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MGL-0795 + resmetirom
- Development stage
- Preclinical
- Lead developer
- Madrigal Pharmaceuticals
- Modality
- Small Molecules, Chemically Modified siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Conjugated siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics
- Administration
- Oral
01
Overview
MGL-0795 + resmetirom is a combination therapeutic candidate being developed by Madrigal Pharmaceuticals in collaboration with Arrowhead Pharmaceuticals for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). The combination pairs MGL-0795 (also known as ARO-PNPLA3), a small interfering RNA (siRNA) that silences the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, with resmetirom, an orally active, liver-directed, selective thyroid hormone receptor-beta (THR-β) agonist. PNPLA3 mutations are a significant genetic risk factor for liver fat accumulation and progression to fibrosis, while THR-β activation improves hepatic lipid metabolism and reduces lipotoxicity. By combining these two distinct mechanisms, the therapy aims to provide a comprehensive approach to reducing liver fat, inflammation, and fibrosis in patients with MASH. The program is currently in the preclinical stage of development.
- Brand names
- Rezdiffra
- Other names
- MGL-0795/resmetirom combinationARO-PNPLA3 + resmetirom
02
Targets
THRB (Thyroid hormone receptor beta)PPARG (Peroxisome proliferator-activated receptor gamma)PNPLA3 (Patatin-like phospholipase domain-containing protein 3)THRA (Thyroid hormone receptor alpha)ASGPR (Asialoglycoprotein Receptor 1)
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