Isis Pharmaceuticals Adds New Cardiovascular Drug to Development Pipeline

CARLSBAD, Calif., Jan. 11 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today that it has added a new drug, ISIS-APOCIIIRx, to its development pipeline. ISIS-APOCIIIRx provides a novel approach to treat hypertriglyceridemia, or high levels of triglycerides (TG). Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Hypertriglyceridemia is also a hallmark of metabolic syndrome, which occurs in a large percentage of people with type 2 diabetes. ISIS-APOCIIIRx is the second new drug added to Isis' expanding cardiovascular pipeline in the past year.

"Managing high levels of triglycerides is important not only in cardiovascular disease but also in metabolic and some inflammatory diseases. We believe that ISIS-APOCIIIRx will provide patients and physicians with a novel treatment option to lower triglycerides," said Stanley T. Crooke, M.D., Ph.D., Chairman and Chief Executive Officer of Isis. "ApoC-III is a novel target to lower triglycerides and adds to our pipeline an alternate, yet complementary, approach to lipid management."

ISIS-APOCIIIRx is designed to reduce apolipoprotein C-III (apoC-III), a key regulator of serum TG levels. ApoC-III is synthesized in the liver and has been difficult to approach using traditional therapeutics, making it an ideal target for Isis' antisense technology. In preclinical studies, ISIS-APOCIIIRx mitigated symptoms of metabolic syndrome and reduced atherosclerosis in mice. Isis is developing ISIS-APOCIIIRx as part of its strategy to discover and develop drugs for lipid management.

Additionally, Dr. Rosanne Crooke, Isis' Executive Director of Cardiovascular Diseases, will present data on ISIS-APOCIIIRx in an oral presentation titled "Development of Novel Antisense Inhibitors for the Treatment of Hypertriglyceridemia." The presentation will take place on Wednesday, January 13 at the Keystone Symposia on Triglycerides and Triglyceride-Rich Particles in Health and Disease in Big Sky, Montana.

More detail on ISIS-APOCIIIRx and other drugs in Isis' pipeline will also be presented at J.P. Morgan's 28th Annual Healthcare Conference on Wednesday, January 13, 2010, at 9:30 a.m. PT in San Francisco. A live audio webcast of this presentation will be available on the "Investors & Media" section of the Company's Web site, www.isispharm.com.

ABOUT APOC-III

ApoC-III is a 79-amino acid glycoprotein synthesized in the liver that plays a central role in the regulation of serum TGs. Recent data suggest that loss-of-function mutations within the apoC-III gene lower TG levels and appear to improve health and extend longevity. Clinical studies have demonstrated an association between apoC-III, metabolic syndrome and coronary heart disease (CHD). In addition, insulin resistance has been shown to be mediated through apoC-III, leading to worsening of the metabolic syndrome.

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 22 drugs in development. Isis' drug development programs are focused on treating cardiovascular, metabolic, and severe neurodegenerative diseases and cancer. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development and commercialization of microRNA therapeutics. Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,600 issued patents worldwide. Additional information about Isis is available at www.isispharm.com.

This press release includes forward-looking statements regarding the development, activity, therapeutic potential and safety of ISIS-APOCIIIRx in the treatment of hypertriglyceridemia. Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs 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 products. 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, 2008, 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.

Isis Pharmaceuticals is a registered trademark of Isis Pharmaceuticals, Inc. Regulus Therapeutics is a trademark of Regulus Therapeutics Inc.

SOURCE Isis Pharmaceuticals, Inc.