Farabursen

近期，全球多肽和寡核苷酸（TIDES）领域迎来系列进展。Avacta Therapeutics公司公布其主打在研多肽偶联药物AVA6000（FAP-Dox）的1期临床试验积极数据。接受≥250 mg/m²剂量的唾液腺癌患者，疾病控制率达到91%。诺华（Novartis）的放射配体疗法（RLT）Pluvicto（177Lu vipivotide tetraxetan，镥[177Lu]特昔维匹肽注射液）的新适应症监管申请获得中国国家药监局药品审评中心（CDE）受理。此外，诺华达成合并协议收购Regulus Therapeutics。欢迎读者长按/扫描以下二维码，申请获取含有完整表格整理的《2025年5月第1期TIDES疗法进展盘点》。▲长按识别上方二维码，申请获取《2025年5月第1期TIDES疗法进展盘点》AVA6000：1期试验结果公布Avacta Therapeutics公司日前公布了其主打在研多肽偶联药物AVA6000的1期临床试验积极数据。AVA6000是一种在肿瘤微环境中特异性激活的多柔比星（doxorubicin）前药，旨在减少传统化疗的全身性副作用。在1a期剂量递增研究中，无论是每三周一次（Q3W）还是每两周一次（Q2W）的给药方案，AVA6000均显示出良好的耐受性。即使剂量升高至每三周385 mg/m²，也未达到最大耐受剂量（MTD）。在唾液腺癌患者（n=11）中，接受≥250 mg/m²剂量水平的AVA6000治疗后，多位患者获得确认缓解，疾病控制率达到91%。中位无进展生存期（PFS）尚未达到，当前中位随访时间已超过25周。Avacta Therapeutics公司目前正在1b期扩展队列中持续招募包括唾液腺癌、三阴性乳腺癌以及高级别软组织肉瘤的患者，相关数据预计将于2025年底公布。Pluvicto：新适应症监管申请获得受理日前，中国国家药监局药品审评中心官网公示，诺华的前列腺特异性膜抗原（PSMA）靶向放射配体疗法Pluvicto的新适应症监管申请获得受理，并被拟纳入优先审评，用于治疗既往接受过雄激素受体通路抑制剂（ARPI）治疗的PSMA阳性转移性去势抵抗性前列腺癌（mCRPC）成年患者。针对该项适应症，Pluvicto于今年3月获得了美国FDA批准。Pluvicto是通过静脉注射的放射配体疗法，由靶向配体与治疗性放射性核素镥结合而成。进入血液后，Pluvicto可靶向结合表达PSMA的前列腺癌细胞。结合后，放射性同位素释放的能量可破坏靶细胞，抑制其复制能力和/或引发肿瘤细胞死亡。图片来源：CDE官网今年3月，诺华宣布FDA批准Pluvicto用于接受过一种ARPI治疗且被认为适合延迟化疗的PSMA阳性的mCRPC患者。此适应症获批是基于3期PSMAfore临床研究的结果，将符合Pluvicto治疗条件的患者人群扩大约三倍。研究结果显示，与更换ARPI方案相比，Pluvicto将PSMA阳性mCRPC患者的影像学进展或死亡风险降低59%，Pluvicto组的中位影像学无进展生存期显著延长（9.3个月vs. 5.6个月，p<0.0001）。诺华达成协议收购Regulus TherapeuticsRegulus Therapeutics日前宣布，已与诺华达成一项合并协议。根据该协议，诺华将以8亿美元的初始付款收购Regulus。此外，Regulus也将在该公司的主打在研产品farabursen达成潜在监管里程碑时，获得额外9亿美元的款项，使交易总额最高可达约17亿美元。Regulus Therapeutics是一家专注于发现和开发靶向微RNA（microRNA）创新药物的生物医药公司。该公司充分发挥其在寡核苷酸药物发现和开发领域的专长，已建立了一系列在研药物管线。Regulus Therapeutics的主打在研疗法farabursen是一款靶向miR-17的新型、下一代寡核苷酸药物，用于治疗常染色体显性多囊肾病（ADPKD）。该药物近期已完成一项1b期多剂量递增临床试验。限于篇幅，本文仅针对部分重要进展做简单介绍。欢迎读者长按/扫描以下二维码，申请获取含有完整表格整理的《2025年5月第1期TIDES疗法进展盘点》。▲长按识别上方二维码，申请获取《2025年5月第1期TIDES疗法进展盘点》参考资料：[1] Avacta Therapeutics Presents Data from Lead pre|CISION® Candidate FAP-Dox (AVA6000) at the 2025 AACR Annual Meeting. Retrieved May 1, 2025 from https://www.globenewswire.com/news-release/2025/04/28/3069067/0/en/Avacta-Therapeutics-Presents-Data-from-Lead-pre-CISION-Candidate-FAP-Dox-AVA6000-at-the-2025-AACR-Annual-Meeting.html[2] 中国国家药监局药品审评中心（CDE）官网. Retrieved Apr 28，2025, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c[3] FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. Retrieved May 2, 2025 from https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication[4] Regulus Therapeutics Enters into Agreement to be Acquired by Novartis AG. Retrieved April 30, 2025 from https://www.prnewswire.com/news-releases/regulus-therapeutics-enters-into-agreement-to-be-acquired-by-novartis-ag-302442023.html免责声明：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。版权说明：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「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

The upfront cash payment represents a significant premium over Regulus’ recent stock prices. Credit: Judith Linine/Shutterstock. Novartis has agreed to acquire US-based Regulus Therapeutics and its oligonucleotide, farabursen, to bolster its renal disease offerings. The upfront cash payment represents a significant premium over Regulus’ recent stock prices and a contingent value right (CVR) tied to regulatory milestones. Total consideration for the acquisition, including the CVR, could reach $1.7bn if the regulatory milestone is met. The transaction has received unanimous approval from both companies’ boards of directors. Novartis will commence a tender offer through an indirect wholly owned subsidiary to purchase all outstanding Regulus shares. Shareholders of Regulus will receive $7 per share in cash on closure, along with the CVR worth up to an additional $7 per share, contingent upon regulatory approval of the therapy. Post completion, Novartis plans to combine the acquiring subsidiary with Regulus, making it an indirect wholly owned subsidiary of the company. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence Anticipated closure will take place in the second half of 2025, contingent on customary closing conditions, including the tender of a majority of Regulus’ common stock outstanding shares and necessary regulatory approvals. Both companies will operate as independent entitiesuntil then. Evercore is the exclusive financial advisor to Regulus, and Latham & Watkins is providing legal counsel. Regulus’ farabursen targets microRNA (miR)-17 with preferential kidney exposure and is intended for treating autosomal dominant polycystic kidney disease (ADPKD). The treatment decreases cyst growth and the size of the kidney, potentially delaying ADPKD’s severity. In March 2025, Regulus completed its Phase Ib multiple-ascending dose trial of the therapy, demonstrating safety and clinical efficacy. Novartis Development president and chief medical officer Shreeram Aradhye stated: “With limited treatment options currently available for patients suffering from ADPKD, farabursen represents a potential first-in-class medicine with a profile that may provide enhanced efficacy, tolerability and safety versus standard of care.” In February 2025, Novartis agreed to acquire Anthos Therapeutics, a Boston-based clinical-stage biopharmaceutical company, for an upfront payment of $925m.