Isis Highlights Robust Drug Portfolio for Diabetes and Obesity at ADA ...(iabetic animals and reduced fed and fast...),Health

while also ameliorating diabetic complications, including slowing

progression of cataract formation.

-- Lowered SGLT2 mRNA levels in the kidney by approximately 80% in all

species tested, with doses as low as 1-2 mg/kg/week with no effect on

SGLT1, a related protein, where levels of activity is desirable.

-- Showed no changes in urinary or plasma markers of renal function and

no harmful effects such as low blood glucose.

"In preclinical models, lowering levels of SGLT2 in the kidney by an antisense drug demonstrated very potent reduction in blood glucose that supports the possibility of an infrequent monthly injectable dosing or, potentially, a cost effective oral administration. Furthermore, our SGLT2 inhibitor complements our diabetes drugs in development, and offers a unique and complementary approach to treat diabetes," said Sanjay Bhanot, M.D., Ph.D., Vice President of Metabolic Diseases Research & Development of Isis Pharmaceuticals. "We are moving ISIS 388626, our human antisense SGLT2 inhibitor, toward human clinical proof-of-concept as rapidly as possible, and we look forward to continuing to populate our metabolic disease pipeline with exciting drugs arising from our research program."

As part of Isis' metabolic disease franchise, data from eight additional research programs conducted by Isis and its collaborators were presented at ADA this year, evaluating the effects of antisense drugs against eight promising new targets in a variety of species and models, including diabetic animals. Results of the studies showed that antisense technology reduced mRNA target levels in specific tissues and provided early signs of therapeutic benefit in various models of disease, offering robust and sustained effects for the treatment of obesity, type 2 diabetes and lipid metabolism disorders. Complete abstracts for these presentat
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