Addex Drug Candidate Effective in Alzheimer’s Disease Model

Addex Drug Candidate Effective in Alzheimer’s Disease Model

Geneva, Switzerland, 2 September 2010
 – Allosteric modulation company Addex Pharmaceuticals Ltd (SIX: ADXN) announced today that it has observed efficacy in a model of Alzheimer’s disease using a recently discovered orally-available drug-candidate. The proprietary molecule specifically inhibits a receptor subtype called the metabotropic glutamate receptor 2 (mGluR2) via negative allosteric modulation (NAM). An Addex mGluR2 NAM is scheduled to enter Phase I clinical testing in healthy volunteers during 2011.

“Specifically targeting the signaling of the neurotransmitter glutamate using mGluR2 NAM is one of the most promising avenues of research for treating cognitive symptoms of Alzheimer’s disease,” said Vincent Mutel, CEO of Addex. “We are excited that our mGluR2 NAM has shown that it can improve memory in this pathophysiologically relevant model. Although we are years away from knowing if the drug will work in humans, recently published academic research suggests that mGluR2 inhibition also may slow the progression of this devastating disease.”

The Addex mGluR2 NAM was tested in a model that mimics aspects of the pathophysiology and cognitive impairment, including progressive memory impairment, observed in human Alzheimer’s disease. In the preclinical study, the mGluR2 NAM dose-dependently reversed memory deficit exhibited after beta-amyloid protein administration. Working memory impairment was measured using the novel object recognition (NOR) test. The statistically significant effect was similar to the active comparator used in the same experiment, donepezil (Aricept), the benchmark marketed drug currently used to treat symptoms of Alzheimer’s disease. Furthermore, the mGluR2 NAM did not change locomotor activity compared to vehicle.

Alzheimer’s disease is a progressive brain disease affecting up to 5.3 million Americans and the seventh-leading cause of death in the United States. It destroys brain cells causing memory loss and problems with thinking and behavior. There is no cure and marketed drugs offer temporary moderate efficacy.

mGluR2 is a G-protein coupled receptor (GPCR) that is expressed in the brain on presynaptic nerve terminals where it slows glutamate release. Research has shown that too much signaling by mGluR2 may negatively impact the survival of brain cells involved in memory, contributing to the cause of Alzheimer’s disease. Additional research, including the data discussed above, suggests that mGluR2 inhibition can improve working memory, even in cases where memory already has been impaired.

Addex Pharmaceuticals ( discovers and develops allosteric modulators for human health and is focused on validated therapeutic targets for diseases of the central nervous system, metabolic disorders and inflammation. Subject to regulatory approvals, Phase II clinical trials are expected to start soon in four indications for two lead products: ADX48621, an mGluR5 negative allosteric modulator (NAM), in dystonia and Parkinson’s disease levodopa-induced dyskinesia (PD-LID); and ADX71149, an mGluR2 positive allosteric modulator (PAM), in schizophrenia and anxiety. A third product, ADX71943, GABA-B receptor PAM with potential for chronic pain, is scheduled to enter Phase I testing in 2011. In addition, Merck & Co., Inc. has licensed rights to two preclinical products: mGluR4 PAM for Parkinson's disease and mGluR5 PAM for schizophrenia. Additional preclinical discovery stage programs include: GLP1R PAM, IL1R1 NAM and TNFR1 NAM. Roche Venture Fund and SR-One, corporate venture arm of GlaxoSmithKline, are investors in Addex.

Chris Maggos
Investor Relations & Communications
Addex Pharmaceuticals
+41 22 884 15 11

Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Pharmaceuticals Ltd, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Pharmaceuticals Ltd regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding  allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Pharmaceuticals Ltd is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.