Madrigal Secures Global Rights To Six siRNA Programs To Advance Genetic Therapies In MASH, Expands With $4.4B siRNA Licensing Deal From RiboLife Science

Madrigal Pharmaceuticals has entered into an exclusive global license agreement with Suzhou Ribo Life Science and its subsidiary Ribocure Pharmaceuticals for six preclinical small interfering RNA (siRNA) programs targeting metabolic dysfunction-associated steatohepatitis (MASH). The deal strengthens Madrigal’s growing pipeline in liver disease by adding genetically targeted therapies designed to silence key disease-driving proteins. Ribo will receive $60 million upfront, with the potential to earn up to $4.4 billion in milestone payments, along with royalties on future net sales.

“We believe meeting future patient needs in MASH will require combination approaches and treatments tailored to genetic drivers of disease. Madrigal is uniquely positioned to shape the future treatment landscape in this rapidly expanding market,” said Bill Sibold, Chief Executive Officer of Madrigal. “At the start of 2025, Madrigal was a single-product company launching the first medication for MASH. Today, we have the foundational therapy in Rezdiffra, a fully enrolled F4c outcomes study, and an industry-leading MASH pipeline with more than 10 programs targeting different drivers of the disease.”

siRNA therapies work by selectively degrading messenger RNA (mRNA), thereby reducing the production of proteins linked to disease progression. When conjugated with a GalNAc ligand, these molecules are delivered directly into liver cells (hepatocytes), enabling targeted gene silencing. Madrigal plans to explore combining this precision genetic approach with its approved therapy, Rezdiffra, to determine whether dual targeting of metabolic and genetic drivers can enhance treatment outcomes. IND-enabling activities for the initial candidates are expected to begin in 2026.

“Our R&D strategy is focused on developing innovative compounds targeting validated mechanisms of disease, so we can deliver better outcomes for more patients with MASH,” said David Soergel, M.D., Chief Medical Officer of Madrigal. “siRNAs are highly liver targeted, and there are several genes implicated in MASH that could be addressed with an mRNA-knockdown approach. The precision of siRNA gene silencing, combined with Rezdiffra, has the potential to create the next generation of MASH treatment: genetically targeted therapies for patients with unmet needs.”

The agreement complements Madrigal’s broader MASH portfolio. The company is currently running a fully enrolled Phase 3 trial of Rezdiffra in patients with compensated MASH cirrhosis (F4c). Its pipeline also includes MGL-2086, an oral GLP-1 receptor agonist entering first-in-human studies in Q2 2026, and ervogastat, a Phase 2 oral DGAT-2 inhibitor, for which Madrigal plans to conduct a drug-drug interaction study with Rezdiffra and discuss a Phase 2 combination trial design with the FDA this year. Together, these programs position Madrigal to expand its leadership in MASH through both metabolic and gene-targeted therapeutic strategies.