Release Details

* ISIS 301012 has broad and pronounced lipid-lowering activity when dosed as a single agent and in coadministration with moderate or high-dose statins * ISIS 301012 treatment results in significant reductions in apoB and atherogenic lipids in patients with routine high cholesterol and homozygous familial hypercholesterolemia (FH) * ISIS 301012 is well tolerated with over 200 subjects treated to date * Live webcast at 7:00 am CT at www.isispharm.com

NEW ORLEANS and CARLSBAD, Calif., March 27, 2007 /PRNewswire-FirstCall via COMTEX News Network/ -- Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) today summarized new data from three Phase 2 studies presented this week at the American College of Cardiology Annual Scientific Session (ACC) in New Orleans. Involving nearly 150 drug-treated patients, the Phase 2 studies demonstrated that ISIS 301012 significantly reduced harmful lipids and was well tolerated. In addition, Isis summarized its development plans for ISIS 301012.

Thomas Michel, M.D., Ph.D., Professor of Medicine, Harvard Medical School and Senior Physician, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, stated, "The data are compelling. These are really elegant studies, carefully executed and thoughtfully analyzed. The conclusions are clear, and I am entirely convinced of the tolerability, activity and unparalleled therapeutic potential of ISIS 301012."

The key conclusions from the Phase 2 studies are that treatment with ISIS 301012:

    *  Resulted in linear, dose-dependent, prolonged reductions of apoB and
       related atherogenic lipids including LDL-cholesterol (LDL-C) and
       triglycerides in patients with polygenic hypercholesterolemia (routine
       high cholesterol) and in patients with homozygous familial
       hypercholesterolemia (HoFH).

    *  Was similarly effective when administered as a single agent, when
       coadministered with moderately-dosed statins and when added to
       maximally-tolerated lipid-lowering therapies.

    *  Had no effect on HDL-cholesterol (HDL-C), and caused marked reductions
       in the ratios of apoB to apoA-1 (the protein components of LDL-C and
       HDL-C particles, respectively) and total cholesterol (TC) to HDL-C.

    *  Enable most patients to achieve target levels for three major
       cardiovascular risk markers: LDL-C less than 100 mg/dL, non-HDL-C less
       than 130 mg/dL and apoB less than 90 mg/dL.

       *  At 400 mg/week as a single agent:  100% of patients achieved targets
          for all three major risk markers and 75% achieved LDL-C levels less
          than 70 mg/dL.

       *  At 300 mg/week as a single agent:  75% of patients achieved targets
          for all three major risk markers and 63% achieved LDL-C levels less
          than 70 mg/dL.

       *  At 300 mg/week when added to moderate-dose statin therapy:  88% of
          patients achieved targets for all three major risk markers.

    *  Resulted in highly consistent and predictable responses.

    *  Was well tolerated in Phase 2 trials as monotherapy in routine high
       cholesterol patients, as an add-on to moderately-dosed statins in
       routine high cholesterol patients, and as an add-on to
       maximally-tolerated lipid-lowering therapies in HoFH.

       *  There were no liver chemistry findings that would suggest risk of
          drug-induced liver injury.

       *  All injection site reactions were mild to moderate.

       *  There was no evidence of clinically significant drug interactions or
          side effects such as central nervous system, muscle, or renal
          toxicity.

William Cromwell, M.D., Medical Director, Division of Lipoprotein Disorders, Presbyterian Center for Preventive Cardiology, Presbyterian Cardiovascular Institute, Charlotte, North Carolina, said, "These data strongly support the activity and tolerability of ISIS 301012, both as a single agent and in coadministration with statins, among patients needing substantial LDL-C lowering to reach target levels. The substantial, prolonged, dose-dependent reduction of atherogenic lipoproteins documented among a variety of hypercholesterolemic patients treated with ISIS 301012 is especially meaningful given the large number of patients who fail to achieve lipid goals with existing medical therapies. The ability to bring patients to defined lipid goals, coupled with the low risk of drug-induced adverse events seen in these trials, makes ISIS 301012 an exciting potential therapy."

Erik Stroes, M.D., Ph.D., Principal Investigator, Department of Internal Medicine, Division of Vascular Medicine, Academic Medical Center, University of Amsterdam, and study investigator, commented, "ISIS 301012 very selectively targets the production of apoB in the liver. Such a selective and potent LDL-C-lowering agent that acts through a pathway distinct from the HMG-CoA reductase pathway targeted by statins, is crucial to further optimize clinical care of hypercholesterolemia. The primary indications are obviously homozygous and severe heterozygous FH, but also having the potential to benefit from ISIS 301012 treatment are patients who experience side effects during statin therapy and High-Risk patients not reaching target LDL-C levels on routine therapy. Weekly subcutaneous dosing is easy and well tolerated by patients. The vast majority of patients who have participated in the studies are enthusiastic about ISIS 301012. We are already receiving referrals of patients seeking to be included in future studies."

Henry Ginsberg, M.D., Professor of Medicine at Columbia University in New York, noted, "The results in the homozygous FH patients are remarkable and suggest that ISIS 301012's Orphan Drug status is appropriate to enable rapid development of this promising treatment for this terrible disease. When compared with the recent studies in similar patients with a microsomal triglyceride transfer protein inhibitor, ISIS 301012 is at least as active, but has far less-concerning effects on liver enzymes."

Stanley Crooke, M.D., Ph.D., Isis' Chairman and Chief Executive Officer, added, "In the past several months, we have completed important studies in animal models that confirm ISIS 301012 has a unique therapeutic profile. We have also successfully completed long-term toxicology studies. The data we have presented at ACC underscore and expand ISIS 301012's exciting profile. We look forward to continuing to aggressively and prudently develop this potentially important new drug."

    Isis is aggressively developing ISIS 301012:

    *  Familial hypercholesterolemia pivotal studies are expected to begin in
       the 2nd half of 2007.

    *  Remaining Phase 2 studies in progress and planned:

       *  Results from the double-blind, placebo-controlled evaluation of 200
          and 300 mg/week ISIS 301012 added to statin therapy for three months
          in routine high cholesterol patients are expected to be reported in
          the 2nd half of 2007.

       *  Results from the double-blind, placebo-controlled, dose-escalation
          study of ISIS 301012 added to maximally-tolerated lipid-lowering
          therapy in heterozygous FH are expected to be reported in the 2nd
          half of 2007.

       *  Longer-term trials adding ISIS 301012 to statins in routine high
          cholesterol patients to define maintenance doses expected to be in
          the range of 100 - 200 mg/week are planned to begin in the 2nd half
          of 2007.

    *  Six-month and one-year toxicity studies in animals have been
       successfully completed.

    *  Manufacturing, formulation and analytical methods are well established.

    Webcast Information

Isis will summarize Phase 2 data for ISIS 301012 and outline development plans for the drug in an investor webcast starting at 7:00 am CT (8:00 am ET / 5:00 am PT) today. To access the webcast, visit www.isispharm.com.

About ISIS 301012 and Cholesterol

ISIS 301012 is a second-generation antisense drug that reduces the production of apoB-100, a protein critical to the synthesis and transport of "bad" cholesterol and a target that has proved to be undruggable using traditional, small-molecule approaches. Cholesterol can be carried in the bloodstream in a variety of forms, with high-density lipoprotein, or HDL-C, being the good form, and low-density lipoproteins, or LDL-C, and very low-density lipoproteins, or VLDL-C, being bad forms directly involved in heart disease. Collectively, LDL-C, VLDL-C, and other bad forms of cholesterol are referred to as "non-HDL-C." The lowering of non-HDL-C is a key component in the prevention and management of cardiovascular disease. Isis plans to develop ISIS 301012 as the drug of choice for patients who are unable to achieve target cholesterol levels with statins alone or who are intolerant of statins.

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 www.isispharm.com.

This press release includes forward-looking statements regarding the development, activity, therapeutic potential and safety of ISIS 301012 in treating high cholesterol. 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, including those statements that are described as Isis' goals or projections. 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, in developing and commercializing systems to identify infectious organisms that are effective and commercially attractive, 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, 2006, which is on file with the SEC. Copies of this and other documents are available from the Company.

SOURCE Isis Pharmaceuticals, Inc.

Kate Corcoran, Ph.D., Vice President, Corp. Development, +1-760-603-2712, or William
C. Craumer, Executive Director, Corp. Communications, +1-760-603-2773, both of Isis
Pharmaceuticals, Inc.

http://www.isispharm.com

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