MetaVia Inc. (Nasdaq: MTVA) has reported encouraging results from Part 2 of its Phase 1 multiple ascending dose (MAD) trial evaluating DA-1726, a dual oxyntomodulin analog that targets both the GLP-1 and glucagon receptors. The investigational therapy is being developed for obesity and related metabolic conditions.
In the latest 28-day study involving 36 subjects, the highest tested dose of 32 mg—administered without titration—yielded a maximum body weight loss of 6.3% and an average reduction of 4.3% by Day 26. These changes were statistically significant (p=0.0005), underscoring the compound’s strong weight-lowering potential in a short duration.
The drug also produced a pronounced glucose-lowering effect, with fasting glucose reductions reaching up to 18 mg/dL and a mean decrease of 5.3 mg/dL at the same dose. This signals potent GLP-1 receptor activity, which is often linked to improved glycemic control.
Waist circumference—a key metabolic marker—also showed a maximum reduction of 3.9 inches, with an average of 1.6 inches lost by Day 33. These findings suggest the glucagon receptor agonism of DA-1726 may be mobilizing visceral fat stores, supporting preclinical observations shared at EASL 2024.
Additionally, the therapy demonstrated a favorable tolerability profile. At the 32 mg dose, only mild gastrointestinal side effects were reported in four out of six participants, with symptoms resolving within 24 hours. No serious adverse events or discontinuations related to treatment were observed across all cohorts.
The company also noted that early satiety was reported by 83% of participants on the 32 mg dose, further indicating DA-1726’s efficacy in appetite regulation.
Given its dual mechanism—leveraging GLP-1’s glucose-lowering action and glucagon’s energy expenditure benefits—MetaVia believes DA-1726 could appeal to a broader range of obese patients, including those with comorbidities such as Type 2 diabetes and metabolic dysfunction-associated steatohepatitis (MASH).
MetaVia plans to expand its Phase 1 study by adding new cohorts at higher doses to further assess the maximum tolerated dose. Additionally, Part 3 of the study will specifically include patients who discontinued Wegovy® early, aiming to evaluate DA-1726’s comparative tolerability, safety, and efficacy.
Hyung Heon Kim , President and Chief Executive Officer of MetaVia stated, “It is well known that many patients on current GLP-1 agonists discontinue treatment due to tolerability issues, with 20% to 30% stopping within the first month and up to 70% within a year. With DA-1726’s balanced activation of GLP1R and glucagon receptors enhancing energy expenditure, we remain confident in its potential to become a best-in-class obesity drug, with the further potential to offer superior tolerability than currently marketed GLP-1 agonists and those in late-stage clinical trials.”
About MetaVia
MetaVia Inc. is a clinical-stage biotechnology company focused on transforming cardiometabolic diseases. The company is currently developing DA-1726 for the treatment of obesity and is developing DA-1241 for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH). DA-1726 is a novel oxyntomodulin (OXM) analogue that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist. OXM is a naturally occurring gut hormone that activates GLP1R and GCGR, thereby decreasing food intake while increasing energy expenditure, thus potentially resulting in superior body weight loss compared to selective GLP1R agonists. DA-1241 is a novel G-protein-coupled receptor 119 (GPR119) agonist that promotes the release of key gut peptides GLP-1 , GIP, and PYY. In pre-clinical studies, DA-1241 demonstrated a positive effect on liver inflammation, lipid metabolism, weight loss, and glucose metabolism, reducing hepatic steatosis, hepatic inflammation, and liver fibrosis, while also improving glucose control. In a Phase 2a clinical study, DA-1241 demonstrated direct hepatic action in addition to its glucose-lowering effects.
For more information, please visit www.metaviatx.com.
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