8-K: Galectin Therapeutics Presents Promising NAVIGATE Trial Results at EASL 2025 Congress

Galectin Therapeutics' NAVIGATE trial shows belapectin 2 mg/kg significantly reduces new varices in MASH cirrhosis patients in the per-protocol population.

Summary

• Galectin Therapeutics presented NAVIGATE trial results at the European Association for the Study of the Liver (EASL) 2025 Congress.
• The NAVIGATE study evaluated belapectin in patients with MASH cirrhosis and portal hypertension.
• 355 patients were randomized to receive belapectin at 2 mg/kg, 4 mg/kg, or placebo every other week for 18 months.
• In the per-protocol population (PPP, N=287), the incidence of varices was 11.3% in the belapectin 2 mg/kg group, 13.5% in the 4 mg/kg group, and 22.3% in the placebo group.
• The 2 mg/kg dose demonstrated a 49.3% reduction in incidence of new varices compared to placebo (p=0.04).
• Liver stiffness, measured via FibroScan, showed a notably lower proportion of patients with worsening in liver stiffness in the belapectin groups.
• The safety profile of belapectin remains encouraging, with adverse events comparable across the three cohorts.

Sentiment

Score: 7

Explanation: The document presents positive results from the NAVIGATE trial, particularly the statistically significant reduction in varices with the 2 mg/kg dose. The safety profile is also encouraging. However, the lack of statistical significance in the ITT population and the need for further development temper the overall sentiment.

Positives

• Statistically significant reduction in new varices with belapectin 2 mg/kg in the per-protocol population.
• Fewer patients experienced worsening liver stiffness with belapectin treatment.
• Encouraging safety profile with adverse events comparable to placebo.
• The 2 mg/kg dose demonstrated a 49.3% reduction in incidence of new varices compared to placebo (p=0.04).
• The 2mg/kg group significantly outperformed placebo by 66% (p=0.02) and 51% (p=0.03) respectively in each category of liver stiffness.

Negatives

• The 4 mg/kg dose did not show statistically significant reduction in new varices compared to placebo.
• The primary endpoint in the ITT population was not statistically significant.

Risks

• Full analysis of the NAVIGATE trial data may not produce positive data.
• Galectin may not be successful in developing effective treatments and/or obtaining the requisite approvals for the use of belapectin or any of its other drugs in development.
• The Company may not be successful in scaling up manufacturing and meeting requirements related to chemistry, manufacturing and control matters.
• The Companys current clinical trial and any future clinical studies may not produce positive results in a timely fashion, if at all, and could require larger and longer trials, which would be time consuming and costly.
• Regardless of the results of any of its development programs, Galectin may be unsuccessful in developing partnerships with other companies or raising additional capital that would allow it to further develop and/or fund any studies or trials.
• Galectin has incurred operating losses since inception, and its ability to successfully develop and market drugs may be impacted by its ability to manage costs and finance continuing operations.

Future Outlook

Galectin Therapeutics hopes that its development program for belapectin will lead to the first therapy for the treatment of MASH with cirrhosis and that its lead compounds will be successful in cancer immunotherapy and in other therapeutic indications. Advancement of these additional clinical programs is largely dependent on finding a suitable partner.

Management Comments

• Dr. Naim Alkhouri commented that the NAVIGATE study reinforces belapectin's potential in addressing a significant unmet need in patients with MASH cirrhosis and clinically significant portal hypertension.
• Dr. Naga Chalasani stated that the NAVIGATE study contributes meaningful new evidence supporting belapectin's therapeutic potential in MASH cirrhosis and that belapectin is showing benefit evidence across several clinically important endpoints.

Industry Context

The announcement highlights the growing interest in therapies for MASH cirrhosis and portal hypertension, a significant unmet medical need. Galectin Therapeutics is positioning belapectin as a potential first-in-class treatment in this area, with a focus on preventing varices and halting disease progression.

Comparison to Industry Standards

• The NAVIGATE trial's focus on preventing esophageal varices aligns with a growing interest in this clinical endpoint across the field of MASH cirrhosis research.
• The use of FibroScan to measure liver stiffness is a standard non-invasive assessment method in liver disease trials, allowing for comparison with other studies.
• The trial design, including the use of a per-protocol population, is consistent with regulatory expectations for MASH trials, particularly in the context of biopsy results.

Stakeholder Impact

• Positive impact on patients with MASH cirrhosis and portal hypertension due to the potential for a new treatment option.
• Potential benefit to shareholders due to positive clinical trial results.
• Opportunity for employees to contribute to the development of a novel therapy.

Next Steps

• Ongoing analyses for 18-month data, with additional biomarker data expected by the end of the second quarter 2025.
• Exploring partnership opportunities.
• Continued clinical development of belapectin.

Key Dates

Keywords

belapectin, MASH cirrhosis, portal hypertension, NAVIGATE trial, Galectin Therapeutics, varices, liver stiffness, EASL 2025, galectin-3 inhibitor