Madrigal Pharmaceuticals has entered into a preclinical collaboration with Suzhou Ribo Life Science and its subsidiary Ribocure Pharmaceuticals to develop six small interfering RNA (siRNA) programs focused on liver diseases. The agreement includes a $60 million upfront payment from Madrigal, with the potential for up to $4.4 billion in milestone payments across the programs, in addition to royalties on net sales.
The partnership is intended to advance investigational siRNA therapies targeting metabolic dysfunction-associated steatohepatitis (MASH). Madrigal plans to evaluate these candidates in combination with its approved MASH therapy, Rezdiffra. The company expects to begin investigational new drug (IND)-enabling activities for initial candidates from the Ribo collaboration in 2026.
SiRNAs are short, non-coding RNA molecules that bind to a target messenger RNA (mRNA), preventing its translation into protein. According to Madrigal, this approach enables precise gene silencing in the liver, where multiple genes have been implicated in MASH.
Chief Medical Officer David Soergel stated in a company release, “SiRNAs are highly liver targeted, and there are several genes implicated in MASH that could be addressed with an mRNA-knockdown approach.” He added that combining this method with Rezdiffra has the potential to create the next generation of MASH treatment.
Madrigal did not disclose specific preclinical data for siRNA candidates. The company also did not identify the genes to be targeted or the disease pathways involved. However, it noted that, following the Ribo agreement, its MASH portfolio includes more than 10 molecules addressing different drivers of the disease.
Rezdiffra, a thyroid hormone receptor-beta (THR-beta) agonist, received U.S. Food and Drug Administration approval in March 2024 as the first therapy authorized for MASH. Since approval, Madrigal has continued clinical development of the drug, which is currently being evaluated in a late-stage study for compensated MASH cirrhosis. According to the company’s third-quarter 2025 presentation, data from that trial are expected in 2027.
Commercial performance of Rezdiffra has increased since its launch. In 2024, the drug was used in more than 11,800 patients and generated $180.1 million in net sales. In the third quarter of 2025, net revenue reached $287.3 million, compared to $62.2 million during the same period the previous year. Madrigal is scheduled to report its full-year 2025 earnings on Feb. 19 and has stated that it expects full-year 2025 sales to exceed $1 billion.
The Ribo collaboration follows other recent transactions aimed at broadening Madrigal’s MASH pipeline. Last month, the company licensed Pfizer’s DGAT2 inhibitor, ervogastat, for $50 million upfront. The oral therapy is in mid-stage development for MASH, and Pfizer may receive additional milestone payments under that agreement. In July 2025, Madrigal paid $120 million to China’s CSPC Pharmaceutical for a preclinical GLP-1 receptor agonist, with plans to pair the asset with Rezdiffra.
CEO Bill Sibold commented that at the start of 2025, Madrigal was a single-product company launching the first medication for MASH and that the company now has Rezdiffra as its foundational therapy, along with a pipeline of more than 10 programs targeting different drivers of the disease.
Madrigal Expands MASH Pipeline with Major Ribo siRNA Deal
Madrigal has significantly expanded its metabolic dysfunction-associated steatohepatitis (MASH) pipeline by entering into an exclusive global licensing agreement with Ribo for six preclinical small interfering RNA (siRNA) programs aimed at liver disease. Under the terms of the deal, Madrigal will pay Ribo a $60 million upfront fee, with the potential for cumulative milestone payments of up to $4.4 billion if certain development, regulatory, and commercial targets are met. The agreement also includes royalties on future sales.
The six siRNA candidates from Ribo leverage its GalSTAR™ liver-targeting platform, designed to deliver precision gene silencing aimed at key drivers of MASH. These gene-silencing therapies complement existing and emerging modalities in Madrigal’s pipeline, which now exceeds ten distinct programs focused on treating various aspects of MASH progression.
This Ribo siRNA deal positions Madrigal to broaden beyond its foundational therapy, Rezdiffra, by incorporating RNA interference strategies that may enhance therapeutic combinations. Madrigal plans to initiate IND-enabling activities for the initial siRNA candidates in 2026 and expects this gene-silencing approach to inform next-generation treatment regimens for MASH.
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
- Editorial Team
