Isis Highlights Robust Drug Portfolio for Diabetes and Obesity at ADA ...(ionscan be found on the ADA Web site at ...),Health

"In our metabolic disease franchise we have evaluated more than 130 biological targets and identified more than 20 therapeutic targets that have the potential to offer new approaches to treat diseases, such as obesity and diabetes," said Jeffrey Jonas, M.D., Executive Vice President of Isis Pharmaceuticals. "Our research demonstrates the ability of antisense technology to quickly validate novel targets that provide exciting new approaches to treat metabolic diseases. In particular, obesity is an area where we feel our peripherally acting drugs rather than centrally acting drugs could have a profound impact on the activity and tolerability of anti-obesity therapy. Furthermore, our ongoing clinical studies with other antisense drugs provide evidence for the long-term safety of antisense drugs, making them an attractive possibility for the treatment of chronic diseases."

About SGLT2 and ISIS 388626

The sodium dependent glucose transporter type 2 (SGLT2) is the primary mechanism responsible for glucose re-absorption in the kidney. Decreasing SGLT2 function promotes glucose excretion to help reduce blood sugar levels, making it an attractive target for the treatment of diabetes. In preclinical studies, ISIS 388626 and other antisense inhibitors of SGLT2, effectively reduced target mRNA levels in several animal species, increased urinary glucose excretion and consequently lowered blood glucose levels and HbA1c (in hyperglycemic animals) without causing dangerously low levels of blood sugar known as hypoglycemia. These data are consistent with expectations based on human subjects who have mutations in the SGLT2 gene and have increased urine glucose levels but are otherwise asymptomatic. ISIS 388626 effectively and specifically inhibits the production of SGLT2 in the kidney tissue, without having any effect on a related gene product, SGL
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