NeuroBo Pharmaceuticals, Inc. announced positive pre-clinical safety data of DA-1241, a novel G-Protein-Coupled Receptor 119 (GPR119) agonist, in combination with sitagliptin, a DPP4 inhibitor. Additionally, having satisfied its 45-day commitment with the U.S. Food and Drug Administration (FDA) related to its amended protocol, the company has opened enrollment for Part 2 of its Phase 2a clinical trial of DA-1241 when co-administered with sitagliptin for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). The pre-clinical results demonstrated that once daily oral administration in rats, of sitagliptin alone (180 mg/kg/day), DA-1241 alone (100 mg/kg/day), or sitagliptin in combination with DA-1241 (up to 180/100 mg/kg/day sitagliptin+DA-1241) for 13 weeks, was well tolerated with no adverse effects.

Each of the two-parts of the Phase 2a trial of DA-1241 is designed to be a 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel clinical study to evaluate the efficacy and safety of DA-1241 in subjects with presumed MASH. Part 1, currently dosing subjects, is exploring the efficacy of DA-1241 versus placebo, and is expected to enroll approximately 49 subjects, who will be randomized in a 1:2:1 ratio into 3 treatment groups: DA-1241 50 mg, DA-1241 100 mg, or placebo. Part 2 will explore the efficacy of DA-1241 in combination with sitagliptin, versus placebo, is expected to enroll approximately 37 subjects, who will be randomized in a 2:1 ratio into 2 treatment groups: DA-1241 100 mg/sitagliptin 100 mg or placebo.

For both Part 1 and Part 2, the primary endpoint is the change from baseline in alanine transaminase (ALT) levels at Week 16. Secondary efficacy endpoints include the proportion of subjects with normalization of ALT, absolute change in total cholesterol, low and high-density lipoprotein cholesterol, triglyceride, and free fatty acids from baseline, among others. Safety will be evaluated by monitoring adverse events (AEs), serious adverse events (SAEs) and AEs leading to discontinuation and laboratory abnormalities.

DA-1241 is a novel G-Protein-Coupled Receptor 119 (GPR119) agonist with development optionality as a standalone and/or combination therapy for both MASH and T2DM. In preclinical studies, DA-1241 demonstrated that GPR-119 agonism promotes the release of the key gut peptides GLP-1, GIP, and PYY, which have a beneficial effect on liver inflammation, lipid metabolism, weight loss, and glucose metabolism. The therapeutic potential of DA-1241 has been demonstrated in multiple pre-clinical animal models of MASH and T2DM whereby DA-1241 reduced hepatic steatosis, hepatic inflammation, and liver fibrosis, while also improving glucose control.

Furthermore, in Phase 1a and 1b trials, DA-1241 was well tolerated in both healthy volunteers and those with T2DM.