ISIS Pharmaceuticals Promoted to the Large-Cap Russell 1000 Index

CARLSBAD, Calif.,June 29, 2015/PRNewswire/ -- Isis Pharmaceuticals, Inc. (NASDAQ:ISIS) announced today that it has been added to the Russell 1000 Index, effectiveJune 26, 2015. The Russell 1000 Index measures the performance of the large-cap segment of the U.S. equity universe. It is a subset of the Russell 3000 Index and includes approximately 1000 of the largest securities based on a combination of their market cap and current index membership.

"We are pleased to be added to this important index, which helps to raise awareness of our company even more broadly among investors," saidB. Lynne Parshall, chief operating officer at Isis Pharmaceuticals. "Our promotion to the Russell 1000 index is a reflection of the substantial growth in Isis' valuation, the positive results achieved with our pipeline of antisense drugs and the success of our business strategy."

Russell Indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. The Russell 1000 Index is constructed to provide a comprehensive and unbiased barometer for the large-cap segment. The Russell 1000 represents approximately 92% of the U.S. market. All Russell indices are reconstituted on an annual basis to ensure new and growing equities are reflected accurately in each index.

Isis is exploiting its leadership position in RNA-targeted technology to discover and develop novel drugs for its product pipeline and for its partners.  Isis' broad pipeline consists of 38 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic, severe and rare diseases, including neurological disorders, and cancer.  Isis' partner, Genzyme, is commercializing Isis' lead product, KYNAMRO®, inthe United Statesand other countries for the treatment of patients with homozygous FH.  Isis has numerous drugs in Phase 3 development in severe/rare diseases and cardiovascular diseases.  These include volanesorsen, a drug Isis is developing and plans to commercialize through its wholly owned subsidiary, Akcea Therapeutics, to treat patients with familial chylomicronemia syndrome and familial partial lipodystrophy; ISIS-TTRRx, a drug Isis is developing with GSK to treat patients with the polyneuropathy and cardiomyopathy forms of TTR amyloidosis; and ISIS-SMNRx, a drug Isis is developing with Biogen to treat infants and children with spinal muscular atrophy, a severe and rare neuromuscular disease.  Isis' patents provide strong and extensive protection for its drugs and technology.  Additional information about Isis is available atwww.isispharm.com.

This press release includes forward-looking statements regarding Isis Pharmaceuticals' financial position and outlook, Isis' business, and the therapeutic and commercial potential of Isis' technologies and products, including KYNAMRO, volanesorsen, ISIS-SMNRxand ISIS-TTRRx,in development. 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 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 endedDecember 31, 2014, 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.

Isis Pharmaceuticals®is a registered trademark of Isis Pharmaceuticals, Inc.  Akcea Therapeutics™ is a trademark of Isis Pharmaceuticals, Inc.  KYNAMRO®is a registered trademark of Genzyme Corporation.