PRISM Q&A CORNER
Hyung Heon Kim, MetaVia Therapeutics
MetaVia Therapeutics: DA-1726 Advances as a Promising Contender in the Competitive Obesity Drug Landscape
Dual GLP-1 and glucagon receptor agonist demonstrates compelling weight loss and best-in-class potential across waist reduction, glucose control, and tolerability
DA-1241 expands company’s reach into MASH with first-in-class oral GPR119 agonist showing liver and metabolic benefits
The global anti-obesity drug market is forecast to grow from $12.8 billion in 2024 to over $100 billion by 2035, fueled by a new generation of GLP-1-based therapeutics and increased demand for sustainable metabolic interventions. With dominant players like Novo Nordisk (NYSE: NVO), Eli Lilly (NYSE: LLY), Pfizer (NYSE: PFE) and AstraZeneca (Nasdaq: AZN) racing to expand their pipelines, the sector is ripe for innovation.
With the market in rapid expansion, MetaVia (NASDAQ: MTVA) is emerging as a differentiated player in the next wave of cardiometabolic drug development. The company’s lead candidate, DA-1726, is a novel, dual oxyntomodulin analog agonist that targets GLP-1 and glucagon receptors. In recent Phase 1 studies, DA-1726 achieved up to 6.3% weight loss in just four weeks without titration and delivered encouraging improvements in glycemic control and waist circumference.
The company is also advancing DA-1241, a first-in-class oral GPR119 agonist that recently demonstrated hepatoprotective and glucose-regulating effects in patients with presumed metabolic dysfunction-associated steatohepatitis (MASH). With both programs gaining clinical traction, MetaVia is positioning itself to address multiple high-value opportunities across obesity, MASH and type 2 diabetes.
We spoke with Hyung Heon Kim, President and CEO of MetaVia, about the company’s expanding pipeline, recent clinical progress and how its programs aim to address the innovation gap in GLP-1-based therapies.
The topline data from our Multiple Ascending Dose (MAD) study were compelling. At the non-titrated 32-mg. dose, which we believe to be the starting dose level, we observed a mean body weight reduction of 4.3% and a maximum of 6.3% at Day 26. There was no indication of plateauing, which suggests the potential for continued weight loss in longer trials. Importantly, the drug was well tolerated, with no serious adverse events or discontinuations due to side effects.
In addition to weight loss, we observed early satiety in 83% of subjects on the 32 mg dose and significant reductions in waist circumference, up to 3.9 inches. These changes are meaningful from both a clinical and mechanistic standpoint and further reinforce our belief that DA-1726 could represent a best-in-class dual agonist.
The 3:1 ratio was selected based on preclinical and translational studies aimed at optimizing metabolic outcomes while preserving tolerability. GLP-1 receptor activation drives appetite suppression and glucose lowering, while glucagon receptor engagement increases energy expenditure and promotes visceral fat loss.
This balance allows us to harness the benefits of both pathways while minimizing risks such as hyperglycemia or excessive cardiovascular stimulation. In our Phase 1 trial, we saw meaningful reductions in fasting glucose, up to 18 mg/dL, without hypoglycemia, and no clinically significant changes in heart rate or QTc intervals. The data suggest we have struck the right balance, enabling robust weight loss while maintaining a favorable safety profile.
Furthermore, the reduction in waist circumference may indicate preferential reduction in central adiposity. This is clinically relevant for patients with obesity-related comorbidities such as MASH and type 2 diabetes.
Several factors set DA-1726 apart. First, we have demonstrated robust early efficacy of up to 6.3% weight loss in just four weeks with no dose titration at the starting dose level. Second, the safety and tolerability profile has been excellent, even at the 32mg dose. Third, the dual activation of GLP-1 and glucagon receptors provides a mechanism that not only reduces appetite but also enhances energy expenditure.
We are also encouraged by the potential to extend into comorbid indications like MASH and type 2 diabetes, where improvements in glucose control and visceral fat reduction are especially valuable. Our development strategy is designed to unlock long-term therapeutic potential across multiple chronic metabolic conditions.
DA-1241 is a cornerstone of our vision to address the full spectrum of MASH. As a GPR119 agonist, it promotes the secretion of key gut peptides like GLP-1, GIP and PYY. In our Phase 2a trial in presumed MASH patients, DA-1241 significantly reduced ALT levels, liver fat as measured by CAP and systemic inflammation. It also improved glycemic control in patients with and without type 2 diabetes.
These dual benefits, hepatic protection and glucose regulation, highlight the program’s versatility. The compound was well tolerated and did not induce weight loss, which may be beneficial in certain patient populations. We see DA-1241 as both a potential monotherapy and a foundation for future combination regimens.
GSK’s acquisition of efimosfermin signals just how much strategic importance is being placed on advanced MASH assets. It validates the market’s interest in novel mechanisms that address the liver-specific and systemic features of the disease.
DA-1241 is the first oral GPR119 agonist to show both hepatoprotective and glucose-regulating activity in MASH patients. These results reinforce our belief that DA-1241 can be a high-impact, disease-modifying therapy. As we prepare for our End-of-Phase 2 FDA meeting, we are evaluating both standalone and partnered development pathways to realize its full potential.
For DA-1726, we are focused on finding the maximum tolerated dose by running additional Single Ascending Dose (SAD) and MAD cohorts in higher dose levels and preparing for our next phase of development. We hope to see more weight loss effects in those higher dose cohorts and plan to release the data within this year.
For DA-1241, we are looking ahead to our regulatory engagement with the FDA. Strategic partnerships are also an area of focus, as we look to accelerate development timelines and expand market access.
More broadly, our goal is to become a leader in precision metabolic medicine. By advancing two programs with complementary mechanisms, we are building a platform that addresses obesity, type 2 diabetes, MASH and beyond with differentiated therapies that prioritize both efficacy and safety.
