VP Series of Drugs for Neurological Conditions

We are developing the VP Series of investigational drugs, which represents a new class of drugs designed to interact with antigen presenting cells (APCs) of the immune system, to regulate tissue levels of cytokines and control inflammation. VP025, the lead product candidate from this series of drugs, is being developed for the treatment of neuro-inflammatory disorders. Due to the prevalence, morbidity, and mortality associated with these disorders, they represent a significant medical, social, and financial burden. It is estimated that these neurological conditions affect more than five million people in North America and generate costs of care that exceed $75 billion annually.

Data demonstrating the ability of VP025 to reduce levels of inflammation across the blood-brain barrier, in a number of experimental models, have been presented at major neurology conferences. Research showing the ability of VP025 to reverse a correlate of memory impairment associated with aging was presented at the Fourth Federation of European Neuroscience Societies Forum in Lisbon, Portugal, and at Neuroscience 2004, the Society for Neuroscience's 34th Annual Meeting in San Diego. These results, presented by Dr. Marina Lynch and her team from the Department of Physiology at Trinity College in Ireland, showed that VP025 may prevent impairment of memory caused by beta-amyloid, a major component of the plaques found in brains of Alzheimer's disease patients.

Also at Neuroscience 2004, we presented preclinical research carried out at the Department of Anatomy/Neuroscience, Biosciences Institute, University College Cork, Ireland, that demonstrated the ability of VP025 to improve movement abnormalities and provide a significant neuro-protective effect in a well-established model of Parkinson's disease. Evidence is accumulating that inflammation also plays an important role in the pathogenesis of this debilitating condition.

Further preclinical research, presented at both the 128th Annual Meeting of the American Neurological Association in Toronto and at Neuroscience 2004, confirmed the ability of VP025 to significantly delay the onset of symptoms and increase survival in a model of ALS (Lou Gehrig's disease). In ALS, the immune system actively contributes to motor neuron injury through inflammatory processes. This research was conducted under the direction of Dr. Stanley Appel, Chief of Neurology at the Methodist Hospital and Professor of Neurology at Baylor College of Medicine in Houston.

One common theme observed in this research has been a VP025-mediated reduction in the level of activation of microglial cells - inflammatory cells specifically found within the brain and central nervous system - following VP025 administration. The observed changes in inflammatory responses and evidence of a neuro-protective effect have been consistent across these different preclinical models of disease, providing evidence of a common pathway for the therapeutic effect of VP025.

We have successfully completed a double-blind, placebo-controlled phase I trial of VP025. This dose-escalation trial examined the safety and tolerability of three doses of VP025 in healthy volunteers. Results of the study demonstrated that multiple administrations of low, mid-level, and high doses of VP025 were safe and well tolerated when compared to placebo. No drug-related serious adverse events were reported.