|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 fatty liver disease and non-alcoholic steatohepatitis (NASH), 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. |
In addition, MGL-3196 is a NASH target supported by compelling human biology and genetics. NASH is a serious liver disease found in individuals with fatty liver disease that is associated with hypothyroidism, diabetes, obesity, and dyslipidemia. MGL-3196 Phase 1 human data demonstrate safety and benefit in NASH-related dyslipidemia, and data from MGL-3196 treated NASH animal models support efficacy in NASH at doses relevant to humans.