ExonHit Therapeutics, a privately held drug discovery company, plans to start a phase IIa proof-of-concept study in Alzheimer's disease with EHT 0202, its most advanced compound in development, in the early part of 2005, the company announced here.

ExonHit Therapeutics has already demonstrated that EHT 0202 improves attention and cognition and has neuroprotective properties in animal models. Based on these data it is likely that EHT 0202 may prove suitable for symptom relief and as a disease modifying agent in patients with Alzheimer's disease.

Preclinical studies with EHT 0202 have revealed protection from cell death following induction of different stresses (ischemia or toxic treatment) as well as improved learning and cognitive performance in aged rats (water-maze and Barnes tests) and mild anxiolytic properties at higher dosages (10mg/kg). Toxicological studies have also demonstrated that EHT 0202 is well tolerated and well absorbed when given orally. A phase I single dose study by oral route has just been completed and confirmed that EHT 0202 is also well tolerated (Maximum Tolerated Dose of 120 mg) and well absorbed via oral administration in healthy volunteers, the company said here.

Based on these data, a Medical Advisory Board confirmed its interest in initiating a phase IIa proof-of-concept study with EHT 0202. The study is designed as a randomized, double-blind, placebo-controlled, parallel group, multi-centre study evaluating the effects of three doses of EHT 0202 on the cognitive functions and psychomotor performance of patients suffering from probable, mild to moderate Alzheimer's disease. It will enrol 40 patients that will be treated for 28 consecutive days followed by a 14 days observation period without study drug. The study is anticipated to start in early 2005.

"Our goal is to evaluate whether EHT 0202 improves the performance of patients suffering from cognitive disorders on a selected number of tests focusing on attention and learning capabilities", commented Philippe Guillet, VP Clinical Development at ExonHit. "Current treatments are clearly not yet satisfactory and there is a large medical need for drugs with new mechanisms of action that can be associated with acetylcholine esterase inhibitors," he added.

"ExonHit has developed a powerful technology based on RNA splicing analysis, which pinpoints specific targets for therapeutic intervention. This technology combined with our internal medicinal chemistry capabilities will allow us to bring to the clinic additional drugs either with our own resources or through partnerships. If this proof-of-concept study is positive", declared Bruno Tocqué, CEO ExonHit Therapeutics.