Hamburg, Germany | Oxford, UK - Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX 30, "Evotec") today announced the successful completion of the single ascending dose component of the Phase I clinical study with EVT 101, a subtype-specific NMDA receptor antagonist for the treatment of Alzheimer's disease. The study in 48 young healthy subjects of whom 36 received EVT 101 showed that EVT 101 was well absorbed, achieving good exposure levels, was extremely well tolerated with no significant adverse events and had a good pharmacokinetic profile consistent with once or twice daily oral dosing.
 
This result is significant given the unfavourable side-effect profile of non-selective NMDA antagonists.  EVT 101 has now moved into the multiple ascending dose stage of the Phase I study in both young and elderly volunteers. Evotec expects to publish final results of the complete Phase I trials for EVT 101 in Q3 2006.
 
About EVT 101
EVT 101 is being developed for the treatment of Alzheimer's disease. It is a highly potent and selective antagonist of NR2B subunit containing NMDA receptors. In preclinical studies, the compound shows strong efficacy and an improved side effect profile compared to non-selective NMDA receptor antagonists and has good oral bioavailability and in vivo pharmacokinetics.
 
NMDA background
Apart from their normal physiological role in nerve-to-nerve cell communication NMDA receptors are important players in certain pathological disease states such as Alzheimer's disease, Parkinson's disease, neuropathic pain and epilepsy. The hypothesis is that when NMDA receptor over-activation is reduced in these conditions with an "antagonist", disease symptoms are reduced. Extensive studies over the last 15 years have indicated a potential for NMDA receptor antagonists in the treatment of these diseases. However, the clinical development of non-selective antagonists has been limited by unfavourable side-effects, such as hallucinations. In the early 1990's it was found that multiple NMDA receptor subtypes exist which contain different NR2(A-D) subunits. Compounds selectively targeting NR2B subunit-containing receptors retain many of the beneficial effects of earlier non-selective compounds but have much improved side effect profiles. Separating side effects from beneficial effects by selectively targeting the NR2B-subunit allows higher dosing and hence the potential to increase efficacy of the drug.

Contact: Anne Hennecke, Director, Investor Relations & Corporate Communications, Evotec AG, Phone: +49-40-56081-286, anne.hennecke@evotec.com
Contact: Anne Hennecke, Director, Investor Relations & Corporate Communications, Evotec AG, Phone: +49-40-56081-286, anne.hennecke@evotec.com