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Vupanorsen

Generation 2+ LICA antisense drug

Vupanorsen, formerly known as AKCEA-ANGPTL3-LRx, is a Generation 2+ ligand-conjugated antisense (LICA) drug designed to reduce angiopoietin-like 3 protein, or ANGPTL3. Human genetic studies have shown that lower levels of ANGPTL3 are associated with lower plasma triglyceride (TG) and LDL-C and protection against certain cardiovascular diseases1-3. Studies in animals have demonstrated that targeted reduction of ANGPTL3 with antisense drugs results in substantially decreased TG and LDL-C4. A large number of patients with elevated risk of cardiovascular disease are not reaching recommended TG and LDL-C goals. Vupanorsen is being developed to reduce plasma levels of ANGPTL3 with the goal of lowering levels of plasma TG and LDL-C to potentially reduce the risk of future cardiovascular events.

About ANGPTL3 and Cardiovascular Disease
Angiopoietin-like-3, or ANGPTL3, is a well-established regulator of the blood lipids LDL-C and triglycerides. ANGTPL3 has also been identified as an important factor in cardiovascular disease (CVD). Studies have shown that people with a loss of function (LOF) mutations and/or decreased ANGPLT3 plasma levels have reduced risk for CVD. For example, genomic analysis of over 180,000 individuals with genetic variations that cause a LOF in ANGPTL3 demonstrated a 34% reduction in risk of coronary heart disease among carriers of ANGPTL3 LOF mutations1. In addition, circulating ANGPTL3 concentrations were found to be lower in healthy control subjects than in those who have had heart attacks. Additionally, individuals with complete ANGPTL3 deficiency showed no evidence of atherosclerosis relative to control subjects who had a mean total atherosclerotic plaque burden of about 39%. Thus, treatment to lower ANGPTL3 plasma levels could be an important advance in cardiovascular therapy for individuals at risk for ischemic heart disease who have elevated LDL-C and plasma triglycerides, which usually reflects elevated plasma remnant cholesterol.