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ION449

Chemistry: Generation 2.5 LICA

ION449 (formerly IONIS-AZ4-2.5-LRx), also known as AZD8233, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is integrally involved in the regulation of LDL-cholesterol. Genetic studies have shown that individuals with life-long reduction of LDL-C due to reduced function of PCSK9 have substantially reduced risk of cardiovascular disease. Pharmacological inhibition of PCSK9 substantially lowers LDL-C. ION449 is designed to reduce the liver production of PCSK9 and lower the plasma level of LDL-C and thus reduce the risk of cardiovascular disease.

About Cardiovascular Disease
Elevated levels of LDL-C are a key risk factor in the development of cardiovascular disease, including heart attack, stroke and peripheral arterial disease. Higher levels of LDL-C in the blood are directly related to greater risk of vascular disease, while reduction of LDL-C leads to a significant decrease in risk. Despite the presence of several lipid-lowering agents, many patients are unable to achieve recommended LDL-C levels and remain at increased risk for cardiovascular disease. The development of additional, highly potent LDL-C lowering drugs can address this persistent unmet need.