智通财经APP讯,和誉-B(02256)发布公告,于2025年4月28日,上海和誉生物医药科技有限公司其在 2025年4月25日至2025年4月30日于美国伊利诺伊州芝加哥举行的2025年美国癌症研究协会(“AACR”)大会上以壁报的形式发布了四项最新突破性的临床前研究结果。该等研究成果包括EGFR exon20ins抑制剂ABSK112、PRMT5*MTA抑制剂 ABSK131以及pan-KRAS抑制剂ABK-KRAS-1,以及一项研究KRAS G12C抑制剂潜在耐药机制的研究成果。
和誉医药在此次2025年AACR大会上展示的壁报信息如下:
标题1:Preclinical Evaluation of ABSK112, a Selective and CNS-penetrant Compound with Strong HER2 Inhibitory Activity for Treating HER2-Driven Solid Tumors
结论:我们的研究结果表明,ABSK112是一种具有高效、选择性强且可穿透中枢神经系统的HER2抑制剂,支持其作为单药治疗或与靶向HER2的ADC联合使用,进一步在伴有脑转移的HER2阳性癌症患者中进行临床评估。
标题2:Loss-of-Function (LoF) of KEAP1 promotes cell survival through multiple mechanisms, leading to resistance to KRAS G12C inhibitors
结论:KEAP1功能缺失(LoF)突变的非小细胞肺癌(NSCLC)通过降低药物诱导的活性氧 (ROS)积累、代谢适应以及持续激活MAPK和AKT信号通路等多种方式,对KRAS G12C抑制剂产生耐药性。靶向谷氨酰胺代谢(如GLS1抑制剂)、MAPK通路(如 MEK抑制剂)以及PI3K-AKT-mTOR通路(如BEZ235)的联合治疗可逆转耐药性,并在KEAP1突变细胞系中提高治疗效果。这些策略有望恢复对KRAS G12C抑制剂的敏感性,并改善临床疗效。
标题3:The MTA-Cooperative PRMT5 Inhibitor ABSK131 Exhibits Potent Activity and Broad Synergistic Potential in MTAP-Deleted Cancer Models
结论: ABSK131在MTAP纯合缺失的肺癌和胰腺癌模型中表现出显著的抗肿瘤活性,并与多种治疗药物存在较强的协同效应。该等研究成果为ABSK131在MTAP纯合缺失的癌症中以单药或者联合治疗方案的临床开发提供了有力支持。
标题4:Discovery and characterization of a highly potent and orally available small-molecule inhibitor for diverse KRAS mutations
结论:综合来看,ABK-KRAS-1在体外实验表现出对不同KRAS突变的广谱的活性,在KRAS突变的异种突变肿瘤模型中能剂量依赖性地诱导肿瘤消退。此外, ABK-KRAS-1具有良好的成药性。因此ABK-KRAS-1可作为一款用于治疗携带 KRAS突变癌症的非常有前景的治疗候选药物。
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