DPP IV Inhibitors
Arisaph is developing several potent and selective, smart DPP IV inhibitors for the treatment of diabetes. Dipeptidylpeptidase (DPP) IV is a naturally occurring, proteolytic enzyme that rapidly degrades the incretin hormones, gastric inhibitory polypeptide (GIP) and glucagon-like protein (GLP-1). GLP-1 has a favorable anti-diabetic role because it stimulates glucose-dependent insulin secretion from the pancreas, slows gastric emptying and decreases glucagon secretion. Inhibitors to DPP IV improve glycemic control in patients with Type II diabetes by increasing the half-life of native GLP-1. DPP IV is a validated target for the treatment of Type II diabetes and inhibitors of DPP IV have been shown to lower post-prandial glucose and HbA1c levels. Diabetes is a major healthcare problem throughout the world with the prevalence of the disease projected to double to 366 million cases worldwide by the year 2030, according to the World Health Organization.1
The Company has design and synthesized a series of DPP 4 inhibitors that have shown to be significantly more effective than leading DPP 4 inhibitors in pre-clinical studies. For example, ARI-2243 produced a 2.2% reduction in hemoglobin A1c levels (HbA1c) following 8 weeks of daily dosing in a highly refractory diabetic animal model (ZDF rats) compared with no significant change with vildagliptin. In addition to being a pico-molar inhibitor of DPP IV, ARI-2243 is functionally selective through a smart, soft drug inactivation process.2 The long-acting and potent attributes of Arisaph’s DPP 4 inhibitors are expected to yield a differentiated efficacy profile in diabetic patients. In 2008, Arisaph successfully filed an IND and completed a first-in-man Phase 1a clinical trial for ARI-2243.
Diabetes is a disease in which the body does not produce or properly regulate insulin, a hormone needed to convert sugar, starches and other food into energy. There are 23.6 million people in the United States who are estimated to have the disease; 5.7 million of them (or nearly one-quarter) are undiagnosed.3 There are three main types of diabetes: Type I, Type II, and gestational; however, Type II accounts for most diabetes cases. In Type II diabetes, the body most likely still produces insulin, however the body's cells do not use it effectively. Since the body fails to use its insulin appropriately, high levels of sugar build up in the bloodstream. As the levels continue to increase, the likelihood of developing Type II diabetes increases.3
- Wild S, et al.: Global Prevalence of Diabetes, Estimates for the year 2000 and projections for 2030. Diabetes Care 27: 1047-1053, May 2004
- Sanford DG, et al: ARI2243, a highly potent and selective dipeptidyl IV (DPP4) inhibitor with exceptional anti-hyperglycemic activity for the treatment of Type II diabetes. 2007 Chicago American Diabetes Association. Abstract Number: 604-P
- Centers for Disease Control and Prevention Web site. Available at: www.cdc.gov/diabetes/pubs/factsheet07.htm#contents. Accessed June 25, 2008