PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, presented data from the dose escalation phase of its ongoing Phase 1b trial evaluating LYT-200, a first-in-class anti-galectin-9 monoclonal antibody, in patients with relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) at the 2024 American Society of Hematology (ASH) Annual Meeting in San Diego, California.

PureTech Health plc （纳斯达克股票代码：PRTC，伦敦证券交易所代码：PRTC）（”纯科技”或“公司”），一家致力于改变罹患毁灭性疾病患者生活的临床阶段生物治疗公司，在 2024 年临床试验中展示了其正在进行的 1b 期试验剂量递增阶段的数据，该试验评估了 LYT-200（一种首创的抗半乳糖凝集素 9 单克隆抗体）在复发或难治性急性髓系白血病 (AML) 和骨髓增生异常综合征 (MDS) 患者中的疗效。 美国血液学会（ASH）年会加利福尼亚州圣地亚哥。

LYT-200 is currently being evaluated both as a monotherapy and in combination with the standard-of-care venetoclax and hypomethylating agents (HMA) for patients whose disease is relapsed/refractory to at least one line of prior treatment. It targets galectin-9, a glycan-binding protein that is significantly upregulated in AML and MDS and plays a key role in disease development, progression, immune interference and drug resistance. Initial results show a favorable safety profile across both arms and all dose levels with no dose limiting toxicities, as well as evidence of response, hematological improvement and sustained disease management.

LYT-200 目前正在评估其作为单一疗法以及与标准治疗药物维奈克拉和去甲基化药物 (HMA) 联合使用的效果，适用于至少接受过一线治疗后复发/耐药的患者。该药物靶向半乳糖凝集素-9，这是一种糖结合蛋白，在 AML 和 MDS 中显著上调，在疾病发展、进展、免疫干扰和耐药性中起关键作用。初步结果显示，两组和所有剂量水平的安全性良好，没有剂量限制性毒性，并且有证据表明有反应、血液学改善和持续的疾病管理。

"Relapsed/refractory acute myeloid leukemia is one of the most dire cancer diagnoses, with 50% of patients non-responsive to or relapsing after initial treatment and a median survival time of less than six months,[2]" said Luba Greenwood, J.D., Entrepreneur-in-Residence at PureTech who is leading the Gallop Oncology work. "We are encouraged to see that LYT-200 achieved responses as well as long-term disease stabilization in heavily pre-treated patients, and we look forward to progressing LYT-200 as a critical therapeutic option with the potential to treat most AML patients."

“复发/难治性急性髓系白血病是最可怕的癌症诊断之一，50% 的患者对初始治疗无反应或在初始治疗后复发，平均生存期不到六个月，[2] ”卢芭·格林伍德法学博士，入驻企业家 纯科技他是 Gallop 肿瘤学研究的负责人。“我们很高兴看到 LYT-200 在接受过大量治疗的患者中取得了反应以及长期病情稳定，我们期待 LYT-200 能够成为一种关键的治疗选择，有可能治疗大多数 AML 患者。”

In the monotherapy arm, patients received LYT-200 at five dose levels (2.0 mg/kg to 16.0 mg/kg). Across all dose levels, LYT-200 induced clinical benefit and responses in heavily pre-treated, relapsed/refractory AML/MDS patients, even in those with complex cytogenetics and mutations such as KRAS, NRAS, BRAF as well as patients previously fully refractory to standard of care. Out of 22 evaluable patients who received monotherapy, 59% achieved stable disease or better with two partial responses. The mean duration on treatment is greater than two months, which exceeds the standard overall survival of approximately 1.7 months in venetoclax/HMA-refractory patients.[

在单药治疗组中，患者接受 LYT-200 的五种剂量水平（2.0 毫克/千克至 16.0 毫克/千克）。在所有剂量水平下，LYT-200 均在接受过大量治疗的复发/难治性 AML/MDS 患者中产生了临床益处和反应，甚至在那些具有复杂细胞遗传学和突变（如 KRAS、NRAS、BRAF）的患者以及之前对标准治疗完全耐药的患者中也是如此。在 22 名接受单药治疗的可评估患者中，59% 的患者病情稳定或病情更佳，并有两次部分缓解。平均治疗持续时间超过两个月，超过了维奈克拉/HMA 难治性患者的标准总生存期（约 1.7 个月）。

When administered in combination with venetoclax/HMA, results demonstrate that LYT-200 may enhance the efficacy of standard-of-care therapies, even in relapsed or refractory patients. In the combination arm, patients received LYT-200 across three dose levels (4.0 mg/kg to 12.0 mg/kg) with venetoclax/HMA. Out of 15 evaluable patients who received combination therapy, 80% achieved stable disease or better, with two experiencing complete responses and one patient achieving a morphologic leukemia free state (MLFS).1 The combination regimen has also demonstrated clinical benefit in patients with KRAS/NRAS mutations and the mean duration on treatment up until the point of data cut-off is greater than two months.

结果表明，与维奈克拉/HMA 联合使用时，LYT-200 可增强标准治疗的疗效，即使对于复发或难治性患者也是如此。在联合治疗组中，患者接受三种剂量水平（4.0 mg/kg 至 12.0 mg/kg）的 LYT-200 和维奈克拉/HMA。在接受联合治疗的 15 名可评估患者中，80% 的患者病情稳定或更佳，其中两名患者完全缓解，一名患者达到形态学无白血病状态 (MLFS)。1联合治疗方案还显示出对 KRAS/NRAS 突变患者具有临床益处，截至数据截止点的平均治疗持续时间超过两个月。

"Galectin-9 is an essential driver of both disease proliferation and immune suppression in AML that has not yet been addressed therapeutically," said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech. "LYT-200 represents a novel approach for treating AML via a two-gear mode of action that kills cancer cells directly via apoptosis and DNA damage, as well as by re-activating central anti-cancer effectors of the immune system. We are excited by these Phase 1 data that demonstrate the transformative potential of this dual mechanism of LYT-200, both as a single agent and in combination with existing standard-of-care treatments."

“Galectin-9 是 AML 疾病增殖和免疫抑制的重要驱动因素，目前尚未得到治疗，”亚历山德拉·菲利波维奇，医学博士，哲学博士，肿瘤科主任纯科技“LYT-200 代表了一种通过双档作用模式治疗 AML 的新方法，即通过细胞凋亡和 DNA 损伤直接杀死癌细胞，以及通过重新激活免疫系统的中枢抗癌效应器。我们对这些第一阶段的数据感到兴奋，它们证明了 LYT-200 的这种双重机制的变革潜力，无论是作为单一药物还是与现有的标准治疗相结合。”

Pharmacodynamic assessments of treated patients, using gene and protein analyses of patient cells, validate the LYT-200 dual mode of action, and reveal AML cellular pathways as well as specific immune cell types which may be most critical for response.

使用患者细胞的基因和蛋白质分析对接受治疗的患者进行药效学评估，验证了 LYT-200 的双重作用模式，并揭示了 AML 细胞通路以及对反应可能最关键的特定免疫细胞类型。

Based on these data, LYT-200 will continue development in relapsed/refractory AML/MDS towards a Phase 2 clinical trial. PureTech previously announced that it intends to advance LYT-200 via its Founded Entity, Gallop Oncology.

基于这些数据，LYT-200 将继续在复发/难治性 AML/MDS 中开发，以进行第 2 期临床试验。 纯科技此前宣布，它打算通过其创立的实体 Gallop Oncology 推进 LYT-200。