Slide 1: Belapectin for MASH Cirrhosis and Portal Hypertension
Belapectin for MASH Cirrhosis and Portal Hypertension June 2025
Slide 2: Today's Agenda
Khurram Today’s Agenda 01 02 03 04 05 06 Moderator Michael Cozart, LifeSci Consulting Galectin Company Introduction Joel Lewis (CEO & President) Belapectin as Galectin-3 Inhibitor for MASH cirrhosis & Portal Hypertension Khurram Jamil, M.D. (CMO) Unmet Need & Patient Landscape Naga Chalasani, M.D. C
Slide 3: Company introduction
Company introduction Joel Lewis CEO & President
Slide 4: Belapectin as Galectin-3 Inhibitor for MASH cirrhosis & Portal Hypertension
Belapectin as Galectin-3 Inhibitor for MASH cirrhosis & Portal Hypertension Khurram Jamil, M.D. Chief Medical Officer
Slide 5: Belapectin for MASH Cirrhosis and Portal Hypertension
5 Belapectin for MASH Cirrhosis and Portal Hypertension Galectin-3, a β-galactoside-binding lectin, is upregulated in fibrosis and promotes fibroblast activation1 Belapectin a galectin-3 inhibitor reduced galectin-3 expression and fibrogenic activity in pre-clinical studies2,3,4 In a phase 2b trial(
Slide 6: Belapectin: a Proprietary Galectin-3 Inhibitor with Low Toxicity and Anti-fibrotic Activity
Belapectin Preclinical Data: In animal models of MASH (streptozotocin High-Fat Diet mice1) and cirrhosis (thioacetamide treated rats2) belapectin was associated with decreased: Galectin-3 staining and galectin-3 expression in macrophages NAFLD Activity Scores Collagen-1 expression Hepatic collagen d
Slide 7: Unmet Need & Patient Landscape
Unmet Need & Patient Landscape Naga Chalasani, M.D.
Slide 8: MASH disease overview and risk factors
Metabolic dysfunction-associated steatohepatitis (MASH), previously known as non-alcoholic steatohepatitis (NASH), is characterized by fat accumulation, inflammation and fibrosis of the liver1 3%-5% of the global population is estimated to be affected by MASH, though the disease is considered to be
Slide 9: When to Intervene in Cirrhosis - before it's too late
HPVG=hepatic venous pressure gradient. There are no approved therapies to reverse portal hypertension once it develops in MASH Cirrhosis 9 When to Intervene in Cirrhosis- before its too late! Compensated cirrhosis Decompensated cirrhosis No Portal Hypertension Portal Hypertension No varices No varic
Slide 10: Cirrhosis Current Treatment Paradigm
Cirrhosis Current Treatment Paradigm Lifestyle Interventions ± co-morbidity management NASHFibrosis Stage: 3/4 NASHFibrosis Stage: 1/2 NAFL/NASHFibrosis Stage: 0 Bariatric Surgery Pharmacologic TherapyNon selective beta-blockers, statisn Liver Transplantation Non-Metabolic Disease Agents Vitamin E P
Slide 11: Belapectin is a Novel Therapy with First- and Best-in-Class Potential in MASH Cirrhosis
11 Belapectin is a Novel Therapy with First- and Best-in-Class Potential in MASH Cirrhosis 3rd Party Market Opportunity Assessment Suggests1 Potential 35-70% Adoption Rate Limited current treatment options: Cirrhotic management focuses on stabilization and delaying progression Management directed to
Slide 12: Phase 2b Study of Belapectin in Patients with MASH Cirrhosis: GT-026 Trial
Phase 2b Study of Belapectin in Patients with MASH Cirrhosis: GT-026 Trial HVPG = Hepatic Venous Pressure Gradient; LBM=lean body mass, N.S.=non significant. *ITT with LOCF, ANCOVA with baseline as covariate and treatment as factors, Bonferroni-Holm.1. Chalasani N, et al. Gastroentrol. 2020;158:1334
Slide 13: Clinical Results – NAVIGATE Trial design & Results
Clinical Results – NAVIGATE Trial design & Results Naim Alkhouri, M.D. Naga Chalasani, M.D.
Slide 14: NAVIGATE Trial Design
14 NAVIGATE Trial Design Placebo n=119 Screen Belapectin 2 mg/kg/LBM Q2W n=119 78 Weeks Belapectin 4 mg/kg/LBM Q2W n=119 Randomize (N=357 1:1:1) Trial Design Patient Population MASH cirrhosis based on Liver Forum Recommended Criteria for Clinical Trials1 Diagnosis of Portal Hypertension as per Baven
Slide 15: NAVIGATE Study: Patient Population and Efficacy Endpoints
15 NAVIGATE Study: Patient Population and Efficacy Endpoints MASH cirrhosis No varices on EGD CTP Scores <7 Evidence of Portal hypertension: Platelet count <150,000/mm3. Or at least two of the following AST/ALT > 1 Spleen ≥ 14 cm Collaterals by imaging Stiffness ≥ 20 kPa Composite primary end point
Slide 16: Key Populations for Assessment of Varices Outcome
16 Key Populations for Assessment of Varices Outcome ITT population- All randomized subjects minus two subjects who had varices at baseline; Per- Protocol or completer population- All subjects who completed 18 month of therapy and had an EGD at baseline and 18 month Subject were required to complete
Slide 17: NAVIGATE Trial: Baseline Demographics
NAVIGATE Trial: Baseline Demographics (N=355) Placebo (N = 118) Belapectin 2 mg (N = 119) Belapectin 4 mg (N = 118) Mean (Standard Deviation) Mean (Standard Deviation) Mean (Standard Deviation) Age (years) 60.4 (8.50) 60.6 (8.82) 59.0 (9.14) Gender (female), n 72 (61.0) 75 (63.0) 83 (70.3) Ethnicity
Slide 18: NAVIGATE 18-Month Primary Analyses Result – ITT Population
NAVIGATE 18-Month Primary Analyses Result – ITT Population Key points Intent to Treat (ITT) -All randomized subjects Primary end point composite strategy i.e. new varices and/or intercurrent events or drop out Intercurrent events (ICEs) include; Liver related clinical events, AE leading to discontin
Slide 19: NAVIGATE: Significantly Lower Incidence of Varices in Completers at 18 month
NAVIGATE: Significantly Lower Incidence of Varices in Completers at 18 month N = 97 N = 98 N = 95 n = 94 n =97 n = 96 p=0.04 p=0.13 Number of subjects Subjects with new varices Key points NAVIGATE 18-month Primary Analyses Result; Per protocol population n= 287 Completer/Per Protocol: All ITT subjec
Slide 20: NAVIGATE: Improvement in LSM - Baseline to 18 months
NAVIGATE: Improvement in LSM- Baseline to 18 months Per-Protocol (Completers n: 269) Liver Stiffness kPa mean change % Placebo (N=88) 2mg/kg LBM (N=94) 4mg/kg LBM (N=87) Baseline LSM Value (kPA) Mean (SD) 23.4 (11.46) 23.6 (13.19) 25.5 (11.84) Median 22.4 21.5 23.4 18-month LSM Value (kPa) Mean (SD)
Slide 21: Significantly Fewer Subjects Showed Worsening in Liver Stiffness Measure
21 Significantly Fewer Subjects Showed Worsening in Liver Stiffness Measure - LSM (kPa) Increase in LSM of >30% or >10 kpa from baseline; Per-Protocol (n = 269) p 0.03 p 0.02
Slide 22: Safety Summary
22 Safety Summary Discontinuation of the study due to Adverse Events was similar across 3 cohorts: 7 (5.9%) in the Pbo 5 (4.2%) in 2 mg/kg Belapectin 8 (6.7%) in 4 mg/kg Belapectin One subject in each of the three cohorts discontinued the study due to death No drug related SAE reported in the entire
Slide 23: Incidence of New Varices was Significantly Lower in Patients in the U.S.
23 Incidence of New Varices was Significantly Lower in Patients in the U.S. n=13/62 n=4/60 n=8/64 n=8/32 n=7/37 n=5/ 32 p=0.02 p=0.54 p=0.35 NAVIGATE 18-month; Per protocol population (n=287) p=0.2
Slide 24: Use of GLP-1 and Statin was Higher in Patients in the U.S.
Use of GLP-1 and Statin was Higher in Patients in the U.S. 24 Treatment Group Placebo Belapectin 2mg/kg LBM Belapectin 4mg/kg LBM Total U.S. (N=62) (N=60) (N=64) (N=186) Concomitant Use of GLP-1 n (%) 28 (45.2%) 22 (36.7%) 18 (28.1%) 68 (36.6%) Concomitant Use of NSBBs n (%) 5 (7.9%) 3 (5.0%) 3 (4.6
Slide 25: Key Takeaways
Key Takeaways Belapectin 2 mg/kg significantly reduced the incidence of new esophageal varices at 18 months in patients with MASH cirrhosis and portal hypertension Categorical changes in LSM mirror the higher incidence of new varices in the placebo compared to the 2 mg cohort. These findings validat
Slide 26: Galectin
Galectin g)