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Severe hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood which is known to increase the risk of coronary artery disease, the leading cause of death in the U.S. Most forms of hypercholesterolemia can be treated through dietary restrictions and medicines such as statins. However, a large proportion of patients with hypercholesterolemia are not being met by statin therapy including genetic familial hypercholesterolemia patients, acute coronary syndrome patients, and other patient populations that are statin intolerant or statin resistant; severe hypercholesterolemia is estimated to affect more than 500,000 patients worldwide. As a result, there is a significant need for novel therapeutics to treat patients with severe hypercholesterolemia whose disease is inadequately managed by existing therapies.