Madrigal Pharmaceuticals has entered into a licensing agreement with CSPC Pharmaceutical Group for SYH2086, a preclinical oral GLP-1 receptor agonist. The deal includes an upfront payment of $120 million to CSPC and could total more than $2 billion if development, regulatory, and commercial milestones are achieved. CSPC will also receive royalties on net sales.
SYH2086 was developed by CSPC in China and is currently in laboratory testing. According to Madrigal’s July 30 statement, preclinical data show that SYH2086 has “exhibited excellent in vitro agonistic activity as well as in vivo glucose-lowering and weight-loss effects, with a linear pharmacokinetic profile over a wide dose range across multiple animal species, with no significant safety risks observed.”
Madrigal plans to combine SYH2086 with Rezdiffra, its selective thyroid hormone receptor agonist, which is the only U.S. Food and Drug Administration-approved treatment for metabolic dysfunction-associated steatohepatitis (MASH) with moderate-to-advanced liver fibrosis. Rezdiffra was approved in 2023 and brought in $137 million in revenue during the first quarter of 2025.
Madrigal’s Chief Medical Officer, David Soergel, M.D., stated, “The clinical rationale for developing a combination therapy with Rezdiffra and an oral GLP-1 is clear: we want to optimize efficacy and tolerability in MASH by balancing the weight loss from a GLP-1 with the fibrosis and lipid reduction of Rezdiffra in a once-a-day pill.” He also noted that weight reduction of 5% or more enhanced the antifibrotic benefit of Rezdiffra in the phase 3 Maestro-NASH trial and said the company is confident that combining Rezdiffra with SYH2086 has the potential to improve outcomes for patients with MASH.
Under the terms of the agreement, Madrigal will obtain exclusive global rights to SYH2086. CSPC will retain the ability to develop and commercialize other oral GLP-1 compounds within China.
Madrigal CEO Bill Sibold said, “This agreement to acquire global rights to SYH2086 aligns perfectly with our long-term goal to extend our leadership in MASH by building a pipeline anchored by Rezdiffra.” He added that the company sees the combination of Rezdiffra and SYH2086 as having the potential to become a leading oral treatment option for MASH.
Rezdiffra may face future competition from other GLP-1 agonists, including semaglutide, the active ingredient in Novo Nordisk’s Wegovy. Semaglutide demonstrated results in a phase 3 MASH trial earlier in 2025.
During Madrigal’s first-quarter earnings call in May, Sibold mentioned that approximately 25% of Rezdiffra users are also taking a GLP-1 therapy. He noted that the presence of semaglutide in the MASH space is expected to increase diagnosis rates and could contribute to market expansion, which may also support Madrigal’s position.
Other companies have also expressed interest in CSPC’s development programs. In June, AstraZeneca provided CSPC with $110 million in upfront funding for a collaboration focused on discovering oral therapies for chronic diseases.