belapectin (GR-MD-02) / Galectin Therap - LARVOL DELTA

The Matrix Reloaded: The Hepatic Matrisome as a Therapeutic Opportunity to Fight Liver Fibrosis. (PubMed, Biomolecules) - "The antifibrotic potency of drugs that interfere with the matrisome at different levels has been demonstrated in preclinical studies, but translation to clinical trials remains still limited. So far, simtuzumab (LOXL2 inhibitor antibody), imatinib (small-molecule inhibitor against discoidin domain receptors-DDRs), bexotegrast (integrin inhibitor), GR-MD-02 (galectin 3 inhibitor), and BMS-986263 (siRNA-targeting HSP47) have been or are being evaluated in clinical trials related to CLD, and some of them have shown promising results."

Journal • Review • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • SERPINH1

The poster presentation (REG26-612), presented by Dr. Naim Alkhouri, MD, FAASLD, Chief Academic Officer at Summit Clinical Research and Director of the Steatotic Liver Program at North Shore Gastroenterology, presents new analyses from the NAVIGATE trial demonstrating risk reduction in clinically significant portal hypertension. (The Manila Times) - "Notably, this abstract has been designated a TOP Poster by EASL, recognizing it among the best abstracts in the Portal Hypertension (cirrhosis and non-cirrhosis) session...Across the NAVIGATE dataset, belapectin 2 mg/kg demonstrated a statistically significant reduction in new varices at 18 months in the per-protocol population (p=0.04) and statistically significant reductions in liver stiffness at multiple timepoints. Fewer belapectin-treated patients experienced clinically meaningful worsening of liver stiffness (>30% increase) versus placebo (11.7% vs. 23.9%; p=0.03). At 18 months, a greater proportion of belapectin-treated patients improved to the no/low-risk Baveno category relative to baseline compared with placebo (p=0.0073). These data collectively support belapectin’s potential as a disease-modifying therapy in MASH cirrhosis."

P2/3 data • Hypertension • Metabolic Dysfunction-Associated Steatohepatitis

Data from the oral presentation (REG26-611), presented by Mazen Noureddin, M.D., MHSc, Director of Houston Research Institute and Professor of Medicine at Houston Methodist Hospital, demonstrate belapectin’s impact on fibrosis modulation in patients with high-risk MASH cirrhosis, as reflected by changes in the Pro-C3/CTX-III ratio - a marker of fibrogenesis balance. (The Manila Times) - "Favorable shifts in this ratio were associated with reduced varices development and improvements in broad markers of fibrosis including liver stiffness measure and other markers of fibrosis including Pro-C3, supporting belapectin’s potential to modify disease progression by targeting underlying fibrotic pathology."

P2/3 data • Metabolic Dysfunction-Associated Steatohepatitis

Upcoming Catalysts (Yahoo Finance) - "Additional biomarker analyses from the NAVIGATE trial, including evaluation of belapectin’s impact on liver stiffness and fibrogenesis, will be presented in oral and poster presentations at the European Association for the Study of the Liver Congress in Barcelona, Spain...Upcoming FDA meeting to align on next steps for advancing the belapectin program and informing future clinical development plans in 2Q 2026."

FDA event • P2/3 data • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Galectin Therapeutics Highlights Belapectin Data in MASH Cirrhosis KOL Event, Eyes Next Steps (MarketBeat) - "Galectin Therapeutics...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...He then outlined the NAVIGATE trial...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."

Clinical • Trial status • Metabolic Dysfunction-Associated Steatohepatitis

Galectin Therapeutics Provides Regulatory Update Following FDA Written Response and Announces an Additional $10 Million Line of Credit from Richard E. Uihlein Sufficient to Cover Expected Expenditures Through March 2027 (Galectin Therapeutics Press Release) - "The FDA converted the Company’s initial request for an in-person or teleconference meeting to a written response...Based on FDA’s written feedback, the Company believes there is alignment with the Agency on the patient population proposed for enrollment in a registration trial...Pursuant to the written response from FDA, Galectin Therapeutics will pursue a follow-up Type C meeting to finalize remaining components of the next clinical trial design that were not fully resolved in the written response....'This additional financing will enable us to continue to explore multiple strategies for the advancement of belapectin.'"

FDA event • Financing • Metabolic Dysfunction-Associated Steatohepatitis

NAVIGATE: Study Evaluating the Efficacy and Safety of Belapectin for the Prevention of Esophageal Varices in NASH Cirrhosis (clinicaltrials.gov) - P2/3 | N=357 | Terminated | Sponsor: Galectin Therapeutics Inc. | Trial completion date: Sep 2025 ➔ Apr 2025 | Active, not recruiting ➔ Terminated; Based on FDA feedback, Stage 1 of NAVIGATE was analyzed as a stand-alone trial. Study was not prematurely terminated for safety reasons.

Trial completion date • Trial termination • Fibrosis • Gastroenterology • Hepatitis C • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Rewiring PD-1/PD-L1 combination therapy via glyco-immune targeting of galectins: Toward clinical translation. (PubMed, Biochim Biophys Acta Rev Cancer) - "Several galectin inhibitors (e.g., GR-MD-02, GB1211, LYT-200) are under clinical evaluation. Early trials showing encouraging efficacy-toxicity profiles and some combinations received FDA Fast Track designations. This review summarizes mechanistic and clinical advances and highlights their translational implications for galectin-targeted combination therapies."

Journal • Review • Oncology • PD-L1

The company has submitted the NAVIGATE data package to the FDA and requested feedback on proposed next steps, with guidance anticipated by year-end. (Galectin Therapeutics Press Release)

FDA event • Metabolic Dysfunction-Associated Steatohepatitis

Galectin Therapeutics Presented NAVIGATE Trial Results at the American Association for the Study of Liver Diseases (AASLD) 2025 Annual Meeting (Galectin Therapeutics Press Release) - "When patients were stratified using FDA-approved Enhanced Liver Fibrosis (ELF) score cutoffs, belapectin 2 mg/kg demonstrated a consistently lower incidence of new varices across all fibrosis categories, with the largest reduction observed among patients with ELF >11.3, representing those at highest risk for liver complications (22.7% vs 42.9% for placebo)...Additionally, analysis of the Pro-C3 fibrosis biomarker showed that baseline levels were comparable across all groups (placebo: 50.2 ng/mL; 2 mg/kg: 45.9 ng/mL; 4 mg/kg: 43.4 ng/mL). At 78 weeks, patients receiving 2 mg/kg belapectin achieved a mean –6.4 ng/mL reduction in Pro-C3, representing >50% improvement from baseline compared with placebo (–4.5 ng/mL), while the 4 mg/kg dose showed a –1.7 ng/mL change."

P2b data • Metabolic Dysfunction-Associated Steatohepatitis

Galectin Therapeutics to Host Virtual KOL Event to Discuss Belapectin for Treatment of MASH Cirrhosis and Portal Hypertension (Galectin Therapeutics Press Release) - " Galectin Therapeutics Inc...announced that it will host a virtual key opinion leader (KOL) event on Monday, June 16, 2025 at 12:00 PM ET...The event will highlight results from Galectin's NAVIGATE Phase 3 clinical trial evaluating belapectin for the treatment of MASH cirrhosis and portal. Belapectin is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of MASH and fibrosis."

P3 data • Metabolic Dysfunction-Associated Steatohepatitis

Galectin Therapeutics Presented NAVIGATE Trial Results at the European Association for the Study of the Liver (EASL) 2025 Congress (GlobeNewswire) - P2/3 | N=357 | NAVIGATE (NCT04365868) | Sponsor: Galectin Therapeutics Inc. | "In the PPP population, the incidence of varices was 11.3% in the belapectin 2 mg/kg group and 13.5% in the 4 mg/kg group, compared to 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), whereas the 4 mg/kg dose showed a 39.5% reduction in new varices compared to placebo (not statistically significant)....As in prior trials, the safety profile of belapectin remains highly encouraging with incidence of adverse events and serious adverse events comparable across the three cohorts. Rates of discontinuation, adverse events (AEs), and serious adverse events (SAEs) were comparable to placebo, with no drug-related SAEs reported in the NAVIGATE trial."

P2/3 data • Metabolic Dysfunction-Associated Steatohepatitis

NAVIGATE: Study Evaluating the Efficacy and Safety of Belapectin for the Prevention of Esophageal Varices in NASH Cirrhosis (clinicaltrials.gov) - P2/3 | N=357 | Active, not recruiting | Sponsor: Galectin Therapeutics Inc. | Phase classification: P2b ➔ P2/3 | Trial completion date: Dec 2024 ➔ Sep 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2025

Phase classification • Trial completion date • Trial primary completion date • Fibrosis • Gastroenterology • Hepatitis C • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Galectin Therapeutics to Present at the European Association for the Study of the Liver (EASL) 2025 Congress (GlobeNewswire) - "'We are excited that data from our NAVIGATE study, evaluating belapectin, a galectin-3 inhibitor, in patients with MASH cirrhosis and portal hypertension, has been accepted as a late-breaking oral presentation....Additionally, we continue to analyze biomarker data from NAVIGATE, including the stand-alone 18-month trial data, as well as the 57 subjects completing 36-months. As patients are no longer being treated, we expect to share additional results in the second quarter of 2025'."

P2/3 data • Metabolic Dysfunction-Associated Steatohepatitis

Galectin Therapeutics Reports 2024 Financial Results and Provides Business Update (Galectin Therapeutics Press Release) - "NASH Cirrhosis: The Company is currently conducting the full analysis of the NAVIGATE trial data and anticipates having additional biomarker data in the second quarter of 2025....Research and development expenses for the year ended December 31, 2024 were $36.6 million compared with $32.1 million for the year ended December 31, 2023. The increase was primarily due to costs related to our NAVIGATE clinical trial and other supportive activities."

P2/3 data • Fibrosis • Metabolic Dysfunction-Associated Steatohepatitis

Galectin Therapeutics Reports Significant Reduction in New Varices with Belapectin in U.S. Patient Population from the NAVIGATE Trial (GlobeNewswire) - P2/3 | N=357 | NAVIGATE (NCT04365868) | Sponsor: Galectin Therapeutics Inc. | "Galectin...announced additional results showing a statistically significant reduction in new varices in per-protocol patients (completers) enrolled in the U.S. from the NAVIGATE trial....Following the favorable trend observed in the completers, the Company further analyzed the two thirds of the completer patients in the NAVIGATE trial enrolled in the U.S. (n=186). The incidence of varices in this population was significantly reduced by 68.1% (p=0.02) in patients treated with belapectin 2 mg (4 out of 60) vs placebo (13 out of 62) in the U.S. While all three cohorts of patients in the U.S. had a higher percentage use of GLP-1 and statins than the rest of the world, the belapectin cohorts performed much better than placebo in the U.S....'We look forward to sharing additional clinical updates as data becomes available in the first quarter of 2025.'"

P2/3 data • Metabolic Dysfunction-Associated Steatohepatitis

Galectin Therapeutics Reports the Positive Outcome of the Fourth Data and Safety Monitoring Board Meeting for NAVIGATE, its Seamless, Adaptive Phase 2b/3 Study of Belapectin in Patients with Portal Hypertension Caused by Non-Alcoholic SteatoHepatitis Liver Cirrhosis (GlobeNewswire) - "Galectin Therapeutics, Inc...today reported the positive outcome of its fourth data and safety monitoring board (DSMB) meeting for NAVIGATE, its seamless, adaptive, Phase 2b/3 study of belapectin in patients with portal hypertension caused by non-alcoholic steatohepatitis (NASH) liver cirrhosis....Interim topline data from the Phase 2b portion of NAVIGATE is expected in the fourth quarter of 2024....The objective of this fourth independent DSMB was to further review the emerging tolerance and safety profiles of belapectin. Based on its deliberation, which included an unblinded review of the data collected thus far, the DSMB concluded that NAVIGATE can continue as designed, without modifications."

DSMB • P2b data • Liver Cirrhosis • Metabolic Disorders • Non-alcoholic Steatohepatitis

GR-MD-02 + Pembrolizumab Versus Pembrolizumab Monotherapy in Melanoma and Squamous Cell Head and Neck Cancer Patients (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Providence Health & Services | N=92 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Metastases • Monotherapy • Trial withdrawal • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CCR7 • CD27 • CD8 • FAS • FOXP3 • IL2RA • ISG20 • LGALS3

GR-MD-02 Plus Pembrolizumab in Melanoma, Non-small Cell Lung Cancer, and Squamous Cell Head and Neck Cancer Patients (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Providence Health & Services | Active, not recruiting ➔ Completed | N=22 ➔ 36 | Trial completion date: May 2025 ➔ Oct 2022

Enrollment change • Metastases • Trial completion • Trial completion date • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • CD4

GR-MD-02 + Pembrolizumab Versus Pembrolizumab Monotherapy in Melanoma and Squamous Cell Head and Neck Cancer Patients (clinicaltrials.gov) - P2 | N=92 | Suspended | Sponsor: Providence Health & Services | Trial completion date: Mar 2031 ➔ Jul 2031 | Trial primary completion date: Mar 2027 ➔ Jul 2027

Metastases • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CCR7 • CD27 • CD8 • FAS • FOXP3 • IL2RA • ISG20 • LGALS3

Galectin Therapeutics Reports 2022 Financial Results and Provides Business Update (GlobeNewswire) - "'Additionally, we are furthering our efforts by continuing to evaluate options and develop plans for a potential Phase 2 clinical trial of belapectin in combination with Keytruda in patients with advanced head and neck cancers'....Research and development expenses for the year ended December 31, 2022, were $31.7 million compared with $23.8 million for the year ended December 31, 2021. The increase was primarily due to costs related to our NAVIGATE clinical trial and other supportive activities, including hiring additional employees."

Commercial • New P2 trial • Head and Neck Cancer • Oncology • Solid Tumor

NAVIGATE: Study Evaluating the Efficacy and Safety of Belapectin for the Prevention of Esophageal Varices in NASH Cirrhosis (clinicaltrials.gov) - P2b | N=357 | Active, not recruiting | Sponsor: Galectin Therapeutics Inc. | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Jun 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Fibrosis • Gastroenterology • Hepatitis C • Hepatology • Immunology • Non-alcoholic Steatohepatitis • Solid Tumor

NAVIGATE: Study Evaluating the Efficacy and Safety of Belapectin for the Prevention of Esophageal Varices in NASH Cirrhosis (clinicaltrials.gov) - P2b | N=357 | Active, not recruiting | Sponsor: Galectin Therapeutics Inc. | Recruiting ➔ Active, not recruiting | N=1010 ➔ 357

Enrollment change • Enrollment closed • Fibrosis • Gastroenterology • Hepatitis C • Hepatology • Immunology • Non-alcoholic Steatohepatitis • Solid Tumor

Study Evaluating the Efficacy and Safety of Belapectin (GR-MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis (clinicaltrials.gov) - P2b; N=1010; Recruiting; Sponsor: Galectin Therapeutics Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Dyslipidemia • Fibrosis • Hepatitis C • Hepatology • Immunology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

GR-MD-02 + Pembrolizumab Versus Pembrolizumab Monotherapy in Melanoma and Squamous Cell Head and Neck Cancer Patients (clinicaltrials.gov) - P2 | N=92 | Suspended | Sponsor: Providence Health & Services | Trial completion date: Dec 2030 ➔ Mar 2031 | Trial primary completion date: Dec 2026 ➔ Mar 2027

Metastases • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CCR7 • CD27 • CD8 • FAS • FOXP3 • IL2RA • LGALS3