Release Details

First Oral Antisense Drug to Enter the Clinic for the Lowering of High Cholesterol

CARLSBAD, Calif., March 15 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today it has initiated a Phase I study of an oral capsule formulation of ISIS 301012, a second-generation antisense inhibitor of apoB-100, for the lowering of high cholesterol. The initiation of this trial expands the Company's clinical development program for ISIS 301012. The subcutaneous form of the drug is completing a Phase 1 study and is expected to enter Phase 2 clinical trials later this year. Data previously reported from the Phase 1 trial showed that subcutaneously administered ISIS 301012 produced rapid and prolonged reductions of its target, apoB-100, as well as low density lipid (LDL), very low density lipid (VLDL) and total cholesterol in healthy volunteers with elevated cholesterol. ApoB-100 is the sole lipoprotein of LDL cholesterol, the "bad" lipid involved in heart disease.

Goals of the oral formulation Phase 1 trial are to evaluate the oral bioavailability of ISIS 301012, and to demonstrate safety and the pharmacological effects of the drug in healthy volunteers. In the trial, volunteers will receive either oral ISIS 301012 or placebo over a one month period. In animal studies, the oral formulation of ISIS 301012 reduced apoB-100, LDL cholesterol and total cholesterol.

"This study is our first opportunity to measure drug levels in blood and look for pharmacological activity in man after oral administration. If successful, an oral formulation of ISIS 301012 would dramatically broaden the therapeutic and commercial potential of this drug," said Mark Wedel, M.D., J.D., Isis' Vice President of Development and Chief Medical Officer. "Furthermore, it will have implications not only for ISIS 301012, but for our entire second-generation pipeline. Because all of our second-generation drugs are very similar chemically, what we demonstrate for one drug can be applied to them all."

Isis' experience with oral formulation development is substantial. Previous work with oral formulations had established the feasibility of oral delivery of oligonucleotide drugs. With these studies, Isis continues to move its oral technology platform forward. Oral antisense drugs may offer patients and physicians increased convenience and enhance patient compliance, and provide the technology with a significant competitive advantage in the marketplace.

ABOUT CARDIOVASCULAR DISEASE

The American Heart Association estimates that nearly 105 million American adults have borderline high cholesterol and approximately 46.5 million have levels of 240 or above. Researchers have shown a strong correlation between high cholesterol levels and subsequent cardiovascular diseases. According to the National Institutes of Health, cardiovascular disease is the leading cause of death in the U.S.

ABOUT ISIS PHARMACEUTICALS, INC.

Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover and develop novel human therapeutic drugs for its pipeline and for its partners. The company has successfully commercialized the world's first antisense drug and has 10 antisense products in development to treat metabolic, cardiovascular and inflammatory diseases, and cancer. Through its Ibis division, Isis is developing a system to identify infectious organisms. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of more than 1,500 issued patents worldwide. Additional information about Isis is available at http://www.isispharm.com.

This press release includes forward-looking statements regarding the development, therapeutic potential and safety of the oral and subcutaneous formulations of ISIS 301012 in treating high cholesterol and cardiovascular disease. Any statement describing our 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' clinical 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 technology and systems used to identify infectious agents, and in the endeavor of building a business around such products and services. Our forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Although our forward-looking statements reflect the good faith judgement of our management, these statements can only be based on facts and factors currently known by us. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' research and development programs are described in additional detail in Isis' Annual Report on Form 10-K for the year ended December 31, 2003, and quarterly report on Form 10-Q for the quarter ended September 30, 2004, which are on file with the U.S. Securities and Exchange Commission (SEC). Copies of these and other documents are available from the company.

SOURCE Isis Pharmaceuticals, Inc.
03/15/2005
CONTACT: Claudine Prowse, Ph.D. of Isis Pharmaceuticals, Inc., +1-760-603-2331

Web site: http://www.isispharm.com
(ISIS)
03/15/2005 13:42 EST http://www.prnewswire.com