Vanderbilt, AstraZeneca partner on neurological candidates

Drug candidates to target M4 receptor as potential treatments for neuropsychiatric symptoms of Alzheimer 's, schizophrenia

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NASHVILLE, Tenn.—Vanderbilt University has announced thesigning of a research collaboration agreement with AstraZeneca to identifypotential drug candidates for the treatment of psychosis and otherneuropsychiatric symptoms associated with major neurological conditions such asAlzheimer's diseases and schizophrenia.
"We believe the new model for furthering neuroscience drugdiscovery created by AstraZeneca fits perfectly with the mission of the VCNDD,making this an ideal partnership for advancing treatment of these devastatingdisorders," P. Jeffrey Conn, Ph.D., director of the Vanderbilt Center forNeuroscience Drug Discovery (VCNDD) and Lee E. Limbird Professor inPharmacology, said in a press release. "Ultimately it takes the pharmaceuticalindustry to fully develop and market a drug. Anything we can do to increase theprobability of success and build a clear rationale for AstraZeneca to invest inclinical trials for this area of unmet medical need will have tremendous impacton patients and the economy."
Per the terms of the agreement, AstraZeneca has beenlicensed exclusive rights to compounds developed by the VCNDD that act on theM4 muscarinic acetylcholine receptor. The two organizations will collaborate onthe identification of additional M4 compounds and the further development ofthe existing compounds. Though specific financial details were not disclosed,Vanderbilt will receive an upfront payment and research funding for two years,and will be eligible for success-based milestone payments as well as royaltieson global sales of any products that result from the collaboration.
"This exciting new collaboration with AstraZeneca furtherexemplifies the unique, industry-style drug discovery engine that the VCNDD hasestablished within a traditional academic environment," Craig Lindsley, Ph.D.,VCNDD director of Medicinal Chemistry and William K. Warren Jr. Chair inMedicine, said in a statement.
The M4 compounds were developed under Vanderbilt'sparticipation in the National Cooperative Drug Discovery and Development Groupprogram supported by the National Institute of Mental Health. In recentstudies, evidence has suggested that selective activators of subtypes ofmuscarinic acetylcholine receptors can improve certain cognitive impairmentsand behavioral disturbances associated with disorders such as Alzheimer'sdisease and schizophrenia. Selective activation of the M4 receptor in animalmodels through positive allosteric modulation has been shown to block dopaminerelease in several key areas of the brain, leading to antipsychotic-likeeffects and improvement in cognitive performance.
"AstraZeneca is interested in pursuing researchcollaborations across all areas of neuroscience research where the science iscompelling," said Mike Poole, M.D., vice president of the AstraZenecaNeuroscience Innovative Medicines Unit, in a press release. "We believe thatcombining AstraZeneca's deep experience in drug development and translationalscience with VCNDD's expertise in drug discovery is an important step towardbringing new medicines forward for people who are suffering fromneurodegenerative diseases."
The deal is the second neurological agreement Vanderbilt hasannounced in recent months with a large pharmaceutical company. In September2012, Vanderbilt signed a collaboration agreement with Bristol-Myers Squibb todiscover, develop and commercialize novel therapies that act on the mGluR4glutamate receptor for the treatment of Parkinson's disease. Per the agreement,the VCNDD is responsible for identifying drug candidates from their existingprogram, and Bristol-Myers Squibb will have the right to develop andcommercialize resulting products.

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