8-K: MetaVia's DA-1726 Shows Promising Weight Loss Results in Phase 1 Trial, Demonstrating Best-in-Class Potential for Obesity Treatment

MetaVia Inc. reports positive top-line results from its Phase 1 clinical trial of DA-1726, a novel dual agonist for obesity, showcasing dose-dependent weight loss and a favorable safety profile.

Summary

• MetaVia Inc. announced positive top-line results from the Phase 1 clinical trial of DA-1726, a dual oxyntomodulin analog agonist targeting obesity.
• The 28-day study involved 36 subjects and showed a dose-responsive trend in body weight reduction between 8 mg and 32 mg.
• BMI also showed a significant difference between the treatment and placebo groups, supporting the drug's effect on weight-related outcomes.
• DA-1726 did not show clinically significant increases in heart rate or QTcF changes up to 32 mg at 4 weeks.
• At the 32 mg dose, DA-1726 demonstrated a maximum weight loss of -6.3% and a mean weight loss of -4.3% at Day 26.
• The drug also showed a maximum lowering of fasted glucose of -18 mg/dL and a mean lowering of -5.3 mg/dL at Day 26.
• Waist circumference reduction reached a maximum of 3.9 inches and a mean reduction of 1.6 inches at Day 33.
• The company plans a Phase 1 Part 3 study to evaluate DA-1726 in patients who discontinued Wegovy early.
• Additional cohorts will be included to assess the maximum tolerated dose of DA-1726.
• The company's pre-funded warrants were exercised for 1,430,000 shares of common stock following the initial top-line data announcement.

Sentiment

Score: 8

Explanation: The document presents positive clinical trial results, highlighting the potential of DA-1726 as a best-in-class obesity treatment. The safety and tolerability data, along with the dose-dependent weight loss, contribute to a positive outlook. However, risks associated with regulatory approval and commercialization temper the overall sentiment.

Positives

• DA-1726 demonstrated a dose-responsive trend in body weight reduction.
• The drug showed a significant difference in BMI between the treatment and placebo groups.
• DA-1726 did not show clinically significant increases in heart rate or QTcF changes.
• The drug demonstrated compelling weight loss, glucose lowering, and waist circumference reduction.
• DA-1726 showed excellent safety and tolerability in the MAD portion of the study.
• Early satiety was observed in most subjects receiving the 32 mg dose.
• The company's pre-funded warrants were exercised for 1,430,000 shares of common stock.

Negatives

• Four out of six subjects on the 32 mg dose experienced mild gastrointestinal AEs after the first dose, though most resolved within 24 hours.
• Mild vomiting occurred with 3 subjects but resolved within 9 hours, 2 subjects after 1st dose with no reoccurrence.
• Mild nausea occurred with 2 subjects after the 1st dose but resolved within 12 hours, no nausea after 2nd to the last dose.
• Constipation occurred with 2 subjects and resolved within 3 days.
• Abdominal distension with 1 subject and resolved in 14 hours.

Risks

• The forward-looking statements are subject to risks and uncertainties, including the ability to obtain regulatory approval and the cooperation of contract manufacturers and clinical study partners.
• There are risks associated with the company's ability to execute its commercial strategy and the sufficiency of its existing cash on hand.
• Public opinion and scrutiny of treatments for obesity and overweight patients may impact public perception of the company and DA-1726.
• The company may be required to make significant payments under the 2022 License Agreement.
• Preliminary, interim and topline data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.

Future Outlook

The company plans to explore the maximum tolerated dose of DA-1726 and evaluate its efficacy and tolerability in patients who discontinued Wegovy early. They are also actively searching for a combination/licensing partner for DA-1241.

Management Comments

• Hyung Heon Kim, President and Chief Executive Officer of MetaVia, stated that the new Phase 1 MAD data further highlights DA-1726's potential to be a best-in-class obesity treatment.
• Mr. Kim believes that 32 mg will likely be the starting dose for future clinical trials based on the robust safety and tolerability profile of DA-1726.
• Mr. Kim concluded that the body of data for DA-1726 provides a compelling case for its future potential as a treatment for obesity.

Industry Context

The announcement comes amid significant interest and investment in obesity treatments, as evidenced by recent deals involving GLP-1 agonists and other related therapies. MetaVia is positioning DA-1726 as a potentially best-in-class treatment in this competitive landscape.

Comparison to Industry Standards

• DA-1726's 3:1 balanced activation of GLP-1 and glucagon receptors offers a promising alternative to current GLP-1 agonists, addressing tolerability challenges.
• In pre-clinical mouse models, DA-1726 resulted in improved weight loss compared to semaglutide (Wegovy) and cotadutide.
• DA-1726 elicited similar weight reduction, while consuming more food, compared to tirzepatide (Zepbound) and survodutide, while also preserving lean body mass and demonstrating improved lipid-lowering effects compared to survodutide.
• Recent obesity drug transactions include Novo Nordisk/United Biotechnology, AbbVie/Gubra, and Roche/Zealand Pharma, highlighting the industry's focus on GLP-1, GIP, and glucagon-based therapies.

Stakeholder Impact

• Positive results could benefit shareholders through increased stock value.
• Successful development of DA-1726 could provide a new treatment option for patients with obesity.
• Employees may benefit from the company's growth and success.

Next Steps

• The company plans a Phase 1 Part 3 study to evaluate DA-1726 in patients who discontinued Wegovy early.
• Additional cohorts will be included to assess the maximum tolerated dose of DA-1726.
• The company will be actively searching for a combination/licensing partner for DA-1241.
• Release other exploratory end points including MRI-PDFF at major medical conferences.

Key Dates

Keywords

DA-1726, obesity, clinical trial, weight loss, GLP-1, glucagon, cardiometabolic, MASH, MetaVia, agonist