A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel, Phase 2a Clinical Trial to Evaluate the Efficacy and Safety of DA-1241 in Subjects With Presumed Non-alcoholic Steatohepatitis (NASH)

A multicenter, randomized, double-blind, placebo-controlled, parallel, Phase 2a clinical trial to evaluate the efficacy and safety of DA 1241 in subjects with presumed non-alcoholic steatohepatitis (NASH).

Start Date14 Sep 2023

Sponsor / Collaborator

MetaVia, Inc.

NCT03646721

/ CompletedPhase 1

A Phase 1b, Double-Blind, Placebo-Controlled, Multiple Ascending Dose (MAD) Study to Evaluate the Safety, Tolerability, PK and PD of DA-1241 in Healthy Male Subjects and Subjects With T2DM

This is a double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, tolerability, PK and PD of DA-1241 in healthy male subjects and subjects with T2DM

Start Date29 Aug 2018

Sponsor / Collaborator

Dong-A ST Co., Ltd.

NCT03061981

/ CompletedPhase 1

A Phase I, First In Human, Double Blind, Placebo Controlled, Single Ascending Dose Study To Evaluate The Safety, Tolerability, Pharmacokinetics, Pharmacodynamics And Interaction Effect With Metformin Following A Single Oral Dose Of DA-1241 In Healthy Male Subjects

This is a randomized, double blind, placebo controlled, single ascending dose study to assess the safety, tolerability, PK, PD and IE with metformin following a single oral dose of DA-1241 in healthy male subjects.

Start Date29 Mar 2017

Sponsor / Collaborator

Dong-A ST Co., Ltd.

100 Clinical Results associated with DA-1241

100 Translational Medicine associated with DA-1241

100 Patents (Medical) associated with DA-1241

Literatures (Medical) associated with DA-1241

01 Sep 2024·EXPERT OPINION ON INVESTIGATIONAL DRUGS

Investigational new drug approval of DA-1241: what we know about GPR119 targeting for MASH therapy?

Author: Al Smadi, Khaled ; Qureshi, Ammar ; Kayali, Zeid ; Ashouri, Besher

A review.A review discussing DA-1214 is a novel medication that showed promising results in improving steatosis and fibrosis in animal models.It also discusses MASH as a complex and challenging systemic disease, more data including more animal studies on its mechanism of inducing fibrosis regression followed by early clin. trials, are needed before judging the potential role for this drug in the realm of MASH treatment.

01 Oct 2023·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

GPR119 activation by DA-1241 alleviates hepatic and systemic inflammation in MASH mice through inhibition of NFκB signaling.

Article

Author: Yang, Eun-Kyoung ; Lee, Bo Ram ; Chae, Yuna ; Goo, Moon Jung ; Park, Hansu ; Kim, Tae-Hyoung ; Lee, Seung-Ho ; Kim, Mi-Kyung ; Jung, Il-Hoon

BACKGROUND AND PURPOSE:

GPR119 activation has been suggested to improve hyperglycemia, dyslipidemia and hepatic steatosis. But its therapeutic potential for metabolic dysfunction-associated steatohepatitis (MASH) are underexplored. Here, we investigated the effects of DA-1241, a novel GPR119 agonist, on MASH and explored its underlying mechanism of anti-inflammatory effects.

EXPERIMENTAL APPROACH:

The in vivo anti-MASH effect was assessed by examining the preventive effect in MS-MASH and Ob-MASH mice and the therapeutic effect in MASH with severe hyperglycemia and diet-induced obese (DIO)-MASH mice. Histological and biochemical changes in liver tissue were assessed. Both plasma and hepatic biomarkers related to inflammation and fibrosis were comprehensively analyzed. To understand its mode of action, changes in NFκB signaling were determined in HepG2 and THP-1 cells.

KEY RESULTS:

DA-1241 attenuated MASH progression and alleviated the MASH phenotypes in MASH mouse models with different etiologies, regardless of glucose-lowering activity. In DIO-MASH mice, DA-1241 significantly reduced biochemical parameters related to steatosis, inflammation and fibrosis in the liver with reduced plasma liver enzymes. When used in combination with a dipeptidyl peptidase 4 (DPP4) inhibitor, DA-1241 further improved the MASH phenotype by increasing endogenous glucagon-like peptide-1 effect. Notably, DA-1241 alone and in combination reduced liver inflammation and restored inflammation-related hepatic gene expression, leading to remission of systemic inflammation as assessed by plasma inflammatory cytokines and chemokines. We demonstrated that DA-1241 reduces macrophage differentiation through downregulation of NFκB signaling by activating GPR119.

CONCLUSION:

Our data suggest the therapeutic potential of DA-1241, alone and in combination with a DPP4 inhibitor, for MASH.

31 Mar 2022·Diabetes & metabolism journalQ3 · MEDICINE

DA-1241, a Novel GPR119 Agonist, Improves Hyperglycaemia by Inhibiting Hepatic Gluconeogenesis and Enhancing Insulin Secretion in Diabetic Mice

Q3 · MEDICINE

ArticleOA

Author: Park, Hyun Ki ; Kim, Youjin ; Kim, Ryeong-Hyeon ; Lee, Hangkyu ; Kang, Eun Seok ; Lee, Si Woo ; Wang, Hyejin

Background: We investigated the antidiabetic effects of DA-1241, a novel G protein-coupled receptor (GPR) 119 agonist, in vitro and in vivo.Methods: DA-1241 was administrated to high-fat diet (HFD)-fed C57BL/6J mice for 12 weeks after hyperglycaemia developed. Oral/intraperitoneal glucose tolerance test and insulin tolerance test were performed. Serum insulin and glucagon-like peptide-1 (GLP-1) levels were measured during oral glucose tolerance test. Insulinoma cell line (INS-1E) cells and mouse islets were used to find whether DA-1241 directly stimulate insulin secretion in beta cell. HepG2 cells were used to evaluate the gluconeogenesis and autophagic process. Autophagic flux was evaluated by transfecting microtubule-associated protein 1 light chain 3-fused to green fluorescent protein and monomeric red fluorescent (mRFP-GFP-LC3) expression vector to HepG2 cells.Results: Although DA-1241 treatment did not affect body weight gain and amount of food intake, fasting blood glucose level decreased along with increase in GLP-1 level. DA-1241 improved only oral glucose tolerance test and showed no effect in intraperitoneal glucose tolerance test. No significant effect was observed in insulin tolerance test. DA-1241 did not increase insulin secretion in INS-1E cell and mouse islets. DA-1241 reduced triglyceride content in the liver thereby improved fatty liver. Additionally, DA-1241 reduced gluconeogenic enzyme expression in HepG2 cells and mouse liver. DA-1241 reduced autophagic flow in HepG2 cells.Conclusion: These findings suggested that DA-1241 augmented glucose-dependent insulin release via stimulation of GLP-1 secretion, and reduced hepatic gluconeogenesis, which might be associated with autophagic blockage, leading to improved glycaemic control.

News (Medical) associated with DA-1241

14 May 2025

·www.prnewswire.com

MetaVia Reports First Quarter 2025 Financial Results and Provides Corporate Update

Announced Positive Top-Line Phase 1 MAD Trial Results for DA-1726 in Obesity, Demonstrating Compelling Weight Loss and Best-in-Class Potential for Glucose Control, Waist Reduction and Tolerability Additional Cohorts Planned to Determine Maximum Tolerated Dose of DA-1726 Successfully Completed a Private Placement Resulting in $10 Million in Gross Proceeds $11.2 Million in Cash at End of First Quarter, With the Additional $10.0 Million From the Private Placement, is Expected to Fund the Company Into 2026 CAMBRIDGE, Mass., May 14, 2025 /PRNewswire/ -- MetaVia Inc. (Nasdaq: MTVA), a clinical-stage biotechnology company focused on transforming cardiometabolic diseases, today announced financial results for the first quarter ended March 31, 2025, and provided a corporate strategic update. "In the first quarter and beyond, we achieved significant progress advancing the clinical development of our two next-generation cardiometabolic assets, highlighted by the positive results from Part 2 of the multiple ascending dose (MAD) Phase 1 trial of DA-1726, a novel, dual oxyntomodulin (OXM) analog agonist that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) for the treatment of obesity," stated Hyung Heon Kim, President and Chief Executive Officer of MetaVia. "We are now well capitalized into 2026 after a successful private placement of $10 million in aggregate gross proceeds. The data reinforce DA-1726's strong potential as a best-in-class therapy, demonstrating, without titration, a compelling safety and tolerability profile alongside dose-dependent weight loss, reaching a maximum reduction of 6.3% and a mean reduction of 4.3% at the 32 mg dose at Day 26 (p=0.0005). Additionally, at this dose, 83% of patients reported early satiety, and waist circumference decreased by an average of 1.6 inches and a maximum of 3.9 inches by Day 33, consistent with DA-1726's glucagon-driven effects on adipose tissue observed in preclinical models. The drug also achieved fasted glucose reductions of up to -18 mg/dL without hypoglycemic events, further underscoring its potential in obesity and related metabolic diseases. Cardiovascular safety remained favorable, with no QTcF prolongation and a decrease in mean heart rate across most cohorts, despite dual receptor agonism. Gastrointestinal side effects were mild, transient, and infrequent, suggesting a potentially superior tolerability profile compared to existing GLP-1 therapies." "Building on these encouraging findings, we are initiating higher-dose cohorts to identify the maximum tolerated dose and further unlock DA-1726's full therapeutic potential. Our aim is to deliver a safe, effective and sustainable obesity treatment for patients across a broad range of comorbidities, consistent with guidance from the U.S. Food and Drug Administration (FDA)." Mr. Kim continued, "This month, we presented compelling 16-week results, in a late-breaking poster, from our Phase 2a clinical trial of DA-1241, a novel G-Protein-Coupled Receptor 119 (GPR119) agonist, in patients with presumed metabolic dysfunction-associated steatohepatitis (MASH) at the European Association for the Study of the Liver (EASL) Congress 2025. DA-1241 is the first oral GPR119 agonist to demonstrate both liver-protective and glucose-regulating effects. The data showed that DA-1241 significantly reduced markers of liver injury, inflammation, and fibrosis, improved non-invasive liver assessments, CAP and FAST scores, and enhanced glycemic control in patients with prediabetes or type 2 diabetes. It was well tolerated with a favorable safety profile. These findings suggest DA-1241's benefits extend beyond glycemic control, driven by its anti-inflammatory and anti-fibrotic mechanisms. We believe its novel mechanism of action supports further development as monotherapy or in combination for MASH and metabolic diseases, and we are exploring additional combination therapies. We look forward to discussing these findings with the FDA in the first half of 2025." Fourth Quarter 2024 and Subsequent Highlights May 2025: Closed a private placement, which resulted in aggregate gross proceeds of $10 million priced at-the-market under Nasdaq rules. May 2025: Presented data from the 16-week Phase 2a clinical trial of DA-1241 in patients with presumed MASH in a late-breaking poster presentation at EASL Congress 2025. In this trial, DA-1241 significantly decreased plasma ALT levels, with a mean reduction of 22.8 U/L at 16 weeks, Controlled Attenuation Parameter (CAP) Score improved by 23.0 dB/m, indicating reduced liver fat content, while an improvement in FibroScan-AST (FAST) score and NIS-4, supports beneficial effects on liver health. April 2025: Reported additional positive top-line results from the 4-week MAD Part 2 of its Phase 1 clinical trial of DA-1726 for the treatment of obesity further demonstrating its best-in-class potential. DA-1726 demonstrated a clear dose-responsive trend in body weight reduction across the 8 mg to 32 mg range, indicating potentially greater efficacy at higher doses and longer duration of use. Additionally, body mass index, which shows body weight adjusted for height, showed a difference between the treatment group and the placebo 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 or QTcF changes up to 32 mg at 4 weeks of administration. April 2025: Reported 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. April 2025: Announced positive top-line results from the 4-week MAD Part 2 of its Phase 1 clinical trial of DA-1726 for the treatment of obesity. DA-1726 demonstrated excellent safety and tolerability, with positive clinical activity. The cohort receiving 32 mg of DA-1726 with no titration demonstrated a maximum reduction in body weight from baseline ranging up to -6.3%, and a mean body weight reduction of -4.3% at Day 26 (p=0.0005). Four out of six subjects on the 32 mg dose experienced mild gastrointestinal (GI) adverse events (AEs), most of which were resolved after 24 hours of occurrence. There were no treatment-related discontinuations or serious adverse events (SAEs). January 2025: Held an Advisory Committee meeting at the 9th Annual MASH-TAG 2025 Conference, to discuss the positive top-line 16-week results from the two-part Phase 2a clinical trial of DA-1241. Anticipated Clinical Milestones DA-1726 in Obesity: Additional SAD/MAD cohorts to explore the maximum tolerated dose expected to begin in the third quarter of 2025, with data expected in the fourth quarter of 2025. DA-1241 in MASH: The Company expects to have an end-of-Phase 2 meeting with the FDA in the first half of 2025. First Quarter Financial and Operating Results Research and Development (R&D) Expenses were approximately $2.3 million for the first quarter ended March 31, 2025, as compared to approximately $4.9 million for the first quarter ended March 31, 2024. The decrease of approximately $2.6 million was primarily attributable to (i) $2.9 million in lower direct R&D expenses related to DA-1241 product development and (ii) $0.2 million in lower direct other R&D costs. These decreases were partially offset by (i) $0.5 million in higher direct R&D expenses related to DA-1726 product development and (ii) $0.1 million in higher indirect R&D expenses related to employee compensation and benefits. Included in direct R&D costs were expenses totaling $1.1 million and $0.2 million for the three months ended March 31, 2025 and 2024, respectively, related to investigational drug manufacturing, non-clinical and preclinical costs incurred under the Shared Services Agreement with Dong-A (related party). General and Administrative Expenses were approximately $1.6 million for the first quarter ended March 31, 2025, compared to approximately $2.0 million for the first quarter ended March 31, 2024. The decrease of approximately $0.4 million was primarily due to (i) $0.4 million in lower consulting expenditures and (ii) $0.2 million in lower other G&A expenses. These decreases were partially offset by $0.2 million in higher employee compensation and benefits. Total Operating Expenses were approximately $3.9 million for the first quarter ended March 31, 2025, compared to approximately $6.9 million for the first quarter ended March 31, 2024. The approximately $3.0 million decrease was attributable to lower R&D and general and administrative expenses. Total Other Income for the three months ended March 31, 2025 and 2024 remained relatively consistent at $0.2 million. The net increase in the gain from the change in fair value of warrant liabilities during the three months ended March 31, 2025 was partially offset by a decrease in interest income earned on the Company's cash balance during the three months ended March 31, 2025. Net Loss for the first quarter ended March 31, 2025, was $3.7 million, or $0.36 per basic and diluted share, based on 10,264,202 weighted average shares of common stock outstanding, compared with a net loss of $6.7 million, or $1.32 per basic and diluted share, based on 5,089,408 weighted average shares of common stock outstanding for the first quarter ended March 31, 2025. Cash was $11.2 million as of March 31, 2025, compared with $16.0 million as of December 31, 2024. The company expects its cash position, together with the proceeds from the private placement transaction, will be adequate to fund operations into 2026. 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. In a Phase 1 multiple ascending dose (MAD) trial in obesity, DA-1726 demonstrated best-in-class potential for weight loss, glucose control, and waist reduction. 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 . 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 and its subsequent Quarterly Reports on Form 10-Q. 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 [email protected] Rx Communications Group Michael Miller +1-917-633-6086 [email protected] - Tables to Follow - SOURCE MetaVia Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 1Financial StatementPhase 2

09 May 2025

·www.prnewswire.com

MetaVia Announces $10.0 Million Private Placement Priced At-The-Market under Nasdaq Rules

CAMBRIDGE, Mass., May 9, 2025 /PRNewswire/ -- MetaVia Inc. (Nasdaq: MTVA) ("MetaVia"), a clinical-stage biotechnology company focused on transforming cardiometabolic diseases, today announced a private placement that MetaVia estimates will result in gross proceeds of approximately $10.0 million, before deducting the placement agent's fees and other offering expenses payable by the company. MetaVia currently intends to use the net proceeds from the offering for working capital and corporate purposes, including to continue the clinical development of DA-1726 for the treatment of obesity. The terms of the offering include an agreement to purchase (i) 9,479,345 shares of MetaVia's common stock at a price of $0.71 per share, and (ii) 4,605,162 pre-funded warrants to purchase shares of MetaVia's common stock at a price of $0.709 per pre-funded warrant. The pre-funded warrants have an exercise price of $0.001 per pre-funded warrant, and will be exercisable beginning on the effective date of receiving stockholder approval for the shares of MetaVia's common stock issuable upon exercise of the pre-funded warrants. The private placement was priced at-the-market under Nasdaq rules, and the closing of the private placement is expected to occur on or about May 12, 2025, subject to customary closing conditions. The offer and sale of the securities in the private placement, including the shares of common stock underlying the pre-funded warrants, are being made to certain institutional accredited investors in a transaction not involving a public offering pursuant to Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and Rule 506(b) of Regulation D promulgated thereunder, and have not been registered under the Securities Act or applicable state securities laws. Accordingly, the securities to be issued in the private placement and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement with the Securities and Exchange Commission ("SEC") or an applicable exemption from the registration requirements of the Securities Act and such other applicable state securities laws. MetaVia has agreed to file a registration statement with the SEC covering the resale of the shares of MetaVia common stock issued and underlying the pre-funded warrants in the private placement and to obtain stockholder approval for the shares of MetaVia common stock underlying the pre-funded warrants issued in the private placement. Ladenburg Thalmann & Co. Inc. is acting as the exclusive placement agent for the offering. This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. 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 . 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, which include, among other statements, statements regarding the expected timing of the closing of the offering, the satisfaction of customary closing conditions related to the offering, the anticipated use of the net proceeds from the offering, the filing of a registration statement with the SEC, and obtaining stockholder approval for the shares of MetaVia common stock issued and underlying the pre-funded warrants in the private placement. 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; MetaVia's expectations regarding the sufficiency of its existing cash on hand to fund MetaVia's 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 and subsequent Quarterly Reports on Form 10-Q. 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 [email protected] Rx Communications Group Michael Miller +1-917-633-6086 [email protected] SOURCE MetaVia Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Clinical Result

07 May 2025

·www.prnewswire.com

MetaVia Presents Data on DA-1241, a GPR119 Agonist, Demonstrating Both Hepatoprotective and Glucose-Regulating Effects in Patients with Presumed MASH, at the EASL Congress 2025

DA-1241 Significantly Decreased Plasma ALT levels, with a Mean Reduction of 22.8 U/L After 16 Week-Treatment Controlled Attenuation Parameter (CAP) Score Improved by 23.0 dB/m, Indicating Reduced Liver Fat ContentImprovement in Systemic Inflammatory and Fibrosis Biomarkers Supports Beneficial Effects on Liver HealthCAMBRIDGE, Mass., May 7, 2025 /PRNewswire/ -- MetaVia Inc. (Nasdaq: MTVA), a clinical-stage biotechnology company focused on transforming cardiometabolic diseases, today announced that data from its Phase 2a clinical trial of DA-1241, a novel G-Protein-Coupled Receptor 119 (GPR119) agonist, in patients with presumed metabolic dysfunction-associated steatohepatitis (MASH), demonstrates both hepatoprotective and glucose-regulating effects. The data will be presented in late-breaking poster presentation at the European Association for the Study of the Liver (EASL) Congress 2025, taking place May 7-10, 2025, in Amsterdam, the Netherlands. Continue Reading ALT & HbA1c A total of 109 subjects with presumed MASH and qualifying baseline alanine transaminase (ALT) and imaging analysis were randomized to receive DA-1241 50 mg, DA-1241 100 mg alone, DA-1241 100 mg with a dipeptidyl peptidase 4 inhibitor (DPP4i), or placebo (PBO) in a 1:2:2:2 ratio, once daily for 16 weeks. The primary efficacy endpoint was the change from baseline in ALT after 16 weeks of treatment. "The full data from our Phase 2 clinical study, as presented at the prestigious EASL Congress, confirm that DA-1241 is the first oral GPR119 agonist to demonstrate both hepatoprotective and glucose-regulating effects in presumed MASH patients," stated Hyung Heon Kim, President and Chief Executive Officer of MetaVia. "Importantly, treatment with DA-1241 significantly reduced key markers of liver injury, inflammation, and fibrosis, while also improving non-invasive liver assessments such as CAP and FibroScan-AST (FAST) scores. In addition, DA-1241 efficiently improved glycemic control in patients with comorbid prediabetes and type 2 diabetes. DA-1241 was well tolerated across patient groups, with a favorable safety profile. These results suggest that DA-1241's hepatoprotective effects are likely driven by its anti-inflammatory and anti-fibrotic actions rather than just glucose lowering, offering a promising multi-faceted therapeutic approach for patients at risk of progressive liver disease. Based on this data, we continue to believe that the novel mechanism of action of DA-1241 supports further development as either a monotherapy or combination therapy for MASH and metabolic diseases. We continue to conduct pre-clinical studies to explore other combination therapies for DA-1241, which may provide additional benefits to treat patients along the full spectrum on MASH. We look forward reviewing these findings at an end of Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in the first half of 2025." In subjects with baseline ALT levels between 40 and 200 U/L, DA-1241 treatment led to dose-dependent reductions in ALT, with the 100 mg dose producing a significant 22.8 U/L decrease after 16 weeks (p < 0.05 vs. placebo). These effects were observed regardless of diabetes status and were accompanied by improvements in non-invasive tests (NITs) used to monitor MASH progression such as FAST, CAP, MRI-PDFF and NIS-4 score. Specifically, the average FAST score declined from 0.559 to 0.371, indicating improvements in liver fibrosis and fat accumulation. Liver fat, measured by CAP, was reduced by 23.0 dB/m with DA-1241 100 mg compared to just 1.4 dB/m with placebo. Importantly, the 100 mg dose significantly lowered biomarkers of systemic inflammation (hs-CRP, CCL2) and fibrosis (TIMP1) (p < 0.05 vs. placebo), consistent with results from MASH mouse studies. Cytokeratin 18, a marker of liver cell death, also decreased significantly by 30.5% (p < 0.05 vs. placebo). Beyond liver-related outcomes, DA-1241 100 mg produced rapid and significant reductions in hemoglobin A1c (HbA1c) of 0.37%p, 0.41%p, and 0.54%p at weeks 4, 8, and 16, respectively, from a baseline of 6.99%—despite nearly half of the participants being non-diabetic (p < 0.05 vs. placebo). In the subgroup of presumed MASH patients with type 2 diabetes, HbA1c decreased by 1.08%p. When 100 mg DA-1241 was co-administered with a DPP4 inhibitor pill preventing degradation of endogenous GLP-1, metabolic benefits were further enhanced without causing weight loss. DA-1241 was well tolerated among presumed MASH patients, with no treatment-emergent adverse events (TEAEs) leading to discontinuation, except for one case in the placebo group. Presentation Details: Title: DA-1241, a GPR119 Agonist, Demonstrates Hepatoprotective and Glucose-Regulating Effects in a 16-week Randomized Placebo-Controlled Trial in Presumed Metabolic Dysfunction-Associated Steatohepatitis (MASH) Patients Presenting Author: Rohit Loomba, MD, MHSc, Professor of Medicine in the Division of Gastroenterology, and Adjunct Professor in the Division of Epidemiology at University of California, San Diego. Final Abstract ID: LBP-005 Session: Late Breaker Posters Presentation Start: May 7, 2025, 8:30 am CET A copy of the poster is available on the Posters section of the MetaVia website. About DA-1241 DA-1241 is a novel G-Protein-Coupled Receptor 119 (GPR119) agonist with development optionality as a standalone and/or combination therapy for both MASH and type 2 diabetes (T2D). Agonism of GPR119 in the gut promotes the release of key gut peptides GLP-1, GIP, and PYY. These peptides play a further role in glucose metabolism, lipid metabolism and weight loss. DA-1241 has beneficial effects on glucose, lipid profile and liver inflammation, supported by potential efficacy demonstrated during in vivo preclinical studies. The therapeutic potential of DA-1241 has been demonstrated in multiple pre-clinical animal models of MASH and T2D where DA-1241 reduced hepatic steatosis, inflammation, fibrosis, and improved glucose control. Furthermore, in Phase 1a, 1b and 2a trials, DA-1241 was well tolerated in both healthy volunteers and those with T2DM. In a Phase 2a clinical study, DA-1241 demonstrated direct hepatic action in addition to its glucose lowering effects. 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. In a Phase 1 multiple ascending dose (MAD) trial in obesity, DA-1726 demonstrated best-in-class potential for weight loss, glucose control, and waist reduction. 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 . 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. 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 [email protected] Rx Communications Group Michael Miller +1-917-633-6086 [email protected] SOURCE MetaVia Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 2Phase 1

100 Deals associated with DA-1241

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 2	United States	Neuromed Pharmaceuticals Ltd.	30 Jan 2022
Nonalcoholic Steatohepatitis	Phase 2	United States	Neuromed Pharmaceuticals Ltd.	30 Jan 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06054815 (PRNewswire) Manual	Phase 2	Nonalcoholic Steatohepatitis	109	DA-1241 50 mg	mjhqdsgkyn(rhtzstmane) = oivqrrniey jarfhhilul (lhewsdllgu ) View more	Positive	07 May 2025
				DA-1241 100 mg	mjhqdsgkyn(rhtzstmane) = ajickonzfh jarfhhilul (lhewsdllgu ) View more
NCT03646721 (Part 2, EASD2021)	Phase 1	Diabetes Mellitus, Type 2 HbA1c \| body weight \| glucose AUC 0-4h ... View more	84	DA-1241 25mg	lfeqcphkgd(bztcqpezsx) = The most frequent TEAEs were mild GI side effects (nausea, diarrhea, abdominal pain), all resolved spontaneously qgftwxwptn (rbbkafsbey )	Positive	01 Oct 2021
				Placebo
NCT03646721 (Part 1 of a phase 1b multiple ascending dose (MAD) study, EASD2021)	Phase 1	-	24	DA-1241 50mg	eienivsxbv(tmjdolesxq) = wvbkifsema bbpkmnpobv (allzlzjpgk ) View more	Positive	30 Sep 2021
				DA-1241 100mg	eienivsxbv(tmjdolesxq) = lbbzmiwyal bbpkmnpobv (allzlzjpgk ) View more
ADA2021	Not Applicable	-	24	DA-1241 50 mg	vzhtwakpkz(xmgfbuspkk) = imwkckwepp nnumsducmz (gqjbzfdtfz ) View more	-	01 Jun 2021
				DA-1241 100 mg	vzhtwakpkz(xmgfbuspkk) = jlrbkpzeey nnumsducmz (gqjbzfdtfz ) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

DA-1241

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation