Urocortin 2

Need for New Drugs for Congestive Heart Failure (CHF)

Congestive heart failure (CHF) is a condition where the heart cannot pump enough blood to supply all of the body’s organs or avoid fluid build up in the lungs. While there are a variety of causes of CHF, including heart attacks, diabetes and high blood pressure, the breathing difficulty, swelling in the legs and, for some, death result. In the case of rapid deterioration in CHF, patients require urgent treatment in the hospital. According to 2008 data from the American Heart Association, over 5 million people experience CHF and about 660,000 new cases are diagnosed each year in the United States. CHF becomes more prevalent with age and the number of cases is expected to grow as the overall age of the population increases. Current treatment options include a cocktail of drugs consisting of diuretics to remove excess water, beta blockers and digitalis to improve heart muscle contraction, and/or ACE inhibitors and vasodilators to expand blood vessels. There are in excess of one million hospitalizations each year in the United States for CHF (Mattson Jack 2006, AMA 2008).

Market Opportunities

Morbidity and mortality associated with acute CHF, especially in the months following the initial discharge from the hospital, are notoriously high and the cost to the U.S. healthcare system is more than $20 billion annually. The commercial opportunity for a new agent with a demonstrated improvement on long term morbidity and mortality associated with acute CHF is significant.

Mechanism of Action

Urocortin 2 was designed to mimic the effect of the recently discovered protein urocortin 2. Urocortin 2 selectively stimulates the CRF2 receptor and can improve cardiac output with minimal increase in heart rate. It also has the potential to provide cardioprotection via a novel mechanism for regulating calcium cycling enzymes/channels in heart muscle cells.

Urocortin 2 for Congestive Heart Failure

Urocortin 2 was discovered in the laboratory of Neurocrine’s co-founder, Dr. Wylie W. Vale, Professor and Head, Clayton Foundation for Research for Peptide Biology from the Salk Institute. Neurocrine licensed urocortin 2 from the Clayton Foundation for Research to further expand the Company’s franchise in corticotropin-releasing factor (CRF) research.

Clinical Results

During 2009, The Christchurch Cardioendocrine Research Group at University of Otago, Christchurch School of Medicine and Health Sciences, New Zealand, began a pilot study of urocortin 2 in 50 patients with Acute Decompensated Heart Failure through a grant from the Health Research Council of New Zealand. In this blinded study, standard-of-care treatment (i.e. diuretics and vasodialators) will be compared to standard of care treatment plus a four hour infusion of urocortin 2; enrollment of subjects is currently underway. A subset of 10 subjects will also undergo right heart catheterization for more detailed evaluation of their cardiac status and response to treatment. Enrollment in this study began in September 2009 and is expected to take approximately one year depending on recruitment activities.

Additional urocortin 2 studies are to be conducted by the Centre for Cardiovascular Sciences at The University of Edinburgh through a British Heart Foundation grant. Nine studies will be conducted in both healthy volunteers and patients with stable CHF to determine the impact of urocortin 2 infusions on biomarkers of cardiovascular function and dysfunction. The studies are anticipated to begin in early 2010.