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Isis Earns Milestone Payment From Lilly

CARLSBAD, Calif., Feb. 1 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals,

Inc. (Nasdaq: ISIS) announced today that Eli Lilly and Company (NYSE: LLY) has

initiated clinical trials of LY2275796 in cancer patients. LY2275796, a

second-generation antisense drug, targets eukaryotic initiation factor-4E

(eIF-4E), a protein involved in the translation of key growth and survival

factors that contribute to tumor progression and the spread of cancers.

LY2275796 was discovered in the Isis-Lilly drug discovery collaboration, and

is the second antisense drug candidate from this strategic alliance to advance

into Phase 1 development. Lilly will pay Isis $750,000 for the accomplishment

of this milestone. In addition, Lilly is funding the development of LY2275796

and will make additional payments on the achievements of certain development

and regulatory milestones, and royalties on product sales to Isis.

"Advancing our second drug into clinical trials from the Isis-Lilly

collaboration is an important milestone in the discovery and development of

novel antisense drugs to treat significant diseases," said C. Frank Bennett,

Ph.D., Senior Vice President, Antisense Research at Isis. "eIF-4E is a drug

target that oncologists believe may play a key role in initiating and

maintaining various cancers, yet considered 'undruggable' with traditional

drug discovery technologies. Our specific and potent antisense drug has the

potential to help patients suffering from cancer, including breast, head and

neck, colon, prostate, bladder, and lung cancer."

ABOUT LY2275796 AND eIF-4E

LY2275796 targets eIF-4E, a protein that is increased in a variety of

cancers, including breast, head and neck, prostate, lung, bladder, colon,

thyroid and non-Hodgkin's lymphomas. The molecule facilitates the synthesis

of tumor angiogenic factors (factors that facilitate the growth of new blood

vessels to support the development and progression of tumors), growth factors

and survival factors by selectively enhancing their translation. Based on

scientific literature, there is a strong indication that eIF-4E may act as a

critical "switch" in cancer progression.


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

12 antisense drugs in development to treat metabolic, cardiovascular, ocular

and inflammatory diseases, and cancer. In its Ibis division, Isis is

developing and commercializing the TIGER 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 http://www.isispharm.com.

This press release includes forward-looking statements regarding Isis'

collaboration with Eli Lilly and the development of LY2275796 to treat cancer.

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, 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, 2004, and its

quarterly report on Form 10-Q for the quarter ended September 30, 2005, which

are on file with the SEC. Copies of these and other documents are available

from the Company.

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