Galecto 在 AASLD 展示了积极的临床数据，显示失代偿期肝硬化

StephenW

Galecto 在 AASLD 展示了积极的临床数据，显示失代偿期肝硬化患者的重要肝脏参数有统计学意义的改善

美国东部时间 2022 年 11 月 8 日 06:00 |资料来源：Galecto, Inc.

    ALT、AST 和 GGT 显着降低，支持 GB1211 在严重肝病中的进一步开发
    将于美国东部时间今天（2022 年 11 月 8 日）上午 8 点在电话会议和虚拟网络研讨会上讨论的调查结果

波士顿，2022 年 11 月 8 日 (GLOBE NEWSWIRE) -- Galecto, Inc.（纳斯达克股票代码：GLTO）是一家临床阶段的生物技术公司，也是半乳凝素生物学领域的全球领导者，专注于开发纤维化和癌症的新型治疗方法，该公司宣布将于 11 月 8 日星期二 8:00 在电话会议和虚拟网络研讨会上讨论其最近完成的 1b/2a 期 GULLIVER-2 试验 (NCT05009680) 的主要数据和其他分析，包括观察到的具有统计学意义的肝脏保护迹象美国东部时间上午。该研究被选为美国肝病研究协会 (AASLD) The Liver Meeting® 2022 的最新口头报告。

一线数据显示，治疗 12 周后，肝酶 ALT (p<0.0005)、AST (p<0.005) 和 GGT (p<0.05) 显着降低，ALP 降低 (p<0.09) 令人鼓舞。 GB1211 还显示出生化肝功能标志物和靶标接合、细胞凋亡和纤维化标志物的改善和一致的活性迹象，包括 galectin-3 (p<0.05) 和 CK-18 (M65) (p<0.002) 的减少。胆红素、白蛋白、国际标准化比值（INR）等生化指标保持稳定。即使与之前针对较轻肝病患者的研究数据进行比较，这些研究结果也是独一无二的，并且接受了较长时间的治疗，并表明 GB1211 提供了肝细胞保护并改善了肝脏状态，进一步支持了严重肝病的临床开发。

芝加哥大学医学教授兼肝病学主任 Michael Charlton 博士评论说：“这是对非病毒病因的 Child-Pugh B 级失代偿期肝硬化患者群体进行的第一项研究，显示出一系列肝脏的变化。具有潜在临床意义的参数。随着时间的推移，其中几个参数的值进一步提高，并与 galectin-3 的减少有关，表明目标参与。这些结果，加上良好的耐受性，为 GB1211 值得进一步研究提供了额外的证据，并可能为肝病提供可耐受的干预措施。”

治疗 7 天后观察到肝酶（AST、ALT 和 GGT）降低，并在治疗 12 周后继续降低。与研究结束两周后的基线相比，这些肝酶水平仍然下降，这表明持久的影响和肝脏炎症的减少。在 GULLIVER-2 试验中使用 GB1211 表明，经过 12 周的治疗，肝脏健康生物标志物的数值改善令人鼓舞。

GB1211 在 Child-Pugh B 失代偿期肝硬化患者中表现出良好的耐受性。使用 GB1211 的 15 名患者中有 5 名和使用安慰剂的 15 名患者中有 4 名分别报告了 9 次和 8 次治疗出现的不良事件 (TEAE)。一名患者在 GB1211 中观察到 3 次严重的 TEAE，但被认为与 GB1211 无关。

“我们现在报告了来自 IPF、COVID-19 和肝硬化的三项独立临床试验的数据，显示了抑制 galectin-3 的益处。 GULLIVER-2 一线结果表明临床活性有希望的迹象，表明 GB1211 可能是严重肝病患者的优秀治疗候选药物，”Galecto 首席执行官 Hans T. Schambye 博士说。 “尽管肝病造成了巨大的健康负担，但治疗方面的科学进步令人失望。对于晚期肝硬化患者延迟或替代肝移植的疾病改善疗法仍然存在显着需求。有了这些有希望的数据，我们计划进行未来的研究，探索 GB1211 在肝病患者中的应用。”
GULLIVER-2 试验的主要结果与 Galecto 对 GB1211 的研究结果一致。在几个临床前模型中，半乳糖凝集素 3 抑制已证明肝酶（ALT、AST 和 GGT）显着降低，表明对肝功能和肝细胞有积极作用。此外，GB1211 减少了临床前肝脏模型中的纤维化，为 Galecto 治疗严重肝病的方法提供了临床前概念证明。此外，有大量证据表明，高水平的半乳糖凝集素 3 与肝病严重程度的增加有关。由于 galectin-3 在失代偿性肝硬化中升高并且是肝细胞癌 (HCC) 的预后生物标志物，因此 Galecto 认为抑制 galectin-3 为严重肝病提供了一种可行的治疗选择。

GULLIVER-2 Topline 数据网络广播信息：

Galecto 将于 2022 年 11 月 8 日星期二美国东部时间上午 8:00 举行现场电话会议和网络直播。
美国拨入号码：1-877-300-8521
国际拨入号码：1-412-317-6026
会议编号：10172584
网络直播：点击这里


演示文稿和海报材料以及电话会议的重播将在 Galecto 的投资者关系网站 https://ir.galecto.com 上提供。

关于肝病
肝脏疾病，包括肝纤维化或肝硬化，是全球健康负担。肝硬化——主要由非酒精性脂肪性肝炎、酒精性肝病和肝炎引起——是进行性肝纤维化的终末期，也是全球肝脏相关死亡的主要原因。

关于 GULLIVER-2 试验
GULLIVER-2试验（NCT05009680）是一项1b/2a期试验，旨在评估GB1211在多达54名参与者中的安全性、耐受性、药代动力学和潜在活性。本研究包括失代偿期肝硬化患者（Child-Pugh B 级和 C 级）。

GULLIVER-2 试验的第 2 部分是一项在 30 名患者中进行的 2 期、随机、双盲、安慰剂对照试验，旨在评估 12 周重复口服 GB1211 对一系列肝脏标志物的影响失代偿期肝硬化患者的功能和结构（Child-Pugh B）。患者以 1:1 的比例随机接受口服 GB1211 100mg 或安慰剂，每天两次，持续 12 周。主要终点是 GB1211 的安全性和 PK。次要终点包括评估 GB1211 对肝脏临床实验室参数、肝脏硬度和肝脏脂肪含量的影响，通过振动控制瞬时弹性成像 (VCTE) 测量，以及评估终末期肝病模型 (MELD) 评分。

GULLIVER-2 试验的第 1 部分和第 3 部分是开放标签、单剂量研究部分，旨在评估 GB1211 在中度至重度肝功能不全（分别为 Child-Pugh B 和 C）患者中的安全性和药代动力学，并与匹配的健康的受试者。

关于GB1211
Galecto 正在开发 GB1211，一种口服有效的小分子 galectin-3 抑制剂。 Galecto 对 GB1211 的初始目标适应症是肝硬化，一种最终导致肝功能衰竭的严重的进行性疾病，以及非小细胞肺癌，一种具有高度未满足需求的癌症适应症。

GB1211在多个临床前模型中显示出抗纤维化活性和抗癌作用，并已在78名健康志愿者中成功完成1期试验。在 1 期试验中，GB1211 具有良好的耐受性并表现出剂量依赖性药代动力学。

StephenW

Galecto Presents Positive Clinical Data at AASLD Showing Statistically Significant Improvements in Important Liver Parameters in Decompensated Cirrhosis Patients

November 08, 2022 06:00 ET | Source: Galecto, Inc.

    Statistically significant reductions observed in ALT, AST and GGT, supporting further development of GB1211 in severe liver diseases
    Findings to be discussed in a conference call and virtual webinar today, November 8, 2022, at 8 a.m. ET

BOSTON, Nov. 08, 2022 (GLOBE NEWSWIRE) -- Galecto, Inc. (NASDAQ: GLTO), a clinical-stage biotechnology company and a world leader in galectin biology focused on the development of novel treatments for fibrosis and cancer, announced it will discuss topline data and additional analyses from its recently completed Phase 1b/2a GULLIVER-2 trial (NCT05009680), including the observed statistically significant signs of liver protection, in a conference call and virtual webinar today, Tuesday, November 8th at 8:00 a.m. ET. The study was selected for a late-breaking oral presentation at the American Association for the Study of Liver Diseases’ (AASLD) The Liver Meeting® 2022.

Topline data showed statistically significant reductions in the liver enzymes ALT (p<0.0005), AST (p<0.005) and GGT (p<0.05), with encouraging reductions for ALP (p<0.09), after 12 weeks of treatment. GB1211 also demonstrated improvement and consistent signs of activity across biochemical liver function markers and markers of target engagement, apoptosis, and fibrosis, including reductions in galectin-3 (p<0.05) and CK-18 (M65) (p<0.002). Bilirubin, albumin, international normalized ratio (INR) and other biochemical measurements remained stable. These findings are unique even when compared to data from previous studies in patients with less severe liver disease and treated over longer periods of time, and suggest that GB1211 provided liver cell protection and improved liver status, further supporting clinical development in severe liver disease.

Dr. Michael Charlton, Professor of Medicine and Chief of Hepatology at the University of Chicago, commented, “This is the first study in a population of Child-Pugh Class B decompensated cirrhosis patients of non-viral etiology showing changes in a series of liver parameters that are potentially clinically meaningful. The values of several of these parameters improved further over time and were linked to a reduction in galectin-3, demonstrating target engagement. These results, coupled with a favorable tolerability profile, provide additional evidence that GB1211 merits further investigation and may offer a tolerable intervention in liver diseases.”

Liver enzyme (AST, ALT, and GGT) reductions were observed after seven days of treatment and continued to decrease over the 12 weeks of treatment. These liver enzyme levels remained decreased compared to baseline two weeks after the study’s conclusion, suggesting durable effects and a decrease in liver inflammation. The use of GB1211 in the GULLIVER-2 trial showed encouraging numerical improvements in liver health biomarkers after 12 weeks of therapy.

GB1211 exhibited a favorable tolerability profile in Child-Pugh B decompensated liver cirrhosis patients. Five of 15 patients on GB1211 and four of 15 patients on placebo reported nine and eight treatment-emergent adverse events (TEAEs), respectively. Three serious TEAEs were observed in one patient on GB1211, but were deemed to be unrelated to GB1211.

“We have now reported data from three separate clinical trials in IPF, COVID-19 and liver cirrhosis showing the benefits of galectin-3 inhibition. The GULLIVER-2 topline results indicate promising signs of clinical activity, suggesting that GB1211 could be an excellent therapeutic candidate for patients with severe liver disease,” said Galecto CEO Hans T. Schambye, M.D., Ph.D. “Despite the substantial health burden that liver disease poses, scientific advances in therapeutics have been disappointing. There remains a significant need for disease modifying therapies that postpone or replace liver transplantation in late-stage liver cirrhosis patients. With these promising data in hand, we plan to conduct future studies that will explore the use of GB1211 in patients with liver disease.”
The topline results from the GULLIVER-2 trial are aligned with the findings from Galecto’s research of GB1211. Galectin-3 inhibition has demonstrated a marked reduction in liver enzymes (ALT, AST, and GGT) across several pre-clinical models, indicating a positive effect on liver function and a protection of the liver cells. Further, GB1211 reduced fibrosis in preclinical liver models, providing preclinical proof of concept for Galecto’s approach to severe liver disease treatment. Additionally, there is a body of evidence that suggests high levels of galectin-3 are correlated with increasing severity of liver disease. Since galectin-3 is elevated in decompensated liver cirrhosis and is a prognostic biomarker of hepatocellular carcinoma (HCC), Galecto believes the inhibition of galectin-3 offers a viable therapeutic option in severe liver disease.

GULLIVER-2 Topline Data Webcast Information:

Galecto will host a live conference call and webcast at 8:00 am ET on Tuesday, November 8, 2022.
U.S. Dial-in Number:        1-877-300-8521
Int’l Dial-in Number:        1-412-317-6026
Conference ID:        10172584
Webcast:        Click HERE


The presentation and poster materials along with a replay of the call will be available on Galecto’s investor relation’s website at https://ir.galecto.com.

About Liver Disease
Liver diseases, including liver fibrosis or cirrhosis, are a global health burden. Cirrhosis – primarily caused by non-alcoholic steatohepatitis, alcoholic liver disease and hepatitis – is the end stage of progressive liver fibrosis and the leading cause of liver-related death globally.

About the GULLIVER-2 Trial
The GULLIVER-2 trial (NCT05009680) is a Phase 1b/2a trial designed to assess the safety, tolerability, pharmacokinetics and potential activity of GB1211 in up to 54 participants. This study includes patients with decompensated cirrhosis (Child-Pugh Classes B and C).

Part 2 of the GULLIVER-2 trial is a Phase 2, randomized, double-blind, placebo-controlled trial in 30 patients that is designed to assess the effect of 12-week repeated dosing of oral GB1211 on a wide series of markers of hepatic function and structure in patients with decompensated cirrhosis (Child-Pugh B). Patients are randomized 1:1 to receive oral GB1211 100mg or placebo twice daily for 12 weeks. Primary endpoints were safety and PK of GB1211. Secondary endpoints included assessment of GB1211 effect on liver clinical laboratory parameters, liver stiffness, and liver fat content, as measured by vibration controlled transient elastography (VCTE), and assessment of the model for end-stage liver disease (MELD) scores.

Parts 1 and 3 of the GULLIVER-2 trial are open-label, single dose study parts designed to evaluate the safety and pharmacokinetics of GB1211 in patients with moderate to severe hepatic impairment (Child-Pugh B and C, respectively) and compare with matched healthy subjects.

About GB1211
Galecto is developing GB1211, an orally available and potent small molecule galectin-3 inhibitor. Galecto’s initial target indications for GB1211 are liver cirrhosis, a severe, progressive disease that ultimately leads to liver failure, and non-small cell lung cancer, a cancer indication with a high unmet need.

GB1211 demonstrated antifibrotic activity and anti-cancer effects in multiple preclinical models and has successfully completed a Phase 1 trial in 78 healthy volunteers. In the Phase 1 trial, GB1211 had a favorable tolerability profile and exhibited dose-dependent pharmacokinetics.