Glucose-Dependent Insulinotropic Receptors May Improve Glucose Control In Patients With Type 2 Diabetes

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Clinical study results for APD668, an oral drug candidate discovered by Arena and being investigated for the treatment of type 2 diabetes under a partnership with Ortho-McNeil Pharmaceutical, Inc., suggest that Glucose-Dependent Insulinotropic Receptors, or GDIRs, may improve glucose control in patients with type 2 diabetes.

Ortho-McNeil's initial clinical studies evaluated healthy volunteers and patients with type 2 diabetes in randomized, double-blind, placebo-controlled trials evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple (14 day) escalating doses of APD668. Based on the data from those studies, Ortho-McNeil has decided to put APD668 on hold and has advanced a potentially more potent Arena discovered GDIR agonist into preclinical development.

"We are encouraged by the clinical study results supporting GDIR agonists as effective modulators of glucose homeostasis in patients with type 2 diabetes, and we look forward to the results of Ortho-McNeil advancing another of Arena's GDIR compounds into development," stated Dominic P. Behan, Ph.D., Arena's Senior Vice President and Chief Scientific Officer.

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About the Glucose-Dependent Insulinotropic Receptor (GDIR)

The GDIR is an orphan G protein-coupled receptor, or GPCR, discovered by Arena. It is expressed in beta cells, the cells in the pancreas responsible for producing insulin in response to increases in blood glucose. Stimulation of the GDIR is intended to more efficiently promote insulin release by beta cells in response to elevated blood glucose levels. In addition, in preclinical studies, the GDIR stimulates the release of GLP and GIP, two incretins that are important for proper insulin regulation, which may enhance glucose homeostasis. GDIR stimulation has also been found to increase the levels and activity of intracellular factors thought to be involved in the preservation of beta cells. The GDIR is amenable to small molecule, orally active, drug development.

About Diabetes

Diabetes is a major worldwide disease. Based on 2003 data, the International Diabetes Federation estimated that in 2005 there were 194 million adults with diabetes worldwide, an increase of over 40% since 1995. Approximately 90%, or 175 million, of diabetics worldwide suffer from type 2 diabetes, the adult-onset form of the disease. Type 2 diabetes is characterized by inadequate response to insulin or inadequate secretion of insulin as blood glucose levels rise. Therapies for type 2 diabetes are directed toward correcting the body's inadequate response with oral or injectable medications, or directly modifying insulin levels by injection of insulin or insulin analogs. The worldwide market for diabetes medications exceeded $10 billion in 2004, of which oral drugs exceeded $6 billion.

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