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Metabolex Reports Positive Phase 1 Clinical Trial for Treatment of Type 2 Diabetes

Posted on: Thursday, 3 March 2005, 09:00 CST

HAYWARD, Calif., March 3 /PRNewswire/ -- Metabolex, Inc. today announced positive early clinical trial results for MBX-2044, a novel investigational, oral insulin sensitizer for type 2 diabetes. MBX-2044 is designed to eliminate the dose-limiting side effects of the currently marketed sensitizers. Data from the Phase 1 dose-escalating study showed that the drug was well tolerated in healthy volunteers.

"The insulin sensitizers currently on the market can effectively control blood glucose levels. However, they do have significant side effects in terms of edema and weight gain," said Kenneth S. Polonsky, M.D., Professor of Medicine, Washington University School of Medicine. "Metabolex is applying its expertise in the biology of diabetes to develop improved insulin sensitizers that can lower glucose levels without causing these side effects."

Insulin sensitizers, with worldwide sales of nearly $4 billion, represent an attractive treatment option for type 2 diabetes because they target insulin resistance, the underlying cause of the disease. Both MBX-2044 and Metabolex's lead compound, metaglidasen (formerly MBX-102), are insulin sensitizers that have chemical structures and methods-of-action that are different than current insulin sensitizers on the market.

"MBX-2044 is an excellent complement to our portfolio of second-generation product candidates, and the results of this trial enable us to move it forward to proof-of-efficacy studies," said David B. Karpf, M.D., Chief Medical Officer of Metabolex and Clinical Associate Professor of Medicine at Stanford. "The marketed insulin sensitizers cause weight gain which can lead many patients to stop taking them. Moreover, many patients should not even start therapy with these drugs because they can induce edema, or fluid retention, which can lead to the serious side-effect of congestive heart failure."

"By developing optimized insulin sensitizers, we hope to improve the care of patients with type 2 diabetes, and also to potentially study these compounds for the prevention of type 2 diabetes in patients at increased risk of developing this debilitating disease," added Dr. Karpf.

The lead candidate in Metabolex's clinical development program, metaglidasen is now completing Phase 2 trials. Results will be presented at the 3rd International Symposium on PPARS Efficacy and Safety in Monte Carlo on March 22, 2005. An interim safety analysis of the Phase 2 trial indicated that the incidence of edema and weight gain was no greater than placebo.

MBX-2044 Study Design

In the Phase 1 clinical trial for MBX-2044, healthy volunteers were given a single dose ranging from 1.5 mg to 120 mg. There were seven dosing cohorts and each cohort consisted of six non-diabetic men and women who were either overweight or normal weight. MBX-2044 was well tolerated at all doses and showed a reduction in uric acid levels, a property also shared by metaglidasen, after a single dose.

Novel Method-of-Action

PPARs (peroxisome proliferator-activated receptors) control the expression of genes involved in glucose metabolism, lipid metabolism and inflammation. Metaglidasen and MBX-2044 are Selective PPAR Modulators (SPPARMs) that modulate the genes needed for insulin sensitization, but not those responsible for edema and weight gain.

About Diabetes

Type 2 diabetes is a disease characterized by insulin resistance, in which the body does not properly use insulin, the hormone that converts glucose into energy. According to the American Diabetes Association, it is the 6th leading cause of death in the United States and affects about 18.2 million people, while about 41 million people in the U.S. are prediabetic. Most diabetics have type 2, or adult-onset, diabetes and the incidence is expected to rise to 10 percent of the population by the year 2010.

The cause of diabetes is unknown, although genetics and environmental factors such as lack of exercise and obesity appear to play a role. Treatment includes dietary changes, insulin injections, and oral therapies.

About Metabolex

Metabolex is a privately held biotechnology company dedicated to the discovery and development of novel therapeutics to transform the treatment of diabetes and related metabolic disorders. Metabolex has drawn on its deep understanding of diabetes to create the largest database of genes involved in diabetes and to build a rich pipeline of product candidates and drug discovery targets. The company's clinical program is focused on developing next- generation insulin sensitizers that lower blood glucose without the serious safety and tolerability issues associated with currently marketed products.

For additional information about Metabolex and its development pipeline, visit http://www.metabolex.com/.

Metabolex, Inc.

CONTACT: Mark Bagnall, Metabolex Chief Business Officer,+1-510-293-8800, or mbagnall@metabolex.com; or Daryl Messinger of WeissCommPartners, Inc., +1-415-999-2361, or daryl@weisscommpartners.com, forMetabolex, Inc.

Web site: http://www.metabolex.com/

Source: PRNewswire

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