Alzheimer's Club

"Predix Pharmaceuticals, a drug discovery and development company, has initiated the second of two Phase Ib multiple dose studies with PRX-03140, its highly selective, proprietary serotonin 4 (5-HT4) receptor agonist intended to treat Alzheimer's disease and other disorders of memory and cognition. This Phase Ib study is the first Predix study in patients with Alzheimer's disease. The primary objectives of the Phase Ib studies in both healthy subjects and patients with Alzheimer's disease are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the compound over a 14-day period.

This study is a double-blind, placebo-controlled trial, in which patients with mild to moderate Alzheimer's disease receive a once-daily dose of the study drug. The trial will investigate the effects of PRX-03140 on cognitive function and memory, electroencephalograms and biochemical markers of Alzheimer's disease pathology.

"We are pleased to announce that PRX-03140 was well-tolerated in healthy volunteers for 14 days at concentrations that were previously associated with beneficial effects in animal models," said Stephen Donahue, MD, Vice President of Clinical and Regulatory Affairs. "We believe there is a significant unmet medical need for a well-tolerated, effective treatment for Alzheimer's disease that can be given once daily, and we are excited about the early data we are seeing for PRX-03140."

About PRX-03140: PRX-03140 is Predix's second of three clinical drug candidates discovered utilizing computer-generated GPCR models and optimized with integrated computational-medicinal chemistry. PRX-03140 has a selective receptor binding profile, and preclinical studies have shown that it improves cognitive function, as well as increases levels of acetylcholine (ACh), soluble amyloid precursor protein (sAPP) and brain-derived neurotrophic factor (BDNF) in regions of the brain known to be important for memory.

In single and multiple ascending dose studies in healthy volunteers, adverse events have been mild or moderate in intensity, with no serious adverse events or adverse events resulting in discontinuation. The drug concentrations in humans increased in proportion to increases in dose, and results indicate that the drug can be administered once daily. Results suggest that at well-tolerated doses, PRX-03140 is active at the 5-HT4 receptor in humans, and is eliciting central nervous system effects.

About Alzheimer's Disease: An estimated 4.5 million Americans have Alzheimer's disease (AD), with data pointing to a continuing increase in incidence levels. Currently, nearly one in 10 people over age 65 and as many as five in 10 people over age 85 have AD. According to recent research data, by the year 2050, the range of individuals with AD could range from 11.3 million to 16 million.

Acetylcholinesterase (AChE) inhibitors are active provided that endogenous production of ACh is sufficient to maintain local levels. As AD progresses, ACh production declines, and brain levels of this critical neurotransmitter decline. In parallel with effective therapeutics in other neurodegenerative diseases (e.g., Parkinson's Disease), replacement of the prominent neurotransmitter lost in AD should provide significant clinical benefit. However, neither ACh nor its components can be given in sufficient quantities to increase brain ACh levels with tolerable side effects. The search for agents which increase the production and/or secretion of ACh, which can be used alone or in combination with AChE inhibitors, may therefore yield a drug candidate with significant clinical benefit.

About Predix: Predix is a privately held, clinical stage drug development company that uses a proprietary discovery and lead optimization system to develop drugs for G-protein coupled receptor (GPCR) and ion channel targets. Over the past two and a half years, the company has discovered several novel drug candidates, three of which are now in human clinical trials. Predix has initiated a Phase IIa trial with PRX-00023, a 5-HT1A receptor agonist for anxiety and depression, two Phase Ib trials with PRX-03140, and a Phase I trial with PRX-08066, a novel 5-HT2B antagonist for pulmonary hypertension and other hypoxia-associated diseases. For more information on Predix, please visit www.predixpharm.com. Contact: Predix Pharmaceuticals Kim Drapkin, 781-372-3272 or Media Contact: Andrea Johnston, 910-681-1088"

Source: Predix Pharmaceuticals Announces Initiation of Phase Ib Clinical Trial in Alzheimer's Patients; Provides Initial Dose Study Update. Genetic Engineering News (7 July 2005) [FullText]