Isis Adds Three New Drugs to Its Development Pipeline

CARLSBAD, Calif., Dec. 14, 2011 /PRNewswire/ -- 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. 

Conference Call

At 12:00 p.m. Eastern Standard Time Thursday, December 15, Isis will conduct a live webcast conference call to discuss these three new development candidates and ISIS-AATRx, which was added to Isis' pipeline this quarter.  Interested parties may listen to the call by dialing 866-825-3308 and refer to passcode 'Isis2011', or access the webcast at www.isispharm.com.  A webcast replay will be available for a limited time at the same address.

ABOUT ISIS PHARMACEUTICALS, INC.

Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners.  Isis' broad pipeline consists of 28 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic and severe and rare/neurodegenerative diseases, and cancer.  Isis' partner, Genzyme, plans to commercialize Isis' lead product, mipomersen, following regulatory approval, which is expected in 2012.  Isis' patents provide strong and extensive protection for its drugs and technology.  Additional information about Isis is available at www.isispharm.com.

ISIS PHARMACEUTICALS' FORWARD-LOOKING STATEMENT

This press release includes forward-looking statements regarding the discovery, development, activity, therapeutic potential and safety of ISIS-APOARx, ISIS-FVIIRx, and ISIS-DGAT2Rx.  Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs, including the planned commercialization of mipomersen, is a forward-looking statement and should be considered an at-risk statement.  Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs.  Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements.  Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis.  As a result, you are cautioned not to rely on these forward-looking statements.  These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended December 31, 2010 and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the Company.

In this press release, unless the context requires otherwise, "Isis," "Company," "we," "our," and "us" refers to Isis Pharmaceuticals and its subsidiaries, including Regulus Therapeutics Inc., its jointly owned subsidiary.

Isis Pharmaceuticals® is a registered trademark of Isis Pharmaceuticals, Inc.  Kynamro™ is a trademark of Genzyme Corporation.

SOURCE Isis Pharmaceuticals, Inc.