LOXL2

Galecto, Inc. (NASDAQ: GLTO), a clinical stage biotechnology company focused on the development of novel treatments for fibrosis and cancer, today announced positive topline results from a Phase 2a trial of GB2064 for the treatment of myelofibrosis (the “MYLOX-1 trial”, NCT04679870). 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. Professor Claire Harrison, Guy’s and St Thomas’ NHS Foundation Trust, and Chair of the Safety Review Committee for the MYLOX-1 trial, commented, “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. 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.” 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 Galecto, commented, “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. 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.” 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. 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. Galecto is a clinical stage company incorporated in the U.S. that is developing small molecule-based inhibitors of galectin-3 and LOXL2. Galecto has multiple Phase 2 clinical opportunities in fibrosis and cancer, including (i) an orally active LOXL2 inhibitor (GB2064) for the treatment of myelofibrosis; (ii) an orally active galectin-3 inhibitor (GB1211) for the treatment of liver cirrhosis; and (iii) an orally active galectin-3 inhibitor (GB1211) in combination with a checkpoint inhibitor for various oncology indications. The content above comes from the network. if any infringement, please contact us to modify.

Fibrosis affects the production of blood cells, leading to anemia, weakness and fatigue. Galecto is giving potential buyers and investors more data to chew over. Three months into a review of strategic alternatives, the biotech has posted topline results from a phase 2a clinical trial of a potential treatment for the bone marrow cancer myelofibrosis. Boston-based Galecto laid off 70% of its staff and began looking for a buyer in September. The review followed the phase 2 failure of an inhaled treatment for idiopathic pulmonary fibrosis. While looking for a way out of its predicament, the biotech continued to track patients in a phase 2a trial of another drug candidate, the LOXL2 inhibitor GB2064. Galecto posted topline data from the trial after the market closed Thursday. The study dosed 18 people with myelofibrosis, including 11 who had previously received Incyte’s JAK inhibitor Jakafi. Ten patients discontinued treatment because of an adverse event or disease progression.  Six of the 10 evaluable patients who received the drug candidate for at least six months had a one-grade or greater reduction in collagen fibrosis of the bone marrow. Fibrosis affects the production of blood cells, leading to anemia, weakness and fatigue. Galecto presented the finding as evidence that “GB2064 could impact the progression of the disease and be disease-modifying.” The six patients with reduced fibrosis had stable hematological parameters, including hemoglobin, white blood cell count and platelets. One patient had a 35% or greater reduction in spleen volume. Two people experienced a 50% or greater reduction on a symptom scale. Four patients have entered the extension stage of the study. In a statement, Galecto CEO Hans Schambye said the study showed a “strong anti-fibrotic impact in a very challenging patient population.” However, the biotech will defer decisions on funding more trials of GB2064 until it has completed its strategic alternative process. Investors appeared unsure what to make of the data. After spiking in the immediate aftermath of the news, Galecto’s share price fell 3% to 61 cents in pre-market trading.

Partial response seen in three of five patients with advanced non-small cell lung cancer who received GB1211 100 mg plus atezolizumab for at least three weeksBOSTON, Oct. 23, 2023 (GLOBE NEWSWIRE) -- Galecto, Inc. (NASDAQ: GLTO), a clinical-stage biotechnology company focused on the development of novel treatments for fibrosis and cancer, today presented a poster with new and encouraging clinical data, including two additional partial responders, from the dose-finding Part A of its Phase 1b/2a trial (NCT05240131) (the GALLANT-1 trial) at the European Society of Medical Oncology (ESMO) Congress 2023 in Madrid, Spain. The GALLANT-1 trial is designed to study the combination of atezolizumab (Tecentriq®) and GB1211, Galecto’s first-in-class, oral small-molecule galectin-3 inhibitor candidate, in the first-line treatment of patients with metastatic/advanced non-small cell lung cancer (NSCLC). At the recommended Phase 2 dose level of 100 mg GB1211 twice daily, investigator-assessed objective tumor responses (defined as partial responses per RECIST criteria 1.1) were observed in three of five patients (60%) who received GB1211 for at least three weeks. Response rates of only 22–38% have been observed with atezolizumab monotherapy in the first-line treatment of advanced NSCLC, suggesting a potential benefit of adding GB1211 to atezolizumab. The Company believes that GALLANT-1 is the first clinical trial to show that combining an oral galectin-3 inhibitor with a checkpoint inhibitor may enhance the effect of checkpoint inhibitors. In addition, insights from early biomarker analyses revealed a trend showing that responders had increased levels of galectin-3 at baseline, and stable or decreasing galectin-3 levels during treatment. In contrast, patients with progressive disease demonstrated increasing levels of galectin-3 during treatment. This correlation suggests that the detection of galectin-3 levels could potentially be used to select and monitor patient populations. Overall, the combination of GB1211 100 mg and atezolizumab appeared to be well-tolerated, with predominantly Grade 1 and Grade 2 treatment emergent adverse effects observed. At the 200 mg twice daily dose-level, two severe dose-limiting skin reactions were observed that may indicate lymphocyte activation in line with the GB1211 mode of action, which resulted in a reduction to the 100 mg GB1211 dose level. Importantly, these skin rashes were not observed at the recommended Phase 2 dose level of 100 mg GB1211 twice daily. As part of Galecto’s recently announced strategic alternative process, Galecto has determined that it will not initiate Part B of the GALLANT-1 trial and will instead reallocate its resources to focus on the treatment of severe liver diseases. Galecto will continue to supply GB1211 100 mg for the upcoming investigator-initiated Phase 2 trial at Providence Portland Medical Center’s Earle A. Chiles Research Institute (EACRI). This trial, which is expected to be initiated in early 2024, will evaluate the safety and efficacy of GB1211 in combination with pembrolizumab (Keytruda®). Galecto plans to explore external options for partnering and/or funding additional oncology-focused activities for GB1211 as part of its strategic alternative process. Following the poster presentation at the ESMO Congress, the poster will be available on the Scientific Conferences page of Galecto’s investor relations website at https://ir.galecto.com/news-and-events/scientific-events. About GB1211 and Galectin-3 Mechanisms in CancerIncreased galectin-3 expression in tumors is linked to tumor growth, invasiveness and metastatic potential. In the tumor tissue, galectin-3 supports the creation of fibrosis, tumor proliferation, metastasis, and immune avoidance. Galectin-3 uses a host of mechanisms to increase tumor growth and metastasis. Furthermore, increased levels of galectin-3 in the tumor microenvironment facilitates tumor escape from the immune response by suppressing essential T-cell functions and activating tumor-protecting macrophages. Evidence suggests that galectin-3 can enhance PD-1 and PD-L1 binding and avert the interference of anti-PD-1/anti-PD-L1 therapies by blocking the binding of the antibodies to their respective targets. GB1211 is designed to counter these effects. About the GALLANT-1 trialThe Phase 1b/2a trial of GB1211 in combination with atezolizumab (Tecentriq®) was designed to be a randomized, double-blind, placebo-controlled trial in patients with NSCLC in the first-line setting. Part A of the GALLANT-1 trial was an open-label trial that determined the 100 mg dose of GB1211 to be the recommended dose in future oncology trials. Part B of the GALLANT-1 trial had been designed to evaluate safety and tumor shrinkage in NSCLC patients and explore tumor response rate based on RECIST criteria (version 1.1), clinical activity, and immune biomarkers. About GalectoGalecto is a clinical stage company incorporated in the U.S. that is developing small molecule-based inhibitors of galectin-3 and LOXL2. Galecto has multiple Phase 2 clinical programs in fibrosis and cancer, including (i) an orally active LOXL2 inhibitor (GB2064) in a Phase 2a trial for the treatment of myelofibrosis; (ii) an orally active galectin-3 inhibitor (GB1211) in a recently completed Phase 1b/2a trial in liver cirrhosis; and (iii) an orally active galectin-3 inhibitor (GB1211) in combination with atezolizumab (Tecentriq®) in a separate Phase 2a trial for the treatment of NSCLC. Galecto intends to use its website as a means of disclosing material non-public information. For regular updates about Galecto, visit www.galecto.com. Forward-Looking StatementsCertain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include statements about the potential safety and efficacy of GB1211; the timing of initiating clinical trials not being conducted by Galecto; and Galecto’s focus and plans for clinical development of its 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, Galecto claims the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from Galecto's expectations. Factors that could cause actual results to differ materially from the forward-looking statements include risks and uncertainties related to the development of Galecto’s product candidates and their therapeutic potential, having adequate funds and their use, and those disclosed in Galecto’s filings with the Securities and Exchange Commission (SEC), including, but not limited to, Galecto’s Annual Report on Form 10-K, as filed with the SEC on March 9, 2023. These forward-looking statements represent Galecto's judgment as of the time of this release. Galecto disclaims any intent or obligation to update these forward-looking statements, other than as may be required under applicable law. For more information, contact: Galecto, Inc. Hans Schambye, CEO Jon Freve, CFO +45 70 70 52 10 Investors/USMedia/EUAshley R. RobinsonSandya von der Weidarr@lifesciadvisors.comsvonderweid@lifesciadvisors.com+1 617 430 7577+41 78 680 0538