Madrigal Pharmaceuticals is developing novel, high-quality small-molecule drugs addressing major unmet needs in cardiovascular and metabolic diseases. The Company is targeting treatment of both niche and prevalent indications, including diabetes, dyslipidemia and cardiovascular disease. Madrigal’s lead drug candidate is MGL-3196, a Phase 2 ready orally administered liver-directed thyroid hormone receptor-ß (THR-ß) agonist. In Madrigal’s 14-day multiple dose Phase 1 study in healthy volunteers with mildly elevated LDL cholesterol, MGL-3196 demonstrated safety and excellent tolerability at all doses tested. In the multiple dose study, MGL-3196 demonstrated proof-of-concept for lipid lowering including dose-dependent, highly significant, up to 30% lowering of LDL cholesterol and non-HDL cholesterol, and a strong trend of up to 60% triglyceride lowering. These results suggest that MGL-3196 has a unique lipid lowering profile as compared with other agents and a potential to significantly reduce cholesterol, triglycerides and liver triglycerides. Elevated cholesterol, triglycerides and fatty liver are an underlying cause of many metabolic and cardiovascular diseases, which, themselves, are associated with increased mortality.

Madrigal is also developing a Diacylglycerol Acyltransferase 1 (DGAT1) inhibitor for diabetes, a target with potential additional application in weight control and dyslipidemia.