Madrigal Expands MASH Pipeline with siRNA Licensing Deals from Arrowhead and Ribo

Madrigal Pharmaceuticals (Nasdaq: MDGL), a biopharma focused on metabolic dysfunction-associated steatohepatitis (MASH), has announced two exclusive global license agreements to expand its MASH pipeline with small interfering RNA (siRNA) assets. The company has licensed ARO-PNPLA3 from Arrowhead Pharmaceuticals and six preclinical siRNA programs from Suzhou Ribo Life Science and its subsidiary Ribocure Pharmaceuticals AB.

Under the agreement with Ribo, Madrigal obtained exclusive worldwide rights to develop, manufacture and commercialize the six siRNA candidates. Ribo will receive an upfront payment of $60 million and cumulative payments across the programs could reach $4.4 billion if certain milestones are achieved, as well as tiered royalties on net sales. Shares of Ribo Life edged up around 2% to HK$70.35 on the news, while Madrigal was unchanged. The collaboration will utilize Ribo's validated liver targeting siRNA GalSTAR platform, and both parties have the option to expand the scope of collaboration onto new siRNA programs including bi-specific siRNAs that target two disease-causing genes simultaneously. Madrigal anticipates submitting an investigational new drug application for each of the initial siRNA candidates to the FDA in 2026.

Separately, Madrigal announced an exclusive global license agreement with Arrowhead Pharmaceuticals for ARO-PNPLA3, a clinical-stage siRNA asset targeting patatin-like phospholipase domain-containing protein 3 (PNPLA3), a key genetic driver of MASH. siRNAs offer a precision approach to gene silencing in MASH by selectively reducing the production of disease-driving proteins.

Madrigal intends to evaluate the siRNA programs in combination with Rezdiffra, its approved therapy for MASH, to determine whether addressing disease drivers at the genetic level can enhance treatment outcomes. Rezdiffra is the first approved therapy for MASH, a once-daily, oral, liver-directed THR-β agonist, prescribed in conjunction with diet and exercise for adults with MASH with moderate-to-advanced liver fibrosis. The drug was commercially launched in the United States in April 2024 and received conditional marketing authorization in the European Union for MASH in August 2025. Madrigal is further evaluating Rezdiffra in a late-stage study for patients with compensated MASH cirrhosis (F4c).

Beyond Rezdiffra, Madrigal's pipeline includes MGL-2086, an oral GLP-1 receptor agonist, for which it anticipates initiating first-in-human studies in the second quarter of 2026, and ervogastat, a phase II oral DGAT-2 inhibitor acquired from Pfizer in January. The company plans to conduct a drug-to-drug interaction study with Rezdiffra and consult the FDA on designing a phase II combination study for MASH patients this year. Over the past year, shares of Madrigal have risen 36.8% compared with the industry's 2.8% growth.