By David Bautz, PhD

NASDAQ:MTVA

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Positive Phase 1 MAD Data for DA-1726

On April 15, 2025, MetaVia Inc. (NASDAQ:MTVA) announced positive results from the Phase 1 Part 2 multiple ascending dose (MAD) trial of DA-1726 in obesity. The results showed that the cohort receiving 32 mg of DA-1726 with no titration had a maximum reduction in body weight from baseline ranging up to -6.3% and a mean body weight reduction of -4.3% (-3.1% placebo adjusted; P=0.0005). In addition, patients in the 32 mg cohort had a mean waist circumference reduction of 1.6 inches along with a mean reduction in fasting glucose of -5.3 mg/dL. Importantly, gastrointestinal (GI) adverse events (AEs) were generally mild and most were only seen after the first dose and resolved within 24 hours of occurrence.

The following chart shows the average weight loss on Day 26 for the different dosing cohorts. The 4 mg cohort had an outlier that skewed the overall average weight loss, however the 8 mg, 16 mg, and 32 mg cohorts show a clear dose response.

DA-1726 showed an overall favorable safety and tolerability profile, as shown in the following chart. All of the AEs in the 32 mg cohort were considered mild and there were no treatment-related discontinuations. In addition, there was no diarrhea reported as well as no significant changes in heart rate in this cohort. The three subjects who experienced vomiting in the 32 mg cohort all reported it after the first dose but with no reoccurrence. Similarly, the two subjects who experienced mild nausea after the first dose reported that it resolved within 12 hours and there were no additional reports of nausea after the 2^nd and subsequent doses. Overall, we view the AE profile observed thus far as a clear differentiator for DA-1726.

The MAD data reported for DA-1726 compares well with other weight loss therapies, both in terms of efficacy and tolerability. The following charts are intended to put the MAD data for DA-1726 into context with what else has been reported and is not intended as a direct head-to-head comparison, particularly given the differences in the various clinical trials. However, it is clear that 32 mg DA-1726 (while still early with only 4-week data reported) has a number of positive characteristics, most notably in the tolerability profile, that could make it competitive in the obesity treatment space.

In particular for the tolerability profile, we note that DA-1726 did not induce diarrhea (unlike the other four listed compounds), showed a lower rate of nausea (33% compared to 42.9-91%), and had no discontinuations due to AEs (compared to 7.5% at 6 weeks for survodutide). With reports that up to approximately 1/3^rd of patients discontinue GLP-1 agonist therapy within 12 months of initiating (Do et al., 2024), a strong safety and tolerability profile is an important differentiating factor for an obesity therapy.