MYLOX-1 Trial Opens to Evaluate Novel Anti-Fibrotic Agent GB2064 in Myelofibrosis


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The phase 2a MYLOX-1 trial is evaluating GB2064, a novel, oral LOXL2 inhibitor, as a potential anti-fibrotic treatment option for patients with myelofibrosis.

Srdan Verstovsek, MD, PhD

Srdan Verstovsek, MD, PhD

The phase 2a MYLOX-1 trial (NCT04679870) is evaluating GB2064 (formerly PAT-1251), a novel, oral LOXL2 inhibitor, as a potential anti-fibrotic treatment option for patients with myelofibrosis, according to a news release from Galecto, Inc.1

The ongoing study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GB2064 in patients with primary or secondary myelofibrosis.2 Additionally, the trial will investigate the effects of GB2064 on fibrosis, as well as quantify the tissue targeting of the agent.1

“We are looking at alternative options in terms of targeting fibrosis. The next wave of clinical studies that we can anticipate [will include] an expansion of our efforts to look at the biology of the disease to try to eliminate fibrosis or prevent fibrosis from developing. I would hope that in the near future we are going to be talking about prevention studies rather than intervention studies,” principal investigator Srdan Verstovsek, MD, PhD, director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms and chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, said in an interview with OncLive®.

GB2064 is a selective, mechanism-based, small molecule inhibitor with high-affinity for LOXL2, an upregulated enzyme in myelofibrosis fibrotic tissue that drives fibrosis and disease progression in the tumor microenvironment.1,2

Rather than widely target all LOX enzymes, agents that specifically target LOXL2 can spare some iso-enzymes that are less upregulated in active myelofibrosis.1,3 Moreover, the therapy is hypothesized to be disease modifying unlike currently available therapies in myelofibrosis.3

“I have long been excited about the prospect of LOXL2 inhibitors in myelofibrosis, and with GB2064 we have a novel and elegant method of inhibiting the enzyme, which plays a key fibrotic role,” said Verstovsek in the news release.1 “There are a significant number of patients who are in desperate need of novel treatment options, and I look forward to further investigating the potential of GB2064 to address this.”

Findings from the phase 1 SAD/MAD study (NCT02852551) of GB2064 successfully demonstrated that the agent was tolerated among healthy participants.1

In August 2021, the first patient enrolled on the MYLOX-1 trial received their first treatment with GB2064. The experimental regimen consists of four, 250-mg tablets of GB2064 given twice daily and will be dosed over 9 months.2 The estimated enrollment is 21 patients.

Eligible patients must be at least 18 years of age at the time of enrollment and have a diagnosis of intermediate-2 or high-risk primary or secondary myelofibrosis in accordance with the Dynamic International Prognostic Scoring System–plus criteria. If patients have low-risk disease, they must also have symptomatic splenomegaly defined by sonographic assessment as spleen length of more than 12 cm or by physical assessment as at least 5 cm below the left costal margin. 

Additional inclusion criteria state that patients cannot be currently receiving JAK inhibitors, such as ruxolitinib (Jakafi) or fedratinib (Inrebic). Therefore, patients must be refractory to, intolerant of, or ineligible for JAK inhibitors.

Exclusion criteria state that patients who have a history of treatment with JAK inhibitors within 2 weeks of enrollment are not eligible for the trial.
The estimated primary completion date of the study is April 30, 2022. The estimated study completion date is October 30, 2022.

[With currently available therapies in myelofibrosis], “we are talking about controlling the spleen, symptoms, and anemia, [while] hopefully prolonging life in these patients with advanced disease. However, can we prevent fibrotic progression from happening? [Can we] institute a therapy at the time of diagnosis that makes patients with earlier-stage disease live longer without talking about terrible anemia or progression to [acute myeloid leukemia]? I hope that anti-fibrotic medications will make that possible,” concluded Verstovsek. 


  1. Galecto announces first patient treated in phase 2a trial of the oral LOXL2 inhibitor GB2064 in myelofibrosis (the MYLOX-1 trial). News release. Galecto. August 18, 2021. Accessed August 31, 2021.
  2. A study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of oral GB2064 in participants with myelofibrosis. Updated August 23, 2021. Accessed August 31, 2021.
  3. First-in-class small-molecule anti-fibrotic and anti-cancer agents. Galecto. August 2021. Accessed August 31, 2021.
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