ARO-033

ARO-033 is an investigational RNA interference (RNAi) therapeutic developed by Arrowhead Pharmaceuticals for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Utilizing Arrowhead's proprietary Targeted RNAi Molecule (TRiM) platform, ARO-033 consists of a small interfering RNA (siRNA) conjugated to a GalNAc ligand, which facilitates targeted delivery to hepatocytes via the asialoglycoprotein receptor. The drug is designed to silence the expression of the **HSD17B13** (Hydroxysteroid 17-Beta Dehydrogenase 13) gene in the liver. Genetic studies have identified that loss-of-function variants in HSD17B13 are associated with a reduced risk of progressing from simple steatosis to more advanced forms of chronic liver disease, such as fibrosis and cirrhosis. By reducing the production of the HSD17B13 enzyme, ARO-033 aims to mimic this protective genetic effect and provide a therapeutic benefit for patients with MASH.