和誉医药与艾力斯合作研发的新一代EGFR抑制剂ABK3376获批进入临床试验

和誉医药与艾力斯医药于2023年3月1日，就ABK3376达成授权许可协议，艾力斯医药就此项授权向和誉医药支付总计最高不超过18,790万美元的首付款、开发及销售里程碑付款，以及相应比例净销售额的许可提成费。

ABK3376 是一款高选择性、可入脑的新一代EGFR口服小分子抑制剂，可高效抑制三代EGFR TKI 耐药后产生的C797S突变。根据临床前的研究成果显示，ABK3376具有四大优势：首先，ABK3376对C797S突变伴随各种其他突变情况的活性都比较优异且较均衡。第二，ABK3376有对EGFR野生型抑制的良好选择性，在临床上可能带来更好的安全性。第三，ABK3376的潜在脱靶副作用小。第四，ABK3376具有高效穿透血脑屏障的特性，可在中枢神经系统获得有效的药物暴露，将可用于治疗或预防非小细胞肺癌的中枢神经系统转移。

ABK3376有望成为精准治疗伴有EGFR-C797S耐药突变非小细胞肺癌的新一代靶向治疗药物。ABK3376除了单药的潜力以外，更大的优势是它与三代EGFR-TKI联用的效果。我们在临床前的模型中已经证实，该药与艾力斯的伏美替尼联用具有优异的药效。

关于ABK3376 （AST2303）

ABK3376 （AST2303）是由上海和誉生物医药科技有限公司发现，并由上海艾力斯医药科技股份有限公司（以下简称“艾力斯”）开发的一种新分子实体，主要针对EGFR L858R+C797S或Del19+C797S的双位点突变的非小细胞肺癌。它具有口服、相较于野生型EGFR和其他激酶高选择性，以及可能进入中枢神经系统的特点。艾力斯计划开发ABK3376（AST2303），主要用于治疗第三代EGFR-TKI耐药后携带EGFR L858R+C797S或Del19+C797S的双位点突变的非小细胞肺癌。

September 24 2024, Abbisko Therapeutics (HKEX code: 02256) announced that the China National Medical Products Administration (NMPA) has approved the first-in-human (FIH) phase I clinical study of ABK3376, an independently discovered next-generation EGFR oral small molecule inhibitor currently in an ongoing collaboration with Allist Pharmaceuticals, for the treatment of non-small cell lung cancer (NSCLC) with EGFR-C797S mutation.

Abbisko Therapeutics and Allist Pharmaceuticals previously completed a licensing agreement for ABK3376 on March 1, 2023. Based on the terms of the agreement, Abbisko Therapeutics is eligible to receive up to US$187.9 million, inclusive of upfront, development, and commercial milestone payments. Additionally, Abbisko is entitled to tiered royalty payments based on net sales. 

ABK3376 is a highly selective, brain-penetrating, next-generation EGFR oral small-molecule inhibitor that is highly effective against the C797S mutation caused by third-generation EGFR TKI resistance. Preclinical results highlights four major advantages: 1）ABK3376 exhibits excellent and balanced inhibitory activity against the C797S mutation, even when accompanied by various other mutations. 2）ABK3376 demonstrates high selectivity over wild-type EGFR, potentially offering better safety in clinical practice. 3）ABK3376 has minimal potential for off-target side effects. 4）ABK3376 efficiently penetrates the blood-brain barrier, achieving effective drug exposure in the central nervous system (CNS) and making it suitable for the treatment and/or prevention of CNS metastasis in NSCLC.

ABK3376 is expected to become a next-generation targeted therapy for the treatment of NSCLC with EGFR-C797S mutation.In addition to its potential as a standalone drug, ABK3376 demonstrates significant advantages when combined with a third-generation EGFR-TKI. Preclinical models of ABK3376 in combination with Allist’s furmonertinib demonstrate excellent efficacy.

About ABK3376 (AST2303)

ABK3376 (AST2303) is a novel molecular entity discovered by Shanghai-Abbisko Therapeutics Co., Ltd. and developed by Shanghai Allist Pharmaceuticals Co., Ltd. (“Allist”). This compound primarily targets non-small cell lung cancer (NSCLC) with EGFR L858R+ C797S or Del19+ C797S mutations. It is characterized by its oral administration, higher selectivity compared to wild-type EGFR and other kinases, and its potential to penetrate the central nervous system. Allist aims to develop ABK3376 (AST2303) mainly for treating NSCLC with EGFR L858R+ C797S or Del19+ C797S mutations following resistance to third-generation EGFR-TKIs.

关于和誉

和誉医药（香港联交所代码：02256）是一家立足中国，着眼全球的创新药研发公司。公司的创始人和管理团队拥有多年顶尖跨国药企的研发和管理经验，并参与了多个临床及上市新药的研发。和誉医药专注于肿瘤新药研发，以小分子肿瘤精准治疗和小分子肿瘤免疫治疗药物为核心，着眼病患及医药市场的需求，秉承国际新药开发的理念和标准，致力于开发新颖及高潜力药物靶点的潜在first-in-class或best-in-class创新药物，用于改善中国及全球病人的生活质量。

自2016年成立以来，和誉医药已拥有由16种候选药物组成的产品管线，全面涵盖肿瘤精准治疗领域以及肿瘤免疫治疗领域。

更多信息，欢迎访问 www.abbisko.com。