Dong-A ST and its subsidiary NeuroBo Pharmaceuticals said Friday that they will present preclinical research findings on their metabolic dysfunction-associated steatohepatitis (MASH) treatment, DA-1241, at the European Association for the Study of the Liver (EASL) Congress 2024.

The event will occur from June 5 to 8 in Milan, Italy. It is a leading liver disease research conference that gathers experts worldwide to share the latest trends and developments in liver disease treatments.

DA-1241 is a first-in-class synthetic drug that activates GPR119 and can be administered orally once a day. In animal studies, DA-1241 significantly improved blood sugar and lipid levels and reduced liver inflammation and fibrosis. DA-1241 is undergoing a global phase 2 clinical trial, with completion expected in the second half of this year.

At the EASL Congress, Dong-A ST and NeuroBo Pharmaceuticals will present two posters showcasing the preclinical efficacy of DA-1241 when combined with the GLP-1 receptor agonist semaglutide.

The combination therapy was tested on two MASH mouse models, each representing different disease pathogenesis and progression stages.

In a diet-induced MASH mouse model, the combination of DA-1241 and semaglutide over eight weeks improved the NAFLD Activity Score (NAS) by at least one point in all treated mice, with over 80 percent showing an improvement of two points or more.

This improvement is attributed to the metabolic enhancement and anti-inflammatory effects of DA-1241, coupled with the weight loss effects of semaglutide.

Further analysis of liver tissue gene expression revealed that the combination therapy also more effectively improved the expression of genes associated with inflammation and fibrosis than either drug alone.

These findings were corroborated in a liver fibrosis mouse model, where DA-1241 significantly reduced liver fibrosis without causing weight loss.

Combined with semaglutide, the therapy resulted in statistically significant improvements in fibrosis compared to either drug alone, without additional weight changes.

Notably, DA-1241 increased the expression of fibrosis inhibitory factors in the liver, suggesting its mechanism of action involves suppressing hepatic stellate cell activation, thereby inhibiting fibrosis.

The efficacy of DA-1241 was further demonstrated in human liver stellate cells, where it increased the expression of fibrosis inhibitory factors.

"These data validate the potential of GPR119 and GLP-1 based combination therapy to inhibit liver fibrosis and inflammation,” NeuroBo CEO Kim Hyung-heon said. “We are committed to presenting the results of the global phase 2 trial for DA-1241 by the end of the year."