Galectin Therapeutics (NASDAQ:GALT) hosted a virtual key opinion leader (KOL) event to discuss belapectin as a potential treatment for patients with metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis and portal hypertension, a population the speakers described as having substantial unmet medical need and no FDA-approved pharmacologic therapies.
Rising prevalence and limited treatment options
Khurram Jamil, the company’s chief medical officer, said the prevalence of MASH cirrhosis continues to rise in the U.S., driven largely by increasing rates of obesity and type 2 diabetes. He described MASH cirrhosis as a progressive, life-threatening condition that can lead to hepatic decompensation, liver failure, and the need for transplant, noting that MASH cirrhosis has become the leading indication for liver transplant in the U.S.
Belapectin mechanism and development rationale
Jamil said galectin-3 is upregulated in multiple chronic inflammatory conditions and is a driver of fibrosis. He described belapectin as a complex carbohydrate that binds with galectin-3 receptors to reduce its expression. According to Jamil, animal and human clinical studies have shown that targeting galectin-3 can reduce fibrosis and inflammation, and preclinical studies have shown reductions in galectin-3 expression, collagen deposition, portal pressure, and overall fibrosis.
KOL perspective on cirrhosis progression and clinical need
Dr. Naga Chalasani, professor of medicine at Indiana University School of Medicine, provided an overview of the clinical course of cirrhosis, describing an initial compensated stage followed by development of portal hypertension and, later, decompensation. He characterized portal hypertension as an “ominous milestone” that can lead to esophageal varices and variceal bleeding, which he said can be catastrophic and carry mortality risk during hospitalization.
Chalasani said there are currently no approved treatments for NASH cirrhosis. He noted that resmetirom and semaglutide have been approved conditionally for compensated stage 2 and stage 3 fibrosis patients, but not for cirrhosis. He said current management for NASH cirrhosis largely centers on lifestyle interventions and comorbidity management, with bariatric surgery less frequently pursued once portal hypertension is present due to higher risk. He added that clinicians screen cirrhosis patients for varices through periodic endoscopy and for liver cancer due to elevated risk.
NAVIGATE trial design and varices findings
Chalasani reviewed Galectin’s prior phase 2b study (GT-026), published in Gastroenterology, which evaluated placebo versus belapectin 2 mg/kg and 8 mg/kg. The primary endpoint was change in hepatic venous pressure gradient (HVPG) at 12 months, which he described as the “gold standard” for portal hypertension. He said the 2 mg/kg group showed significant benefit on HVPG change and a significant reduction in development of varices, while the 8 mg/kg group did not, which he attributed to a pharmacokinetic explanation.
He then outlined the NAVIGATE trial, a 78-week study that enrolled patients with NASH cirrhosis and portal hypertension determined non-invasively, with baseline endoscopy confirming no esophageal varices. The trial included placebo, belapectin 2 mg/kg, and belapectin 4 mg/kg. Chalasani highlighted what he called a “brilliant aspect” of the design: centralized adjudication of endoscopy by three blinded expert endoscopists at baseline and end of study, which he said has since been protocolized by other cirrhosis trials.
According to Chalasani, the composite primary endpoint in the intention-to-treat population was not met, though he noted a numerical difference of nearly 10 percentage points lower with 2 mg/kg. He emphasized that the incidence of new varices appeared lower with belapectin 2 mg/kg, consistent with GT-026, describing about a 50% reduction in new-onset esophageal varices. He also pointed to a treatment effect on medium and large varices, while cautioning the trial was not powered for those outcomes. Chalasani said safety was “excellent,” with no signal for drug-induced liver injury.
Biomarker data and non-invasive monitoring
Dr. Naim Alkhouri, chief academic officer at Summit Clinical Research and director of the Cirrhotic Liver Program at North Shore Gastroenterology, reviewed biomarker data from NAVIGATE at 18 months. He said the study population represented advanced disease, with protocol-defined signs of portal hypertension, including lower platelet counts, liver stiffness around 23.5, and enlarged spleen size (average about 13.8 cm). He said over 55% met criteria for clinically significant or probable portal hypertension based on Baveno criteria.
Alkhouri described results showing an 8.4% decrease in liver stiffness with belapectin compared to a slight increase with placebo, along with fewer patients meeting thresholds for clinically significant worsening (including a ≥30% increase in liver stiffness or an increase of ≥5 kilopascal units). He also discussed analyses incorporating the enhanced liver fibrosis (ELF) score, stating that patients with ELF above 11.3 have been shown in other studies to be at higher risk of decompensating events. In that subgroup, he said about 43% developed varices on placebo versus 22% on belapectin.
Alkhouri also reviewed “concordant” biomarker endpoints combining liver stiffness and ELF changes, and additional fibrosis biomarkers including YKL-40, PRO-C3, a PRO-C3 to CTX-III ratio (which he described as reflecting fibrogenesis versus fibrolysis), and PRO-C4. He said these measures generally showed less worsening or improvement with belapectin compared to placebo. He reiterated that safety, serious adverse events, and discontinuation rates were comparable to placebo.
During Q&A, Chalasani said he was not aware of other trials studying the same population or focusing on prevention of varices and variceal bleeding, calling it a unique aspect of belapectin’s program. Alkhouri said the two most clinically informative fibrosis markers are vibration-controlled transient elastography (VCTE) and ELF, and argued that combining an imaging biomarker with a blood-based marker can improve confidence in changes over time, particularly given VCTE accuracy challenges in higher-BMI MASH patients.
Both KOLs said liver biopsy is no longer routinely required to diagnose cirrhosis in clinical practice and has largely been replaced by non-invasive modalities, with biopsy reserved for diagnostic uncertainty or when histology-driven trial endpoints require baseline biopsies.
In closing remarks, Jamil said the company is focused on advancing discussions with regulators and identifying a partner to move the belapectin program forward, and said Galectin plans to continue sharing updates on regulatory progress in coming weeks and months.
About Galectin Therapeutics (NASDAQ:GALT)
Galectin Therapeutics, Inc is a clinical-stage biotechnology company focused on the development of novel therapies that target galectin proteins, which are implicated in fibrotic, inflammatory and malignant diseases. The company’s lead product candidate, belapectin (formerly GR-MD-02), is a galectin-3 inhibitor being evaluated in Phase 2 clinical trials for nonalcoholic steatohepatitis (NASH) with cirrhosis. In addition to its core pipeline in fibrotic liver disease, Galectin Therapeutics continues to explore the potential of its galectin inhibitors in oncology and other indications driven by abnormal tissue remodeling.
Founded in 2000, the company is headquartered in Norcross, Georgia, where it oversees discovery research, preclinical studies and clinical trial coordination.
