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The Rappaport Institute looks forward to continuing to make substantial future contributions in biomedical research"

Professor Karl Skorecki

Alteon's ALT-2074 Demonstrates Ability to Reduce Infarct Size by 80 Percent in Mice with Haptoglobin 2-2 Genotype

13 November, 2006

- Abstracts Presented at the American Heart Association Scientific Sessions 2006 Suggest ALT-2074 May be Used For Significant Myocardial Protection -

- Identify Haptoglobin Genotype as Important Cardiovascular Risk Factor and Promising Diagnostic Tool -

PARSIPPANY, N.J., Nov. 13 /PRNewswire-FirstCall/ -- Alteon Inc. (Amex: ALT) announced today that data demonstrating the ability of its compound ALT-2074 (formerly BXT-51072 licensed from OXIS International, Inc., OTC Bulletin Board: OXIS.OB), to reduce myocardial injury in mice is the subject of an abstract being presented at the American Heart Association Scientific Sessions 2006 in Chicago, IL, by a research team from the Rappaport Institute, Israel. The study suggests that a haptoglobin (Hp) genotype, specifically Hp 2-2, determines myocardial infarction (MI) size in diabetes, and that the administration of ALT-2074 to mice with this genotype undergoing ischemic-reperfusion injury, resulted in a reduction in myocardial injury by over 80%. The company believes that these significant results support the development of ALT-2074, a glutathione peroxidase mimetic, as a potential pharmacogenomically driven therapy for diabetic patients with the Hp 2-2 genotype. ALT-2074 is currently in Phase 2a human clinical trials. Additional abstracts being presented at the meeting demonstrate that Hp genotyping may play a role in predicting atherosclerotic risk, as well.

The poster presentation "Haptoglobin Genotype Determines Myocardial Infarct Size in Diabetic Mice" by authors Shany Blum, M.D., and Andrew P. Levy, M.D., Ph.D., of the Rappaport Institute of the Technion University, Haifa, Israel, summarizes work using mice expressing Hp1-1, the naturally occurring Hp in mice, and Hp 2-2 (introduced transgenically). The mice were exposed to a model of myocardial infarction called ischemia-reperfusion injury (IR). MI size was significantly increased in Hp 2-2 mice as compared to Hp 1- 1 mice (44.3 plus/minus 9.3% vs. 21.0 plus/minus 4.0%, p=0.03). These larger infarctions were associated with significantly increased redox active iron and lipid peroxidation and significantly decreased levels of IL-10 (an anti- inflammatory cytokine). The administration of ALT-2074 to Hp 2-2 mice reduced myocardial injury after IR by over 80% (44.3 plus/minus 9.3 % vs. 7.0 plus/minus 3.1%, p=0.003) but no myocardial protection was provided by ALT- 2074 in Hp 1-1 mice.

Dr. Levy noted, "these data suggest that the Hp 2-2 genotype may confer significant cardiovascular risk in diabetic patients and that strategies such as ALT-2074 designed to decrease the iron-mediated lipid peroxidation associated with this genotype may provide significant myocardial protection."

"We congratulate Dr. Levy and his colleagues for producing this award-winning translational work that addresses the biology underlying an epidemiological phenomenon he and his colleagues have reported over the past several years, in which Hp2-2 may account for more than 30% of the increased cardiovascular risk (restenosis after angioplasty, and death or heart failure following myocardial infarction) often attributed to diabetes," said Noah Berkowitz, M.D., Ph.D., President and Chief Executive Officer of Alteon. "As licensors of cardiovascular-related, haptoglobin technology from the Rappaport Institute, we are pleased to see Dr. Levy's work which has seamlessly connected epidemiology and mechanistic biology."

Additional studies being presented at the AHA by Dr. Levy and colleagues at the Mount Sinai School of Medicine relate to technology licensed by Alteon from the Rappaport Institute and further elucidate the cardiovascular risks associated with the haptoglobin 2-2 genotype. "Haptoglobin Genotype is a Determinant of Oxidation and Inflammation in the Atherosclerotic Plaque" demonstrates that atherosclerotic plaques from ApoE-/- Hp 2-2 mice are associated with increased iron deposition, lipid peroxidation and macrophage infiltration indicating that the Hp genotype may play a critical role in the oxidative and inflammatory response to intraplaque hemorrhage. Another preclinical study, summarized in a poster entitled "Intra-Plaque Hemorrhage Is Associated With Decreased Content of Macrophage Scavenger Receptor CD-163 in Diabetic Atherosclerosis" demonstrates a link between the haptoglobin 2-2 genotype and the atherosclerotic plaque instability associated with diabetes mellitus. The CD163 haptoglobin receptor, found on many cell types of the immune system, is known to scavenge free hemoglobin from circulation and tissues, thus eliminating a major source of oxidative stress and damage resulting from free iron found in the vasculature after hemorrhage. The study suggests that in diabetics with the Hp 2-2 genotype, a decrease in the CD163 on scavenger macrophages may be responsible for enhanced damage and instability within atherosclerotic plaque.

About Alteon

Alteon is a product-based biopharmaceutical company engaged in the development of small molecule drugs to treat and prevent the inflammatory aspects of cardiovascular disease and diabetes. The Company has identified several promising product candidates that it believes represent novel approaches to some of the largest pharmaceutical markets.

Alagebrium, a product of Alteon's drug discovery and development program, is being developed for the treatment of diastolic heart failure. This disease represents a rapidly growing market of unmet medical need, particularly common among diabetic patients. Alagebrium has demonstrated relevant clinical activity in two Phase 2 clinical trials in heart failure, as well as in animal models of heart failure and nephropathy, among others. Alagebrium has been tested in approximately 1,000 patients in multiple Phase 1 and Phase 2 clinical trials, which represents a sizeable human safety database.

The Company's portfolio also includes orally bioavailable, organoselenium mimics of glutathione peroxidase that metabolize lipid peroxides and have the potential to limit myocardial damage subsequent to a myocardial infarction. Alteon's lead compound for that program, ALT-2074, is in Phase 2 clinical trials. The Company also has rights to a diagnostic assay that identifies a large subset of diabetic patients at highest risk for cardiovascular complications, because of a defect in oxidized lipid metabolism that results in increased cardiovascular inflammation. For more detailed information about Alteon's research and development, please visit Alteon'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 the impact of the preclinical results described in this press release on the future clinical development of Alteon's product candidates (including the possibility that early preclinical or 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), Alteon's ability to obtain sufficient funding to continue as a going concern and continue the development of alagebrium and ALT-2074, technology and product development regulatory approval processes, intellectual property rights and litigation, competitive products, and other risks identified in Alteon's filings with the Securities and Exchange Commission. Further information on risks faced by Alteon are detailed under the caption "Risk Factors" in Alteon's Annual Report on Form 10-K for the year ended December 31, 2005 and in its subsequent Quarterly Reports on Form 10-Q. These filings are available on a website maintained by the Securities and Exchange Commission at http://www.sec.gov. 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.

 

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