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Phase II Trial Initiated for ALT-711 in Endothelial Function

PARSIPPANY, N.J., Feb. 11 /PRNewswire-FirstCall/ -- Alteon Inc. (Amex: ALT - News) announced today that a Phase 2 clinical trial of the effects of its novel drug ALT-711 on endothelial function has been initiated at Johns Hopkins University School of Medicine under grants from the National Heart, Lung and Blood Institute and the Society of Geriatric Cardiology. The new Phase 2 study is an additional component to Alteon's ongoing Phase 2 programs for ALT-711 in systolic hypertension and heart failure, and is designed to extend and confirm positive findings from the Phase 2a DIAMOND trial of ALT-711 in diastolic dysfunction.

The endothelium, a single-cell lining of the arteries that acts as an interface between the blood and arterial wall, is impaired in many cardiovascular conditions. Endothelial damage, and the resulting inability of smaller vessels to react to changes in blood pressure, can be a predictor of present and future artery and heart disease. Recent evidence suggests that when arteries become stiffer, endothelial function is worsened even when the endothelial cells themselves are normal. The loss of vascular tone due to the interaction between arterial stiffening and endothelial function may be important in explaining why stiff arteries are a major risk factor for cardiovascular disease. ALT-711 is the first compound in advanced clinical trials to demonstrate the potential to reverse age-related cardiovascular disease and restore flexibility and function to the arteries and heart by cleaving pathological protein-glucose structures called Advanced Glycosylation End-product (A.G.E.) Crosslinks.

The Hopkins endothelial study will enroll approximately 25 patients, male or female 50 years of age or greater, with systolic hypertension (systolic blood pressure >140 mm Hg and a diastolic blood pressure "This study will help us further define the beneficial effects of ALT-711 on the entire cardiovascular system, and give us additional insights into the drug's mechanism of action. This data, along with data from our upcoming Phase 2 trials in systolic hypertension and heart failure, will help pave the way for potential Phase 3 development of ALT-711," said Kenneth I. Moch, President and Chief Executive Officer.

How ALT-711 Works
ALT-711 is the first in a new class of compounds that have been shown in vitro and in vivo to reverse A.G.E. crosslinking, thereby restoring more normal function to tissues, vessels and organs that have lost flexibility. Alteon believes that ALT-711's mechanism of action is new and novel, and is unrelated to that of any pharmaceutical agent either currently prescribed or in clinical development. Importantly, ALT-711 does not disrupt the natural enzymatic glycosylation sites or peptide bonds that are responsible for maintaining the normal integrity of the collagen chain. Thus, normal structure and function is preserved while abnormal crosslinking is reduced.

In addition to restoring elasticity of stiffened tissues by breaking pathological crosslinks, in preclinical studies ALT-711 consistently demonstrates the ability to reverse the over-expression of genes for proteins and growth factors known to be associated with the pathological hypertrophy (enlargement) of tissues. Hypertrophy of the aorta and the left ventricle is correlated with the development of heart failure. These results indicate that restoration of normal tissue dynamics through breaking A.G.E. crosslinks may restore normal control of gene function.

ALT-711 has demonstrated safety and efficacy in several Phase 2 trials and is actively being developed for systolic hypertension and heart failure. Alteon announced initial results from the Phase 2b SAPPHIRE/SILVER trial in July 2003 showing that, as measured by ambulatory blood pressure measurements, treatment with ALT-711 resulted in a statistically significant systolic blood pressure lowering effect over and above placebo in the difficult-to-treat high blood pressure population. This data is expected be presented and published in an upcoming scientific forum. In addition, the DIAMOND trial of ALT-711 in patients with diastolic heart failure showed that treatment with ALT-711 over 16 weeks demonstrated a statistically significant reduction in left ventricular mass and a marked improvement in left ventricular diastolic filling, as well as statistically significant improvements in multiple quality of life measurements. Patients with Class III heart failure at baseline, the sickest patients in the study, appeared to benefit the most from ALT-711 treatment. Additional Phase 2 trials in systolic hypertension and heart failure are expected to be initiated in the first half of 2004.

Source: Alteon Inc.

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