mRNA Rabies Vaccine (Everest Medicines)

▎药明康德内容团队报道2023年美国临床肿瘤学会（ASCO）年会将于6月2日至6日在美国芝加哥举行。根据ASCO年会官网，今年有2900+摘要入选，其中多家中国公司开发的新药研究入选大会口头报告。公开资料显示，入选ASCO口头报告的摘要一般是不同癌症领域比较有代表性的研究，对于患者的治疗具有重要意义。本文将结合ASCO摘要标题统计及公开信息，分享部分入选本届ASCO大会口头摘要专场、临床科学研讨会和快速摘要专场的中国新药口头报告，看看它们的亮点有哪些？（按公司名首字母排序，如有遗漏，欢迎补充）百济神州：泽尼达妥单抗作用机制：HER2双抗适应症：HER2扩增性胆道癌根据百济神州新闻稿，其在研产品泽尼达妥单抗治疗既往经治的HER2扩增性胆道癌（BTC）的关键性2b期HERIZON-BTC-01研究结果入选了本次大会口头报告。泽尼达妥单抗（ZW25）是一款靶向HER2的双特异性抗体，可以同时结合两个非重叠的HER2表位，即双互补位结合。百济神州通过与Zymeworks公司合作，获得了该产品在亚洲（日本除外）、澳大利亚和新西兰的开发和推广的独家授权。此前，泽尼达妥单抗已在中国被纳入突破性治疗品种，拟单药治疗既往接受系统化疗失败的HER2阳性的局部晚期不可切除或转移性胆道癌。百利天恒：BL-B01D1作用机制：EGFR/HER3双抗ADC适应症：实体瘤根据百利天恒新闻稿，其在研抗体偶联药物（ADC）BL-B01D1用于局部晚期或转移性实体瘤患者的1期临床研究入选了本次大会口头报告。BL-B01D1是一款可同时靶向EGFR和HER3的双特异性抗体ADC药物，EGFR和HER3在大多数上皮肿瘤中呈高表达。据百利天恒新闻稿介绍，BL-B01D1在多个上皮肿瘤适应症中均有实现突破性疗效的潜力，目前该公司正在推进其关键注册临床研究的沟通交流。传奇生物：西达基奥仑赛作用机制：BCMA靶向CAR-T适应症：多发性骨髓瘤根据传奇生物新闻稿，该公司开展的3期CARTITUDE-4研究结果将以口头报告的形式在ASCO大会上展示，该试验比较了西达基奥仑赛与标准治疗在既往接受过1-3线治疗的复发且来那度胺耐药的多发性骨髓瘤患者中的疗效。今年4月该公司披露的数据显示，西达基奥仑赛将多发性骨髓瘤患者疾病进展/死亡风险降低了74%！西达基奥仑赛（cilta-cel，LCAR-B38M）是一种靶向BCMA的CAR-T产品，它使用嵌合抗原受体（CAR）的转基因对患者自身的T细胞进行修饰，以识别和消除表达BCMA的细胞。2017年12月，传奇生物与杨森（Janssen）公司达成全球独家许可和合作协议，以共同开发和商业化该产品。目前，西达基奥仑赛已在美国获批上市，在中国已递交新药上市申请并被纳入优先审评和突破性治疗品种。晨泰医药：佐利替尼（zorifertinib，AZD3759）作用机制：新一代EGFR-TKI适应症：非小细胞肺癌（NSCLC）根据晨泰医药新闻稿，其新一代EGFR-TKI佐利替尼的3期随机对照研究EVEREST入选了本次大会口头报告，由吴一龙教授汇报，针对伴中枢神经系统（CNS）转移EGFR敏感突变的晚期NSCLC患者。佐利替尼是由阿斯利康（AstraZeneca）联合晨泰医药共同开发的新一代EGFR-TKI，专门为伴CNS转移EGFR敏感突变晚期NSCLC患者的临床需求而开发。该产品通过保留EGFR靶点作用的喹唑啉苯胺母核、引入受约束的构象提高分子刚性等技术优化药物分子理化性质，从而显著提高药物的血脑屏障通透性。迪哲医药：戈利昔替尼作用机制：JAK1抑制剂适应症：外周T细胞淋巴瘤根据迪哲医药新闻稿，其JAK1抑制剂戈利昔替尼治疗复发/难治性外周T细胞淋巴瘤（r/r PTCL）的关键性注册试验将以口头报告形式在本次大会亮相。戈利昔替尼是一款针对T细胞淋巴瘤的高选择性JAK1抑制剂，正在中国、美国、韩国和澳大利亚等地开展治疗r/r PTCL的关键性注册临床试验。截至2021年5月31日，国际多中心1/2期临床试验显示，戈利昔替尼单药肿瘤缓解率达到42.9%，且其中一半以上患者达到了完全缓解，最长缓解持续时间（DoR）超过14个月。此前，戈利昔替尼还曾获美国FDA授予快速通道资格。迪哲医药：舒沃替尼作用机制：EGFR-TKI适应症：NSCLC根据迪哲医药新闻稿，其EGFR-TKI舒沃替尼首个中国注册临床研究WU-KONG6（悟空6）将以口头报告形式在本次大会亮相，针对携带EGFR 20号外显子插入突变的NSCLC。舒沃替尼是一款口服、不可逆、针对多种EGFR突变亚型的高选择性EGFR-TKI，曾获FDA突破性疗法认定，目前已在中国递交治疗标准治疗失败的EGFR 20号外显子插入突变NSCLC的上市申请并被纳入优先审评和突破性治疗品种。目前，该产品正在中国、美国、欧洲、韩国、澳大利亚等国家和地区开展注册临床试验。亘喜生物：GC012F作用机制：BCMA/CD19双靶点FasTCAR-T适应症：复发/难治性多发性骨髓瘤根据亘喜生物新闻稿，其FasTCAR-T疗法GC012F的一项1期、开放性、由研究者发起的临床试验（IIT）长期随访数据入选了本次大会口头报告，针对既往接受过重度治疗的复发/难治性多发性骨髓瘤（RRMM）患者。GC012F是一款BCMA/CD19双靶点FasTCAR-T疗法，有望为癌症治疗带来快速、深入且持久的效果，并且在安全性上具有一定优势。目前，亘喜生物正在开展GC012F的多项IIT研究，适应症覆盖多发性骨髓瘤、B细胞非霍奇金淋巴瘤（B-NHL）等。恒瑞医药：卡瑞利珠单抗 + 阿帕替尼作用机制：抗PD-1单抗、酪氨酸激酶抑制剂适应症：子宫内膜癌根据ASCO官网，恒瑞医药在研产品卡瑞利珠单抗与阿帕替尼构成的联合疗法的一项单臂2期试验入选了本次大会口头报告，针对至少一次系统治疗失败的晚期或复发性子宫内膜癌患者。卡瑞利珠单抗是一款人源化PD-1单克隆抗体，已在中国获批多项适应症，涉及经典型霍奇金淋巴瘤、肝细胞癌、鳞状/非鳞状NSCLC、食管鳞癌、鼻咽癌等不同肿瘤。阿帕替尼是一款口服酪氨酸激酶抑制剂，已在中国获批治疗晚期胃腺癌或胃食管结合部腺癌和肝细胞癌。今年1月，卡瑞利珠单抗与阿帕替尼构成的“双艾”组合还在中国获批晚期肝细胞癌一线治疗适应症。恒瑞医药：SHR-1701 + SHR2554作用机制：PD-L1/TGF-β双抗、EZH2抑制剂适应症：淋巴瘤和实体瘤根据ASCO官网，恒瑞医药在研产品SHR-1701与SHR2554联合治疗既往接受过治疗的晚期淋巴瘤和实体瘤患者的1期研究入选了本次大会口头报告。SHR-1701是一款PD-L1/TGF-β双特异性抗体，目前正在开展针对晚期结直肠癌、胃癌等适应症的多项3期临床研究。SHR2554是一款新型、高效、选择性的口服EZH2抑制剂，曾在中国被纳入突破性治疗品种，用于复发或难治的外周T细胞淋巴瘤（PTCL）。君实生物：特瑞普利单抗作用机制：抗PD-1单抗适应症：NSCLC、三阴性乳腺癌、胃或胃食管交界部癌、黏膜黑色素瘤根据君实生物新闻稿及ASCO官网，该公司抗PD-1单抗特瑞普利单抗有多项临床研究入选本次大会口头报告，包括：1）用于可切除II/III期NSCLC围手术期治疗的3期Neotorch研究；2）治疗复发或转移性三阴性乳腺癌的3期TORCHLIGHT研究；3）治疗无EGFR/ALK突变晚期NSCLC的3期CHOICE-01研究；4）治疗局部晚期胃或胃食管交界部癌的2期研究；5）黏膜黑色素瘤切除后的辅助治疗研究等。特瑞普利单抗是一款以PD-1为靶点的单抗药物，此前已在中国获批多项适应症，涵盖黑色素瘤、鼻咽癌、尿路上皮癌、食管鳞癌、非鳞状NSCLC等瘤种。科伦博泰：KL590586作用机制：RET抑制剂适应症：实体瘤根据ASCO官网，科伦博泰下一代选择性RET抑制剂KL590586在RET变异实体瘤患者中开展的1期研究入选了本次大会口头报告。KL590586是一款小分子选择性靶向RET激酶抑制剂。临床前研究表明，该产品对RET激酶具有高选择性，在动物模型中显示出良好的抗肿瘤活性和安全性。此外，KL590586在动物血/脑暴露量方面也有一定优势，具有治疗肿瘤脑转移和克服临床耐药突变的潜力。目前，该产品正在携带RET融合或突变基因的晚期实体瘤患者中开展多中心1/2期临床研究。信达生物：信迪利单抗作用机制：抗PD-1单抗适应症：鼻咽癌根据信达生物新闻稿，该公司开展的一项代号为CONTINUUM的多中心、随机对照、3期临床研究结果将以口头报告的形式在ASCO大会上展示，该试验比较了抗PD-1单抗信迪利单抗联合诱导性化疗和同步放化疗（IC-CCRT）相比IC-CCRT治疗局部晚期鼻咽癌的疗效和安全性。信迪利单抗是信达生物和礼来（Eli Lilly and Company）合作开发的一款创新PD-1抑制剂，已在中国获批多项适应症，覆盖鳞状/非鳞状NSCLC、肝细胞癌、食管鳞癌、胃及胃食管交界处腺癌等一线治疗及经典型霍奇金淋巴瘤等瘤种。除了上述研究，还有很多其它新药研究也将亮相本届大会。我们将会持续跟踪本届ASCO会议的信息，为大家分享更多癌症研究领域的前沿动态。相关阅读：ASCO中国之声，这些中国公司即将亮相ASCO LBA报告集锦，这些重磅研究值得关注   参考资料（可上下滑动查看） [1]传奇生物将于2023ASCO和EHA年会公布多项多发性骨髓瘤患者潜在治疗方案的最新进展. Retrieved May 17 , 2023. From https://mp.weixin.qq.com/s/5zORB0wovCVAzJ_HxeXcsw[2]信达生物多项临床数据将在2023年ASCO大会及EHA年会公布. Retrieved May 17 , 2023. From https://mp.weixin.qq.com/s/LSstNbwLU-ON3ORlmtsq2Q[3] 君实生物多项研究成果重磅来袭， 2023ASCO精彩纷呈 . Retrieved Apr 27, 2023, from https://mp.weixin.qq.com/s/hjoTKUmj_nwU_tgxC_uqNQ[4]百利天恒(688506.SH)：5项临床研究成果入选2023年美国临床肿瘤学会(ASCO)年会. Retrieved Apr 10, 2023, from https://data.eastmoney.com/notices/detail/688506/AN202304091585241773.html[5] 百济神州将在2023年ASCO年会上展示其广泛的肿瘤产品组合. Retrieved Apr 26, 2023, from https://mp.weixin.qq.com/s/mWmNpO_BQ3wAIYkj1akvlw[6]亘喜生物将在2023 ASCO年会期间公布BCMA/CD19双靶点FasTCAR-T GC012F的最新临床数据. Retrieved Apr 27, 2023, from https://mp.weixin.qq.com/s/A1vcixMy8QO1X14gT_EL1w[7]中国声音闪耀2023 ASCO | 迪哲医药 4 项研究成果入选，舒沃替尼和戈利昔替尼关键性研究斩获2项口头报告. Retrieved Apr 27, 2023, from https://mp.weixin.qq.com/s/9i5uJgw9hJijYT10xB-1cg[8] 伴中枢神经系统转移的EGFR敏感突变非小细胞肺癌的药物治疗——尚未终结的临床挑战（疾病和机制篇）. Retrieved May 15, 2023, from https://mp.weixin.qq.com/s/6ZRkD9Ji3PaGuyh4NxDqLA[9]ASCO大会官网.From https://conferences.asco.org/am/abstracts本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

Rabies program, as the first non-COVID19 vaccine developed with a specialized mRNA platform, highlights Everest's discovery capabilities Clinically validated mRNA platform is shown to generate differentiated products across a range of indications SHANGHAI, Dec. 14, 2022 /PRNewswire/ -- Everest Medicines (HKEX 1952.HK, "Everest"), a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products that address critical unmet medical needs for patients in Greater China and other parts of Asia, announced today that the company has achieved the preclinical proof-of-concept milestone for its mRNA rabies vaccine program. This new vaccine candidate for rabies post-exposure prophylactic was developed in partnership with Providence Therapeutics Holdings Inc. ("Providence") utilizing a clinically validated mRNA technology platform. "The mRNA rabies vaccine program is an important validation of our discovery capability and the mRNA platform as the first of several non-COVID mRNA vaccine/therapeutics candidates," said Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines. "We continue to advance our Omicron-containing bivalent booster candidate, EVER-COVID19-M1.2, in China and other Everest territories and plan to initiate clinical trials in 2023. Building on the momentum of promising mRNA infectious disease vaccine candidates, we are well-positioned to continue innovating novel candidates using this mRNA technology platform across a wide range of disease indications." In a head-to-head immunogenicity comparison study with a commercial inactivated rabies vaccine, mice dosed with Everest's pre-clinical rabies vaccine candidate produced higher levels of serum neutralizing antibodies than those of mice dosed with the comparator vaccine. Everest's candidate also induced a significantly higher degree of T-cell-mediated immune response than the comparator vaccine. These positive results support the clinical development of the rabies vaccine. Everest and Providence hold 50/50 global rights to develop and commercialize the new rabies vaccine. About Rabies Rabies is a zoonotic, viral disease. While it remains a serious threat to public health, the disease is vaccine-preventable with proper treatment. Every year, more than 29 million people worldwide receive a post-bite rabies vaccination[1], which – if received soon after exposure – can effectively prevent the onset of symptoms. Once clinical symptoms appear, however, the disease is virtually 100% fatal. Notably, over 95% of human deaths from rabies occur in the Asia and Africa regions, predominately affecting vulnerable populations who live in remote rural locations. Post-exposure prophylaxis (PEP) is the immediate treatment of a bite victim after rabies exposure, which includes delivering a course of a potent and effective rabies vaccine as well as immediate wound washing and administration of rabies immunoglobulin.[2] About Everest Medicines Everest Medicines is a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products that address critical unmet medical needs for patients in Asian markets. The management team of Everest Medicines has deep expertise and an extensive track record from both leading global pharmaceutical companies and local Chinese pharmaceutical companies in high-quality clinical development, regulatory affairs, CMC, business development and operations. Everest Medicines has built a portfolio of potentially global first-in-class or best-in-class molecules, many of which are in late-stage clinical development. The Company's therapeutic areas of interest include cardio-renal diseases, autoimmune disorders, and infectious diseases. For more information, please visit its website at . Forward-Looking Statements: This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law. SOURCE Everest Medicines