Isis Reports Positive Phase 1 Data Demonstrating ISIS-FXIRx Reduces Factor XI Activity Without

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today positive results from a Phase 1 study with ISIS-FXIRx. The results demonstrated that treatment with ISIS-FXIRx produced dose-dependent statistically significant reductions of up to 78 percent in Factor XI activity. ISIS-FXIRx was safe and well tolerated with no increase in bleeding. These data were presented today at the 2011 American Society of Hematology (ASH) Annual Meeting in San Diego.

"High levels of Factor XI increase the risk of thrombosis, aberrant blood clot formation that is responsible for most heart attacks and strokes and is the number one cause of death and disability in the United States and worldwide. Elevated levels of Factor XI also increase the risk of venous thrombosis, a common problem after surgery, particularly major orthopedic procedures, such as knee or hip replacement. Although currently available anticoagulants (blood thinners) reduce the risk of these complications, they are associated with increased bleeding that can be fatal," said Jeffrey Weitz, M.D., F.A.C.P., F.R.C. P.(C), Professor of Medicine at McMaster University and Executive Director of the Thrombosis and Atherosclerosis Research Institute. "Factor XI is a unique target for new blood thinning therapies because Factor XI plays a key role in clot formation, but its inhibition does not induce bleeding. Consequently, Factor XI-targeted therapy holds the promise of reducing thrombosis with a potentially better safety profile than currently available anticoagulants."