Isis announces addition of three new drug development candidates

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today that it has added three new drugs to its development pipeline, ISIS-APOARx, ISIS-DGAT2Rx and ISIS-FVIIRx.  Isis will conduct a conference call tomorrow, December 15, at 12:00 p.m. Eastern Time to provide more detail on these important new drugs. 

"2011 has been an extremely successful year for Isis and positions us for an even more successful 2012.  Most importantly this year, the European marketing application for Kynamro has been submitted and Genzyme is finalizing the United States NDA submission.  We look forward to Genzyme's launch of Kynamro next year, which would be the first systemic antisense drug to reach the market," said Stanley T. Crooke, M.D., Ph.D., Chairman of the Board and Chief Executive Officer at Isis.  "Our successes go beyond Kynamro.  We have reported positive data demonstrating safety and activity in Phase 1 studies for many of our drugs and are advancing these drugs into later-stage clinical development.  The new drugs we added today expand the breadth of both our cardiovascular and metabolic franchises and exemplify our efforts to develop safe and effective drugs that could change the therapeutic landscape in these life-threatening diseases."

ISIS-APOARx reduces apolipoprotein(a) in the liver and is designed to offer a direct approach to reducing Lp(a), an independent risk factor for cardiovascular disease.  High levels of Lp(a) are associated with an increased risk of atherosclerosis, coronary heart disease, heart attack and stroke.   Lp(a) promotes premature plaque buildup, or atherosclerosis, in arteries.   Commonly prescribed lipid-lowering drugs have little or no effect on Lp(a) levels.  Patients who are able to control their LDL-C levels, but still have high levels of Lp(a) remain at high risk of cardiovascular events.  There is a significant need for a highly specific drug that can lower Lp(a).   Isis is developing ISIS-APOARx as part of its strategy to create a cardiovascular disease franchise comprised of drugs that target all the key components of cardiovascular disease, including various atherogenic lipids, inflammation and thrombosis.  Isis plans to develop ISIS-APOARx to treat patients with high Lp(a) levels who are at severe risk of experiencing cardiovascular events.

ISIS-DGAT2Rx specifically inhibits diacylglycerol acyltransferase-2, or DGAT-2, a key component in the synthesis of triglycerides.  ISIS-DGAT2Rx is designed to reduce liver fat in patients with nonalcoholic steatohepatitis (NASH), a common and often asymptomatic liver disease that can cause irreversible damage to the liver, and lead to liver cirrhosis and cancer.   The incidence of NASH in the United States is estimated to be more than 20 million, and is expected to increase as the rate of obesity rises.  There are no effective therapies available for patients with NASH and current treatments consist only of lifestyle changes.  In addition, because increase in liver fat is strongly associated with insulin resistance, ISIS-DGAT2Rx could also be beneficial for patients with type 2 diabetes who are insulin resistant.   

ISIS-FVIIRx is designed to reduce Factor VII, a key component of the tissue factor coagulation pathway, for the treatment or prevention of thrombotic diseases without causing bleeding, which is a common side effect of currently available anti-thrombotic drugs.  Elevated levels of Factor VII activity are indicative of poor prognosis in several thrombotic diseases, such as heart attacks.  Furthermore, elevated levels of Factor VII activity are strongly linked to cancer-associated thrombosis, which is the second leading cause of death in cancer patients.   In preclinical studies, antisense inhibition of Factor VII rapidly reduced Factor VII activity by more than 90 percent in three days, suggesting that ISIS-FVIIRx­ has the potential to be used in acute clinical settings, such as following surgery, in which patients are at high risk for developing blood clots.  ISIS-FVIIRx is the second drug to enter development as part of Isis' strategy to create more potent and safer anti-thrombotic drugs that do not increase bleeding.