Full Press Release Details
Belapectin for MASH Cirrhosis and Portal Hypertension June 2025
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.
Clinical Results - NAVIGATE Trial design & Results Naim Alkhouri & Naga Chalasani Closing Remarks Joel Lewis (CEO & President) 2
Company introduction Joel Lewis CEO & President
Belapectin as Galectin-3 Inhibitor for MASH cirrhosis & Portal Hypertension Khurram
Jamil, M.D. Chief Medical Officer
5 Belapectin for MASH Cirrhosis and Portal Hypertension Galectin-3, a
-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(GT-026),
Belapectin 2 mg dose significantly improved portal pressure (HVPG) and reduced the incidence of esophageal varices in patients without baseline varices at 52 week5 Currently no FDA approved therapies exist to reverse fibrosis in MASH
cirrhosis Compensated MASH cirrhosis with portal hypertension remains a high-risk and under served population with significant unmet need.
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 deposition Hepatic
fibrosis Portal pressure In toxicology studies, including monkeys, belapectin: Was well-tolerated even at high doses Accumulated in macrophages with a residence time longer than in plasma 1. Traber PG, et al. PLoS One.
2013;8(12):e83481. 2. Traber PG, et al. PLoS One. 2013; ;8(10):e75361. 6 Belapectin: a Proprietary Galectin-3 Inhibitor with Low Toxicity and Anti-fibrotic Activity Belapectin is a polysaccharide polymer comprising galacturonic acid,
galactose, arabinose, rhamnose and smaller amounts of other sugars
Unmet Need & Patient Landscape Naga Chalasani, M.D.
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
underdiagnosed2 There are genetic predisposition to MASH, yet certain health conditions put patients at increased risk:3 1. Fatty Liver Foundation. https://www.fattyliverfoundation.org/#gsc.tab=0. .2. Sherif ZA, et al. Dig Dis Sci.
2016;61(5):1214-25. 3. NIDDK. NAFLD and MASH. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/symptoms-causes. 4. Datamonitor Healthcare. MASH Disease Analysis. 5. Scientific Registry of Transplant Recipients. OPTN/SRTR
2021 Annual Data Report: Liver. https://srtr.transplant.hrsa.gov/annual_reports/2021/Liver.aspx. 6. Stepanova M, et al. Hepatol Commun. 2022;6(7):1506-1515. 7. Zobair M. Younossi, et al, Prevalence and predictors of cirrhosis and portal
hypertension in the United States, American Association for the Study of Liver Disease, DOI: 10.1097/HEP.0000000000001243. Being overweight or obese Having hypertension, high cholesterol or high triglyceride levels Having type 2 diabetes,
insulin resistance or prediabetes 8 MASH Cirrhosis Represents a Significant Market Opportunity in the U.S. with No FDA-Approved Treatment 30% of those listed for liver transplant will die waiting1 MASH cirrhosis is expected to become the
most frequent reason for a liver transplant6 Prevalence increased >2x in the past decade 4 Addressable market in the U.S. ~8.7K Liver transplantations in the U.S.5 100M Americans have fatty liver disease (most don't know it)1 20M
Develop liver fibrosis1 5M Progress to MASH cirrhosis1 3.3M MASH cirrhosis and portal hypertension7 Only curative treatment is liver transplant1 ~8.7K Liver transplantations in the U.S.5
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 varices Varices,
small to large Varices Bleeding, ascites, encephalopathy 10 One year mortality 1-3% 6 One year mortality ~50%
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 Pioglitazone Metabolic Disease Agents SGLT2 inhibitor GLP-1RA Pemafibrate Screening for Varices and HCC Lifestyle interventions are used to promote weight-loss, a key component to improve the histopathologic feature of this
disease Pharmacologic therapy Non-selective beta blockers (NSBB) and statins to manage portal hypertension. Non-Metabolic disease agents: vitamin E may be used in patients without diabetes, data is mixed with potential safety concerns
(e.g., increase in mortality); Pioglitazone has been shown to reduce the incidence of NAFLD in T2D/obese patients and improve fibrosis Metabolic disease agents may be prescribed to NASH patients with diabetes, depending on physician
preference Bariatric surgery is promising for patients who are unable to achieve sufficient weight loss at 6 months; histologic improvement has been observed post-operatively Screening is recommended every 6 mos. for 3 fibrosis or for
those with non-invasive markers highly suggestive of advanced fibrosis Liver transplant is typically considered when patients have developed cirrhosis, complications (e.g., ascites), or a MELD score 15. Transplant is currently the only
option for advanced cirrhotic patients Treatment Progression Disease Progression Goal Hepatic Lipid Reduction Improved NASH Regressed Fibrosis Madrigal's THR- agonist Rezdiffra approved for F2/3 population Madrigal's Rezdiffra
recently approved for F2/3 patients; Limited late-stage options Sources: 1. Up to Date; 2. Zhang et al 2021; 3. Paternostro et al 2022; 4. Chalasani et al 2017; 5. Chalasani et al 2018; 6. Canbay et al 2016 10
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 towards
comorbidities Highly favorable perception of belapectin indication, MoA and safety by HCPs Payers believe in the high unmet need in MASH cirrhosis 1. LifeSci Consulting Belapectin Commercial Opportunity Assessment contracted by the
Company. United States Estimates1 A significant unmet need exists for MASH compensated cirrhosis patients with portal hypertension due to disease severity and risk of decompensation $18B 5M 1.7M Patients with compensated MASH cirrhosis
in 2024 Patients with compensated cirrhosis and portal hypertension with no varices in 2024 Peak belapectin sales in U.S.
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;158:1334-45. Subjects with no
varices at baseline p=0.02 p=0.44 Baseline 1 year Baseline 1 year Baseline 1 year Belapectin Reduces Emergence of Varices in Patients with MASH Cirrhosis1,* No patients on 2 mg/kg/LBM developed new varices
Clinical Results - NAVIGATE Trial design & Results Naim Alkhouri, M.D. Naga
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
Baveno VI criteria (via non-invasive markers) No gastroesophageal varices by endoscopy at baseline Assessment of Varices thru central adjudication of endoscopy videos by multiple blinded reviewers based on standardized protocol.
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 in
ITT population Incidence of Varices in per protocol population (Completers) Hepatic decompensation events All-cause mortality Proportion of patients with large varices or red wale sign Varices requiring treatment MELD 15 Liver
transplant ALT=alanine aminotransferase ; AST=aspartate transaminase; CTP=Child-Turcotte-Pugh; EGD=Esophagogastroduodenoscopy; MELD=model for end-stage liver disease. *Intercurrent events include; Liver related clinical events, any AE
leading to discontinuation, TIPS Trans-jugular intrahepatic portosystemic shunt; 12-month use of GLP-1 or NSBB ITT- Intent to Treat Key inclusion criteria Primary endpoint Composite secondary endpoint
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 the study even after
development of varices unless subject dropped out for other reasons Composite Primary end point: Any subject who developed esophageal varices or had an intercurrent event or dropouts without an EGD/intercurrent event Intercurrent events
included; Liver related clinical events, AE leading to discontinuation TIPS-Trans-jugular intrahepatic portosystemic shunt 12-month use of GLP-1 or NSBB
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
(Hispanic), n 34 (28.8) 39 (32.8) 33 (28.0) Race (white), n 104 (88.1) 107 (89.9) 111 (94.1) BMI (Kg/m2) 33.82 (6.46) 34.88 (6.68) 34.53 (6.22) Hypertension 89 (75.4) 89 (74.8) 82 (69.5) Type 2 Diabetes 80 (67.8) 79
(66.4) 79 (66.9) HbA1C % 6.4 (1.27) 6.3 (1.13) 6.4 (1.09) Alanine Aminotransferase (ALT), U/L 46.3 (29.92) 38.9 (26.88) 39.7 (20.22) Aspartate Aminotransferase (AST), U/L 46.7 (23.52) 41.8 (24.40) 43.6 (21.90) Platelets (per
L) 130.1 (39.66) 127.6 (48.39) 136.4 (53.62) Liver Stiffness Measurement (kPa) 24.22 (12.17) 24.63 (13.54) 25.67 (13.19) Spleen (cm) 13.79 (2.7) 13.97 (2.6) 13.87 (2.4) Child Pugh Score 5.1 (0.29) 5.1 (0.31) 5.0
(0.18) Statins (n) 49 (41.5) 55 (46.2) 47 (39.8) GLP-1 agonist (n) 24 (20.3) 26 (21.8) 27 (22.9) 17
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 discontinuation, TIPS; 12-month
use of GLP-1 or NSBB Overall Target Significance level- 2-sided p value of 0.05; p: 0.048, using CMH test, stratified by Type 2 diabetes status at randomization. p 0.139 p 0.552 n = 118 n = 119 n = 118 ITT Population Number of
subjects with new varices Composite Primary Endpoint, ITT (All Randomized) 18
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 subjects who
completed 18 months of treatment with an end of treatment (EOT) EDG Overall Target Significance level - 2-sided p value of 0.05; using CMH test, stratified by Type 2 diabetes status at randomization. 19
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) 22.7 (13.62) 20.7 (12.66) 22.4 (12.20) Change from Baseline in LSM Value (kPa) @ 18 months Mean (SD) -0.7 (10.81) -2.9 (11.50) -3.1 (9.94) % Change from Baseline @ 18 months LSM Value (kPa)
* Mean % -3.1 (41.10) -12.3 (38.73) -12.1 (35.60) Belapectin 20
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
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 trial No
Adjudicated Drug-Induced Liver Injury (DILI) Events. Adverse Events Treatment-Emergent Adverse Events (TEAEs) Treatment-Emergent Serious Adverse Events (TESAEs) Similar proportion of subjects reported Treatment-Emergent Adverse Events
TEAEs across 3 cohorts: 112 (94.9%) in Pbo 116 (97.5%) in 2 mg/kg Belapectin 116 (96.7%) in 4 mg/kg Belapectin Similar proportion of subjects reported Treatment-Emergent Serious Adverse Events (TESAEs) across 3 cohorts: 23 (19.5%) in
Pbo 27 (22.7%) in 2 mg/kg Belapectin 25 (20.8%) in 4 mg/kg Belapectin
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
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%) 11 (5.9%) Concomitant Use of Statins n (%) 34 (54.8%) 31 (51.7%) 26 (40.6%) 93 (48.9%) Concomitant Use of ACE Inhibitors n (%) 15 (23.8%) 17 (28.3%) 18 (27.7%) 50
(26.6%) EX-U.S. (N=32) (N=37) (N=32) (N=101) Concomitant Use of GLP-1 n (%) 5 (15.6%) 8 (21.6%) 12 (37.5%) 25 (24.5%) Concomitant Use of NSBBs n (%) 2 (6.3%) 2 (5.4%) 3 (9.4%) 7 (6.9%) Concomitant Use of Statins n (%) 8
(25.0%) 14 (37.8%) 16 (50%) 38 (37.6%) Concomitant Use of ACE Inhibitors n (%) 4 (12.5%) 12 (32.4%) 11 (34.4%) 28 (27.5%) Concomitant medication Use U.S. vs Ex- U.S.- Per Protocol 24
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 validate prior favorable
observations from the GT-026 trial. Favorable safety profile with adverse events, serious adverse events, and discontinuation rates comparable to placebo. Belapectin has the potential to address the critical unmet need of patients with MASH
cirrhosis and portal hypertension 25 01 02 03 04 05