MetaVia unveils synergistic liver disease data on DA-1241 and Efruxifermin at ADA 2025

MetaVia Inc. (Nasdaq: MTVA) showcases pre-clinical findings from a novel liver disease therapy at the 85th ADA Scientific Sessions, highlighting synergistic benefits in MASH mouse models.

Why are institutional investors tracking MetaVia’s DA-1241 and Efruxifermin liver disease combination presented at ADA 2025?

MetaVia Inc. (Nasdaq: MTVA), the clinical-stage American biotech company targeting cardiometabolic diseases, revealed compelling pre-clinical data on June 21, 2025, highlighting the combined therapeutic potential of its investigational asset DA-1241 and Efruxifermin in a mouse model of metabolic dysfunction-associated steatohepatitis (MASH). These findings, presented at the 85th Scientific Sessions of the American Diabetes Association (ADA) in Chicago, signal an advancement in dual-drug strategies that aim to tackle liver fat accumulation, inflammation, and fibrosis concurrently—an area of significant unmet need in metabolic liver disorders.

MetaVia’s poster presentation, scheduled for June 22, builds on earlier human clinical data for DA-1241, where monotherapy showed positive liver function modulation and glucose regulation in presumed MASH patients. This pre-clinical investigation in a biopsy-confirmed MASH mouse model now provides quantitative insights into how combining DA-1241, a G-Protein-Coupled Receptor 119 (GPR119) agonist, with the fibroblast growth factor 21 (FGF21) analogue Efruxifermin may yield additive or synergistic effects in reversing multiple aspects of liver pathology.

The dual-drug combination elicited measurable improvements in liver biomarkers, including a ≥2-point NAFLD activity score improvement in 94% of treated mice, a key surrogate for efficacy in NASH and MASH studies. The American biotech company’s growing clinical pipeline and exploratory combination strategy has garnered rising interest from institutional investors seeking exposure to next-generation liver disease treatments beyond GLP-1 monotherapy options.

What were the key biomarker reductions observed with MetaVia’s DA-1241 and Efruxifermin combination in the MASH model?

MetaVia Inc. used a rigorous 48-week study design where mice were first fed a Gubra Amylin NASH (GAN) diet for 36 weeks to establish histological features consistent with human MASH. The animals were then randomized across four treatment groups: vehicle, DA-1241 monotherapy (100 mg/kg daily, oral), Efruxifermin monotherapy (1 mg/kg weekly, subcutaneous), and a combination of both over a 12-week period.

While Efruxifermin monotherapy led to a statistically significant 17% reduction in body weight, DA-1241 was weight-neutral. No further weight loss was detected in the combination group, which reinforces the interpretation that the hepatoprotective and anti-inflammatory effects were driven by mechanisms unrelated to weight reduction.

Both drugs alone showed a reduction in plasma transaminases and hepatic cholesterol, but the combination amplified these effects. Histological improvements were most striking in the dual-treatment group, where almost all mice exceeded the 2-point threshold improvement in the NAFLD activity score. This level of response outperformed both single agents.

Further analysis revealed that the liver’s lipid area and the proportion of steatotic hepatocytes decreased more significantly in the combination group. Liver immunohistochemistry indicated a more pronounced reduction in inflammatory markers like galectin-3 and fibrotic proteins such as type 1 collagen and α-SMA. Molecular analyses mirrored this pattern, with combination therapy leading to sharp reductions in inflammatory gene transcripts—TNFα (-58%), CXCL10 (-56%), CCL2 (-77%), and galectin-3 (-87%)—and fibrotic transcripts—collagen α1 (-72%), α-SMA (-59%), and TIMP1 (-88%).

Importantly, the combination therapy triggered a 321% increase in hedgehog-interacting protein (HIP), a known inhibitor of hepatic stellate cell activation, suggesting a mechanistic basis for the improved anti-fibrotic effect. Systemic inflammation also appeared to decline, with plasma TNFα levels dropping further than in monotherapy arms.

How do analysts interpret MetaVia’s liver-focused pipeline and cardiometabolic therapeutic strategy?

Analysts view MetaVia’s strategic positioning in the cardiometabolic disease space as timely and differentiated. As biopharmaceutical focus shifts toward treating comorbidities in metabolic disorders—including obesity, type 2 diabetes (T2D), and liver fibrosis—MetaVia’s dual-pathway exploration for MASH stands out. With two investigational compounds—DA-1241 and DA-1726—in its pipeline, MetaVia is leveraging biologic synergies not only between gut peptides and liver targets but also across metabolic organs.

DA-1241 functions by activating GPR119, a receptor expressed in intestinal L-cells and pancreatic β-cells, stimulating secretion of GLP-1, GIP, and PYY—gut hormones that regulate glucose homeostasis, lipid metabolism, and satiety. This drug candidate has already been tested in Phase 1a, 1b, and 2a studies, with results showing tolerability and improvement in both liver and metabolic parameters in patients with T2D and suspected MASH.

Meanwhile, DA-1726 is an oxyntomodulin (OXM) analogue acting on both GLP-1 and glucagon receptors, which could represent a superior weight-loss agent compared to selective GLP-1 receptor agonists. In a recent Phase 1 multiple ascending dose (MAD) trial for obesity, DA-1726 showed promising reductions in body weight and waist circumference.

Institutional sentiment has remained cautiously optimistic, with several funds reportedly adding to positions following the Phase 2a DA-1241 data. The addition of Efruxifermin—a drug already under evaluation in other liver disease pipelines—into a novel combination regimen could expand the market potential for DA-1241 if further validated in human trials.

What is the future clinical development pathway for MetaVia’s DA-1241 in combination with liver-targeted agents?

MetaVia Inc. is expected to continue developing DA-1241 under both monotherapy and combination paradigms. While Phase 2a data already confirmed glucose-lowering and hepatoprotective activity, this new pre-clinical evidence strengthens the rationale for a combination trial with FGF21 analogues such as Efruxifermin.

Given the encouraging results, analysts anticipate that MetaVia may initiate a Phase 2b combination trial targeting biopsy-confirmed MASH or NASH patients in 2026. Such a trial would likely use liver histology as a primary endpoint, supported by non-invasive biomarker tracking and metabolic assessments. The additive benefits demonstrated in this ADA poster suggest that targeting MASH through both gut and liver mechanisms simultaneously could yield better efficacy than current standard approaches.

Further regulatory dialogue is also likely. If the combination pathway proceeds, MetaVia may seek expedited pathways for rare metabolic diseases, such as Breakthrough Therapy designation or Fast Track review, especially if early human combination data replicate these pre-clinical findings.

For now, MetaVia’s poster—authored by Lead Research Scientist Yuna Chae of Dong-A ST Research Center—will remain accessible through the ADA conference site and will also be published in Diabetes®, the ADA’s flagship journal.