- |||||||||| GB0139 / Galecto
Journal: Galectin-3 inhibitor GB0139 protects against acute lung injury by inhibiting neutrophil recruitment and activation. (Pubmed Central) - Aug 26, 2022 In vitro, GB0139 inhibited Gal-3-induced neutrophil activation, monocyte IL-8 secretion, T cell apoptosis and the upregulation of pro-inflammatory genes encoding for IL-8, TNFα, IL-6 in alveolar epithelial cells in response to mechanical stretch. These data indicate that Gal-3 adopts a pro-inflammatory role following the early stages of lung injury and supports the development of GB0139, as a potential treatment approach in ALI.
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Galectin-3 inhibitors: The discovery and exploration of C2 monosaccharide dimers (Virtual-only (Zoom)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_13126; Recent clinical studies detailed a thiodigalactoside, TD139, as a galectin-3 (gal-3) inhibitor aimed at treating idiopathic pulmonary fibrosis (IPF)...While exploring these monosaccharides, intermolecular interactions between a single ligand molecule bound to monomeric protein and a second ligand molecule bound to a different protein monomer were observed in the extended crystalline lattice. This work describes the exploration of C-2 monosaccharide dimers designed to further probe this observation and explore the potential of binding to dimeric or higher order multimeric gal-3 assemblies.
- |||||||||| GB2064 / Galecto
MYLOX-1: AN OPEN-LABEL, PHASE IIA STUDY OF THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ORAL LOXL2 INHIBITOR, GB2064, IN MYELOFIBROSIS () - May 13, 2022 - Abstract #EHA2022EHA_2191; There have been no significant safety concerns observed at a dose of 1000 mg BID to date. Conclusion MYLOX-1 is designed to explore the safety and clinical effects of GB2064, a novel small-molecule LOXL-2 inhibitor, addressing bone marrow fibrosis as a main element of myelofibrosis, with the aim of decreasing extramedullary haematopoesis and improving haematological parameters, symptom burden and the quality of life for patients with MF.
- |||||||||| GB0139 / Galecto
Journal: Galectin-3 regulates microglial activation and promotes inflammation through TLR4/MyD88/NF-kB in experimental autoimmune uveitis. (Pubmed Central) - May 7, 2022 The specific inhibitor of Galectin-3, TD139 was found to ameliorate the clinical and histological manifestations of EAU mice...In conclusion, Galectin-3 may play important roles in a variety of immune related diseases including autoimmune uveitis. Additionally, the inhibition of Galectin-3 may attenuate the microglial activation and inflammatory response through TLR4/MyD88/NF-κB pathway, highlighting a potential therapeutic target of Galectin-3 for autoimmune uveitis.
- |||||||||| GB1211 / Galecto, Tecentriq (atezolizumab) / Roche
GALLANT-1: Galectin-3 (Gal-3) inhibitor GB1211 plus atezolizumab (atezo) in patients with non–small cell lung cancer (NSCLC)—A randomized, double-blind trial. (Available On Demand; 130b) - Apr 28, 2022 - Abstract #ASCO2022ASCO_2916; P1/2 Exclusion criteria: symptomatic, untreated, or actively progressing central nervous system metastases; prior systemic chemotherapy for treatment of recurrent advanced or metastatic disease, except if part of neoadjuvant/adjuvant therapy; prior treatment with immune CPIs and/or GB1211; presence of EGFR mutation and ALK, ROS1, and RET alterations; treatment with antineoplastic or systemic immunotherapeutic agents prior to first GB1211 dose; severe infectious disease < 4 weeks prior to first GB1211 dose; active hepatitis B or C, HIV, or COVID-19. The study is being initiated; updated enrollment status will be presented at the meeting.
- |||||||||| selvigaltin (GB1211) / Galecto
Enrollment closed: GULLIVER-2: A Single and Repeat Dose Trial in Participants With Hepatic Impairment (clinicaltrials.gov) - Apr 24, 2022 P1/2, N=54, Active, not recruiting, These findings harmonize excellently with in vivo and clinical data showing an association between Gal-3 expression and lack of efficacy of PD-1/PD-L1 targeted checkpoint inhibitors. Recruiting --> Active, not recruiting
- |||||||||| GB0139 / Galecto
Journal: An Evaluation of the Mechanisms of Galacto-Oligosaccharide (GOS)-Induced IgE Cross-Linking on Basophils in GOS Allergy. (Pubmed Central) - Apr 8, 2022 Basophil activation test to GOS and control allergen, Blomia tropicalis (Blo t) extract were performed in the presence or absence of four sugar-based galectin inhibitors (lactose, thiodigalactoside [TDG], TD139, and GB1107) and one peptide-based inhibitor, G3-C12...Basophil activation is performed using purified basophils suggested that cell surface receptors on other blood cells were not required to induce basophil activation. In conclusion, our results suggest that GOS, a low molecular weight sugar, is able to cross-link IgE independently.
- |||||||||| GB0139 / Galecto
Journal: Secretory Galectin-3 promotes hepatic steatosis via regulation of the PPARγ/CD36 signaling pathway. (Pubmed Central) - Apr 1, 2022 Systemic inhibition of Gal3 by injection of TD139 reduced the accumulation of lipid in the livers of HFD-fed mice, accompanied by the decreased expression of CD36 and peroxisome proliferator-activated receptor-gamma (PPARγ)...It was additionally discovered that Gal3 positively regulates CD36 transcription by increased activation of PPARγ, thereby increasing fatty acid uptake, resulting in hepatic steatosis. In conclusion, the present study confirmed the roles of Gal3 in hepatic lipid metabolism in both in vitro and in vivo studies and revealed that Gal3 is a secretory protein that promotes hepatic steatosis through the PPARγ-CD36-dependent pathway, suggesting that targeting Gal3 may represent a potential therapeutic approach for the treatment of NAFLD and related metabolic disorders.
- |||||||||| GB0139 / Galecto
Journal: Molecular mechanism of interspecies differences in the binding affinity of TD139 to Galectin-3. (Pubmed Central) - Mar 23, 2022 Additionally, molecular dynamics simulations of both wild type and mutant structures revealed the sustained favorable non-covalent interactions between the fluorophenyl ring and the active site A146 (human Gal-3 and mouse V160A) that corroborate the finding from biophysical studies. Current findings have ramifications in the context of optimization of drug candidates against Gal-3.
- |||||||||| GB1211 / Galecto
Characterisation of the novel Galectin-3 inhibitor GB1107 on CCl4-induced liver fibrosis in mice (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_1139; P1, P1/2 Small molecular weight and orally active inhibitors of galectin-3 show promise as potential new oral anti-fibrotic agents for the treatment of liver fibrosis. A first-inhuman study with GB1211, an analogue of GB1107, has shown it to be both safe and well tolerated in man, demonstrating a PK profile that supports twice daily dosing (NCT03809052).
- |||||||||| GB0139 / BMS, Galecto
Journal: Selective Myeloid Depletion of Galectin-3 Offers Protection Against Acute and Chronic Lung Injury. (Pubmed Central) - Sep 18, 2021 Previous work has shown that global deletion of galectin-3 reduces collagen deposition in a bleomycin-induced pulmonary fibrosis model (MacKinnon et al., Am...An inhaled Gal-3 inhibitor, GB0139, is undergoing Phase II clinical development for idiopathic pulmonary fibrosis (IPF)...In contrast, no differences in BAL Gal-3 levels or fibrosis were observed in Pdgfrb-cre /LgalS3 mice. Myeloid cell derived Galectin-3 drives acute and chronic lung inflammation and supports direct targeting of galectin-3 as an attractive new therapy for lung inflammation.
- |||||||||| olitigaltin (GB0139) / Galecto
Enrollment closed, Phase classification, Enrollment change, Trial completion date, Trial primary completion date: DEFINE - Evaluating Therapies for COVID-19 (clinicaltrials.gov) - Sep 16, 2021 P1/2, N=200, Active, not recruiting, Myeloid cell derived Galectin-3 drives acute and chronic lung inflammation and supports direct targeting of galectin-3 as an attractive new therapy for lung inflammation. Recruiting --> Active, not recruiting | Phase classification: P2/3 --> P1/2 | N=60 --> 200 | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Jul 2021 --> Dec 2022
- |||||||||| GB0139 / Galecto
Clinical, Journal: Target-inhibition of Galectin-3 by Inhaled TD139 in Patients with Idiopathic Pulmonary Fibrosis. (Pubmed Central) - Jul 7, 2021 P1/2 Inhibition of Gal-3 expression in the lung was associated with reductions in plasma biomarkers centrally relevant to IPF pathobiology (PDGF-BB, PAI-1, Gal-3, CCL18 and YKL-40).TD139 is safe and well tolerated in healthy subjects and IPF patients. It was shown to suppress Gal-3 expression on BAL macrophages and, in a concerted fashion, decrease plasma biomarkers associated with IPF progression.
- |||||||||| GB0139 / BMS, Galecto
Journal, PARP Biomarker: Galectin-3 Inhibitors Suppress Anoikis Resistance and Invasive Capacity in Thyroid Cancer Cells. (Pubmed Central) - May 27, 2021 In the present study, we aimed to investigate the therapeutic potential of novel galectin-3 inhibitors by treating thyroid cancer cells with different concentrations of GB1107 or TD139...In conclusion, these novel galectin-3 inhibitors suppressed the anoikis resistance, motility, and invasive capacity of thyroid cancer cells at least partly through the AKT/β-catenin pathway. Galectin-3 inhibitors are potentially suitable for preclinical evaluation of treatment and/or prevention of metastatic spread in thyroid cancer.
- |||||||||| nintedanib / Generic mfg.
Journal: Galectin-3 levels are elevated following nintedanib treatment. (Pubmed Central) - Mar 13, 2021 Nintedanib elevates Gal-3 levels in both experimental models, along with patient samples. These findings highlight the possibility of using combined inhibition therapy for patients with IPF.
- |||||||||| GB0139 / BMS, Galecto
Preclinical, Journal: In Vivo Veritas - F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors. (Pubmed Central) - Jul 29, 2020 The data obtained allowed us to infer the different in vivo fate of TD139 and GB1107 and rationalize how different administration routes could boost efficacy. Whereas the fast excretion profile of the TD139 surrogate indicated that systemic application of disaccharides is unfavorable, the extended biological half-life of the GB1107 surrogate indicated that systemic administration is possible for monosaccharides.
- |||||||||| olitigaltin (GB0139) / Galecto
New P2/3 trial: DEFINE - Evaluating Therapies for COVID-19 (clinicaltrials.gov) - Jul 16, 2020 P2/3, N=60, Recruiting, Whereas the fast excretion profile of the TD139 surrogate indicated that systemic application of disaccharides is unfavorable, the extended biological half-life of the GB1107 surrogate indicated that systemic administration is possible for monosaccharides. .
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