lenumlostat (GB2064) / Damora Therapeutics - LARVOL DELTA

Structure-guided computational identification of novel competitive inhibitors targeting the human LOXL2 active site | Poster Board #1318 (ACS-Fall 2026) - "A series of novel inhibitors was developed using the scaffolds of SNT-5382, PXS-5505, and PAT-1251 as structural baselines. Superior binding affinities and Induced Fit Scores, relative to existing benchmarks, were demonstrated through computational validation of specific scaffold modifications. A translational path for the development of high-affinity inhibitors designed to attenuate fibrosis across varying disease severities is provided by these findings."

Fibrosis • Immunology

Structure-guided computational identification of novel competitive inhibitors targeting the human LOXL2 active site | Poster Board #1738 (ACS-Fall 2026) - "A series of novel inhibitors was developed using the scaffolds of SNT-5382, PXS-5505, and PAT-1251 as structural baselines. Superior binding affinities and Induced Fit Scores, relative to existing benchmarks, were demonstrated through computational validation of specific scaffold modifications. A translational path for the development of high-affinity inhibitors designed to attenuate fibrosis across varying disease severities is provided by these findings."

Fibrosis • Immunology

Identification of Nitric Oxide-Donating Lenumlostat Derivatives with Dual Activities of Extracellular Matrix Dysregulation Inhibition and Pulmonary Vasodilation for the Treatment of Pulmonary Arterial Hypertension. (PubMed, J Med Chem) - "Meanwhile, LNO 9 demonstrated superior efficacy in reducing right ventricular systolic pressure compared to lenumlostat. In short, the present study has demonstrated unequivocally that a therapeutic approach for PAH that combines NO donors for vasodilation with extracellular matrix inhibitors to suppress vascular remodeling represents a promising treatment."

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

GB2064 (lenumlostat) shows preliminary evidence of bone marrow collagen fibrosis reduction with manageable tolerability in JAK inhibitor-refractory myelofibrosis: results from the MYLOX-1 phase IIa study. (PubMed, Haematologica) - "Not available."

Journal • P2a data • Fibrosis • Immunology • Myelofibrosis

Design and Optimization of LOXL2 and sGC Dual-Target Regulators Targeting Extracellular Matrix Dysregulation and Vasodilation for the Treatment of Pulmonary Arterial Hypertension. (PubMed, J Med Chem) - "In a hypoxia-induced PAH rat model, its esterified derivative 9k markedly alleviated vascular remodeling and reduced pulmonary artery pressure, showing efficacy comparable to the combination of riociguat and PAT-1251. Consequently, this study proposes a novel strategy for the development of bifunctional PAH drugs, with a focus on extracellular matrix dysfunction and vasoconstriction, and has identified a promising lead compound."

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

A novel cell-permeable LOXL2 inhibitor PAT-1251 potently suppresses biliary liver fibrosis via collagen crosslinking-dependent and -independent mechanisms. (PubMed, Hepatol Commun) - "While having comparable extracellular effects on collagen crosslinking in vivo, the cell-permeable LOXL2 inhibitor PAT-1251 exerted potent antifibrotic activity in hepatic progenitors and HSC cultures compared with the anti-LOXL2 antibody. PAT-1251 substantially outperformed the anti-LOXL2 antibody in the BALB/c. Mdr2-/- model of biliary fibrosis, suggesting that intracellular LOXL2 targeting is therapeutically important in addition to its well-characterized extracellular collagen crosslinking activity."

Journal • Cardiovascular • Fibrosis • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Portal Hypertension • Primary Biliary Cholangitis • ABCB4

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