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].

The global burden of these diseases, including alcohol-associated cirrhosis, non-alcoholic steatohepatitis (NASH) cirrhosis, and liver cancers, is immense [2, 3, 4], and there are no approved treatments. The overall survival for patients with decompensated cirrhosis is poor, with a median survival of approximately 2 years [5].

The only intervention/treatment available is liver transplantation. We believe that our expertise in galectin biology can bring substantial improvements to the treatment landscape of these liver diseases.

Galectin-3 is elevated in alcoholic and non-alcoholic cirrhosis as well as in alcoholic hepatitis. Moreover, galectin-3 have been demonstrated to be a prognostic biomarker of hepatocellular carcinoma (a complication of 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 [6–9].

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.

Galecto, Inc. develops small molecules for the treatment of cancer and severe liver diseases. The company is built on nearly 15 years of research centering on the role of galectin-3 and the use of modulators of these proteins to treat cancer and severe liver diseases. These assets, combined with BRM-1420, a novel dual ENL-YEATS / FLT3 inhibitor, provide Galecto with a unique therapeutic platform.

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