# CRF research beginning



## trbell (Nov 1, 2000)

Personalize News Back to Headlines... Neurocrine Biosciences and GlaxoSmithKline Announce Worldwide Collaboration For CRF Receptor Antagonists Including the Phase I Compound NBI-34041 Largest Collaboration in Neurocrine's History PR Newswire SAN DIEGO, July 24 /PRNewswire/ via NewsEdge Corporation -- Neurocrine Biosciences (Nasdaq: NBIX) and GlaxoSmithKline (NYSE: GSK) announced today that the two companies signed a worldwide research, development and commercialization agreement for Corticotropin Releasing Factor Receptor Antagonists (CRF-R1 and CRF-R2), an entirely new class of compounds to treat psychiatric, neurological and gastrointestinal diseases including anxiety, depression and irritable bowel syndrome (IBS). Neurocrine's CRF-R1 Antagonist, NBI 34041, is currently in Phase I development for anxiety and depression.Under the terms of the agreement, Neurocrine and GlaxoSmithKline will conduct a collaborative research program for up to five years to identify and develop CRF-R antagonist compounds. The collaboration also includes worldwide development and commercialization of NBI-34041 as well as back-up candidates resulting from the joint research program. Neurocrine will receive upfront fees and early milestone payments totaling $25.5 million and annual fees. In addition, Neurocrine is eligible to receive milestone payments as compounds progress through the research and development process, royalties on any future product sales and co-promotion rights in the United States. Although financial terms have not been disclosed the total collaborative value makes it the largest collaboration in Neurocrine's history."GlaxoSmithKline is an ideal partner with their leadership position in the antidepressant field and with their extensive experience in the development and commercialization of treatments for CNS and gastrointestinal (GI) diseases," said Gary A. Lyons, President and CEO of Neurocrine Biosciences. "Combining our broad CRF portfolio together with GlaxoSmithKline's research and development and commercial expertise we are enhancing our abilities to maximize the novel area of CRF-R1 and CRF-R2 antagonists as potential therapeutics for the treatment of some of the major diseases in CNS and related areas.""In addition to advancing Neurocrine's current proprietary CRF-R antagonists through development, the collaboration will exploit the combined knowledge and understanding of several novel chemical series in both companies from which additional candidates will be selected," said John Saunders, Vice President Research (Chemistry) for Neurocrine Biosciences. "The collaboration will also focus on the identification of potent CRF-R2 antagonists to determine their therapeutic utility in a variety of psychiatric and metabolic conditions. By combining GlaxoSmithKline's vast experience in genomics and CNS/GI small molecule development with Neurocrine's expertise in CRF biology and chemistry, we are confident that we will maintain our worldwide leadership position in this very exciting area.""We are delighted that Neurocrine Biosciences and GSK have entered into this collaboration. We are confident that by combining our expertise in CRF receptors and CNS/GI drug discovery and development we can make a unique, world class contribution to this exciting area of research. This collaboration is a great example of how to make the best use of the two companies strengths and assets to provide real synergy. The novel area of CRF R antagonists have the potential to broaden our understanding of major CNS disorders with the eventual goal of the development of novel therapeutics," said Emiliangelo Ratti, Senior VP, Psychiatry Center of Excellence in Drug Discovery, GSK.Neurocrine Biosciences, Inc. is a product-based biopharmaceutical company focused on neurological and endocrine diseases and disorders. Our product candidates address some of the largest pharmaceutical markets in the world including insomnia, anxiety, depression, malignant brain tumors and peripheral cancer, diabetes, multiple sclerosis, irritable bowel syndrome, eating disorders, pain and stroke and certain female health disorders. Neurocrine Biosciences, Inc. news releases are available through the Company's website via the Internet at http://www.neurocrine.com. GlaxoSmithKline -- one of the world's leading research-based pharmaceutical and healthcare companies -- is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, visit GlaxoSmithKline on the World Wide Webb at www.gsk.com.BackgroundIn March 2001 Neurocrine announced the results of a Phase I clinical trial with a CRF antagonist for the treatment of depression and anxiety. This Phase I, randomized, double blind, placebo-controlled, single-dose trial was conducted in 48 normal healthy volunteers to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics, including endocrine profiles, over a range of six escalating doses. Initial pharmacokinetic evaluation indicates rapid absorption and good dose-proportionality, plasma half-lives and good safety profile. Neurocrine is currently preparing this compound for a multiple dose clinical trial in 24 subjects to further evaluate the safety and pharmacokinetic and endocrine profiles of the drug. Neurocrine is also advancing multiple back up compounds through preclinical development for future clinical evaluation.Dr. Wylie Vale, Neurocrine co-founder, first identified and cloned the CRF receptor along with his colleagues at the Salk Institute. CRF functions as a neurotransmitter in the brain and plays a critical role in coordinating the body's response to stress. The CRF-R1 receptor subtype largely mediates these effects. In preclinical models, selective CRF-R1 receptor antagonists block stress-related responses providing further evidence that this novel mechanism may result in improved anti-anxiety and anti-depressant properties. Neurocrine scientists were the first to isolate a second CRF receptor, called CRF-R2. The distribution of CRF-R2 in the brain suggests that CRF-R2 could play a role in some forms of anxiety and eating disorders. Neurocrine researchers have demonstrated that administration of a CRF-R2 antagonist reduces measures of anxiety in studies of obsessive-compulsive disorder and conditioned fear.In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. Among the factors that could cause actual results to differ materially from those indicated in the forward looking statements are risks and uncertainties associated with Neurocrine's CRF research and development program and business and finances including, but not limited to, risk that NBI-34041 will not successfully proceed through clinical trials or that the collaboration will not be successful in identifying and developing other CRF receptor antagonists suitable for clinical development and commercialization; risk that GSK could terminate the collaboration; risk that determinations by regulatory and governmental authorities could delay or impede development of collaboration products; risk associated with uncertainties relating to patent protection and intellectual property rights of third parties in the CRF field; risk associated with impact of competitive products and technological changes; risk associated with lack of availability of capital and/or cost of capital; and other material risks. A more complete description of these risks can be found in the Company's Form 10K for the year ended December 31, 2000, as amended, the current form 10Q and its most recent registration statement, as filed with the Securities and Exchange Commission, each of which should be read before making any investment in Neurocrine common stock. Neurocrine undertakes no obligation to update the statements contained in this press release after the date hereof.MAKE YOUR OPINION COUNT - Click Here http://tbutton.prnewswire.com/prn/11690X51848918 SOURCE Neurocrine Biosciences/CONTACT: Claudia Jones or Paul Hawran of Neurocrine Biosciences,+1-858-658-7600; or UK Media, Martin Sutton or Philip Thomson,(020) 8966 8000, Alan Chandler, (020) 8975 2290, or European Analyst/Investor,Jennie Younger, (020) 8966 8378, Duncan Learmouth, (020) 8966 5961, or AnitaKidgell, (020) 8966 8369, or US Media, Nancy Pekarek, +1-215-751-7709, MaryAnne Rhyne, +1-919-483 2839, or US Analyst/Investor, Frank Murdolo,+1-212-308-5185, Tom Curry, +1-215-751 5419, all of GlaxoSmithKline//Web site: http://www.gsk.com //Web site: http://www.neurocrine.com /(NBIX GSK)<< Copyright ï¿½2001 PR Newswire >> Home | sciBASE | TheScientificWorldJOURNAL | i-PUBLISH | worldMEET | labSHELF | SupportAbout Us | Job Opportunities | Contact Us | FAQ | HelpThis site is best viewed with I.E. 5.5. Please click here to download now.Copyright ï¿½ 2001 TheScientificWorld. All rights reserved. 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## william brown (Feb 22, 2001)

tom-- what does this mean for IBS? when I looked into the sites, nothing come up regarding IBS, only depression, etc. Does this relate? Bill


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## trbell (Nov 1, 2000)

just a mention, Bill, but I think this is the next step in treating IBS as well as depression, stress, etc. As I understand the way it works serotonin influences CRF and intead of just altering the messenger to CRF like drugs do for depression, ibs, etc., they might be able to modify the CRF directly. This is admittedly somewhat beyond me but time will tell. maybe flux or eric or kay have other thoughts.tom"SAN DIEGO, July 24 /PRNewswire/ via NewsEdge Corporation -- Neurocrine Biosciences (Nasdaq: NBIX) and GlaxoSmithKline (NYSE: GSK) announced today that the two companies signed a worldwide research, development and commercialization agreement for Corticotropin Releasing Factor Receptor Antagonists (CRF-R1 and CRF-R2), an entirely new class of compounds to treat psychiatric, neurological and gastrointestinal diseases including anxiety, depression and irritable bowel syndrome (IBS). Neurocrine's CRF-R1 Antagonist, NBI 34041, is currently in Phase I development for anxiety and depression.


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## Mike NoLomotil (Jun 6, 2000)

Corticotrpin Releasing Factor and the Brain-Gut Motor response to StressCanadian Journal of GastroenterologyMarch 1999 http://www.ncbi.nlm.nih.gov/entrez/query.f...4&dopt=Abstract This is what it has to do with IBS, also I have some study somewhere which cmpared CRFand motilin levels between D-types and C-types...cannot find it quickly will try to look tomorrow.MNL


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## trbell (Nov 1, 2000)

interesting. this seems to be where smoking fits into the stress and ibs picture?tom


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