Isis Initiates Phase 1 Study of ISIS 325568 Targeting Glucagon Receptor to Treat Type ... (evidence forthe drug's activity as well ...)

Isis Initiates Phase 1 Study of ISIS 325568 Targeting Glucagon Receptor to Treat Type 2 Diabetes

Date:9/4/2007

evidence for the drug's activity as well as help inform dose selection for future studies."

ISIS 325568 Targets the Glucagon Receptor (GCGR)

Glucagon is a hormone that opposes the action of insulin and stimulates the liver to produce glucose. In type 2 diabetes, unopposed action of glucagon can lead to increased blood glucose levels. Reducing the expression of liver GCGR using antisense inhibitors, and thereby reducing excessive liver glucose production, is expected to lower blood glucose levels and help control type 2 diabetes. In preclinical studies, antisense inhibitors of GCGR led to improved glucose control and reduced levels of blood triglycerides without producing hypoglycemia. In addition, treatment with ISIS 325568 led to an increase in circulating glucagon-like peptide, or GLP-1, which is a hormone that helps to preserve pancreatic function, thereby enhancing insulin secretion.

ABOUT ISIS PHARMACEUTICALS, INC.

Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 17 drugs in development. Isis' drug development programs are focused on treating cardiovascular and metabolic diseases. Isis' partners are developing drugs for cancer, and inflammatory and other diseases. Ibis Biosciences, Inc., Isis' wholly owned subsidiary, is developing and commercializing the Ibis T5000 Biosensor System, a revolutionary system to identify infectious organisms. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,500 issued patents worldwide. Additional information about Isis is available at http://www.isispharm.com.

This press release includes forward-looking statements regarding Isis' discovery and development of drugs for diabetes and metabolic diseases, and the potential of the antise
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