selvigaltin (GB1211) / Damora Therapeutics - LARVOL DELTA

GB1211 and Pembrolizumab Versus Pembrolizumab and Placebo in Patients With Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Providence Health & Services | Trial completion date: Feb 2030 ➔ Jul 2027 | Trial primary completion date: Feb 2028 ➔ Jul 2027

Trial completion date • Trial primary completion date • Head and Neck Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

GB1211 and Pembrolizumab Versus Pembrolizumab and Placebo in Patients With Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Providence Health & Services | Recruiting ➔ Active, not recruiting | N=92 ➔ 12

Enrollment change • Enrollment closed • Head and Neck Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Galectin-3 inhibitor selvigaltin dosed therapeutically in vivo in a rabbit model of metabolic syndrome induced by high-fat diet: effects on rabbit differentiated adipocytes. (PubMed, Front Physiol) - "Selvigaltin restores mitochondrial health, suggesting its potential as a therapeutic option for metabolic disorders involving VAT dysfunction. Further studies are needed to confirm its clinical relevance."

Journal • Preclinical • Cardiovascular • Dyslipidemia • Fibrosis • Genetic Disorders • Hypertension • Immunology • Inflammation • Metabolic Disorders • Obesity • GATA3 • IL1B • IL6 • LGALS3 • TBX21 • TLR2 • TLR4 • TNFA

Galectin-3 inhibition supports HCC growth via pro-tumorigenic liver reprogramming (EASL 2026) - P1/2 | "Despite its anti-fibrotic benefits, Galectin-3 inhibition with GB1211 accelerates HCC progression by fostering an immunosuppressive tumor microenvironment. These findings emphasize the necessity for careful tumor surveillance in patients undergoing Galectin-3 inhibiting therapies in order to safely exploit the potential of Selvigaltin for treatment of liver fibrosis."

Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Oncology • AFP • ARG1 • CD8 • CD86 • IL10 • IL1B • MRC1 • PD-1 • TGFB1

The role of galectins in modulating the tumor microenvironment and driving metastasis in skin cancers. (PubMed, Biol Res) - "Recent preclinical and early clinical trials targeting galectins, such as the Gal-3 inhibitors belapectin and GB1211, highlight their translational potential as adjuncts to immunotherapy. This review summarizes current knowledge on galectin expression and function in melanoma and non-melanoma skin cancers, emphasizing their contribution to immune escape and therapeutic resistance, as well as challenges and perspectives for galectin-targeted interventions."

Biomarker • IO biomarker • Journal • Review • Genetic Disorders • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor • HAVCR2 • LGALS1 • LGALS3 • LGALS8 • LGALS9

Selvigaltin With Standard of Care Treatment for the Treatment of Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Roswell Park Cancer Institute | N=21 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Hematological Malignancies • Multiple Myeloma • Oncology

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

Selvigaltin With Standard of Care Treatment for the Treatment of Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=21 | Not yet recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Sep 2028 ➔ Feb 2028 | Initiation date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Sep 2027 ➔ Feb 2028

Trial completion date • Trial initiation date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Selvigaltin With Standard of Care Treatment for the Treatment of Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=21 | Not yet recruiting | Sponsor: Roswell Park Cancer Institute

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Binding free energy analysis of galectin-3 natural ligands and synthetic inhibitors. (PubMed, Protein Sci) - "Synthetic drug molecules GB0139, GB1107, and GB1211 were estimated to have binding free energies of -4.3, -6.7, and -9.5 kcal/mol respectively. We find that while the hydroxyl groups of the natural ligands interact reasonably well with residues in galectin-3's binding pocket, structural dynamics weaken the binding pose and favor interactions with water, sometimes yielding to dissociation. In contrast, the more favorable binding energy of GB1211, leading inhibitor in clinical studies, is associated with strong and constant electric fields across the bonds investigated, suggesting a stiffer binding pose with a stabilizing σ-hole interaction."

Journal

Galecto Reports Full-Year 2024 Financial Results (GlobeNewswire) - "Phase 2 investigator-initiated trial (IIT) of GB1211 in combination with pembrolizumab (Keytruda) in metastatic melanoma and head and neck squamous cell carcinoma continues to enroll patients."

Enrollment status • Melanoma • Squamous Cell Carcinoma of Head and Neck

Development and Characterization of a High-Affinity Selective Galectin-3 Mouse Tool Compound in Mouse Models of Cancer. (PubMed, J Med Chem) - "The first orally available galectin-3 inhibitor, GB1211 (h-galectin-3 Kd = 0.025 μM), is currently in phase 2 clinical trials...To better support translation into clinical studies, a new improved mouse galectin-3 tool compound, GB2095, was developed. Dosing this new compound in in vivo syngeneic mouse models of cancer resulted in reduction of the growth of breast and melanoma cancers."

Journal • Preclinical • Fibrosis • Immunology • Melanoma • Oncology • Solid Tumor

Galecto Completes Strategic Review to Focus on Oncology and Liver Disease and Acquires Acute Myeloid Leukemia Preclinical Asset from Bridge Medicines (GlobeNewswire) - "Galecto, Inc...announced that, following an intensive strategic review process, Galecto has determined to focus on cancer and liver disease, leveraging its existing clinical stage asset GB1211, which has shown positive results in non-small cell lung cancer (NSCLC) and decompensated cirrhosis clinical studies. Galecto further announced that it has bolstered its pipeline with the acquisition of the global rights to BRM-1420, a novel, first-in-class asset developed by Bridge Medicines, a company co-founded by Takeda...As consideration for the acquisition of the global rights of BRM-1420, Galecto issued 62,594 shares of common stock to Bridge Medicines...As part of the strategic alternative review process, Galecto has determined not to further advance GB2064, its LOXL-2 inhibitor candidate, at this time....Galecto plans to file an IND for BRM-1420 in the US in late 2025 or early 2026 and initiate clinical studies in patients with AML thereafter."

Commercial • Discontinued • IND • Pipeline update • Acute Myelogenous Leukemia • Myelofibrosis • Non Small Cell Lung Cancer

Single‑Dose Pharmacokinetics and Safety of the Oral Galectin‑3 Inhibitor, Selvigaltin (GB1211), in Participants with Hepatic Impairment. (PubMed, Clin Drug Investig) - P1/2 | "Hepatic impairment increased selvigaltin exposure without safety concerns. These data can inform dose recommendations for future clinical programmes."

Journal • PK/PD data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis

Relative bioavailability and food effect of the galectin-3 inhibitor selvigaltin (GB1211) administered as a tablet in healthy participants (GALBA-1). (PubMed, Cancer Chemother Pharmacol) - P1 | "The tablet formulation of selvigaltin displayed higher bioavailability vs. the capsule formulation, with minimal effect of food on PK. Selvigaltin was well-tolerated during all treatments. These findings warrant further clinical development of the tablet formulation of selvigaltin without specific food restrictions."

Journal • Fibrosis • Oncology • LGALS3

The galectin-3 inhibitor selvigaltin reduces liver inflammation and fibrosis in a high fat diet rabbit model of metabolic-associated steatohepatitis. (PubMed, Front Pharmacol) - "Selvigaltin (previously known as GB1211) is a novel orally active galectin-3 small molecule inhibitor that has high affinity for galectin-3 (human KD = 25 nM; rabbit KD = 12 nM) and high oral bioavailability in rabbits and man...These data support the human selvigaltin dose of 100 mg b.i.d. that has been shown to reduce key liver biomarkers during a clinical study in liver cirrhosis."

Journal • Preclinical • Fibrosis • Gastroenterology • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • IL6 • LGALS3 • SNAI2 • TGFB1

Galecto Announces First Patient Dosed in an Investigator-Initiated Phase 2 Trial of GB1211 in Combination with Pembrolizumab (GlobeNewswire) - "Galecto...announced that the first patient has been enrolled in an investigator-initiated Phase 2 trial to evaluate GB1211, Galecto’s first-in-class, oral small molecule galectin-3 inhibitor candidate....The randomized, double-blind placebo-controlled, investigator-initiated Phase 2 trial will evaluate whether the addition of GB1211 increases the response rate of pembrolizumab in metastatic melanoma and HNSCC patients. The study will employ a fixed dose of GB1211 in conjunction with the standard therapeutic dose of pembrolizumab in patients with unresectable or metastatic MM or recurrent or metastatic HNSCC progressing during or after platinum-containing chemotherapy....It is anticipated that early data from this trial could be available as early as 2025."

P2 data • Trial status • Melanoma • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

GALLANT-1: A Study to Investigate the Safety and Efficacy of GB1211 (a Galectin-3 Inhibitor) in Combination With Atezolizumab in Patients With Non-Small Cell Lung Cancer (NSCLC). (clinicaltrials.gov) - P1/2 | N=88 | Active, not recruiting | Sponsor: Galecto Biotech AB | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2024 ➔ Nov 2025 | Trial primary completion date: Jul 2023 ➔ May 2024

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LGALS3 • PD-L1

GB1211 and Pembrolizumab Versus Pembrolizumab and Placebo in Patients With Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=92 | Recruiting | Sponsor: Providence Health & Services | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Head and Neck Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • LGALS3

GB1211 and Pembrolizumab Versus Pembrolizumab and Placebo in Patients With Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=92 | Not yet recruiting | Sponsor: Providence Health & Services | Trial completion date: Dec 2030 ➔ Feb 2030 | Trial primary completion date: Dec 2028 ➔ Feb 2028

Metastases • Trial completion date • Trial primary completion date • Head and Neck Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • LGALS3

GB1211 and Pembrolizumab Versus Pembrolizumab and Placebo in Patients With Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=92 | Not yet recruiting | Sponsor: Providence Health & Services

Metastases • Trial completion date • Trial initiation date • Trial primary completion date • Head and Neck Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • LGALS3

GULLIVER-2: A SUBGROUP ANALYSIS COMPARING TRANSAMINASE AND MODEL FOR END-STAGE LIVER DISEASE RESPONSES IN GB1211- VS PLACEBO-TREATED PATIENTS WITHOUT PHENOTYPIC NON-ALCOHOLIC STEATOHEPATITIS (AASLD 2023) - P1/2 | "The effects of GB1211 in pts without phenotypic NASH were consistent with those seen in the overall population of pts with Child-Pugh B liver cirrhosis (Lindmark et al. AASLD 2022). The safety and efficacy of GB1211 will be further explored in future studies in a defined population with NASH, as well as in pts with alcohol-related liver disease."

Clinical • Fibrosis • Gastroenterology • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Steatohepatitis • KRT18 • LGALS3

THE GALECTIN-3 INHIBITOR GB1211 DOSE DEPENDENTLY REDUCES INFLAMMATION AND FIBROSIS IN A HIGH FAT DIET RABBIT MODEL OF NASH (AASLD 2023) - P1/2 | "GB1211 normalized inflammation & fibrosis in a HFD rabbit model of NASH & liver fibrosis following therapeutic dosing for 4 weeks in a dose dependent manner. This data supports the human GB1211 dose of 100 mg b.i.d. that has been shown to reduce key biomarkers of disease in a phase 2b study in liver cirrhosis (NCT05009680)."

Preclinical • Addiction (Opioid and Alcohol) • Fibrosis • Gastroenterology • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Steatohepatitis • IL1B • LGALS3 • TLR4 • VIM

GALLANT-1: GB1211 galectin-3 (Gal-3) inhibitor plus atezolizumab (atz) for first line treatment in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC) (ESMO 2023) - P1/2 | "Conclusions This is the first clinical study to show that combining GB1211 with atz may enhance the CPI effect. As the AEs have been manageable, Part A will continue with the 100 mg GB1211 dose to confirm the selected dose for Part B."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LGALS3

Galecto Presents Updated Clinical Data at ESMO Congress 2023 and Provides Update on Phase 1b/2a GALLANT-1 Trial (GlobeNewswire) - P1/2 | N=102 | NCT05240131 | Sponsor: Galecto Biotech AB | "At the recommended Phase 2 dose level of 100 mg GB1211 twice daily, investigator-assessed objective tumor responses (defined as partial responses per RECIST criteria 1.1) were observed in three of five patients (60%) who received GB1211 for at least three weeks. Response rates of only 22–38% have been observed with atezolizumab monotherapy in the first-line treatment of advanced NSCLC....As part of Galecto’s recently announced strategic alternative process, Galecto has determined that it will not initiate Part B of the GALLANT-1 trial and will instead reallocate its resources to focus on the treatment of severe liver diseases. Galecto will continue to supply GB1211 100 mg for the upcoming investigator-initiated Phase 2 trial ...This trial, which is expected to be initiated in early 2024, will evaluate the safety and efficacy of GB1211 in combination with pembrolizumab (Keytruda)"

New P2 trial • P1/2 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor