8-K: MetaVia Extends DA-1726 Phase 1 Trial to 8 Weeks

MetaVia Inc. announced an extension of its DA-1726 Phase 1 clinical trial for obesity to 8 weeks, aiming for more robust efficacy and safety data.

Summary

• MetaVia Inc. extended the 48 mg multiple ascending dose (MAD) cohort of its Phase 1 clinical trial for DA-1726 from 4 weeks to 8 weeks.
• DA-1726 is a novel, dual oxyntomodulin (OXM) analog agonist (GLP1R and GCGR) for the treatment of obesity.
• The first patient in the 48 mg cohort has received a fifth weekly dose.
• The extension is designed to assess longer-term early efficacy, patient safety, tolerability, and further explore the non-titrated maximum tolerated dose.
• Top-line data from the extended 48 mg cohort is expected in the fourth quarter of 2025.
• Previously reported data from the 32 mg dose demonstrated mean weight loss of 4.3% (max 6.3%) by Day 26, early satiety in 83% of patients, and waist reductions of up to 3.9 inches by Day 33.
• The Phase 1 trial is a randomized, double-blind, placebo-controlled study investigating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DA-1726 in obese, otherwise healthy subjects (BMI 30-45 kg/m2).
• Nine subjects are randomized in each cohort in a 6:3 ratio, receiving either DA-1726 or placebo weekly.

Sentiment

Score: 8

Explanation: The announcement is highly positive, indicating confidence in the drug's potential by extending the trial to gather more robust data, and highlights strong early efficacy and a differentiated tolerability profile compared to competitors.

Positives

• The extension of the trial duration from 4 to 8 weeks is designed to provide more robust data and evaluate longer-term early efficacy and patient exposure.
• Previous 32 mg dose data demonstrated strong weight loss effects (mean 4.3%, max 6.3% by Day 26).
• Early satiety was observed in 83% of patients in the 32 mg cohort.
• Waist reductions of up to 3.9 inches were observed by Day 33 in the 32 mg cohort.
• DA-1726 showed a favorable glycemic and cardiovascular safety profile.
• The drug exhibited a mild, transient gastrointestinal (GI) profile, suggesting a potentially superior tolerability profile compared to existing GLP-1 therapies, which have high discontinuation rates (20-30% within the first month and up to 70% within a year).
• DA-1726's 3:1 balanced activation of GLP-1 and glucagon receptors may offer a differentiated safety profile.
• In pre-clinical mouse models, DA-1726 resulted in improved weight loss compared to semaglutide (Wegovy) and cotadutide.
• In pre-clinical mouse models, DA-1726 elicited similar weight reduction while consuming more food compared to tirzepatide (Zepbound) and survodutide, while also preserving lean body mass and demonstrating improved lipid-lowering effects compared to survodutide.
• The 32 mg dose demonstrated 'best-in-class potential' for weight loss, glucose control, and waist reduction.

Risks

• Forward-looking statements are based on current expectations and are not guarantees of future performance.
• Actual events or results may differ materially from those in the forward-looking statements.
• Forward-looking statements are subject to limitations listed in Exhibit 99.1 and other reports filed with the Securities and Exchange Commission.

Future Outlook

Top-line data from the extended 48 mg cohort is expected in the fourth quarter of 2025, which may further validate DA-1726's longer-term safety, early efficacy, and differentiated tolerability profile compared to current GLP-1 therapies.

Management Comments

• "Extending DA-1726 administration by an additional 4 weeks—for a total of 8 weeks—in the 48 mg cohort represents a meaningful step forward as we seek to evaluate longer-term early efficacy and patient exposure to DA-1726, while also exploring the non-titrated maximum tolerated dose." Hyung Heon Kim, President and Chief Executive Officer.
• "After reviewing the original trial design and previous results, we feel confident that the 4-week extension can potentially provide more robust data, which we believe may position DA-1726 more strongly against current treatments and those in late-stage clinical trials." Hyung Heon Kim.
• "By extending exposure to the drug, we aim to more fully evaluate DA-1726’s therapeutic profile across primary, secondary and exploratory endpoints—including safety, tolerability, body weight, waist circumference, and body mass index (BMI), among others—and to further unlock its full therapeutic potential." Hyung Heon Kim.
• "We continue to believe that DA-1726’s 3:1 balanced activation of GLP-1 and glucagon receptors may offer a differentiated safety profile that addresses the well-documented tolerability issues seen with current GLP-1 agonists, where discontinuation rates reach 20-30% within the first month and up to 70% within a year." Hyung Heon Kim.

Industry Context

The announcement positions DA-1726 within the highly competitive and rapidly growing market for obesity treatments, particularly GLP-1 and dual GLP-1/glucagon receptor agonists. MetaVia aims to differentiate DA-1726 through a potentially superior tolerability profile and enhanced efficacy compared to existing and late-stage therapies, addressing a significant unmet need for more tolerable weight loss solutions.

Comparison to Industry Standards

• DA-1726's 32 mg dose demonstrated strong weight loss (mean 4.3%, max 6.3% by Day 26) and waist reductions (up to 3.9 inches by Day 33), with 'best-in-class potential' for weight loss, glucose control, and waist reduction.
• The drug's mild, transient GI profile and favorable glycemic/cardiovascular safety suggest a superior tolerability profile compared to existing GLP-1 therapies, which have high discontinuation rates (20-30% within first month, up to 70% within a year).
• In pre-clinical mouse models, DA-1726 resulted in improved weight loss compared to semaglutide (Wegovy) and cotadutide (another OXM analogue).
• In pre-clinical mouse models, DA-1726 elicited similar weight reduction while consuming more food compared to tirzepatide (Zepbound) and survodutide, while also preserving lean body mass and demonstrating improved lipid-lowering effects compared to survodutide.

Stakeholder Impact

• Shareholders: Positive impact due to potential for stronger clinical data, which could increase the drug's value and market position, potentially leading to higher stock valuation.
• Patients: Potential for a new, more tolerable, and effective obesity treatment option.
• Employees: Positive impact from continued progress in drug development, potentially securing future growth and stability.
• Competitors: Increased competitive pressure in the obesity treatment market.

Next Steps

• Continue administering weekly doses of DA-1726 or placebo in the extended 48 mg cohort.
• Report top-line data from the extended 48 mg cohort in the fourth quarter of 2025.

Key Dates

Recommendation

The extension of the Phase 1 trial, driven by a desire for more robust efficacy and safety data, signals strong internal confidence in DA-1726. The previously reported 32 mg data already demonstrated 'best-in-class potential' for weight loss and a superior tolerability profile compared to existing GLP-1 therapies, which is a significant differentiator given high discontinuation rates for current treatments. Positive pre-clinical comparisons to market leaders like Wegovy and Zepbound further underscore its potential. The upcoming top-line data in Q4 2025 represents a key catalyst. This update suggests a high probability of favorable outcomes, positioning MetaVia for significant future growth in the lucrative obesity market.

Keywords

Obesity treatment, DA-1726, Phase 1 clinical trial, GLP-1 receptor agonist, Glucagon receptor agonist, Oxyntomodulin analog, Cardiometabolic diseases, Biotechnology, Clinical-stage, Weight loss, Metabolic dysfunction