Alteon's Investigational Drugs Demonstrate Ability to Reduce Atherosclerosis - Preclinical Study in 'Diabetes' Also Identifies Important Role of Sugar in Atherosclerosis - PARSIPPANY, N.J., June 29 /PRNewswire-FirstCall/ -- Alteon Inc. announced today that a preclinical study published in the July issue of Diabetes: Journal of the American Diabetes Association (1) identifies the role of sugar- protein bonds, or Advanced Glycation End-products (A.G.E.s), as a culprit in the progression of atherosclerosis. The study, conducted in a well- characterized mouse model of diabetes-associated atherosclerosis, further demonstrates that drugs designed to target the A.G.E. Pathway, specifically Alteon's A.G.E. Crosslink Breaker alagebrium and A.G.E. Inhibitor pimagedine, reduce measures of atherosclerosis in diabetic mice. The authors conclude that the A.G.E.s play an important role in atherosclerosis, and provide investigators with new therapeutic options to explore as part of an approach to reduce cardiovascular disease accelerated by diabetes. Advanced Glycation End-products are permanent glucose structures that form when sugar binds to the surface of proteins. Some A.G.E.s further crosslink between proteins. In healthy individuals, this process occurs naturally, though slowly, as the body ages. In diabetic patients, because of higher levels of circulating blood glucose, the rate of A.G.E. accumulation and the extent of protein cross-linking is accelerated. Many of these proteins, including structural proteins such as collagen and elastin, play an integral role in the maintenance of cardiovascular elasticity function and vascular wall integrity. When these proteins become cross-linked due to A.G.E. formation, the elastic properties of the tissues in which these proteins reside are reduced, impairing the normal function of organs throughout the body that depend on flexibility for normal function, such as blood vessels and cardiac muscle. A.G.E.s have been implicated in many diseases of aging and diabetes; this new study further identifies their damaging role in atherosclerosis. In the study, "Advanced Glycation End Product Interventions Reduce Diabetes-Accelerated Atherosclerosis," researchers from the Baker Medical Research Institute in Melbourne, Australia, and the University of South Carolina, explored atherosclerosis in streptozotocin-induced diabetic mice that were randomized to receive A.G.E. Crosslink Breaker alagebrium (formerly ALT-711), A.G.E. Inhibitor pimagedine (formerly aminoguanidine), or no treatment for 20 weeks. Diabetes caused a sixfold increase in atherosclerotic plaque in the animals; alagebrium reduced the plaque area by 30% and pimagedine by 40%. Diabetes-associated accumulation of A.G.E.s in aortas and plasma were ameliorated by both treatments. In addition, in both treatment groups there were improvements in skin collagen solubility and a reduction in levels of transforming growth factor and connective tissue growth factor which were increased in diabetes. In the alagebrium treatment group, there was a significant reduction in systolic blood pressure, total cholesterol, LDL cholesterol and triglycerides, but no statistical changes in the pimagedine group. The study was supported by grants from the Juvenile Diabetes Research Foundation (JDRF), the National Heart Foundation of Australia, and U.S. Public Health Service Grant DK-19971. "These findings underscore the importance of developing drugs such as alagebrium that have an impact on the A.G.E. Pathway," said Kenneth I. Moch, President and CEO. "Alteon is the pioneer and clear leader in this effort, having advanced alagebrium into several ongoing Phase 2 human clinical trials in cardiovascular disease. This new study in Diabetes provides further support for the therapeutic potential of alagebrium." About Alteon Alteon is developing several new classes of drugs that reverse or slow down diseases of aging and complications of diabetes. These compounds have an impact on a fundamental pathological process caused by protein-glucose complexes called Advanced Glycation End-products (A.G.E.s). The formation and crosslinking of A.G.E.s lead to a loss of flexibility and function in body tissues, organs and vessels and have been shown to be a causative factor in many age-related diseases and diabetic complications. Alteon has created a library of novel classes of compounds targeting the A.G.E. Pathway. Alteon's lead compound alagebrium chloride (formerly ALT-711), the only A.G.E. Crosslink Breaker in advanced human testing, has demonstrated safety and efficacy in several Phase 2 trials and is actively being developed for systolic hypertension and heart failure. Ongoing clinical trials include SPECTRA (Systolic Pressure Efficacy and Safety Trial of Alagebrium) and PEDESTAL (Patients with Impaired Ejection Fraction and Diastolic Dysfunction: Efficacy and Safety Trial of ALagebrium). For more information on Alteon, visit the company's website at http://www.alteon.com/. Any statements contained in this press release that relate to future plans, events or performance are forward-looking statements that involve risks and uncertainties including, but not limited to, those relating to technology and product development (including the possibility that early clinical trial results may not be predictive of results that will be obtained in large-scale testing or that any clinical trials will not demonstrate sufficient safety and efficacy to obtain requisite approvals or will not result in marketable products), regulatory approval processes, intellectual property rights and litigation, competitive products, ability to obtain financing, and other risks identified in Alteon's filings with the Securities and Exchange Commission. The information contained in this press release is accurate as of the date indicated. Actual results, events or performance may differ materially. Alteon undertakes no obligation to publicly release the result of any revision to these forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. (1) Josephine M. Forbes, Louis Teo Loon Yee, Vicki Thallas, Markus Lassila, Riccardo Candido, Karin A. Jandeleit-Dahm, Merlin C. Thomas, Wendy C. Burns, Elizabeth K. Deemer, Susan M. Thorpe, Mark E. Cooper, and Terri J. Allen: Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. 'Diabetes,' 53:000-000, 2004. DATASOURCE: Alteon Inc. CONTACT: Susan M. Pietropaolo, Director, Corporate Communications & Investor Relations, of Alteon, +1-201-934-5000, fax, +1-201-934-8880 Web site: http://www.alteonpharma.com/

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