8-K: MetaVia Advances Obesity Drug DA-1726 with Dosing of First Patient in Higher Dose Cohort

MetaVia Inc. announced the dosing of the first patient in the 48 mg multiple ascending dose cohort of its Phase 1 clinical trial for DA-1726, a dual GLP1R and GCGR agonist for obesity, with top-line data expected in the fourth quarter of 2025.

Summary

• MetaVia Inc. has dosed the first patient in the 48 mg, multiple ascending dose (MAD) cohort of its Phase 1 clinical trial for DA-1726, a novel dual oxyntomodulin (OXM) analog agonist for the treatment of obesity.
• DA-1726 functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist.
• Top-line data from this 48 mg MAD cohort is anticipated in the fourth quarter of 2025.
• The primary objective of adding a higher dose to the Phase 1 trial is to define the maximum tolerated dose and further explore the full potential of DA-1726.
• Previously reported data from the 32 mg dose demonstrated dose-dependent weight loss, with a mean reduction of 4.3% and a maximum of 6.3% by Day 26 (p=0.0005).
• At the 32 mg dose, 83% of patients reported early satiety, and average waist reductions were 1.6 inches (maximum 3.9 inches) by Day 33.
• The drug also lowered fasting glucose by up to 18 mg/dL without inducing hypoglycemia.
• Gastrointestinal side effects observed were mild, transient, and infrequent.
• The Phase 1 trial is a randomized, double-blind, placebo-controlled study assessing the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending doses of DA-1726 in obese, otherwise healthy subjects with a BMI between 30 and 45 kg/m2.
• Each cohort involves nine subjects randomized in a 6:3 ratio, receiving either four weekly administrations of DA-1726 or placebo.

Sentiment

Score: 8

Explanation: The announcement reflects positive progress in a key clinical trial for a promising obesity drug. The previously reported data from lower doses are highly encouraging, indicating strong efficacy and a favorable safety profile compared to existing treatments. The move to a higher dose cohort is a logical and positive progression, suggesting confidence in the drug's potential and addressing a significant market need.

Positives

• Dosing of the first patient in the 48 mg MAD cohort represents a significant milestone for the DA-1726 cardiometabolic asset.
• Clinical data for DA-1726 has shown best-in-class potential, exhibiting a favorable safety and tolerability profile without requiring titration.
• The 32 mg dose achieved significant dose-dependent weight loss (mean: 4.3%, max: 6.3%, p=0.0005 at Day 26).
• A high percentage of patients (83%) reported early satiety at the 32 mg dose.
• Observed average waist reductions of 1.6 inches (max: 3.9 inches) by Day 33 are consistent with glucagon-driven adipose effects.
• DA-1726 lowered fasting glucose by up to 18 mg/dL without inducing hypoglycemia, indicating good glucose control.
• Favorable cardiovascular safety was noted, with no QTcF prolongation and a reduction in heart rate across most cohorts.
• Gastrointestinal side effects were mild, transient, and infrequent, suggesting a potentially superior tolerability profile compared to existing GLP-1 therapies.
• The 3:1 balanced activation of GLP-1 and glucagon receptors by DA-1726 is believed to offer a promising alternative to current GLP-1 agonists, addressing significant tolerability challenges that lead to high discontinuation rates (20-30% within the first month, up to 70% within a year).
• Pre-clinical mouse models showed improved weight loss for DA-1726 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.

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.
• Information furnished in this report is not deemed 'filed' for purposes of Section 18 of the Securities Exchange Act of 1934, limiting associated liabilities.

Future Outlook

Top-line data from the 48 mg multiple ascending dose cohort of the Phase 1 clinical trial for DA-1726 is expected in the fourth quarter of 2025. The previously reported 32 mg dose is anticipated to serve as the starting dose for future clinical trials.

Management Comments

• "The dosing of the first patient in the 48 mg cohort marks the achievement of another key milestone for this promising cardiometabolic asset." Hyung Heon Kim, President and Chief Executive Officer of MetaVia.
• "To date, clinical data for DA-1726 has demonstrated best-in-class potential, with a favorable safety and tolerability profile, without the need for titration." Hyung Heon Kim, President and Chief Executive Officer of MetaVia.
• "The addition of a higher dose to the Phase 1 trial will help define the maximum tolerated dose and further unlock the full potential of DA-1726." Hyung Heon Kim, President and Chief Executive Officer of MetaVia.
• "The previously reported data from the 32 mg dose—which we anticipate may serve as the starting dose for future clinical trials—highlight DA-1726’s strong therapeutic potential." Hyung Heon Kim, President and Chief Executive Officer of MetaVia.
• "We continue to believe that DA-1726’s 3:1 balanced activation of GLP-1 and glucagon receptors offers a promising alternative to current GLP-1 agonists, addressing significant tolerability challenges that result in discontinuation rates of 20-30% within the first month and up to 70% within a year." Hyung Heon Kim, President and Chief Executive Officer of MetaVia.
• "We look forward to reporting top-line data from the 48 mg MAD cohort later this year." Hyung Heon Kim, President and Chief Executive Officer of MetaVia.

Industry Context

The announcement positions MetaVia as a key player in the rapidly evolving cardiometabolic disease market, particularly in the development of obesity treatments. By focusing on a novel dual GLP-1R and GCGR agonist, DA-1726 aims to differentiate itself from existing GLP-1 therapies by potentially offering superior tolerability and efficacy, addressing a significant unmet need in patient adherence due to side effects. This aligns with a broader industry trend towards more comprehensive and better-tolerated weight management solutions.

Comparison to Industry Standards

• DA-1726's favorable safety and tolerability profile without the need for titration is highlighted as potentially superior to existing GLP-1 therapies, which often face discontinuation rates of 20-30% within the first month and up to 70% within a year due to tolerability issues.
• 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.
• The 32 mg dose of DA-1726 demonstrated "best-in-class potential" for weight loss, glucose control, and waist reduction in its Phase 1 multiple ascending dose (MAD) trial.

Stakeholder Impact

• Shareholders: Positive impact due to significant progress in a key clinical trial for a potentially high-value drug, which could enhance company valuation and future revenue prospects.
• Patients (Obesity): Potential for a new, more effective, and better-tolerated treatment option for obesity, addressing current drug limitations and improving adherence.
• Healthcare Providers: A new therapeutic option for managing obesity with a potentially improved safety and tolerability profile.

Next Steps

• Define the maximum tolerated dose of DA-1726 through the ongoing Phase 1 trial.
• Report top-line data from the 48 mg MAD cohort in the fourth quarter of 2025.
• Potentially use the 32 mg dose as the starting dose for future clinical trials.

Key Dates

Recommendation

Keywords

Biotechnology, Obesity, Clinical Trial, Phase 1, DA-1726, GLP-1, Glucagon, Dual Agonist, Weight Loss, Cardiometabolic Diseases, Drug Development, Pharmacokinetics, Pharmacodynamics, MASH, DA-1241