Isis Initiates Clinical Trial of CRP Drug

   Reduction of CRP with ISIS 353512 could provide therapeutic benefit in

              cardiovascular, renal and inflammatory diseases



    CARLSBAD, Calif., Aug. 13 /EMWNews/ -- Isis

Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today it has initiated a

Phase 1 study of ISIS 353512, an antisense drug that inhibits the

production of C-reactive protein (CRP). CRP levels are frequently elevated

in patients with a variety of diseases including cardiovascular disease,

Crohn's disease, rheumatoid arthritis and end-stage renal disease. The

Phase 1 study of ISIS 353512 is a blinded, randomized, placebo-controlled,

dose-escalation study designed to assess the safety and pharmacokinetic

profile of ISIS 353512 as well as to assess the initial effects of the drug

on baseline CRP levels in healthy volunteers. In addition, Isis is

designing a broad Phase 2 program to investigate multiple indications for

ISIS 353512.



    "We believe that CRP plays an important causal role not only in

cardiovascular disease but also in renal and inflammatory diseases. Based

on our preclinical data, and the safety and pharmacological data we will

obtain from this study, we plan to create a Phase 2 development plan that

evaluates several of the most scientifically and commercially attractive

indications for ISIS 353512," said Stanley Crooke, Chairman and Chief

Executive Officer of Isis. "CRP is an excellent example of the power of our

technology which enables us to efficiently develop drugs to any target and

to select targets that provide the most significant therapeutic benefit in

disease areas where new treatment options are desperately needed."



    ISIS 353512 Targets CRP



    ISIS 353512 is an antisense drug that targets CRP. For many years, CRP

has been used as a clinical biomarker of diseases with an inflammatory

component, such as cardiovascular disease, Crohn's disease, rheumatoid

arthritis and end-stage renal disease. Elevated levels of CRP have been

linked to coronary artery disease and a growing body of evidence from

clinical trials implicates CRP in cardiovascular disease progression.

Although CRP's active participation in these diseases remains to be

determined, several lines of evidence support a causal role of CRP in

disease, suggesting that it may be therapeutically beneficial to decrease

CRP levels in patients who are at risk for coronary events. In addition,

elevated CRP levels have been associated with a worsening of overall

outcome in conditions such as end-stage renal disease, suggesting that

lowering CRP in these patients would be beneficial. In preclinical studies,

ISIS 353512 produced dramatic suppression of liver and serum CRP levels.



    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 18

drugs in development. Isis' drug development programs are focused on

treating cardiovascular and metabolic diseases. Isis' partners are

developing antisense drugs invented by Isis to treat a wide variety of

diseases. Ibis Biosciences, Inc., Isis' majority-owned subsidiary, is

developing and commercializing the Ibis T5000(TM) Biosensor System, a

revolutionary system to identify infectious organisms. Isis is a joint

owner of Regulus Therapeutics LLC, a joint venture focused on the

discovery, development and commercialization of microRNA therapeutics. 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 http://www.isispharm.com.



    This press release includes forward-looking statements regarding Isis'

discovery and development of drugs for cardiovascular diseases, and the

potential of the antisense drug ISIS 353512 to treat cardiovascular, renal

and inflammatory diseases. 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. 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, 2007, and its quarterly report on

Form 10-Q for the quarter ended June 30, 2008, 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.



    Isis Pharmaceuticals is a registered trademark of Isis Pharmaceuticals,

Inc. Ibis Biosciences and Ibis T5000 are trademarks of Ibis Biosciences,

Inc. Regulus Therapeutics is a trademark of Regulus Therapeutics LLC.