplasia.

NMDA inhibitors block the interaction of excitatory amino acids with the N-methyl-D-aspartate (NMDA) receptor.  The clinical use of NMDA inhibitors in treating antifolate (e.g. methotrexate) neurotoxicity was pioneered by Dr. Barton Kamen at the University of Medicine and Dentistry in New Jersey (UMDNJ).  The exclusive worldwide rights to NMDA inhibitors in treating antifolate neurotoxicity were licensed from UMDNJ.

• Drachtman, R.A., Cole, P.D., Golden, C.B., James, S.J., Melnyk, S., Aisner, J., and Kamen, B.A.  Dextromethorphan is effective in the treatment of subacute methotrexate neurotoxicity.  Pediatr. Hematol. Oncol., 19:319-327 (2002).