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Study Presented at ACC Shows Treatment With ISIS 301012 Added to,Statins for Only 5 Weeks Results in 75% of Patients Achieving LDL-C,Levels Less Than 100 mg/dL and 50% of Patients Achieving LDL-C,Levels of Less Than 70 mg/dL

l session, results of an ongoing trial of ISIS 301012 added to maximal lipid lowering therapies in homozygous familial hypercholesterolemia (FH) patients were reported. Results of polygenic hypercholesterolemic patients treated with up to 400 mg/week of ISIS 301012 for up to three months as a single agent are the subject of a v-cast poster presentation. Results for the extended three-month treatment cohorts at 200 and 300 mg/week doses in the statin coadministration study are expected later in the year. Also later in the year, results from an ongoing double-blind, placebo-controlled, dose-escalation study in patients with heterozygous FH will be reported.

ISIS 301012 has been granted orphan drug status for the treatment of homozygous FH and Isis plans to begin registration-directed studies for FH in 2007.

About ISIS 301012 and Cholesterol

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 ISIS 301012 as the drug of choice for patients who are unable to achieve target cholesterol levels with statins alone or who are intolerant of statins.

Adult Treatment Panel III Recommendations

The National Cholesterol Education Program's Adult Treatment Panel III guidelines for target LDL-C levels High-Risk patients is less than 100 mg/dL, with an optional target
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