Wednesday, May 03, 2023
NeuroBo Pharmaceuticals, Inc., a clinical-stage biotechnology company on a quest to transform cardiometabolic diseases, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for DA-1241, a novel G-Protein-Coupled Receptor 119 (GPR119) agonist. The company plans to initiate a two-part, Phase 2a clinical trial of DA-1241, for the treatment of nonalcoholic steatohepatitis (NASH), in the third quarter of 2023.
"Clearance of the IND for DA-1241 brings us one step closer to our goal of bringing this very promising cardiometabolic asset into clinical trials in patients with NASH, for which there is currently no approved treatment," stated Joe Hooker, Interim President and Chief Executive Officer of NeuroBo. "In Phase 1a/1b clinical studies, DA-1241 was well tolerated in both healthy volunteers and in patients with type 2 diabetes mellitus (T2DM). Importantly, preclinical studies demonstrated that DA-1241 attenuated NASH progression by reducing pro-inflammatory cytokines and chemokines, stellate cell activation, and collagen deposition in the liver, thereby improving inflammation, hepatic steatosis, and fibrosis. In those studies, DA-1241 also improved both lipid metabolism and glucose control. For these reasons, we believe that the mechanism of action of DA-1241 will translate into a safe and effective treatment for NASH. We are eager to initiate the two-part, Phase 2a clinical trial of DA-1241, which we expect will occur in the third quarter of this year. The two-part design provides optionality for an interim analysis in the first half of 2024 and we anticipate full data in the second half of 2024.
"Looking ahead, we expect additional, near-term value creating milestones, including advancement of DA-1726, our second asset, through the IND process, with the goal of initiating a Phase 1a safety study in the first half of 2024 and an expected data readout in the second half of 2024. DA-1726 is a novel oxyntomodulin (OXM) analogue that acts as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist. The drug candidate is in development for the treatment of obesity and has demonstrated superior body weight loss in preclinical studies compared with other selective GLP1R agonists.
"It is truly an exciting time at NeuroBo, following the recent in-licensing of DA-1241 and DA-1726, with a new focus on cardiometabolic diseases and the enormous NASH, obesity, and T2DM markets."
The two-part, 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 NASH and confirmed pre-diabetes or T2DM. Part 1 will explore the efficacy of DA-1241 versus placebo, and is expected to enroll 49 subjects, with a planned maximum of 55 subjects to account for early discontinuations. Subjects 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, and will begin after completion of a confirmatory preclinical safety study of DA-1241 in combination with sitagliptin. It is expected to enroll 37 subjects, with a planned maximum of 43 subjects to account for early discontinuations, and subjects will be randomized in 2:1 ratio into 2 treatment groups: DA-1241 100 mg/sitagliptin 100 mg or placebo. Randomization of Part 1 and Part 2 will be stratified by T2DM status at baseline.
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, relative percent change in liver fat fraction from baseline, absolute change in liver fat from baseline, and proportion of subjects with a 30% or more reduction in liver fat 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.