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Unmet Needs

Metabolex is focused on developing transformative treatments for metabolic diseases. These diseases represent a worldwide health problem and a skyrocketing source of morbidity, mortality and health care costs in the United States and abroad. We seek not only best-in-class approaches, but also first-in-class compounds that address these unmet needs in novel ways:
Diabetes
  Diabetes is a worldwide health problem and a rapidly growing source of illness, death, and health care costs. According to the International Diabetes Federation, approximately 246 million adults, or 6 percent of the world’s adult population, had diabetes in 2007. The American Diabetes Association estimates that there were approximately 23.5 million adults in the United States with diabetes in 2007, making up 10.7 percent of the adult population. According to estimates from the ADA, one out of every five health care dollars is spent caring for someone with diagnosed diabetes, while one in ten health care dollars is attributed to diabetes. Type 2 diabetes accounts for 90 to 95 percent of diabetic cases.
  Despite the size and growth of the diabetes market, it is an underserved and compelling opportunity, especially if an insulin sensitizer such as MBX-102 could be developed without the safety concerns observed with the currently marketed insulin sensitizers. The marketed insulin sensitizers are from the thiazolidinedione, or TZD, chemical class. Those products had worldwide sales of over $6 billion in 2006, despite causing weight gain in most patients and increasing the risk of fluid retention, edema and congestive heart failure. Concerns over an increased risk of congestive heart failure in these drugs have prompted the U.S. Food and Drug Administration to put a black box label warning label on the TZDs. Clinical, preclinical and gene expression data consistently suggest that Metabolex’s lead diabetes candidate, MBX-102, carries benefits similar to existing insulin sensitizers without the weight gain and edema that characterize currently marketed insulin sensitizers.
 
Metabolex is also developing MBX-2982 which is a potential first-in-class treatment for type 2 diabetes that targets G protein-coupled receptor 119 (GPR 119), a receptor that interacts with bioactive lipids known to stimulate glucose-dependent insulin secretion.

Dyslipidemia

  Dyslipidemia is a set of disorders characterized by an abnormal composition of lipids in the blood, including high levels of “bad” cholesterol and triglycerides and low levels of “good” cholesterol.
  The risks associated with elevated levels of low-density lipoprotein (LDL or "bad cholesterol") have made treatments for high cholesterol, including the statins and cholesterol absorption inhibitors, the best-selling medications in history. Even with increasing generic competition, sales of lipid-lowering drugs are expected to exceed $30 billion in 2008. People with diabetes are at especially high risk for dyslipidemia, particularly high triglycerides and LDL cholesterol levels and low HDL levels. Thus, there remains a need for new therapies that lower LDL through novel mechanisms, especially ones that have additional beneficial effects on triglycerides and HDL. Such therapies could be used independently or in combination with statins and other lipid treatments to help patients reach target goals and reduce overall cardiovascular risk.
  Metabolex is developing MBX-8025, a potential novel approach to treating dyslipidemia.

Obesity
  More than 30 percent of adults in the U.S. are clinically obese, placing them at high risk of heart disease, stroke, diabetes and other health concerns, and the number is rising. The medical costs, too, are soaring, and the U.S. Centers for Disease Control and Prevention has estimated that more than $75 billion is spent annually treating people who are overweight or obese.
  Obesity is also a significant risk factor for type 2 diabetes, as chronic obesity is a risk factor for the insulin resistance that is the root cause of diabetes. Most patients with type 2 diabetes are overweight and many are clinically obese, according to the CDC.
  Medical options for the management of obesity have shown mixed results in the long-term control of body weight, and efforts to maintain weight control in patients with type 2 diabetes is often complicated by the weight gain associated with the use of currently marketed insulin sensitizers.