Tezampanel for Anti-Platelet Therapy

Thrombosis is a major cause of morbidity and mortality in the United States. In addition to deep vein thrombosis (DVT) and pulmonary embolus (PE), thrombotic mechanisms predominate as the basis for both heart attack and stroke.

During thrombosis, platelets become activated, a process involving a cascade of signaling factors, ultimately leading to aggregation and the formation of a solid mass, the thrombus, within blood vessels.

In addition to such well-known platelet signaling molecules as thromboxane A2 (blocked by aspirin) and adenosine diphosphate (blocked by Plavix®), researchers have recently demonstrated the release of glutamate by platelets during platelet activation. Glutamate release by a platelet acts to stimulate release of glutamate from other platelets, potentiating aggregation and the formation of the thrombus.

Released glutamate acts by binding cell surface glutamate receptors expressed on platelets themselves. One particular type of the glutamate receptor is important in platelet activation, the AMPA receptor. Compounds that specifically activate the AMPA receptor can increase platelet activation. Conversely, compounds that inhibit the AMPA receptor decrease platelet activation.

A particularly potent inhibitor of the AMPA receptor is tezampanel, a molecule developed by Eli Lilly and licensed to Raptor. Tezampanel has been shown to inhibit human platelet activation, subsequent human platelet aggregation, and thrombosis in mice. The inventors of this novel technology are Dr. Charles Lowenstein and Dr. Craig Morrell, currently at the University of Rochester in New York. The use of glutamate receptor antagonists as anti-platelet agents is covered by PCT/US08/00559, assigned to Johns Hopkins University and exclusively licensed to Raptor.

Tezampanel has been extensively tested in Phase I clinical trials. The drug candidate has been demonstrated to be safe over a wide range of doses, without any serious adverse events and without any major abnormal laboratory tests. Human pharmacokinetics of tezampanel, are well characterized. In collaboration with Dr. Lowenstein and Dr. Morrell, Raptor is conducting a Phase I clinical trial in healthy volunteers to determine the efficacy of tezampanel in blocking platelet activation and aggregation.

Learn more about Raptor’s other clinical programs:

• RP103 for Nephropathic Cystinosis
• RP103 for Huntington's Disease
• RP104 for Non-alcoholic Steatohepatitis (NASH)
• Convivia™ for ALDH2 Deficiency

Raptor Announces Positive Data on Oral Tezampanel

On November 23, 2009, Raptor presented positive clinical trial data at the 12th International Conference on the Mechanisms and Treatment of Neuropathic Pain. The results indicated that oral tezampanel could be effective in a variety of neuropathic pain states, which are caused by damage to or dysfunction of the peripheral or central nervous system rather than stimulation of pain receptors.