Amgen and Biovitrum Expand Existing License Agreement for Innovative Treatment of Type 2 Diabetes and Other Metabolic Disorders

Business Wire, Feb 13, 2006

THOUSAND OAKS, Calif. & STOCKHOLM, Sweden -- Amgen (NASDAQ:AMGN) and Biovitrum AB today announced that they have expanded their existing agreement under which Amgen will now receive exclusive worldwide rights to develop and commercialize Biovitrum's small molecule 11(beta)-HSD1 enzyme inhibitors for the treatment of metabolic diseases and certain other medical disorders. The most advanced compound in this collaboration is currently in early clinical development.

The original development and marketing collaboration agreement, announced in September 2003, provides Amgen the exclusive right to commercialize products in North and South America, the European Union, Australia and New Zealand. Under the expanded agreement, Amgen receives exclusive worldwide rights to commercialize all developed products, while Biovitrum retains co-promotion rights in the Nordic region for all products developed.

Amgen will pay an undisclosed amount for the upfront payment related to the expanded licensed territory. Amgen will also fund and conduct all further development and commercialization activities worldwide. Biovitrum may receive additional milestone payments related to development progress and regulatory submissions for metabolic diseases. Once a product has been approved, Biovitrum will receive tiered royalties on future worldwide sales of all products arising from the agreement.

"Amgen continues to believe that this collaboration with Biovitrum will move us toward discovering innovative treatments for type 2 diabetes and related metabolic diseases," said Will Dere, M.D., senior vice president of Global Development and chief medical officer at Amgen.

"Amgen has proven to be an excellent partner for our 11(beta)-HSD1 enzyme inhibitor program and we are very happy to expand this collaboration," said Mats Pettersson, CEO of Biovitrum. "We are confident that Amgen will remain a strong and committed partner for completing development of this innovative approach for helping those suffering from type 2 diabetes and related disorders," commented Mats Pettersson.

Type 2 diabetes, a disease in which insulin resistance leads to elevated blood sugar levels, currently afflicts over 160 million people worldwide. Approximately 20 million Americans currently suffer from type 2 diabetes. Early intervention using innovative therapies has the potential to delay the onset of life-threatening metabolic disorders.

Notes to editors:

About Amgen

Amgen discovers, develops and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a broad and deep pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.

About Biovitrum

Biovitrum is one of the larger biopharma companies in Europe. With operations in Sweden and in the UK Biovitrum conducts research and develops pharmaceuticals for both broad diseases and conditions that affect smaller patient populations. Biovitrum focuses on drugs for the treatment of obesity, diabetes, inflammation and blood diseases as well as a number of well defined niche indications. Biovitrum develops and produces protein-based drugs on a contractual basis and markets a range of specialist pharmaceuticals primarily in the Nordic countries. Biovitrum has approximately 500 employees. For more information see www.biovitrum.com/.> 11(beta)-HSD

Excess glucocorticoids such as cortisol produce visceral obesity and diabetes. 11beta-hydroxysteroid dehydrogenases (11(beta)-HSDs) are enzymes that play an important role in the interconversion of glucocorticoids between the active and inactive forms. Two enzymes have been identified, 11(beta)-HSD1, and 11(beta)-HSD2. These 11(beta)-HSDs play a major role in the modulation of local cortisol levels and the access of active steroid to its receptors in the target tissues. Thereby, the 11(beta)-HSDs are also believed to have important roles in a number of common diseases, including obesity, type 2 diabetes and hypertension.

11(beta)-HSD2 is found primarily in tissues such as kidney, sweat glands and salivary glands. 11(beta)-HSD2 converts active glucocorticoids into inactive steroids and appears to act as an effective barrier to excess cortisol across a wide range of cortisol concentrations. However, in studies where the 11(beta)-HSD2 enzyme activity has been inhibited with liquorice this results in an excess of steroids that cause hypokalemia and hypertension.

11(beta)-HSD1 is present in tissues of importance for metabolism and insulin sensitivity such as the liver and the adipose tissue. Its activity can be altered by factors such as glucocorticoids, stress, sex steroids, growth hormone, cytokines and PPAR agonists. Under normal conditions, 11(beta)-HSD1 is believed to amplify local glucocorticoid concentrations in target tissues, in particular when the circulating plasma cortisol levels are low. However, in obese subjects the levels of 11(beta)-HSD1 are usually markedly increased, at least in adipose tissue. This observation is of importance in the light of a rodent study recently published in Science, demonstrating that animals with an increased 11(beta)-HSD1 activity (i.e. transgenic animals) have an excess of visceral fat and are insulin resistant, diabetic and dyslipidemic. Furthermore, in humans, pharmacological inhibition of 11(beta)-HSD1 with non-selective compounds has previously been shown to result in enhanced insulin sensitivity. This finding indicates that 11(beta)-HSD1 appears to play an important role in type 2 diabetes and the metabolic syndrome also in man, and that selective inhibitors of 11(beta)-HSD1 could become a very useful tool in the treatment of this disorder.