TPTX » Topics » NGX267 and NGX292

This excerpt taken from the TPTX 10-K filed Mar 29, 2007.

NGX267 and NGX292

NGX267 is a partial muscarinic agonist with functionally specific M1 receptor activity. The pharmacological properties of NGX267 partially mimic the action of acetylcholine by stimulating the M1 receptors. Activation of the M1 receptor is thought to have the most potential for improving cognitive function because of the predominance of M1 receptors in areas of the brain involved in memory and cognition. NGX267 has been demonstrated in animal models to be effective in improving cognitive deficits in learning and memory.

In addition to improving cognition, a second mechanism of action, the reduction of Aß42, also supported by preclinical data, suggests that NGX267 may be effective as a treatment to delay the onset or to slow the progression of Alzheimer’s disease. In transgenic mice, a specific animal model used in Alzheimer’s disease studies, NGX267 has been shown to reduce Aß42 and to prevent the formation of amyloid plaques.

Because impairments in memory and learning have been demonstrated in both Alzheimer’s disease patients and schizophrenic patients, we believe that we have a strong rationale to develop NGX267 as a treatment for Alzheimer’s disease and CIAS. We have chosen CIAS as our initial indication for NGX267 because we believe we can generate proof of concept data for the treatment of CIAS more quickly than we can generate proof of concept data for the treatment of Alzheimer’s disease. CIAS targets a younger and somewhat healthier population, potentially aiding clinical trial enrollment. In addition, we believe the design of a clinical trial for the treatment of CIAS may allow for a shorter clinical treatment duration than a clinical trial for the treatment of Alzheimer’s disease. While we anticipate showing beneficial effects on memory and learning, it is unlikely that NGX267 would be effective in controlling symptoms such as hallucinations or delusions that are associated with schizophrenia. Therefore, our clinical program will evaluate NGX267 as adjunctive, or add-on, therapy with commonly used antipsychotics.

NGX292, the major metabolite of NGX267, has demonstrated a biological profile similar to the profile of NGX267. NGX292, also in-licensed from LSRI in 2004, is currently in preclinical development.

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