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VITAE PHARMACEUTICALS, INC filed this Form S-1 on 08/12/2014
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inhibiting 11b HSD1 is supported in the literature by genetic studies. For instance, in a study by Kotelevtsev, et al published in 1997 in the Proceedings of the National Academy of Sciences, mice lacking 11b HSD1 were reported to be protected from becoming hyperglycemic and were insulin responsive, while in a study by Masuzaki, et al published in 2001 in Science, mice with increased 11b HSD1 expression in adipose tissue were reported to gain weight and had findings of metabolic syndrome. In addition, pharmacological experiments inhibiting the enzyme have demonstrated that reduction of cortisol in adipose tissue produces a significant decrease in blood glucose, lipid levels and blood pressure. In a clinical trial assessing type 2 diabetics inadequately controlled by metformin, an 11b HSD1 inhibitor demonstrated significant reductions in blood sugar and cholesterol and modest reductions in weight.

        We believe that any inhibitor of 11b HSD1 needs to be highly specific and avoid inhibition of 11b HSD2. Human genetic studies show that inherited loss of 11b HSD2 activity leads to severely elevated blood pressure and low potassium due to excess cortisol activity in the kidney. Based on clinical and preclinical data generated to date for VTP-34072, we believe that it is highly specific for 11b HSD1 inhibition without inhibiting 11b HSD2.

    Market Opportunity

        Type 2 diabetes is a common and increasingly prevalent diagnosis. According to the American Diabetes Association, in 2010, approximately 17 million Americans had a diagnosis of type 2 diabetes and another 7 million were undiagnosed and may have been unaware that they had type 2 diabetes. If the present trends continue, as many as 1 in 3 American adults are expected to have type 2 diabetes in 2050. Overall, the economic cost of diagnosed type 2 diabetes in the United States was estimated to be $245 billion in 2012 and of that approximately $9.6 billion was spent on prescription products to treat the disease.

        We believe that the most appropriate patient population for VTP-34072 is the approximately 85% of Americans suffering from type 2 diabetes who are classified as having metabolic syndrome. Metabolic syndrome manifests as a linked combination of abnormalities which includes elevated blood pressure, levels of plasma glucose and lipids and weight that together significantly increase a patient's risk for cardiovascular disease. Published data have demonstrated that improving one or more of these conditions can have a direct impact on reducing cardiovascular risk.

        There are many classes of orally active drugs that work in different ways to treat type 2 diabetes. They include sulfonylureas, biguanides, meglitinides, thiazolidinediones, alpha-glucosidase inhibitors, bile acid sequestrants, DPP-4 inhibitors, and SGLT2 Inhibitors. We believe the continued and significant unmet medical need for diabetes treatments is demonstrated by DPP-4s, a new class of drugs which were first approved in the United States in 2006 and by 2013 had sales of $5.2 billion. If approved, we believe that VTP-34072 may be differentiated from currently available treatments for type 2 diabetes because of its potential to have a broader beneficial effect on a patient's overall metabolic syndrome associated cardiovascular risk profile by lowering their glucose, lipids, blood pressure and weight.

    Clinical Trials

        The clinical development of VTP-34072 is being led by BI. Two Phase 1 clinical trials have been completed and a Phase 2 clinical trial was initiated in July 2014, with data expected in the first half of 2015.

        The first Phase 1 clinical trial for VTP-34072 was a single dose escalating trial in 72 healthy, overweight volunteers. VTP-34072 was well tolerated at all doses. There were no clinically relevant changes in vital signs, laboratory values or electrocardiograms. The half-life for clearance from the plasma was 14 to 24 hours, which we believe is consistent with once-a day dosing in humans. The activity of 11b HSD1 was assessed in the adipose tissue biopsies that were taken prior to dosing and at 24 hours after the dose. The enzyme activity in the adipose biopsies showed that 11b HSD1 activity was inhibited by greater than 90% at 24 hours in multiple dose groups. In addition, no evidence of changes in plasma or urinary