Isis Reports New Data for Mipomersen in Routine High Cholesterol Patients and Provides Cumulative Safe...(ects with ALT elevations on-treatment or...),Health

following the last study dose

Max ALT** Placebo 30/50 100 200 >=300

mg/week mg/week mg/week mg/week

(N=40) (N=35) (N=35) (N=87) (N=106)

150-250 5% 9% 0% 7% 14%

IU/L

(3xULN-

5xULN***)

>250 IU/L 0% 0% 0% 1% 4%

(>5xULN***)

** Each subject is counted only once at maximum ALT reading

*** ULN is defined to be 50 IU/L

About Mipomersen and Cholesterol

Mipomersen, formerly ISIS 301012, is a second-generation antisense drug that reduces the production of apoB-100, a protein critical to the synthesis and transport of "bad" cholesterol and a target that has proved to be undruggable using traditional, small-molecule approaches. Cholesterol can be carried in the bloodstream in a variety of forms, with high-density lipoprotein, or HDL-C, being the good form, and low-density lipoproteins, or LDL-C, and very low-density lipoproteins, or VLDL-C, being bad forms directly involved in heart disease. Collectively, LDL-C, VLDL-C, and other bad forms of cholesterol are referred to as "non-HDL-C." The lowering of non-HDL-C is a key component in the prevention and management of cardiovascular disease. Isis plans to develop mipomersen as the drug of choice for patients who are unable to achieve target cholesterol levels with statins alone or who are intolerant of statins. Isis is developing mipomersen at a dose of 200 mg/week in its ongoing and future studies.

Analyst & Investor Day Information

At 9:00 a.m. Eastern Standard Time Tuesday, November 13, Isis will conduct a live webcast presentation of its Analyst & Investor Day. Interested parties may access the webcast at http://www.isispharm.com. A replay
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