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Neurocrine Biosciences Discovers New Small Molecule Growth Factor Technology February 17, 1998 SAN DIEGO, Feb. 16 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced the discovery of a novel strategy which permits the development of small molecule potential therapeutic agents that increase endogenous insulin-like growth factor (IGF) to treat diseases and disorders of the central and peripheral nervous systems as well as the endocrine system. In a paper published in the February 17th issue of " Proceedings of the National Academy of Sciences," scientists from Neurocrine demonstrated that displacement of IGF from their binding proteins is neuroprotective in a clinically relevant model of stroke and may have broader applications for the treatment of other neurodegenerative disorders as well as brain trauma and spinal cord injury. Insulin-like growth factors (IGF-I and IGF-II) are peptides essential for normal growth and development. Their actions are mediated by Type I and Type II IGF receptors and are modulated by a family of six binding proteins, which inactivate the growth factors. Brain injury is commonly associated with increases in IGF and their insulin-like growth factor binding proteins (IGF- BPs). The authors reported that displacement of endogenous IGF from the binding proteins using a selective IGF-BP inhibitor would increase the level of free IGFs. The elevated free IGF levels can then produce neuroprotective effects comparable to those seen with administration of IGF-I. In this study IGF-BP inhibitors gave the same level of protection as IGF-I itself. In addition, both IGF-I and IGF-BP inhibitors showed substantial protection in the middle cerebral artery occlusion (MCAO) model even when administration was delayed for 1 hour after occlusion, similar to the clinical setting. These results have subsequently been reproduced by Neurocrine scientists using small organic "drug like" molecules which elevate endogenons IGFs by inhibiting the binding of this growth factor to IGF binding proteins. In addition, IGF-BP inhibitors modulate the body's own IGF, which may have an improved safety profile over current methods which flood the system with the administration of large amounts of IGF-I. By specifically targeting one of the six IGF-BPs, local increases in IGF may be achieved to provide a regional therapeutic effect and potentially reduce side effects, which may result from body-wide increases in IGF. "The advantage of this approach is that small molecules have the ability to cross the blood-brain barrier, which is essential in the treatment of central nervous system diseases such as stroke. In addition, therapeutic agents can be designed to be active via oral or intravenous (I.V.) administration to treat chronic and acute indications such as stroke, head trauma, Alzheimer's disease, Parkinson's disease, multiple sclerosis, diabetes and Peripheral neuropathies," said Errol B. De Souza, Ph.D Executive Vice President of Research and Development of Neurocrine Biosciences. "Neurocrine has identified small molecule leads and is currently optimizing those leads into drug candidates," added De Souza. Neurocrine Biosciences is a leading neuroimmunology company focused on the discovery and development of novel therapeutics to treat diseases and disorders of the central nervous and immune system such as anxiety, depression, Alzheimer's disease, obesity and multiple sclerosis. Neurocrine Biosciences, Inc. news releases are available free of charge though PR Newswire's Company News On-Call fax service. For a menu of Neurocrine's previous releases, or to receive a specific release via fax call: (800) 758-5804, ext. 604138, or use the Internet via http://www.prnewswire.com. The statements in this press release that relate to research with regard to IGF-BP inhibitors, the Company's development candidates, and the potential development of commercial products are forward looking statements. Such forward looking statements involve risks and uncertainties, including, without limitation, that research will continue in a timely manner consistent with Neurocrine's objectives, that development candidates will successfully proceed through early stage clinical trials, that development candidates will prove effective for treatment in humans in later stage clinical trials, the timely receipt of regulatory clearances required for clinical testing, manufacturing and marketing of products and the potential impact of competitive technologies and potential products. For a discussion of the other risks and uncertainties potentially affecting the Company's business, see the Company's form 10K for the year ending December 31, 1996. Actual results and the timing of certain events could differ materially from those indicated in the forward looking statements as a result of these and other factors. SOURCE Neurocrine Biosciences, Inc. /CONTACT: Elizabeth Foster or Paul Hawran of Neurocrine Biosciences, 619-658-7600/ /Company News On-Call: http://www.prnewswire.com or fax, 800-758-5804, ext. 604138/ /Web site: http://www.neurocrine.com/ (NBIX)