Isis Pharmaceuticals CEO's letter to shareholders

Dear Isis Supporters and Shareholders,

I would like to start by thanking you for your continuing support of Isis. We believe we are at one of the most successful moments in our history. We are truly at the end of the beginning of creating a unique company with a novel drug discovery platform, which we believe addresses many of the issues haunting the pharmaceutical industry.

Our progress is predicated largely upon the success of our flagship drug, mipomersen. Mipomersen continues to perform well and progress toward commercialization. Isis, our investigators and members of the medical community are very encouraged by the results that were presented at the AHA last week. To get a sense of their support of the drug, I would encourage you to listen to the replay of the mipomersen investigator panel presentation that was conducted during AHA last week. I think you will hear not only their enthusiasm for the drug but their hope that mipomersen will provide a new treatment alternative for their patients at very high risk of cardiovascular disease.

We are disappointed with the reaction on Wall Street to what we believe is very positive news. We believe mipomersen will continue to provide results that speak for themselves. Each success brings us closer to getting mipomersen to the market and making the drug available to patients in need.

Our antisense technology provides a direct route from genes to drugs with the opportunity to dramatically improve the productivity of the pharmaceutical industry. With 19 drugs in development, we have one of the largest and most diverse pipelines in our industry. We know that sick people depend on us. We continue to strive for excellence as we create drugs for the future. We also recognize that behind our successes is the support we receive from you. I would like to personally thank you for that.

Sincerely,

Stanley T. Crooke

Isis Chairman and Chief Executive Officer

SOURCE Isis Pharmaceuticals, Inc.