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Madrigal Pharmaceuticals, Inc., a biopharmaceutical company focused on delivering novel therapeutics for MASH, announced that it has entered into an exclusive global license agreement with CSPC Pharmaceutical Group Limited for SYH2086, a preclinical oral small molecule glucagon-like peptide-1 (GLP-1) receptor agonist and orforglipron derivative. Madrigal plans to initiate clinical development in the first half of 2026.
“We’ve made remarkable progress this year advancing our strategic priorities – from the continued successful launch of Rezdiffra, to securing new IP protection through 2044, to laying the groundwork for Rezdiffra’s next stages of growth in F4c and Europe,” said Bill Sibold, chief executive officer of Madrigal. “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. We believe a combination of Rezdiffra and SYH2086 has the potential to deliver a best-in-class oral treatment for patients with MASH.”
David Soergel, M.D., chief medical officer of Madrigal, added, “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. In the pivotal phase 3 MAESTRO-NASH trial, even modest weight loss of five percent or more enhanced Rezdiffra’s antifibrotic benefit, so we are confident that combination therapy with SYH2086 has the potential to provide increased efficacy for patients with MASH.”
“We are pleased to announce the in-license of our oral GLP-1 by Madrigal, an innovative company that pioneered the first approved treatment for MASH,” said Dongchen Cai, chairman of the Board, CSPC. “We believe Madrigal’s strong clinical development and commercial capabilities will help unlock the full potential of SYH2086 to benefit patients.”
Under the agreement, CSPC has granted Madrigal an exclusive global license to develop, manufacture, and commercialize SYH2086. CSPC will receive an upfront payment of $120 million and is eligible to receive up to $2 billion in milestone payments if certain development, regulatory and commercial milestones are achieved, as well as royalties on net sales. CSPC may develop and commercialize other oral GLP-1 agonists in China subject to certain conditions. The transaction is anticipated to close in the fourth quarter of 2025, subject to the applicable regulatory clearance.
SYH2086, a preclinical candidate developed by the CSPC with complete global intellectual property rights, is a novel oral small molecule GLP-1 receptor agonist. GLP-1 receptor agonists are a class of drugs that exert their effects through the GLP-1 receptor and have been developed as treatments for the management of type 2 diabetes and obesity. Their core mechanisms of action include enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite, thereby offering both glycaemic control and weight loss benefits. Preclinical data demonstrated that SYH2086 exhibited excellent in vitro agonistic activity as well as in vivo glucose-lowering and weight-loss effects, with a linear pharmacokinetic (PK) profile over a wide dose range across multiple animal species, with no significant safety risks observed.
Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is a serious liver disease that can progress to cirrhosis, liver failure, liver cancer, need for liver transplantation, and premature mortality. MASH is the leading cause of liver transplantation in women and the second leading cause of all liver transplantation in the US, and the fastest-growing indication for liver transplantation in Europe.
Once patients progress to MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically: these patients have a 10-17 times higher risk of liver-related mortality as compared to patients without fibrosis. Those who progress to cirrhosis face a 42 times higher risk of liver-related mortality, underscoring the need to treat MASH before complications of cirrhosis develop. MASH is also an independent driver of cardiovascular disease, the leading cause of mortality for patients.
As MASH disease awareness improves and disease prevalence increases, the number of diagnosed patients with MASH with moderate to advanced fibrosis or compensated MASH cirrhosis (F2-F4c) is expected to grow.
Madrigal Pharmaceuticals, Inc. is a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), a liver disease with high unmet medical need.
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