MetaVia Reports Additional Positive Top-Line Results From the MAD Part 2 of Its Phase 1 Study of DA-1726, a Novel 3:1 Ratio GLP-1 and Glucagon Dual Receptor Agonist to Treat Obesity, Further Demonstrating Its Best-In-Class Potential
MetaVia (Nasdaq: MTVA) reported additional positive top-line results from Phase 1 Multiple Ascending Dose (MAD) study of DA-1726, its novel 3:1 ratio GLP-1 and glucagon dual receptor agonist for obesity treatment. The 28-day, 36-subject trial demonstrated:
- Dose-dependent body weight reduction across 8-32mg range, with maximum -6.3% and mean -4.3% weight loss at 32mg dose by Day 26
- No significant cardiovascular effects observed, with most treatment groups showing slight decrease in heart rate
- Strong safety profile with only mild gastrointestinal adverse events in 4/6 subjects at 32mg dose, resolving within 24 hours
The drug showed promising results compared to current GLP-1 agonists, with early satiety observed in 83% of subjects at 32mg dose. Additional cohorts are being added to determine maximum tolerated dose, and a Phase 1 Part 3 study is planned to evaluate DA-1726 in patients who discontinued Wegovy®.
MetaVia (Nasdaq: MTVA) ha riportato ulteriori risultati positivi di primo livello dallo studio di Fase 1 con dosi multiple ascendenti (MAD) di DA-1726, il suo innovativo agonista duale dei recettori GLP-1 e glucagone in rapporto 3:1 per il trattamento dell'obesità. Lo studio di 28 giorni condotto su 36 soggetti ha evidenziato:
- Riduzione del peso corporeo dipendente dalla dose nell'intervallo 8-32 mg, con una perdita massima del -6,3% e media del -4,3% al dosaggio di 32 mg al giorno 26
- Nessun effetto cardiovascolare significativo osservato, con la maggior parte dei gruppi di trattamento che hanno mostrato un lieve calo della frequenza cardiaca
- Profilo di sicurezza solido con solo lievi eventi avversi gastrointestinali in 4 su 6 soggetti al dosaggio di 32 mg, risolti entro 24 ore
Il farmaco ha mostrato risultati promettenti rispetto agli agonisti GLP-1 attualmente disponibili, con sazietà precoce osservata nell'83% dei soggetti al dosaggio di 32 mg. Sono in corso ulteriori coorti per determinare la dose massima tollerata e è pianificato uno studio di Fase 1 Parte 3 per valutare DA-1726 in pazienti che hanno interrotto Wegovy®.
MetaVia (Nasdaq: MTVA) informó resultados adicionales positivos preliminares del estudio de Fase 1 con dosis múltiples ascendentes (MAD) de DA-1726, su novedoso agonista dual de receptores GLP-1 y glucagón en proporción 3:1 para el tratamiento de la obesidad. El ensayo de 28 días con 36 sujetos demostró:
- Reducción del peso corporal dependiente de la dosis en el rango de 8 a 32 mg, con una pérdida máxima del -6,3% y media del -4,3% a la dosis de 32 mg al día 26
- No se observaron efectos cardiovasculares significativos, con la mayoría de los grupos de tratamiento mostrando una ligera disminución en la frecuencia cardíaca
- Perfil de seguridad sólido con solo eventos adversos gastrointestinales leves en 4 de 6 sujetos a la dosis de 32 mg, que se resolvieron en 24 horas
El medicamento mostró resultados prometedores en comparación con los agonistas GLP-1 actuales, con saciedad temprana observada en el 83% de los sujetos a la dosis de 32 mg. Se están añadiendo cohortes adicionales para determinar la dosis máxima tolerada, y se planea un estudio de Fase 1 Parte 3 para evaluar DA-1726 en pacientes que suspendieron Wegovy®.
MetaVia (나스닥: MTVA)는 비만 치료를 위한 새로운 3:1 비율 GLP-1 및 글루카곤 이중 수용체 작용제인 DA-1726의 1상 다중 상승 용량(MAD) 연구에서 추가 긍정적인 주요 결과를 보고했습니다. 28일간 36명을 대상으로 한 시험에서 다음과 같은 결과가 나타났습니다:
- 8-32mg 범위 내 용량 의존적 체중 감소, 32mg 용량에서 26일째 최대 -6.3%, 평균 -4.3% 체중 감량
- 심혈관계에 유의한 영향 없음, 대부분의 치료 그룹에서 심박수 소폭 감소 관찰
- 32mg 용량에서 6명 중 4명에게서 경미한 위장관 부작용만 발생했으며 24시간 내 해소되어 안전성 우수
이 약물은 현재의 GLP-1 작용제와 비교해 유망한 결과를 보였으며, 32mg 용량에서 83%의 대상자에게서 조기 포만감이 확인되었습니다. 최대 내성 용량을 결정하기 위해 추가 코호트가 추가 중이며, Wegovy® 복용을 중단한 환자를 대상으로 DA-1726을 평가하는 1상 3부 연구도 계획 중입니다.
MetaVia (Nasdaq : MTVA) a rapporté des résultats positifs supplémentaires de premier plan issus de l'étude de Phase 1 à doses multiples ascendantes (MAD) de DA-1726, son nouvel agoniste double récepteur GLP-1 et glucagon au ratio 3:1 pour le traitement de l'obésité. L'essai de 28 jours portant sur 36 sujets a démontré :
- Une réduction du poids corporel dépendante de la dose dans la plage de 8 à 32 mg, avec une perte maximale de -6,3 % et une moyenne de -4,3 % à la dose de 32 mg au jour 26
- Aucun effet cardiovasculaire significatif observé, la plupart des groupes de traitement montrant une légère diminution de la fréquence cardiaque
- Un profil de sécurité solide avec seulement des événements indésirables gastro-intestinaux légers chez 4 des 6 sujets à la dose de 32 mg, résolus en 24 heures
Le médicament a montré des résultats prometteurs comparés aux agonistes GLP-1 actuels, avec une satiété précoce observée chez 83 % des sujets à la dose de 32 mg. Des cohortes supplémentaires sont ajoutées pour déterminer la dose maximale tolérée, et une étude de Phase 1 Partie 3 est prévue pour évaluer DA-1726 chez des patients ayant arrêté Wegovy®.
MetaVia (Nasdaq: MTVA) berichtete über weitere positive Ergebnisse aus der Phase-1-Studie mit mehrfach ansteigender Dosierung (MAD) von DA-1726, seinem neuartigen 3:1 GLP-1- und Glukagon-Dualrezeptor-Agonisten zur Behandlung von Adipositas. Die 28-tägige Studie mit 36 Probanden zeigte:
- Dosisabhängige Gewichtsreduktion im Bereich von 8-32 mg, mit maximal -6,3% und durchschnittlich -4,3% Gewichtsverlust bei 32 mg am Tag 26
- Keine signifikanten kardiovaskulären Effekte beobachtet, die meisten Behandlungsgruppen zeigten eine leichte Abnahme der Herzfrequenz
- Starke Sicherheitsprofil mit nur milden gastrointestinalen Nebenwirkungen bei 4 von 6 Probanden bei 32 mg, die innerhalb von 24 Stunden abklangen
Das Medikament zeigte vielversprechende Ergebnisse im Vergleich zu aktuellen GLP-1-Agonisten, mit früher Sättigung bei 83% der Probanden bei 32 mg. Weitere Kohorten werden hinzugefügt, um die maximal verträgliche Dosis zu bestimmen, und eine Phase-1-Teil-3-Studie ist geplant, um DA-1726 bei Patienten zu evaluieren, die Wegovy® abgesetzt haben.
- Demonstrated clear dose-dependent weight loss efficacy (-6.3% maximum at 32mg)
- No significant cardiovascular side effects observed
- Strong safety profile with only mild, temporary GI events
- Early satiety observed in 83% of subjects at 32mg dose
- All pre-funded warrants exercised, improving financial position
- 4 out of 6 subjects experienced GI adverse events at 32mg dose
- Maximum tolerated dose not yet determined
Insights
DA-1726 shows promising dose-dependent weight loss of up to 6.3% in just 4 weeks with favorable cardiovascular safety profile and mild GI side effects.
The Phase 1 multiple ascending dose (MAD) results for MetaVia's DA-1726 demonstrate several compelling findings for this novel dual GLP-1/glucagon receptor agonist. The data reveals a clear dose-responsive trend in body weight reduction across the 8-32mg range, with the 32mg dose achieving a maximum weight loss of 6.3% and mean weight loss of 4.3% after just 26 days (p=0.0005) without requiring dose titration.
The cardiovascular safety data is particularly noteworthy. Unlike some competitor dual agonists discontinued due to heart rate concerns, DA-1726 showed no clinically significant increases in heart rate or QTcF changes at the highest 32mg dose. In fact, most treatment groups showed slight decreases in heart rate from baseline (-14 to -0.7 bpm across different dose cohorts) – a significant advantage given that both GLP-1 and glucagon receptor activation typically increase heart rate individually.
The compound demonstrates dual mechanism benefits with clear signals of both GLP-1 efficacy (maximum fasting glucose reduction of 18 mg/dL) and glucagon efficacy (maximum waist circumference reduction of 3.9 inches). The tolerability profile appears favorable, with only mild gastrointestinal adverse events in four out of six subjects at the 32mg dose, most resolving within 24 hours. Importantly, there were no treatment-related discontinuations or serious adverse events.
The high incidence of early satiety (83% of subjects on 32mg) suggests potential for greater weight loss with longer treatment duration. The planned expansion to determine maximum tolerated dose and evaluate DA-1726 in patients who discontinued Wegovy represents a strategic approach to potentially address the high discontinuation rates seen with current GLP-1 therapies (20-30% in first month, up to 70% within a year).
Phase 1 results show DA-1726's potential to compete in the lucrative obesity market with impressive early efficacy data and potentially better cardiac safety.
MetaVia's Phase 1 results position DA-1726 as a potentially competitive entrant in the rapidly expanding obesity therapeutics market. The drug's novel 3:1 ratio of GLP-1:glucagon receptor activation delivers meaningful weight reduction of 4.3% mean weight loss at 26 days with the 32mg dose (p=0.0005), without requiring dose titration – an impressive efficacy signal for an early-stage study.
The cardiovascular safety profile represents a potential differentiation point from competitors. While activation of either GLP-1 or glucagon receptors typically increases heart rate, DA-1726 showed no clinically significant heart rate increases or QTcF prolongation, even contrasting with at least one similar dual agonist discontinued due to heart rate concerns. This safety advantage, if maintained in larger studies, could represent a significant commercial differentiator.
The tolerability profile addresses a critical market need. Current GLP-1 agonists face 20-30% discontinuation rates within the first month and up to 70% within a year due to tolerability issues. DA-1726's promising safety data combined with the planned Phase 1 Part 3 study in patients who discontinued Wegovy demonstrates MetaVia's strategic approach to this market challenge.
The company's decision to add higher-dose cohorts indicates confidence in the compound's safety margin while seeking to maximize efficacy. The complete exercise of all outstanding pre-funded warrants following the initial data release on April 15 suggests increased investor confidence in the program. While these results are promising, it's important to note they come from a small study with 36 subjects in the MAD portion, and larger trials will be needed to confirm these findings and fully establish DA-1726's potential best-in-class status in the obesity treatment landscape.
A Dose-Dependent Response in Body Weight Reduction Was Observed Between 8 mg and 32 mg Doses
Change in BMI and Body Weight Adjusted for Height In the Treatment Groups, Showed a Significant Difference Compared to Placebo, Indicating Potentially Greater Efficacy with Increasing Dosage and Longer Duration of Use
No Drug-Induced Cardiovascular Effects Were Observed In Heart Rate or QTcF Measurements of Subjects Receiving up to 32 mg of DA-1726 at 4-Weeks
Additional Cohorts Being Added to Determine Maximum Tolerated Dose
In the 28-day, 36-subject MAD portion of the study, a clear dose-responsive trend in body weight (BW) reduction was observed across the 8 mg to 32 mg range, indicating potentially greater efficacy at higher doses and longer duration of use. Additionally, body mass index (BMI), which shows body weight adjusted for height, showed a difference between the treatment group and the placebo (PBO) group, which was even more pronounced, further supporting the dose-dependent effect of the drug on weight-related outcomes. Of note, DA-1726 did not show any clinically significant increases in heart rate (HR) or QTcF changes up to 32 mg at 4 weeks of administration.
As previously reported, with no titration, DA-1726, with its novel 3:1 ratio between GLP-1R and GCGR at the 32 mg dose, demonstrated compelling maximum weight loss of -
"This new, additional Phase 1 MAD data further highlights DA-1726's potential to be a best-in-class obesity treatment, showing impressive weight loss results, particularly in terms of BMI reduction," stated Hyung Heon Kim, President and Chief Executive Officer of MetaVia. "Specifically, there was a clear dose-dependent effect on body weight loss between 8 mg and 32 mg, with higher doses leading to greater weight reduction. BMI change from baseline showed the difference between the drug group and the placebo group was even more noticeable. Based on the robust safety and tolerability profile of DA-1726, we believe that 32 mg will likely be the starting dose for future clinical trials."
Mr. Kim continued, "Additionally, activation of either the GLP-1 or glucagon receptors is known to increase heart rate. As a result, dual agonists that simultaneously activate both receptors may raise concerns about excessive heart rate elevation and potential QT interval prolongation. For example, at least one similar dual agonist in clinical trials was discontinued due to an increase in heart rate and other safety concerns. In contrast, the mean heart rate of subjects on DA-1726 showed a slight decrease from baseline in all treatment groups other than the 16 mg cohort where the baseline was significantly lower than other cohorts; the mean decrease after 4 weeks was -14 to -0.7 beats per min (bpm) in the DA-1726 cohorts (4, 8 or 32 mg once weekly) while there was an increase of 7.7 bpm for DA-1726 16 mg cohort. There were no onsets reported in the QTcF (QT interval corrected for heart rate using the method of Fridericia) interval categories >480–500 msec or >500 msec and no risk of cardiovascular events was identified."
Heart Rate (bpm) | Baseline N | Baseline | Day 8 | Day 15 | Day 22 | Day 29 | Mean HR change |
4 mg | 6 | 82.8 | -15.7 | -17.2 | -9.7 | -13.2 | -14.0 |
8 mg | 6 | 77.7 | -4.0 | -6.0 | -5.4 | -6.0 | -5.4 |
16 mg | 6 | 58.8 | 6.0 | 9.5 | 7.7 | 7.5 | 7.7 |
32 mg | 6 | 70.7 | 0.2 | -3.5 | 1.7 | -1.3 | -0.7 |
Pooled Placebo | 12 | 67.6 | -3.0 | -4.0 | -4.4 | 0.7 | -2.7 |
Management also noted that DA-1726's 3:1 balanced activation of GLP-1 and glucagon receptors offers a promising alternative to current GLP-1 agonists, addressing the significant tolerability challenges that lead to 20–
The Phase 1 trial was a randomized, double-blind, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending doses of DA-1726 in obese, otherwise healthy subjects. The MAD portion of the study enrolled healthy adults with a minimum body mass index between BMI 30 – 45 kg/m2. The primary endpoint of the Phase 1 trial was to assess the safety and tolerability of DA-1726 by monitoring adverse events (AEs), serious adverse events (SAEs), treatment emergent adverse events (TEAEs) and AEs leading to treatment discontinuation. Secondary endpoints included the PK of DA-1726, assessed via serum concentrations over time and metabolite profiling at the highest doses of DA-1726. Exploratory endpoints included the effect of DA-1726 on metabolic parameters, cardiac parameters, fasting lipid levels, body weight, waist circumference and body mass index (BMI), among others.
As previously disclosed, in the 28-day, 36-subject MAD portion of the study, DA-1726 demonstrated excellent safety and tolerability, with positive clinical activity. Four out of six subjects on the 32 mg dose experienced mild gastrointestinal (GI) AEs after the first 32 mg dose, most of which were resolved after 24 hours of occurrence. There were no treatment-related discontinuations or SAEs. Early satiety was observed in
Mr. Kim concluded, "After our initial top-line data was announced pre-market on April 15, 2025, the Company's previously issued and outstanding pre-funded warrants were exercised for 1,430,000 shares of the Company's common stock -- leaving no pre-funded warrants outstanding. We continue to believe that the body of data for DA-1726 provides a compelling case for its future potential as a treatment for obesity."
For more information on this clinical trial, please visit: www.clinicaltrials.gov NCT06252220.
About DA-1726
DA-1726 is a novel oxyntomodulin (OXM) analogue functioning as a GLP1R/GCGR dual agonist for the treatment of obesity and Metabolic Dysfunction-Associated Steatohepatitis (MASH) that is to be administered once weekly subcutaneously. DA-1726 acts as a dual agonist of GLP-1 receptors (GLP1R) and glucagon receptors (GCGR), leading to weight loss through reduced appetite and increased energy expenditure. DA-1726 has a well understood mechanism and, in pre-clinical mice models, resulted in improved weight loss compared to semaglutide (Wegovy®) and cotadutide (another OXM analogue). Additionally, in pre-clinical mouse models, DA-1726 elicited similar weight reduction, while consuming more food, compared tirzepatide (Zepbound®) and survodutide (a drug with the same MOA), while also preserving lean body mass and demonstrating improved lipid-lowering effects compared to survodutide.
About MetaVia
MetaVia Inc. is a clinical-stage biotechnology company focused on transforming cardiometabolic diseases. The company is currently developing DA-1726 for the treatment of obesity and is developing DA-1241 for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH). DA-1726 is a novel oxyntomodulin (OXM) analogue that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist. OXM is a naturally-occurring gut hormone that activates GLP1R and GCGR, thereby decreasing food intake while increasing energy expenditure, thus potentially resulting in superior body weight loss compared to selective GLP1R agonists. DA-1241 is a novel G-protein-coupled receptor 119 (GPR119) agonist that promotes the release of key gut peptides GLP-1, GIP, and PYY. In pre-clinical studies, DA-1241 demonstrated a positive effect on liver inflammation, lipid metabolism, weight loss, and glucose metabolism, reducing hepatic steatosis, hepatic inflammation, and liver fibrosis, while also improving glucose control. In a Phase 2a clinical study, DA-1241 demonstrated direct hepatic action in addition to its glucose lowering effects.
For more information, please visit www.metaviatx.com.
Forward Looking Statements
Certain statements in this press release may be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "believes", "expects", "anticipates", "may", "will", "should", "seeks", "approximately", "potential", "intends", "projects", "plans", "estimates" or the negative of these words or other comparable terminology (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this press release, including, without limitation, those risks associated with MetaVia's ability to execute on its commercial strategy; our expectations regarding the sufficiency of our existing cash on hand to fund our operations; the timeline for regulatory submissions; the ability to obtain regulatory approval through the development steps of MetaVia's current and future product candidates; the ability to realize the benefits of the license agreement with Dong-A ST Co. Ltd., including the impact on future financial and operating results of MetaVia; the cooperation of MetaVia's contract manufacturers, clinical study partners and others involved in the development of MetaVia's current and future product candidates; potential negative interactions between MetaVia's product candidates and any other products with which they are combined for treatment; MetaVia's ability to initiate and complete clinical trials on a timely basis; MetaVia's ability to recruit subjects for its clinical trials; whether MetaVia receives results from MetaVia's clinical trials that are consistent with the results of pre-clinical and previous clinical trials; impact of costs related to the license agreement, known and unknown, including costs of any litigation or regulatory actions relating to the license agreement; the effects of changes in applicable laws or regulations; the effects of changes to MetaVia's stock price on the terms of the license agreement and any future fundraising; and other risks and uncertainties described in MetaVia's filings with the Securities and Exchange Commission, including MetaVia's most recent Annual Report on Form 10-K. Forward-looking statements speak only as of the date when made. MetaVia does not assume any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
Contacts:
MetaVia
Marshall H. Woodworth
Chief Financial Officer
+1-857-299-1033
marshall.woodworth@metaviatx.com
Rx Communications Group
Michael Miller
+1-917-633-6086
mmiller@rxir.com
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FAQ
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