Eccogene, a clinical-stage biopharmaceutical company, has announced enrollment of the first patient in MOSAIC, a Phase 2a clinical trial investigating two novel oral small molecules for treating metabolic dysfunction-associated steatohepatitis (MASH). According to the AI Journal, the trial marks a significant advancement in addressing one of the most pressing chronic liver diseases affecting millions globally.
MOSAIC is evaluating ECC4703 and ECC0509 as individual monotherapies and in combination to determine their efficacy and safety in MASH patients over a 12-week treatment period. The trial’s design reflects a sophisticated understanding of MASH’s complexity, testing two distinct biological mechanisms: THR-β agonism and semicarbazide-sensitive amine oxidase (SSAO) inhibition.
The Phase 2a program, which received U.S. FDA clearance for its Investigational New Drug application, is structured as a multicenter, randomized, double-blind, placebo-controlled study enrolling approximately 160 participants with MRI-confirmed or clinically defined MASH. The trial’s primary endpoint measures change in liver fat content using MRI-PDFF, a non-invasive imaging technique providing precise quantification of hepatic steatosis.
ECC4703, an oral once-daily selective liver-targeting full agonist of the thyroid hormone receptor beta (THR-β), represents Eccogene’s lead candidate for MASH and other cardiometabolic diseases. As a full agonist, it engages THR-β with high intrinsic activity, modulating pathways critical to lipid metabolism, hepatic fat clearance, and inflammation. Phase 1 data demonstrated clear target engagement and significant reductions in LDL cholesterol and related lipid biomarkers, suggesting potential therapeutic benefit beyond simple steatosis reversal.
ECC0509, the trial’s second component, is a novel oral once-daily inhibitor of SSAO (also called vascular adhesion protein-1), engineered for high selectivity and minimal brain penetration. Phase 1 studies confirmed dose-dependent SSAO inhibition and significant changes in circulating methylamine, validating target engagement. Beyond its MASH evaluation, ECC0509 is independently being developed for osteoarthritis pain management.
Dr. Rohit Loomba, Chief of the Division of Gastroenterology and Hepatology at University of California San Diego, emphasizes MASH’s multifaceted nature: “MASH is a complex disease with metabolic, inflammatory and fibrotic components, and effective treatment will likely require addressing more than one pathway.” His observation underscores the rationale for MOSAIC’s combination-testing approach, investigating whether complementary biological mechanisms might provide synergistic benefits.
CEO Jingye Zhou highlighted the enrollment milestone’s significance: “This study supports our broader strategy to advance differentiated, next-generation oral therapies aimed at meaningfully reducing the global burden of cardiometabolic diseases.” The statement reflects Eccogene’s commitment to developing innovative treatments addressing unmet clinical needs in chronic metabolic conditions.
