Isis Pharmaceuticals Receives $75 Million Equity Financing Commitment

CARLSBAD, California, May 30, 2006 (PRNewswire-FirstCall) – Isis Pharmaceuticals, Inc. (Nasdaq: ISIS – News), announced today that it has received a commitment for up to $75 million in common stock equity financing from Azimuth Opportunity Ltd. Over the next 18 months, Isis Pharmaceuticals may at its discretion, from time to time, sell registered shares of its common stock at a small discount to the market price to Azimuth Opportunity. Acqua Capital is an advisor to Azimuth Opportunity.

Isis will use the net proceeds from the sale of the securities for research, drug discovery and development activities, capital expenditures and other general corporate purposes, including advancing ISIS 113715 for the treatment of type 2 diabetes and two preclinical drugs in development into clinical trials: ISIS 369645 for the treatment of asthma and ISIS 353512 for the treatment of cardiovascular disease and inflammation. In addition, these funds will be used to accelerate the commercialization of Isis’ IBIS biosensor system, the IBIS T-5000.

The shares of common stock are being offered pursuant to an effective registration statement filed with the SEC on December 22, 2005. This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any state.

Conference Call Information

Isis will conduct a live webcast conference call to discuss this press release on Wednesday, May 31 at 8:30 am Eastern time. To participate over the Internet go to http://www.videonewswire.com/event.asp?id=34158 or http://www.isispharm.com. A replay of the webcast will be available at these addresses for a limited time.

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 15 drugs in development. Isis’ drug development programs are aimed at treating cardiovascular, metabolic and inflammatory diseases. Isis’ partners are focused in disease areas such as inflammatory, ocular, viral and neurodegenerative diseases, and cancer. In its Ibis division, Isis is developing and commercializing the IBIS 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 approximately 1,500 issued patents worldwide. Additional information about Isis is available at www.isispharm.com.

This press release includes forward-looking statements regarding Isis Pharmaceuticals’ business. Any statement describing Isis’ goals, expectations, 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, 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, 2005, and its quarterly report on Form 10-Q for the quarter ended March 31, 2006, which are on file with the U.S. Securities and Exchange Commission (SEC). Copies of these and other documents are available from the Company.