Topline Results from MYLOX-1 Trial Demonstrate Reduction in Fibrosis of the Bone Marrow in Patients with 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, with eight of those patients being refractory and three being intolerant to JAKi therapy. 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, an improvement suggesting that GB2064 could impact the progression of the disease and be disease-modifying.
Fibrosis is a key disease mechanism of myelofibrosis that destroys bone marrow function. Reducing fibrosis is required to slow the progression of the disease. Bone marrow biopsies taken during the study showed that GB2064 penetrated the bone marrow and could exert its anti-fibrotic effect directly in the disease compartment. 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. At six months of treatment, one patient obtained a ≥35% reduction in spleen volume, two patients reduced their Total Symptom Score (TSS) by more than 50% and one patient had an anemia response. Four of these patients have entered the extension phase of the study due to the clinical benefit derived from GB2064 as evaluated by the treating physician, with one patient receiving treatment for more than 30 months.
GB2064 showed a generally acceptable tolerability profile in the MYLOX-1 trial. Eighteen patients were dosed with GB2064 monotherapy in the MYLOX-1 trial. Eight patients completed treatment in the core phase of the MYLOX-1 trial and ten patients discontinued treatment due to an adverse event or disease progression. The most commonly observed treatment-related adverse events were gastrointestinal in nature and were manageable in most patients with standard therapy. The only treatment-related serious adverse event was a case of fall, which was assessed as possibly related to GB2064 by the investigator.
Dr. Hans Schambye, President and Chief Executive Officer of
About the MYLOX-1 Trial
The MYLOX-1 trial was a Phase 2, open-label, single-arm study in myelofibrosis patients who were ineligible, refractory, or intolerant to JAKi therapy. These patients have a progressive disease with poor quality of life, high mortality rates and very limited treatment options. Patients received GB2064 orally at a dose of 1000mg twice daily for nine months and undergo bone marrow biopsies at the beginning of the trial and again at months 3, 6 and 9. The primary endpoint of the MYLOX-1 trial was to assess the safety and tolerability of GB2064.
Apart from evaluating the safety and tolerability of GB2064, key secondary objectives of the MYLOX-1 trial were to evaluate hematological parameters as well as the direct anti-fibrotic activity of GB2064 by blocking lysyl oxidase-like 2 (LOXL2) in an indication that allows for repeated tissue biopsies.
Myelofibrosis is a hematological cancer that causes fibrosis of the bone marrow and disrupts the body’s normal production of blood cells, which can lead to multiple negative impacts and a significantly reduced quality of life and mortality. The bone marrow is destroyed by fibrosis, forcing out the production of blood components and aggravating symptoms, including anemia, thrombocytopenia, leukocytosis, and spleen enlargement. JAKi therapy is the current standard of care for patients with myelofibrosis; however, these therapies do not address the core of the underlying disease biology and have not shown a consistent effect on fibrosis, biomarkers of disease modification, or overall survival.
About LOXL2 and GB2064
GB2064, a potentially first-in-class, oral, lysyl oxidase-like 2 (LOXL2) inhibitor candidate, is in development for the treatment of fibrotic diseases and cancer. LOXL2 is an enzyme that plays a key role in myelofibrosis and contributes to the fibrotic progression of the disease. LOXL2 catalyzes the cross-linking of collagen, forming the backbone of fibrosis. The molecular target for GB2064 is LOXL2, an enzyme that plays a central role in the crosslinking of collagen in tissue fibrosis and is involved in multiple types of fibrotic diseases, including myelofibrosis. In contrast to previous attempts to inhibit LOXL2 with a monoclonal antibody, GB2064 is designed to completely inhibit the LOXL2 enzymatic activity.
This press release contains forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include statements about the safety and efficacy of GB2064 and Galecto’s plans, strategies and prospects for clinical development of GB2064. Such forward-looking statements include statements about Galecto’s focus, plans for clinical development, product candidates and pipeline. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. For such statements,
For more information, contact:
|Hans Schambye, CEO
|+45 70 70 52 10
|+1 617 430 7577
|+41 78 680 0538
Source: Galecto, Inc.