MetaVia Announces Statistically Significant 68% Reduction in Liver Fat from DA-1726 Phase 1 Part 3B Interim Data

DA-1726 shows 68% liver fat and 13.5% weight reduction in Phase 1 interim data.

What the company is saying

MetaVia Inc. (NASDAQ:MTVA) is highlighting statistically significant interim results from Part 3B of its Phase 1 trial for DA-1726, an oxyntomodulin analog targeting GLP-1 and glucagon receptors. The company emphasizes a 68% placebo-adjusted reduction in liver fat and a 13.5% placebo-adjusted reduction in body weight after 16 weeks of once-weekly dosing in obese adults. Management, led by President and CEO Hyung Heon Kim and Chief Medical Officer Sarah Browne, M.D., frames these results as the most compelling clinical data to date for DA-1726 and as a strong rationale for advancing into liver disease indications. The announcement stresses that all DA-1726-treated participants with baseline liver steatosis achieved MRI-PDFF below 5%, and that 83% of DA-1726-treated participants in the MRI substudy achieved at least a 30% reduction in liver fat, compared to none on placebo. The company also notes improvements in HbA1c (from 5.79% to 5.33%), significant reductions in visceral and subcutaneous adipose tissue, and relative preservation of lean tissue and muscle volume. Safety is underscored by the absence of new gastrointestinal adverse events after week 9 and no discontinuations due to such events. MetaVia positions these findings as a foundation for a planned 48-week, non-biopsy Phase 2 study in up to 150 patients with MetALD and ALD, targeted to begin in the second half of 2027, and signals further data releases in the first quarter of 2027.

What the data suggests

The interim analysis included 15 DA-1726-treated and 4 placebo participants, with an MRI substudy of 12 DA-1726 and 4 placebo subjects. After 16 weeks, DA-1726 achieved a 68% placebo-adjusted reduction in liver fat (GMR 0.32; p<0.001), with mean baseline liver fat of 5.2% in the treatment group and 8.0% in placebo. Ten of twelve DA-1726-treated participants (83%) achieved at least a 30% reduction in liver fat, while none in the placebo group did. All five DA-1726-treated participants with baseline steatosis (≥5% MRI-PDFF) fell below 5% by Day 109, with mean MRI-PDFF dropping from 8.3% to 3.0% (5.3 percentage-point reduction, p=0.005). The participant with the highest baseline MRI-PDFF saw a reduction from 12.8% to 4.6%. In contrast, liver fat in the placebo group increased 40.4% from baseline. DA-1726 also produced a 13.5% placebo-adjusted reduction in body weight (−12.19 kg from a 98.6 kg baseline, p<0.001), a 9.1% reduction in waist circumference, and a 0.24 percentage-point placebo-adjusted reduction in HbA1c (from 5.79% to 5.33%, p=0.006). Visceral adipose tissue was 22% lower, abdominal subcutaneous adipose tissue 19% lower, and total adipose tissue 19% lower versus placebo, while lean tissue and muscle volume were relatively preserved (thigh muscle −9%, total lean tissue −8%). Gastrointestinal adverse events were reported in 60% of DA-1726-treated participants, mostly mild to moderate, with one serious event (severe vomiting) that resolved. No new GI events occurred after week 9, and no discontinuations were due to GI events. The data are robust for a small, early-stage trial, but the sample size is limited and the results are interim.

Analysis

The announcement presents detailed and statistically significant interim Phase 1 clinical data for DA-1726, with clear numerical support for efficacy and safety endpoints in a small, controlled population. The language is positive but largely proportionate to the realised results, with most claims about DA-1726's effects on liver fat, body weight, and metabolic markers directly supported by disclosed data. However, the release also includes forward-looking statements about future data releases and the initiation of Phase 2 studies, which are at least 8-20 months away and not yet operationally substantiated. There is no evidence of capital intensity or large outlays at this stage, and the company is at a pre-commercial, clinical development phase where such disclosures are not expected. The main gap is between the strong interim results and the implied future clinical and commercial success, which remains unproven until larger, later-stage trials are completed.

Risk flags

• ●The interim results are based on a small sample size (15 treated, 4 placebo; MRI substudy n=12/4), which limits generalizability and statistical power. Larger studies may yield different efficacy or safety outcomes.
• ●The timeline to Phase 2 initiation is long, with the study targeted to begin in the second half of 2027. This creates a significant gap before potential pivotal data, during which clinical, regulatory, and operational risks could materialize.
• ●Gastrointestinal adverse events were common, with 46.7% of DA-1726-treated participants experiencing vomiting and 13.3% experiencing nausea, diarrhea, or dyspepsia. Although no discontinuations occurred, tolerability in larger and more diverse populations remains unproven.
• ●All efficacy and safety data are interim and limited to a 16-week window; longer-term effects, durability of response, and rare adverse events are unknown. The absence of new GI events after week 9 is encouraging but does not guarantee long-term tolerability.
• ●The company has not disclosed any operational milestones, regulatory submissions, or partnership agreements supporting the future timelines for Phase 2 or subsequent development, increasing execution risk.

Bottom line

MetaVia's interim Phase 1 data for DA-1726 show strong, statistically significant reductions in liver fat (68%) and body weight (13.5%) over 16 weeks, with all participants with baseline steatosis achieving MRI-PDFF below 5%. The safety profile is acceptable for this stage, with no discontinuations due to GI adverse events and no new GI events after week 9, though vomiting and other GI symptoms were frequent. The sample size is small and results are interim, so confirmation in larger, longer trials is essential. The next catalyst is a full data release in early 2027, but Phase 2 is not expected to start until the second half of 2027, leaving a long execution window and substantial clinical and regulatory risk. Investors should view these results as promising but very early, with the main value inflection points still at least 18–24 months away. The most important takeaway is that DA-1726 has demonstrated compelling early efficacy signals, but the path to approval and commercialisation remains long and uncertain.

Announcement summary

(NASDAQ:MTVA) MetaVia Inc. announced positive interim data from Part 3B of its Phase 1 clinical trial of DA-1726, a novel oxyntomodulin (OXM) analog targeting both GLP-1 (GLP1R) and glucagon (GCGR) receptors. The results, presented at the Precision Liver Symposium on November 4, 2026, demonstrated a 68% placebo-adjusted reduction in liver fat and a 13.5% placebo-adjusted reduction in body weight after 16 weeks of once-weekly DA-1726 treatment in otherwise healthy adults with obesity. At Day 109, 10 of 12 DA-1726-treated participants (83%) in the MRI substudy achieved a relative liver fat reduction of at least 30%, compared with none on placebo. All DA-1726-treated participants with baseline liver steatosis achieved MRI-PDFF below 5%. DA-1726 also lowered HbA1c from 5.79% at baseline to 5.33% at Day 109, a 0.24 percentage-point placebo-adjusted reduction in non-diabetic participants, with significant reductions in adipose tissue and relative preservation of lean tissue and muscle volume. The mean baseline liver fat in DA-1726-treated participants was 5.2%, and 8.0% in the placebo group. The absolute MRI-PDFF treatment difference versus placebo was −6.4 percentage points (p=0.007). Among the five DA-1726-treated participants with liver steatosis at baseline (MRI-PDFF ≥5%), all five achieved MRI-PDFF below 5% by Day 109, with mean MRI-PDFF declining from 8.3% to 3.0% (a 5.3 percentage-point reduction, p=0.005). The participant with the highest baseline MRI-PDFF saw a reduction from 12.8% to 4.6%. In the placebo group, liver fat increased 40.4% from baseline. Mean baseline HbA1c was 5.79% in the DA-1726 arm and 5.65% in the placebo arm. At Day 109, mean HbA1c in the DA-1726 arm fell by 0.44 percentage points (p<0.001), while the placebo arm declined by 0.20 percentage points. The difference in mean change versus placebo was −0.24 percentage points (95% CI −0.41 to −0.07; p=0.006). At Day 109, visceral adipose tissue (VAT) was 22% lower versus placebo (GMR 0.78; p<0.001), abdominal subcutaneous adipose tissue (ASAT) was 19% lower (GMR 0.81; p=0.002), and total adipose tissue (TAT) was 19% lower (GMR 0.81; p<0.001). Lean tissue and muscle volume were relatively preserved, with thigh muscle volume 9% lower versus placebo (GMR 0.91; p=0.018) and total lean tissue 8% lower (GMR 0.92; p=0.007). No participant discontinued the study due to a gastrointestinal adverse event, and no new gastrointestinal adverse events were reported after Week 9 through Day 109. Gastrointestinal adverse events were reported in nine of 15 DA-1726-treated participants: vomiting in seven (46.7%), nausea in two (13.3%), diarrhea in two (13.3%), dyspepsia in two (13.3%), constipation in one (6.7%), and abdominal pain in one (6.7%). One serious adverse event of severe vomiting was reported and considered possibly related to treatment; the participant recovered. The interim analysis included 15 participants treated with DA-1726 and four with placebo; the MRI substudy included 12 DA-1726-treated and four placebo participants. DA-1726 was titrated from 16 mg for 4 weeks, to 32 mg for 4 weeks, to a target dose of 64 mg, administered once weekly by subcutaneous injection. MetaVia plans to report full Part 3A and Part 3B data in the first quarter of 2027. A 48-week, non-biopsy Phase 2 study of DA-1726 in up to 150 patients with MetALD and ALD is targeted to begin in the second half of 2027. MetaVia is also advancing vanoglipel (DA-1241) in combination with resmetirom for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH), with a Phase 2a proof-of-concept study targeted to begin in the first half of 2027. Hyung Heon Kim is President and Chief Executive Officer of MetaVia. Sarah Browne, M.D., is Chief Medical Officer and was the presenting author at the symposium.

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