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EnVivo Pharmaceuticals Announces Reversal of Cognitive Deficits in Alzheimer's Disease Transgenic Mouse Model With Gamma-Secretase Modulator

Posted on: Tuesday, 14 July 2009, 11:49 CDT

VIENNA, July 14 /PRNewswire/ -- EnVivo Pharmaceuticals today announced at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease (ICAD) the reversal of behavioral deficits observed in an Alzheimer's disease transgenic animal model after chronic oral dosing of a proprietary gamma-secretase modulator (GSM). The data was disclosed as part of the preclinical characterization of the development candidate EVP-0962.

EVP-0962 is a proprietary small molecule that belongs to a new generation of potential Alzheimer drugs known as gamma-secretase modulators (GSMs). As a gamma-secretase modulator, EVP-0962 selectively inhibits the production of the toxic AB42 peptide without affecting the total amount of AB. As EVP-0962 does not affect other gamma secretase substrates required for normal function, such as Notch, it is predicted to slow the progression of Alzheimer's disease by reducing the disease-associated toxic AB42 species and to display an intrinsically superior safety profile compared to gamma secretase inhibitors (GSIs).

EVP-0962 selectively reduces the production of AB42 in multiple cell lines and in the brains of normal mice and rats after a single dose. It significantly reduces the production of AB42 in the brains of transgenic mice after two months of daily oral administration. In the same transgenic Alzheimer's disease model, mice developed deficits in the hippocampal memory task known as contextual fear conditioning. Chronic dosing with EVP-0962 reverses these deficits back to normal (wild type) levels. EVP-0962 also displays an excellent safety profile in a 14-day rat toxicology study, confirming suitability for clinical development.

"We are very excited about these findings since they represent to us the first demonstration with a bona fide GSM of functional improvement in an Alzheimer's disease model with concomitant lowering of AB42," said Kees Been, president & CEO of EnVivo. "We have also described the acute AB42 lowering effects of EVP-0962 in brains of non-transgenic as well as transgenic rodents. The fact that EVP-0962 also improves the cognitive deficits is very encouraging and confirms that EVP-0962 is an ideal molecule to test the AB-hypothesis in our upcoming human clinical trials."

Based on the success of these experiments, EnVivo has now entered preclinical development with EVP-0962 and expects to begin clinical trials in 2010.

About EnVivo Pharmaceuticals

EnVivo Pharmaceuticals, located in Watertown, Mass., is a biopharmaceutical company dedicated to discovering and developing small molecule therapeutics for disorders of the central nervous system, with a current focus on Alzheimer's disease, Cognitive Disorders and Schizophrenia. The company's lead product is an alpha-7 nicotinic acetylcholine receptor agonist and has been tested in Phase 2a clinical trials for cognition disorders in Alzheimer's disease and Schizophrenia. The company's other programs include an epigenetics program based on Histone Deacetylase inhibition (HDACi) with EVP-0334 as the lead molecule for cognition in Alzheimer's disease which is in Phase 1 studies, and several preclinical programs such as a Gamma Secretase Modulator (for Alzheimer's disease) and a PDE10 inhibitor program (for schizophrenia). For more information about EnVivo, visit www.envivopharma.com.

SOURCE EnVivo Pharmaceuticals

Source: PR Newswire

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