Galecto is developing GB1211 as a potential treatment for patients with severe liver diseases. GB1211 is an orally bioavailable first-in-class, potent and high-affinity small molecule galectin-3 inhibitor, which has demonstrated antifibrotic activity in preclinical therapeutic liver disease models .
Liver diseases, including liver fibrosis or cirrhosis, are a global health burden . Cirrhosis – primarily caused by non-alcoholic steatohepatitis, alcoholic liver disease and hepatitis – is the end stage of progressive liver fibrosis and the leading cause of liver-related death globally [3,4]. The overall survival for patients with decompensated cirrhosis is poor, with a median survival of approximately 2 years .
Galectin-3 is elevated in alcoholic and non-alcoholic cirrhosis and in toxic hepatitis, and is a prognostic biomarker of hepatocellular carcinoma (a complication of liver cirrhosis). Additionally, galectin-3 is essential for TFG-β-mediated myofibroblast activation and matrix production in liver fibrosis and linked to hepatocyte senescence and stellate cell activation. Evidence has shown that galectin-3 inhibition reduces liver cell damage in a number of preclinical models [6–10].
We believe galectin-3 inhibition using GB1211 could be a meaningful intervention in severe liver disease.
- Zetterberg FR, MacKinnon A, Brimert T et al. Discovery and Optimization of the First Highly Effective and Orally Available Galectin‑3 Inhibitors for Treatment of Fibrotic Disease. J Med Chem 2022; 65: 12626–12638.
- An Y, Xu S, Liu Y et al. Role of Galectins in the Liver Diseases: A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8: 744518.
- Roth GA, Abate D, Abate KH et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1736–88.
- Anthony PP, Ishak KG, Nayak NC et al. The morphology of cirrhosis. Recommendations on definition, nomenclature, and classification by a working group sponsored by the World Health Organization. J Clin Pathol 1978; 31: 395–414.
- D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. J Hep 2006; 44: 217–31.
- Hsieh WC, MacKinnon AC, Lu WY et al. Galectin-3 regulates hepatic progenitor cell expansion during liver injury. Gut 2015;64(2):312–21.
- Dragomir AC, Sun R, Mishin V et al. Role of galectin-3 in acetaminophen-induced hepatotoxicity and inflammatory mediator production. Toxicol Sci2012; 127(2):609–19.
- Volarevic V, Milovanovic M, Ljujic B et al. Galectin-3 deficiency prevents concanavalin A-induced hepatitis in mice. Hepatology 2012; 55(6):1954–64.
- Yang F, Zhang F, Ji X et al. Secretory galectin-3 induced by glucocorticoid stress triggers stemness exhaustion of hepatic progenitor cells. J Biol Chem2020;295(49):16852–62.
- Jeftic I, Jovicic N, Pantic J et al. Galectin-3 Ablation Enhances Liver Steatosis, but Attenuates Inflammation and IL-33-Dependent Fibrosis in Obesogenic Mouse Model of Nonalcoholic Steatohepatitis. Mol Med 2015;21(1):453–65.