June 30, 2005

Targacept Compounds Show Long-lasting Improvement in Cognition

Winston-Salem, NC, June 30, 2005 "“ In a review of research to be published in the July issue of Trends In Pharmacological Sciences, Targacept compounds were reported to have a beneficial effect on cognition well after they were no longer present in the central nervous system. For example, in preclinical animal studies, Targacept's compounds TC-1827 and TC-1734 improved cognitive performance for up to 15 and 18 hours, respectively, though the compounds were appreciably metabolized and eliminated in less than an hour.

The authors postulate that the compounds' long duration of effect arises from their ability to normalize levels of acetylcholine, a key neurotransmitter for modulating cognition. This mechanism of action contrasts with currently marketed drugs for conditions marked by impaired learning and/or memory, which can increase, but not normalize, neurotransmitters involved in cognitive processing.

"The lasting effect of our compounds demonstrates their potential to treat CNS disorders such as dementia, depression, anxiety and pain," said J. Donald deBethizy, Targacept's President and Chief Executive Officer. "Furthermore, the findings suggest that we may be able to achieve efficacy with a low, once-daily dose that minimizes side-effects. A simple, daily dosing regimen is particularly important when treating disorders that affect cognition," he added.

"Targacept's compounds act selectively on nicotinic acetylcholine receptor targets, and we anticipated this duration of effect based on extensive research of novel nicotinic compounds demonstrating sustained effects on cognition in animals," said Merouane Bencherif, M.D., Ph.D., Vice President, Preclinical Research. "Further, our research has shown that some of our compounds act on the primary pathways responsible for learning and memory and initiate a cascade believed to precipitate lasting cognitive enhancement," added Dr. Bencherif.

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