Synvista Therapeutics Highlights New Data Demonstrating the Clinical Benefit of Vitamin E Therapy in Patients Identified on the Basis of Haptoglobin Phenotype Testing

Synvista Therapeutics, Inc. announced the results of a clinical trial known as the ICARE study, which was also presented on Nov. 5th at the American Heart Association's (AHA) Scientific Sessions 2007 in Orlando, Florida. The study demonstrated that supplementing Vitamin E therapy in patients with Diabetes Mellitus (DM) who had the Haptoglobin 2-2 (Hp2-2) phenotype met its pre-specified, primary endpoint of decreased cardiovascular events, leading to early termination of the four-year study after just 18 months.

Noah Berkowitz, M.D., Ph.D., President and Chief Executive Officer of Synvista stated "We are thrilled that Dr. Andrew P. Levy and his colleagues at the Rappaport Research Institute in the Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel, and Clalit Health Services, Haifa and Western Galilee, Israel conducted this study to evaluate the efficacy of treating Hp2-2, DM patients with Vitamin E.   Vitamin E has been the subject of significant controversy in recent years, with several meta-analyses showing increased mortality for patients treated with this nutraceutical. We find it validating to identify the possibility, in a large, prospective clinical trial, that patients can test their Haptoglobin type and then receive an inexpensive therapy that has demonstrated clinical benefit. This is targeted therapy at its best. Further, we believe this study provides scientific rationale for our current development platform, which is based on targeting our oxidized lipid reducing product candidate, ALT-2074, to patients with DM who test positive for Hp2-2 with our diagnostic technology for Haptoglobin."

In the placebo-controlled ICARE study, more than 3,000 patients were tested for Haptoglobin phenotype, and 984 of these who had the Hp2-2 phenotype were randomized to receive either natural source Vitamin E (400 IU daily) or placebo. Primary endpoints of the study were non-fatal myocardial infarction (MI--heart attack), stroke and cardiovascular death. Results demonstrated a greater than 50% decrease in cardiovascular events in patients receiving Vitamin E (1.0 percent compared to 3.8 percent, p=0.004), leading to early termination of the study. Investigators determined this result to be predominantly due to a significant decrease in non-fatal myocardial infarction in the Vitamin E group.

Prof. Levy added "Our research group has postulated that the profoundly increased risk of, MI, stroke and cardiovascular death observed in DM patients with Hp2-2, established in many observational studies of more than 20,000 patients in recent years, may be a consequence of a defect in the antioxidant protection of Hp2-2,". "As a member of my group, Dr. Rabea Asleh, reported earlier today, this defect may interfere with reverse cholesterol transport. This in turn may promote a more inflamed and labile atherosclerotic plaque. It is gratifying to have had this opportunity to collaborate with Clalit Health Services, the largest health plan in Israel, in a large prospective clinical trial that provides strong support for the claim that Vitamin E can be targeted to DM patients with Hp2-2 and provide a significant clinical benefit."