GB2064 Displays Preliminary Efficacy, Tolerability in Myelofibrosis

The potential first-in-class, oral, lysyl oxidase-like 2 (LOXL2) inhibitor GB2064 displayed efficacy with a generally acceptable tolerability profile in the treatment of patients with myelofibrosis, according to topline findings from the phase 2a MYLOX-1 trial (NCT04679870).¹

Among evaluable patients with myelofibrosis who were treated with GB2064 monotherapy for a minimum of 6 months (n = 10), 6 experienced a reduction in collagen fibrosis of the bone marrow of at least 1 grade. All patients who achieved this reduction in bone marrow fibrosis displayed stable hematological parameters, including hemoglobin, white blood cell count, and platelet count. This indicates the agent’s potential impact on disease progression and disease-modifying capabilities. At 6 months of treatment, 1 patient experienced a reduction in spleen volume of at least 35%, 2 reduced their Total Symptom Score (TSS) by over 50%, and another patient experienced an anemia response.

“It is exciting and encouraging to see that the data from the MYLOX-1 trial affirms the safety and effectiveness of LOXL-2 inhibition in the challenging landscape of myelofibrosis,” Claire Harrison, MD, FRCP, FRCPath, chair of the Safety Review Committee for the MYLOX-1 trial, a professor of myeloproliferative neoplasms, and the clinical director of Guy’s and St Thomas’ NHS Foundation Trust in London, England, said in a press release. “I am especially intrigued by the unique observed improvements in bone marrow collagen fibrosis, showcasing the targeted impact on a crucial aspect of this relentless disease.”

MYLOX-1 was an open-label, single-arm study that enrolled adult patients with primary or secondary myelofibrosis who were ineligible, refractory, or intolerant to treatment with a JAK inhibitor. Patients had intermediate-2 or high-risk disease by the Dynamic International Prognostic Scoring System-plus, or low-risk disease with symptomatic splenomegaly. Eligible patients were also required to have an ECOG performance status of 2 or less, not be receiving JAK inhibitor therapy, display required baseline laboratory counts, and have a documented history of transfusion records in the preceding 12 weeks to day 1 of study treatment.²

All patients on the study treatment received 1000 mg of oral GB2064 twice daily for 9 months. Patients underwent bone marrow biopsies at the beginning of the trial and again at 3, 6 and 9 months. The primary end point was the safety and tolerability of GB2064; key secondary end points included evaluating hematological parameters and the direct anti-fibrotic activity of GB2064 by blocking LOXL2 in an indication that allows for repeated tissue biopsies.^1,2

The study dosed a total of 18 patients with myelofibrosis. Most patients (61%) had previously received the JAK inhibitor ruxolitinib (Jakafi); 8 of these patients were refractory to JAK inhibitor therapy and 3 were intolerant.¹

Additional assessment of bone marrow biopsies in MYLOX-1 revealed that GB2064 penetrated the bone marrow and could exert its anti-fibrotic effect directly in the disease compartment. Additionally, the agent displayed systemic target engagement by binding to LOXL2 in plasma. Four patients who experienced clinical benefit with GB2046, as determined by the treating physician, have entered the extension phase of MYLOX-1. Notably, 1 of these patients has received treatment for over 30 months.

GB2064 displayed a tolerable safety profile, with 8 of the 18 dosed patients completing treatment in the core phase of MYLOX-1. The remaining 10 patients discontinued treatment due to adverse effects or progressive disease. The most common any-grade treatment-related adverse effects were manageable with standard therapy and gastrointestinal in nature. The lone treatment-related serious adverse effect was a case of fall, which was determined to be possibly related to GB2064 treatment.

“We believe that the topline results from the MYLOX-1 trial reaffirm the anti-fibrotic activity observed in the intermediate assessment of the trial announced in September 2022,” Hans T. Schambye, MD, PhD, the president and chief executive officer of Galecto, said in the press release. “We are very excited with the proof of principle achieved with GB2064, showcasing its strong anti-fibrotic impact in a very challenging patient population. The encouraging topline results from the MYLOX-1 trial reinforce our confidence in GB2064’s potential as a transformative therapy for various cancers and a range of fibrotic diseases, but we will not make any decisions relating to funding additional trials with GB2064 until we complete our previously announced strategic alternative process.”

In September 2023, Galecto announced that it completed a review of its business and would conduct a comprehensive exploration of strategic alternatives focused on maximizing shareholder value. Galecto did not set a timetable for completion of the evaluation and said it did not intend to disclose further developments or guidance on the status of its programs unless it determined that further disclosure is appropriate or necessary.³

References

1. Topline results from MYLOX-1 trial demonstrate reduction in fibrosis of the bone marrow in patients with myelofibrosis. News release. Galecto, Inc. December 21, 2023. Accessed January 16, 2024. https://www.biospace.com/article/releases/topline-results-from-mylox-1-trial-demonstrate-reduction-in-fibrosis-of-the-bone-marrow-in-patients-with-myelofibrosis/
2. A study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of oral GB2064 in participants with myelofibrosis. ClinicalTrials.gov. Updated May 6, 2023. Accessed January 16, 2024. https://clinicaltrials.gov/study/NCT04679870
3. Galecto announces plans to explore strategic alternatives. News release. Galecto, Inc. September 26, 2023. Accessed January 16, 2024. https://ir.galecto.com/news-releases/news-release-details/galecto-announces-plans-explore-strategic-alternatives