17-β-Hydroxysteroid dehydrogenase 13 (HSD17B13) and lipid transferase CIDEB are known to contribute to metabolic dysfunction-associated steatohepatitis (MASH) progression, where HSD17B13 exacerbates hepatic lipid metabolism, while CIDEB mainly mediates lipid droplet dynamics and storage. In this context, Frontier Biotechnologies Inc. has presented data on FB-7033, a bispecific siRNA approach targeting both HSD17B13 and CIDEB for the management of MASH.

Neurotensin receptor 1 (NTSR1) is overexpressed in several aggressive solid tumors, including colorectal and pancreatic cancer, making it a promising therapeutic target. SKL-35501 is a novel 225Ac-labeled radiopharmaceutical developed by SK Biopharmaceuticals Co. Ltd. that targets NTSR1 for α-particle therapy.

At the recent meeting of the Society of Nuclear Medicine and Molecular Imaging, researchers from Actinium Pharmaceuticals Inc. presented preclinical efficacy data on ATNM-400 in models of non-small-cell lung cancer (NSCLC).

Transforming growth factor-β-activated kinase 1 (TAK1) is a crucial central signaling molecule of hepatic cell death, inflammation and fibrogenesis through NF-κB and MAPK in metabolic dysfunction-associated steatotic liver disease (MASLD). Its pharmacological inhibition using the TAK1 inhibitor HS-276 was tested in vivo in a murine model of diet-induced MASLD.

There is a growing consensus that alcohol-related liver disease (ALD) should be considered a metabolic disorder under the influence of the gut-liver axis. Metabolome data have highlighted fatty acid-activated G protein-coupled receptors (GPCRs) as the main affected pathways, where the relationship of G-protein-coupled receptor 119 (GPR119) with ALD remains unexplored.

Adipose triglyceride lipase (ATGL), a central mediator of triglyceride hydrolysis and fatty acid mobilization, modulates hepatic lipid homeostasis and metabolic signaling pathways that contribute to the activation of fibrogenic responses.

Alterations in PNPLA3, particularly the I148M variant, impair lipid metabolism in hepatocytes, leading to lipid accumulation and driving progression from steatosis to fibrosis and cirrhosis. Targeting this genetic driver may offer a strategy to reduce steatosis and limit disease progression.

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by lipid accumulation in the liver and inflammation. Sterol O-acyltransferase 2 (SOAT2) is a key enzyme in intestinal absorption and hepatic secretion of cholesterol. PRD Therapeutics Inc. has developed PRD-001, a selective SOAT2 inhibitor currently in phase I trials for MASH.

Several presentations at EASL highlight a new generation of therapies coming into view, with the work from Tune Therapeutics Inc. standing out as one of the most relevant for the novelty it represents and the step forward it signals. The company is investigating the use of TUNE-401 as a potential treatment for hepatitis B.