lenumlostat (GB2064) / Galecto - LARVOL DELTA

An in vitro model to measure the strength and stiffness of the extracellular matrix synthesized de novo by human fibroblasts. (PubMed, In Vitro Model) - "Treatment with two drugs, incyclinide and PAT 1251 that were developed as potential treatments for diseases of the ECM, altered the strength and stiffness of the rings, thereby demonstrating the utility of the model for testing new therapies that target the biomechanics of the ECM. The online version contains supplementary material available at 10.1007/s44164-025-00081-y."

Journal • Preclinical • Fibrosis • Genetic Disorders • Immunology • TGFB1

LOXL2 Inhibition Rescues Pulmonary Hypertension-Induced Right Ventricular Failure (ASA 2024) - " Adults male Sprague Dawley rats received either a single subcutaneous injection of pulmonary endothelial toxin Monocrotaline (MCT), VEGF-receptor antagonist SU5416 with 3-weeks of hypoxia (10% oxygen) followed by 2-weeks of normoxia (SuHx), or PBS for control (PBS)...Daily administration of either PAT-1251 or ECGC in PAH rats with RV failure significantly improved RV hemodynamics and attenuated RV fibrosis. Our RV transcriptomic analysis of PAH patients and animal models revealed a novel mechanism involving LOXL2 in PAH-induced RV failure. We propose a potential therapeutic strategy where blockade of LOXL2 can rescue RV failure by attenuation of fibrosis."

Cardiovascular • Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CTGF • LOXL2 • TGFB1

LOXL2 Inhibition Rescues Pulmonary Hypertension-Induced Right Ventricular Failure (ASA 2024) - " Adults male Sprague Dawley rats received either a single subcutaneous injection of pulmonary endothelial toxin Monocrotaline (MCT), VEGF-receptor antagonist SU5416 with 3-weeks of hypoxia (10% oxygen) followed by 2-weeks of normoxia (SuHx), or PBS for control (PBS)...Daily administration of either PAT-1251 or ECGC in PAH rats with RV failure significantly improved RV hemodynamics and attenuated RV fibrosis. Our RV transcriptomic analysis of PAH patients and animal models revealed a novel mechanism involving LOXL2 in PAH-induced RV failure. We propose a potential therapeutic strategy where blockade of LOXL2 can rescue RV failure by attenuation of fibrosis."

Cardiovascular • Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CTGF • LOXL2 • TGFB1

LOXL2 IN COLORECTAL CANCER SUPPRESSES ANTI-TUMOUR IMMUNITY THROUGH RECRUITING AND ACTIVATING MDSCS AND IS A THERAPEUTIC TARGET FOR IMMUNOTHERAPY (UEGW 2024) - "Our findings revealed that LOXL2 exerted a pro-tumorigenic role in CRC. LOXL2 recruited and activated MDSCs through CXCL1 and crosslinking of collagen fibers, respectively, subsequently reducing infiltration and activation of anti-tumor CD8+ T cells in the tumor microenvironment. Targeting this axis with PAT-1251 improved the efficacy of immunotherapy in colorectal cancer."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ARG1 • CD8 • CXCL1 • IDO1 • LOXL2

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

LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "Hypoxia induced LOXL2 activation is a causal mechanism in pulmonary artery stiffening in PH, as well as pulmonary artery mechanical and functional decline. LOXL2 inhibition with PAT-1251 could be a promising approach to improve pulmonary artery pressures, right ventricular elastance, cardiac relaxation, and survival in PAH."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • LOXL2

MYLOX-1: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral GB2064 in Participants With Myelofibrosis (clinicaltrials.gov) - P2 | N=21 | Active, not recruiting | Sponsor: Galecto Biotech AB | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2023 ➔ Jun 2026

Phase classification • Trial completion date • Myelofibrosis

Topline Results from MYLOX-1 Trial Demonstrate Reduction in Fibrosis of the Bone Marrow in Patients with Myelofibrosis (GlobeNewswire) - P2a | N=21 | MYLOX-1 (NCT04679870) | Sponsor: Galecto Biotech AB | "Galecto...announced positive topline results from a Phase 2a trial of GB2064 for the treatment of myelofibrosis....The MYLOX-1 trial dosed a total of 18 myelofibrosis patients, of which 11 (61%) patients had previously received janus kinase inhibitor (JAKi) therapy with ruxolitinib....Six out of ten evaluable myelofibrosis patients who received GB2064 monotherapy for at least six months experienced a ≥ 1-grade reduction in collagen fibrosis of the bone marrow....Furthermore, GB2064 demonstrated target engagement systemically by binding to LOXL2 in plasma. All six patients who experienced a > 1-grade reduction in bone marrow fibrosis score also showed stable hematological parameters, including hemoglobin, white blood cell count and platelets."

P2a data • Myelofibrosis

Galecto Announces Topline Results from Phase 2b GALACTIC-1 Trial of GB0139 for the Treatment of Idiopathic Pulmonary Fibrosis (Galectin Therapeutics Press Release) - "Going forward, we are eager to expand our focus on advancing our pipeline of our orally administered compounds, GB1211 and GB2064. We believe that the previously reported promising clinical results with these compounds represent significant and meaningful opportunities in severe liver diseases, including decompensated cirrhosis and hepatocellular carcinoma. We plan to provide greater detail and next steps before the end of October."

Clinical • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Liver Cancer • Myelofibrosis • Oncology • Solid Tumor

Galecto Reports Second Quarter Operating and Financial Results (GlobeNewswire) - "Expected Upcoming Milestones:...Topline results from Phase 2a MYLOX-1 trial (myelofibrosis) with GB2064 in 2H 2023."

P2a data • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

MYLOX-1: A PHASE II STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ORAL LOXL2 INHIBITOR GB2064 (WITH FOCUS ON BONE MARROW COLLAGEN) IN PATIENTS WITH MYELOFIBROSIS (EHA 2023) - P2a | "Pts with MF who received GB2064 had an acceptable safety profile & improvements in BM reticulin & collagen fibrosis that indicated disease-modifying activity. GB2064 demonstrated BM penetration & good target engagement in plasma, thus may be a valid Tx option or disease-modifying combination agent for pts ineligible or intolerant to JAK inhibitors, or in combination with JAK inhibitors & novel therapies. Figure: Bone Marrow Fibrosis, Myelofibrosis, Janus Kinase inhibitor, Clinical trial"

Clinical • P2 data • PK/PD data • Anemia • Gastrointestinal Disorder • Hematological Disorders • Immunology • Myelofibrosis • ASXL1 • CALR

MYLOX-1: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral GB2064 in Participants With Myelofibrosis (clinicaltrials.gov) - P2a | N=21 | Active, not recruiting | Sponsor: Galecto Biotech AB | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Enrollment closed • Trial completion date • Trial primary completion date • Myelofibrosis

Galecto Reports Operating and Financial Results for the Year Ended December 31, 2022 (GlobeNewswire) - "Anticipated 2023 Milestones...Interim safety data from Phase 2a GALLANT-1 trial (NSCLC) (Q2 2023); Top-line results from Phase 2a MYLOX-1 trial (myelofibrosis) (Q4 2023); Initiation of Phase 2 investigator-initiated GB1211 oncology trial (melanoma and HNSCC) (2H 2023)."

New P2 trial • P2 data • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Melanoma • Myelofibrosis • Myeloproliferative Neoplasm • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Mylox-1: An Open-Label, Phase IIa Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral LOXL2 Inhibitor, GB2064, in Myelofibrosis (ASH 2022) - "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 MF, with the aim to decrease extramedullary haematopoiesis and improve haematological parameters, symptom burden and the quality of life for patients with MF."

Clinical • P2a data • PK/PD data • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CHI3L1 • CTGF

Insights into the Phase IIa Mylox-1 trial: assessing efficacy of GB2064 in myelofibrosis (YouTube) - "Srdan Verstovsek, MD...describes the design and rationale of the Mylox-1 trial (NCT04679870), which is assessing the use of the oral LOXL-2 inhibitor GB2064 in myelofibrosis (MF). Prof. Verstovsek explains that novel agents such as GB2064 that can counteract the fibrosis in the bone marrow may improve bone marrow function, particularly if combined with JAK inhibitors, but highlights that this has yet to be confirmed."

Interview • Video

Galecto Announces Upcoming Poster Presentation Detailing Results from the Intermediate Assessment of the MYLOX-1 Trial at the 2022 American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "Galecto...announced that an abstract relating to its ongoing Phase 2 myelofibrosis trial (MYLOX-1) has been accepted for presentation at the 64th American Society of Hematology (ASH) Annual Meeting, taking place in New Orleans, Louisiana and virtually December 10-13, 2022."

P2 data • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

MYLOX-1: AN OPEN-LABEL, PHASE IIA STUDY OF THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ORAL LOXL2 INHIBITOR, GB2064, IN MYELOFIBROSIS (EHA 2022) - "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."

Clinical • P2a data • PK/PD data • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CHI3L1 • CTGF

GB2064 Reduces Fibrosis Grade in Early Results of MYLOX-1 Study of Myelofibrosis (Targeted Oncology) - "'It is wholly unprecedented and very encouraging to observe a reduction in collagen fibrosis in this patient population,' said Srdan Verstovsek, MD, a principal investigator in the MYLOX-1 trial, in a press release of the intermediate results."

Media quote

Myelofibrosis Trial Yields ‘Wholly Unprecedented’ Finding (Healio) - "'It is wholly unprecedented and very encouraging to observe a reduction in collagen fibrosis in this patient population,' researcher Srdan Verstovsek, MD, PhD...said in a Galecto-issued press release. 'It is exciting to see the first clinical validation of LOXL2 as a fibrosis target. I very much look forward to additional developments from this ongoing study in the near future.'"

Media quote

GB2064 Shows Reduction in Fibrosis of the Bone Marrow in Patients with Myelofibrosis, Validating LOXL2 as a Clinical Fibrosis Target (GlobeNewswire) - P2 | N=21 | MYLOX-1 (NCT04679870) | Sponsor: Galecto Biotech AB | "Four out of five evaluable myelofibrosis patients who received GB2064 monotherapy for at least six months in the MYLOX-1 trial experienced a ≥ 1-grade reduction in collagen fibrosis of the bone marrow, an improvement suggesting that GB2064 could impact the progression of the disease and be disease modifying....All four patients who experienced a > 1-grade reduction in fibrosis score also showed stable hematological parameters (hemoglobin, white blood cell count, and thrombocytes) and stable spleen volume over the six month treatment period, and none required transfusion. Two of these patients have entered the extension phase of the study due to the clinical benefit of GB2064 as evaluated by the treating physician."

P2 data • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Galecto Reports Second Quarter Operating and Financial Results (GlobeNewswire) - "Expected Upcoming Milestones...Intermediate review of Phase 2a MYLOX-1 trial [for the treatment of myelofibrosis] later in Q3 2022; Top-line results from...Phase 2a GALLANT-1 trial [of GB1211 in combination with atezolizumab (Tecentriq®) for first-line treatment of non-small cell lung cancer (NSCLC)] in mid-2023."

P2a data • Hematological Malignancies • Lung Cancer • Myelofibrosis • Myeloproliferative Neoplasm • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Galecto Reports Financial Results for the Year Ended December 31, 2021 (GlobeNewswire) - "Initiation of enrollment in Phase 2a GALLANT-1 trial of GB1211 in combination with Tecentriq® in first-line Non-Small-Cell Lung Cancer in Q2 2022. Completion of enrollment in MYLOX-1 Phase 2a trial and GULLIVER-2 Phase 1b/2a trial in Q2 2022."

Enrollment status • Trial status • Hematological Malignancies • Lung Cancer • Myelofibrosis • Non Small Cell Lung Cancer • Oncology

MYLOX-1: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral GB2064 in Participants With Myelofibrosis (clinicaltrials.gov) - P2a; N=21; Recruiting; Sponsor: Galecto Biotech AB; Trial primary completion date: Apr 2022 ➔ Dec 2022

Clinical • Trial primary completion date • Myelofibrosis

Galecto Provides Enrollment Update on Phase 2a MYLOX-1 Trial and Reiterates Expected Timing of Multiple Data Readouts in 2022 (GlobeNewswire) - "Galecto, Inc...announced it has enrolled 10 of the anticipated 16 patients in its Phase 2a trial of its oral LOXL2 inhibitor GB2064 in myelofibrosis...The open label MYLOX-1 trial...is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered GB2064 in 16 patients over 9 months....'We remain on track to report interim data in mid-2022 and topline data from the full trial in the second half of 2022'"

Enrollment status • P2a data • Hematological Malignancies • Myelofibrosis • Oncology

Galecto Reports Third Quarter Operating and Financial Results (GlobeNewswire) - "Upcoming Milestones: (i) Completion of enrollment in MYLOX-1 trial in Q4 2021; (ii) Initiation of enrollment in Phase 2a trial of GB1211 in Combination with Tecentriq® in First Line Non-Small-Cell Lung Cancer (GALLANT-1) in 1H 2022."

Enrollment status • Hematological Malignancies • Lung Cancer • Myelofibrosis • Non Small Cell Lung Cancer • Oncology