Metabolic dysfunction-associated steatohepatitis (MASH) unfortunately has no treatments to reverse the disease or its damage. MASH can be managed through weight loss, regular exercise, and blood sugar management. But identifying ways to reverse fibrosis (scarring) and halt disease progression could significantly benefit those with this disease. Clinical-stage biotechnology NeuroBo Pharmaceuticals (“NeuroBo”) is working to develop a potential treatment in its therapeutic candidate DA-1241.

NeuroBo describes DA-1241 as

a new chemical agent activating G protein-coupled receptor 119 (GPR119) mainly in the pancreas, intestine, and liver. GPR119 activation by DA-1241 in hepatocytes, macrophages, and hepatic stellate cells inhibits lipid accumulation, immune cell filtration, and the production of collagen fibers in the liver [and] has a distinctive role in glucose and lipid metabolism via stimulating secretion of insulin and glucagon-like peptide-1 (GLP-1) in pancreatic beta cells and intestinal L-cells.

The company ran preclinical studies evaluating DA-1241 in conjunction with sitagliptin for MASH and shared that, after amending protocols, enrollment is open for the second portion of a Phase 2a clinical trial evaluating this drug combination. In the same news release, NeuroBo also announced that positive preclinical safety data is now available. The full data readout should be available later this year. Preclinical data evaluated 180mg/kg/daily sitagliptin, 100mg/kg/daily DA-1241, and a combination of up to 180/100mg/kg/daily in rat models of MASH. Over a 13-week period, the research showed that the combination treatment reduces systemic and hepatic inflammation, was safe and well-tolerated, and even had anti-diabetic effects.

In the second portion of the upcoming Phase 2a clinical study, the researchers will evaluate DA-1241 and sitagliptin for around 37 people with MASH. The primary endpoint focuses on ALT normalization, with secondary endpoints focused on cholesterol and triglyceride changes, safety, and efficacy.

What is Metabolic Dysfunction-Associated Steatohepatitis (MASH)?

Previously known as: Non-alcoholic steatohepatitis (NASH); non-alcohol related steatohepatitis

The Cleveland Clinic explains that metabolic dysfunction-associated steatohepatitis (MASH) is the advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD occurs in people who do not drink a lot or at all, though their symptoms and liver progress similarly to those who do use alcohol. MASH occurs when your body stores excess fat in the liver, causing inflammation, scarring, and damage.

An estimated 25% of people in the United States have MASLD; of those, an estimated 20% develop MASH. MASH is more common in people of Asian or Hispanic ethnicity, people over 40 years old, obese individuals, and those with post-menopause, polycystic ovary syndrome, severe protein deficiency, metabolic syndrome, high cholesterol, high blood pressure or blood sugar, diabetes or insulin resistance, or an underactive thyroid or pituitary gland.