DualityBio Inc.

GSK and Duality Biologics have entered into an exclusive option agreement worth over $1bn for DualityBio’s preclinical antibody-drug conjugate (ADC). The deal gives GSK an exclusive option to obtain a licence to develop and commercialise DB-1324 globally, except in mainland China, Hong Kong and Macau. The candidate leverages DualityBio’s Duality Immune Toxin Antibody Conjugate (DITAC) platform against a gastrointestinal cancer target. Gastrointestinal cancers account for one in four cancer cases and one in three cancer-related deaths globally. ADCs are a relatively new class of cancer drugs that combine the selectivity of antibodies with the cell-killing properties of chemotherapy or other anti-cancer agents. Unlike chemotherapy, which works by attacking lots of different cells as well as the cancer, ADCs are designed to target and kill tumour cells while sparing healthy cells. DB-1324 has the potential to “unlock multiple combination therapy opportunities to strategically complement” GSK’s oncology portfolio, according to DualityBio. DualityBio will initially receive $30m upfront and additional pre-option milestone payments and, if GSK exercises its option, the biotech will be in line for an option exercise fee as well as potential development, regulatory and commercial milestone payments totalling up to $975m, plus tiered royalties on net sales in GSK’s territories. Hesham Abdullah, senior vice president, global head oncology, research and development, GSK, said: “Given the unique ability of ADCs to address certain targets on tumour cells while sparing healthy ones, we are confident in our strategic focus on this modality as it could advance new therapeutic treatments for the most challenging tumour types.” Also commenting on the agreement, John Zhu, chief executive officer of DualityBio, said: “We are very glad to have entered into this agreement with GSK. Through this collaboration, we will work together to advance our innovative ADC programme in gastrointestinal cancer to address unmet medical needs.” The deal is not GSK’s first of the month, with the company also recently partnering with Rgenta Therapeutics to develop RNA-targeting small molecule splice modulators for disease areas including oncology in an agreement worth nearly $500m per target. GSK also entered into a strategic partnership worth $650m with Vesalius Therapeutics in November to discover and develop new treatments for Parkinson’s disease and one additional neurodegeneration indication.

礼来公司今日正式公布了SURMOUNT-5临床3b期试验的药结果。 这项试验针对的是患有肥胖/超重、且至少有一种超重并发疾病（如高血压、血脂异常、阻塞性睡眠呼吸暂停或心血管疾病）、且无糖尿病的成年人。该试验在美国和波多黎各随机分配了751名参与者，接受最大耐受剂量的Zepbound或Wegovy治疗。 研究显示，与另一款热门减肥药物Wegovy（semaglutide）相比，礼来的Zepbound（tirzepatide）在减肥效果上展现出显著优势。 在72周的研究周期内，Zepbound组受试者平均体重减轻了20.2%、平均减重50.3磅（22.8公斤），Wegovy组平均体重减轻为13.7%、平均减重33.1磅（15.0公斤）。 这意味着，与Wegovy相比，Zepbound帮助患者实现了47%的相对体重减轻。 除了显著的平均体重减轻外，Zepbound还在主要终点和所有五个关键次要终点上都击败了Wegovy。 在研究中，有31.6%的Zepbound患者实现了至少25%的体重减轻，而Wegovy患者的这一比例仅为16.1%。这一数据进一步证明了Zepbound在减肥方面的卓越效果。 在安全性方面，Zepbound在SURMOUNT-5中的总体安全性特征与先前报道的SURMOUNT试验相似。Zepbound和Wegovy在SURMOUNT-5中最常报告的不良事件与胃肠道相关，但通常严重程度为轻度至中度。这表明Zepbound在提供显著减肥效果的同时，也保持了良好的安全性。 礼来公司表示，将继续评估SURMOUNT-5的结果，并将该结果发表在同行评审期刊上，并在明年的医学会议上展示。 总之，礼来公司宣布的SURMOUNT-5临床试验顶线结果为肥胖症患者带来了新的治疗选择。Zepbound以其卓越的减肥效果和良好的安全性，有望成为未来肥胖症治疗领域的重要药物之一。 参考消息：https://investor.lilly.com/news-releases/news-release-details/lillys-zepboundr-tirzepatide-superior-wegovyr-semaglutide-head 免责声明 本文旨在行业资讯和知识分享，无任何商业用途。文章仅代表作者观点，不代表本站立场。   往期推荐 1.阿斯利康，最新人事任命！有望代替王磊，成为与中国市场间的关键“桥梁” 2.刚刚！信迪利单抗（信达生物）与呋喹替尼（和黄医药）的联合疗法获批上市，适用于子宫内膜癌 3.超10亿美元！上海映恩生物受GSK青睐，授权临床前ADC药物 4.2024医药公司市值回顾：两极分化！礼来领跑，辉瑞、默克等面临挑战 5.91种新药，进医保了！新版国家医保药品目录公 往期链接 “小小疫苗”养成记 | 医药公司管线盘点  人人学懂免疫学 | 人人学懂免疫学（语音版）    综述文章解读 | 文献略读 | 医学科普 | 医药前沿笔记 PROTAC技术 | 抗体药物 | 抗体药物偶联-ADC 核酸疫苗 | CAR技术 | 化学生物学 温馨提示 医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群加作者微信（yiyaoxueshu666）或者扫描公众号二维码添加作者，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。 简单操作即可星标⭐️医药速览，第一时间收到我们的推送 ①点击标题下方“医药速览”   ②至右上角“...”  ③点击“设为星标

Duality Biologics and BioNTech say interim data on one of their partnered ADCs look encouraging, with a preliminary cut from the trial showing that nearly a third of treated patients had unconfirmed responses. In the 238 evaluable patients with at least one post-baseline tumor assessment, 32.4% had an unconfirmed overall response, and the disease control rate was 82.4%. Among the 73 patients with small-cell lung cancer, the unconfirmed ORR was 56.2% and the DCR was 89%. Notably, in patients with castration-resistant prostate cancer (CRPC), radiographic progression-free survival data are not yet mature, but data presented on Friday at ESMO Asia in Singapore show that a median rPFS reached 7.2 months, and the six-month rPFS rate was 94.7%. The Phase 1/2a basket trial is testing various doses of BNT324, also called DB-1311, in 277 heavily pretreated patients. Early positive data were also reported on patients with cervical cancer, hepatocellular carcinoma, head and neck squamous carcinoma, and melanoma. Roughly 61% of enrolled patients had undergone two or more lines of prior therapy. But more data need to be collected. The study’s primary endpoints are safety and objective response rate, so the responses will have to be confirmed. Secondary measures include duration of response, disease control rate and progression-free and overall survival. BNT324 is a topoisomerase I inhibitor-based conjugate targeting the transmembrane glycoprotein B7-H3. Several companies are investigating B7-H3 as a target, including Merck with ifinatamab deruxtecan. A trial of MacroGenics’ B7-H3-directed antibody in head and neck cancer was shuttered after several patient deaths. According to DualityBio, its candidate showed a “manageable” safety profile across all evaluated patients and tumor types in its early trial. The most common treatment-related side effects were nausea, decreased neutrophil count, anemia, decreased white blood cell count, decreased appetite and decreased platelet count. BNT324 has US fast track status for advanced/unresectable or metastatic CRPC and orphan drug designation for advanced or metastatic esophageal squamous cell carcinoma. It is one of three clinical-stage ADCs being developed by BioNTech and DualityBio under a partnership they set up in April 2023. They plan to test some of these ADCs in combination with a bispecific antibody targeting PD-L1 and VEGF-A, dubbed BNT327 or PM8002, in solid tumors. The bispecific is under joint development by BioNTech and Biotheus.