8-K: Galectin Therapeutics Provides Corporate Update and Highlights NAVIGATE Trial Results for MASH Cirrhosis Treatment

Galectin Therapeutics announced results from its NAVIGATE trial of belapectin for MASH cirrhosis, showing a meaningful reduction in the development of new esophageal varices at the 2 mg dose, alongside ongoing analyses and plans to explore partnership opportunities.

Summary

• Galectin Therapeutics is developing belapectin, a galectin-3 inhibitor, for the treatment of MASH cirrhosis and cancer.
• The NAVIGATE trial evaluated belapectin in patients with MASH cirrhosis and portal hypertension, a condition with no approved therapies.
• The 2 mg dose of belapectin showed a 43.2% reduction in the incidence of new varices compared to placebo in the intention-to-treat (ITT) population, though this was not statistically significant.
• In the per-protocol population, the reduction in new varices was 48.9% with the 2 mg dose.
• Belapectin demonstrated a favorable safety profile with a low rate of adverse events and no drug-related serious adverse events.
• The company is analyzing 18-month data and expects 36-month data from available patients by the end of Q1 2025.
• Galectin is exploring partnership opportunities to further develop belapectin for MASH cirrhosis.
• Belapectin is also being studied in combination with pembrolizumab for the treatment of cancer, with encouraging results in a Phase 1 trial.

Sentiment

Score: 5

Explanation: The sentiment is mixed. While the safety profile and some efficacy data are positive, the failure to achieve statistical significance in the primary endpoint and the need for potential partnerships or capital raises temper the overall sentiment.

Positives

• Belapectin has a novel mechanism of action as a galectin-3 inhibitor.
• The 2 mg dose of belapectin demonstrated a meaningful reduction in the development of new esophageal varices in two separate trials.
• Belapectin has a favorable safety profile.
• The company is the only one exclusively focused on treatment for MASH cirrhosis and portal hypertension.
• Encouraging clinical response in difficult-to-treat cancers in combination with a checkpoint inhibitor was observed.
• IND filed and approval to proceed received from FDA for Head & Neck cancer.

Negatives

• The reduction in varices incidence with belapectin 2 mg was not statistically significant in the overall ITT population of the NAVIGATE trial.
• Higher dropout rate in the NAVIGATE trial than expected (18.3% observed vs. 10% expected).
• A lack of dose response was observed at higher doses of belapectin in both the GT-026 and NAVIGATE trials.

Risks

• The NAVIGATE trial's primary analysis was conducted at 18 months instead of 36 months, which may have impacted the results.
• The company has incurred operating losses since its inception.
• Future clinical studies may not produce positive results or could be time-consuming and costly.
• The company may be unsuccessful in developing partnerships or obtaining capital to complete clinical trials.

Future Outlook

The company plans to continue analyzing the 18-month data from the NAVIGATE trial and expects to have 36-month data from available patients by the end of Q1 2025. They are also exploring partnership opportunities to further develop belapectin for MASH cirrhosis and continuing their cancer immunotherapy program.

Management Comments

• Prevention of varices in this high-unmet-need population is a recognized clinical need, and we believe an acceptable regulatory endpoint; FDA accepted central EGD reading.
• The distinct MOA of belapectin as Galectin 3 inhibitor positions it as a favorable and complementary candidate for combination therapy in MASH cirrhosis.

Industry Context

The announcement relates to the broader trend of developing treatments for MASH cirrhosis, a growing health concern with a significant unmet medical need. The results position belapectin as a potential first-in-class therapy for this indication, although it faces competition from other companies developing treatments for MASH and related liver diseases.

Comparison to Industry Standards

• The NAVIGATE trial's results are difficult to directly compare to industry standards as there are no approved therapies for the prevention of varices in MASH cirrhosis.
• However, the reduction in new varices observed with belapectin can be compared to results seen in trials of other MASH therapies, such as:
• Intercept Pharmaceuticals' Ocaliva, which showed a reduction in fibrosis but did not meet its primary endpoint in a Phase 3 trial.
• Madrigal Pharmaceuticals' resmetirom, which demonstrated statistically significant improvements in MASH resolution and fibrosis in a Phase 3 trial.
• Gilead Sciences' selonsertib, which failed to meet its primary endpoint in two Phase 3 trials for MASH.
• The safety profile of belapectin appears favorable compared to some other MASH therapies, which have been associated with adverse events such as pruritus and increased LDL cholesterol.

Stakeholder Impact

• Shareholders: Potential impact due to the mixed trial results and the need for further development and potential partnerships.
• Employees: Continued employment dependent on the company's ability to secure funding and advance its clinical programs.
• Patients: Potential for a new treatment option for MASH cirrhosis if belapectin is successfully developed and approved.
• Suppliers: No significant impact mentioned in the document.
• Creditors: Potential impact if the company is unable to secure funding or generate revenue in the future.

Next Steps

• Analyze 18-month data from the NAVIGATE trial.
• Obtain 36-month data from available patients in the NAVIGATE trial by the end of Q1 2025.
• Explore partnership opportunities for belapectin in MASH cirrhosis.
• Continue the cancer immunotherapy program with belapectin and pembrolizumab.

Key Dates

Keywords

MASH Cirrhosis, Portal Hypertension, Galectin-3 Inhibitor, Belapectin, Esophageal Varices, NAVIGATE Trial, Cancer Immunotherapy, Pembrolizumab, Clinical Trial, Biotechnology