Study Overview

MN-001-NATG-202 was a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of MN-001 in 40 patients with NAFLD and hypertriglyceridemia associated with T2DM. The treatment period was 24 weeks.

Key Results

  • Serum TG: At Week 24, mean serum TG decreased from baseline by 45.8 mg/dL (21.78%) in the MN-001 group and by 14.4 mg/dL (6.97%) in the placebo group. Thus, the mean decrease was 31.4 mg/dL greater with MN-001 than with placebo (p=0.113). At Week 4, mean serum TG decreased from baseline by 54.7 mg/dL (26.05%) in the MN-001 group and by 23.8 mg/dL (11.54%) in the placebo group. The mean decrease was 30.96 mg/dL greater with MN-001 than with placebo, and this difference was statistically significant (p=0.015).
  • Liver fat: At Week 24, the mean controlled attenuation parameter (CAP) score measured by FibroScan® decreased from baseline by 14.1 dB/m (4.24%) in the MN-001 group and by 4.3 dB/m (1.27%) in the placebo group. Thus, the mean decrease was 9.7 dB/m greater with MN-001 than with placebo; however, this difference was not statistically significant (p=0.2438).
  • HDL-C: At Week 24, mean HDL-C increased by 3.3 mg/dL (8.39%) in the MN-001 group but decreased by 2.4 mg/dL (6.23%) in the placebo group. The difference between the MN-001 and placebo groups was 5.7 mg/dL and was statistically significant (p=0.0048).
  • HDL-P: At Week 24, mean HDL-P increased by 3.62 µmol/L (11.80%) in the MN-001 group but decreased by 0.9 µmol/L (3.00%) in the placebo group. The difference between the MN-001 and placebo groups was 4.52 µmol/L and was statistically significant (p=0.018).
  • Body weight: At the end of the study, mean body weight decreased by 4.91 lb (2.28%) in the MN-001 group and by 0.55 lb (0.25%) in the placebo group. Thus, the mean decrease in body weight was 4.36 lb greater with MN-001 than with placebo (p=0.082).



     

Safety and Tolerability

MN-001 was generally safe and well tolerated. Treatment-related adverse events were mild to moderate in severity, and no drug related serious adverse events (SAEs) were reported in the study.

Clinical Significance of the Results

The study demonstrated a statistically significant reduction in serum TG at Week 4 with MN-001 than with placebo. At Week 24, the MN-001 group continued to show a numerical reduction from baseline value, although the difference between the MN-001 and placebo groups were not statistically significant. Statistically significant increases in HDL-C and HDL-P were also observed with MN-001 group while liver fat and body weight showed trends toward improvement. Collectively, these exploratory findings suggest that MN-001 may have beneficial effects across in several metabolic parameters including lipid metabolism, body weight, and liver fat.

The changes in TG, HDL-C, and HDL-P were also consistent with findings from preclinical in-vitro mechanism of action studies and previous MN-001-NATG-201 clinical trial. Together with the clinical findings, these results provide a basis for further evaluation of MN-001 in metabolic and cardiovascular diseases.

Next Steps

This was a proof of concept, exploratory study involving 40 patients. Preliminary review of the topline data indicates that efficacy should be evaluated in a larger study. We will continue detailed analyses of the study data and assess the next stage of clinical development, including the appropriate patient population, endpoints, and sample size.