Liver disease

Liver disease

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 [1].

Liver diseases, including liver fibrosis or cirrhosis, are a global health burden [2]. 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 [5].

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.

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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.

Galecto, Inc. develops small molecules for the treatment of severe diseases, including fibrosis and cancer. The company, founded in 2011, builds on more than 10 years of research centering on the role of galectin-3 and LOXL-2, and the use of modulators of these proteins to treat fibrosis-related diseases and cancer. Combined with a strong patent estate, these assets give Galecto a unique therapeutic platform.

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