Drug intelligence / Profile preview

siRNA + 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, Subcutaneous
01

Overview

The siRNA + resmetirom combination refers to a suite of six preclinical programs developed by Madrigal Pharmaceuticals for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). These programs, in-licensed from Suzhou Ribo Life Science and Ribocure Pharmaceuticals in February 2026, utilize a dual-mechanism approach: liver-directed small interfering RNA (siRNA) agents designed to silence specific disease-driving proteins (leveraging Ribo's GalSTAR platform) and resmetirom (Rezdiffra), an oral, liver-directed thyroid hormone receptor-beta (THR-β) agonist. While resmetirom is already FDA-approved as a monotherapy, these combinations aim to provide synergistic therapeutic effects by targeting multiple pathways in MASH pathology, such as PNPLA3 silencing in the case of the MGL-0795 program. IND-enabling activities for these programs are expected to begin in 2026.

Other names
siRNA/resmetirom combinationsMadrigal Mentalis siRNA programsMadrigal Mentalis pipeline programs
02

Targets

THRA (Thyroid hormone receptor alpha)THRB (Thyroid hormone receptor beta)

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