GB2064 Reduces the Level of Bone Marrow Fibrosis in Myelofibrosis

Srdan Verstovsek, MD, PhD

Treatment with GB2064 monotherapy for at least 6 months led to a reduction in collagen fibrosis of the bone marrow of at least 1 grade in 4 of 5 evaluable patients with myelofibrosis, according to topline findings from a planned intermediate assessment of the phase 2a MYLOX-1 trial (NCT04679870).

Additionally, all 4 patients who responded also experienced stable hematological parameters, including hemoglobin, white blood cell count, and thrombocytes and stable spleen volume over the 6-month treatment course. Moreover, none required transfusion.

Two of these patients have subsequently enrolled in the extension phase of the study because GB206 induced lasting clinical benefit, the treating physician reported.

“It is wholly unprecedented and very encouraging to observe a reduction in collagen fibrosis in this patient population. 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,” Srdan Verstovsek, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, said in a press release.

GB2064 is a potentially first-in-class LOXL2 inhibitor under study for the treatment of patients with fibrotic diseases and cancer. LOXL2 is an enzyme that plays a key role in myelofibrosis and contributes to the fibrotic progression of the disease. Unlike prior attempts to inhibit LOXL2 with a monoclonal antibody, GB2064 is specifically designed to inhibit LOXL2 enzymatic activity entirely.

MYLOX-1 is an ongoing phase 2, open-label, single-arm study evaluating GB2064 in patients with myelofibrosis who are ineligible, refractory or intolerant to JAK inhibitor therapy.

In the study, patients will receive oral GB2064 at a dose of 1000 mg 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 end point of the study is an assessment of safety and tolerability. Secondary end points included bone marrow fibrosis and hematological parameters.

“It is exciting and encouraging to see a clear reduction in collagen fibrosis following the administration of a selective LOXL2 inhibitor in four of the five evaluable patients combined with stabilization of hematological parameters and spleen volume. Stable disease is excellent in a progressive disease such as myelofibrosis,” Claire Harrison, MD, professor, Guy’s & St Thomas NHS Foundation Trust, said.

Regarding safety, GB2064 has been relatively well tolerated. Sixteen patients have received GB2064 and 8 have completed or remain on treatment. Eight patients discontinued treatment because of toxicity or disease progression.

The most frequent treatment-related adverse effects (AEs) were gastrointestinal in nature and were manageable in most patients with standard therapy. None of the 5 patients who completed at least 6 months of treatment with GB2064 experienced treatment-related serious AEs. In the overall population, the only potential treatment-related serious AE was a reported fall.

“We are very excited to have demonstrated proof of principle with GB2064 showing an anti-fibrotic effect in a difficult-to-treat patient population. These intermediate results strengthen our belief that GB2064 has the potential to be a disease-modifying therapy for multiple cancers and fibrotic diseases,” said Hans Schambye, MD, PhD, president and chief executive officer of Galecto.

Reference

GB2064 Shows Reduction in Fibrosis of the Bone Marrow in Patients with Myelofibrosis, Validating LOXL2 as a Clinical Fibrosis Target. News release. Galecto, Inc; September 29, 2022. Accessed September 30, 2022. https://bit.ly/3rkq6kr