AZD-8205

近年来，阿斯利康在肿瘤治疗领域持续发力，通过一系列的战略布局和研发投入，试图为肿瘤患者带来更有效的治疗方案，重塑肿瘤治疗格局。从抗体偶联药物（ADCs）到放射性药物，再到双特异性抗体、T 细胞衔接器和细胞疗法等多个前沿领域，阿斯利康展现出了强大的创新决心和实力。ADC 领域：内外兼修，拓展管线阿斯利康在 ADC 领域成绩斐然，与第一三共合作的 Enhertu 已成为重磅炸弹级药物，今年 1 月另一款 ADC 药物 Datroway 也获得 FDA 批准。如今，阿斯利康开始着重打造内部 ADC 管线，目前已有 6 款处于临床阶段的 ADC 药物，针对实体瘤和血液系统恶性肿瘤。2024 年 9 月欧洲肿瘤内科学会会议上，阿斯利康公布了两款 ADC 药物的关键数据。靶向叶酸受体 α（FRα）的 AZD5335 和针对 B7-H4 的 AZD8205 备受关注。其中，AZD5335 在卵巢癌和肺腺癌的 2 期试验中表现出令人鼓舞的数据。尽管艾伯维已有针对 FRα 的 ADC 药物 Elahere 获批用于特定卵巢癌，但阿斯利康认为 AZD5335 有潜力覆盖更广泛的患者群体，包括不同叶酸受体表达水平的卵巢癌患者及其他适应症患者。放射性药物领域：收购布局，推进研发阿斯利康去年收购 Fusion Pharmaceuticals，强势进军放射性药物领域。此次收购不仅为其带来了 PSMA 靶向放射性偶联物 FPI - 2265 和 EGFR - cMET 靶向放射性偶联物，还获得了 Fusion 的放射化学专业技术和位于加拿大安大略省的制造工厂。目前，FPI - 2265 已进入前列腺癌的 2 期试验，EGFR - cMET 靶向放射性偶联物也开始了 1 期试验的患者给药。虽然这些研究尚处于早期阶段，但阿斯利康对取得积极成果充满期待。双特异性抗体与 T 细胞衔接器：创新设计，抢占先机双特异性抗体是阿斯利康癌症治疗战略的重要组成部分。针对备受争议的 anti - TIGIT 抗体领域，阿斯利康的 PD - 1/TIGIT 双特异性抗体 rilvegostomig 凭借独特设计脱颖而出。它旨在同时阻断 PD - 1 和 TIGIT 靶点，增强免疫反应，同时减少 Fc 效应子功能，有望降低副作用。此外，阿斯利康还在开发 CTLA - 4 和 PD - L1 双特异性抗体 volrustomig，这两款候选药物正在 9 项 3 期试验中接受评估。在 T 细胞衔接器领域，阿斯利康凭借 2022 年对 TeneoTwo 的收购占据先机。其收购的 CD19xCD3 T 细胞衔接双特异性抗体仍在临床开发中，同时一款 CD20 T 细胞衔接器也已进入人体试验阶段。阿斯利康还计划运用条件激活和掩蔽技术，探索更多可靶向的目标，进一步拓展 T 细胞衔接器的应用范围。细胞疗法领域：持续投入，探索新方向在其他药企纷纷对细胞和基因疗法持谨慎态度时，阿斯利康却加大在该领域的投入。上个月，阿斯利康收购 EsoBiotec，进一步强化其细胞疗法布局。目前，阿斯利康有 7 款细胞疗法项目处于临床阶段，其中一款针对多发性骨髓瘤的 BCMA 和 CD19 双靶向 CAR - T 疗法备受关注。此外，阿斯利康还积极探索通用型（即同种异体）细胞疗法领域，展现出在该领域长期发展的决心。阿斯利康通过在多个前沿领域的创新和布局，构建了一个多元化且极具潜力的肿瘤治疗产品线。这些努力能否转化为切实有效的治疗方案，改变肿瘤治疗的现状，值得行业密切关注。未来，阿斯利康在肿瘤治疗领域的持续创新，有望为全球肿瘤患者带来更多希望。参考来源：https://www.fiercebiotech.com/biotech/adcs-radiopharma-how-astrazeneca-aims-redefine-oncology-care识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

The diversity of AstraZeneca\'s oncology portfilio is \"by design,\" Puja Sapra, SVP for Biologics Engineering and Oncology Target Discovery, told Fierce.\n AstraZeneca has been busy in recent years pumping up its oncology pipeline via a shopping list of assets and companies. Now, the U.K.-based pharma is overseeing a range of clinical trials to determine whether these cancer bets will pay off.“We have deliberately made investment in the next-generation technologies which we believe will redefine oncology care, like ADCs [and] radioconjugates,” Puja Sapra, Ph.D., AstraZeneca’s senior vice president for biologics engineering and oncology target discovery, told Fierce Biotech in an interview.AstraZeneca already has a reputation when it comes to antibody-drug conjugates, having turned Enhertu into a blockbuster and then following it up with the FDA approval of another ADC, Datroway, in January.While both Enhertu and Datroway emerged from a collaboration with Daiichi Sankyo, Sapra said the next chapter of AstraZeneca’s ADC story involves “a conscious effort to invest significantly” in its internal pipeline.This has resulted in a clinical-stage line-up of six in-house ADCs aimed across solid tumors and hematological malignancies. AstraZeneca arrived at the European Society for Medical Oncology conference in September 2024 armed with data from two of these: a folate receptor α (FRα) -targeted ADC called AZD5335 and a B7-H4–directed topoisomerase I inhibitor ADC called AZD8205.“This was the first time we had put our proprietary linker-payload technology in the clinic and presented it,” Sapra said. AZD5335 is currently in a phase 2 trial for ovarian cancer and lung adenocarcinoma, while AZD8205 is in its own mid-stage study for solid tumors. Sapra singled out the data for AZD5335 that was shared at ESMO as “very encouraging.” AbbVie already has a FRα-directed ADC on the market in the form of Elahere, which is approved for high FRα-expressing platinum-sensitive ovarian cancer.“We believe with our molecule … we have an opportunity to go into the entire setting of high folate receptor, as well as low folate receptor in ovarian cancer and other indications,” Sapra explained.AstraZeneca plunged into the radiopharmaceuticals space via the acquisition of its partner Fusion Pharmaceuticals one year ago. Since that buyout, AstraZeneca has ushered a PSMA-directed radioconjugate, dubbed FPI-2265, into a phase 2 trial in prostate cancer. An EGFR-cMET targeted radioconjugate that resulted from the previous partnership with Fusion has also entered dosing in a phase 1 trial.“It\'s very, very early days, but we are keeping our fingers crossed to see the first imaging data and responses,” Sapra said of the phase 1 study.Along with a radiopharma pipeline, the buyout included Fusion\'s radiochemistry expertise and a manufacturing plant in Ontario, Canada. Sapra said integrating these aspects into the AstraZeneca family is going “very nicely,\" noting that there are also several preclinical programs tied to the acquisition that are currently in development. Another red-hot R&D area is bispecific antibodies, a therapeutic class that has become an integral part of AstraZeneca’s cancer strategy in recent years. But with BeiGene the latest in a long line of biopharmas abandoning anti-TIGIT antibodies, does Sapra still have confidence in its PD-1/TIGIT bispecific rilvegostomig?“I can wear my biologics engineering hat now and tell you how we designed the molecule, because it’s all in the design,” she said.“TIGIT accesses the same immunosuppressive pathway as PD-1,” she continued. “Now you\'re blocking both the targets at the same time, and it should hopefully help us increase the response rate and durability.”Rilvegostomig is designed to reduce Fc effector functionality. The Fc domain\'s functions are key in helping antibodies drive an effective immune response against a pathogen, Sapra pointed out, “so this should help with unwanted side effects.”“[With the] combination of these two properties, we believe we have a very differentiated molecule,\" the AstraZeneca leader said.In addition to rilvegostomig, the pharma is also developing a CTLA-4 and PD-L1 bispecific called volrustomig. The two candidates are being evaluated in a total of nine phase 3 trials between them.“They are very different designs,” Sapra said. “They go after different population settings and that\'s why we are trying to maximize and put [them] in different settings.”One of the latest trends in Big Pharma dealmaking is T-cell engagers, and here AstraZeneca has had something of a head start, thanks to the acquisition of TeneoTwo in 2022. The main asset from that deal, a CD19xCD3 T-cell engaging bispecific antibody, remains in clinical development, but alongside that AstraZeneca is now working on a CD20 T-cell engager that has recently entered human trials.“We are also thinking about using conditional activation and masking technologies to go after targets which you may think may not be accessible with T cell engagers,” Sapra said.  When it comes to cell therapies, the Big Pharma turned heads last month by acquiring EsoBiotec and its “in vivo” capabilities. AstraZeneca currently has seven cell therapy programs in the clinic, led by a BCMA and CD19 dual-targeting CAR-T for multiple myeloma acquired as part of 2023’s Gracell acquisition. However, executives at the Big Pharma told Fierce as far back as 2022 that they were interested in exploring the off-the-shelf—also known as allogeneic—cell therapy space.The dedication to the space comes amid an industry reckoning, with several other pharmas—such as Takeda, Pfizer and Roche—backing away from cell and gene therapies in recent days.  “We have made broad commitments to cell therapy, and that\'s clear from EsoBiotec, but other things also,” Sapra said. “We have gone from autologous to building the allogeneic [and] now thinking about in vivo. So this is a long-term vision to be in this space.”From ADCs to T-cell engagers and beyond, a flurry of dealmaking in recent years has left AstraZeneca with a wide-ranging oncology portfolio with plenty of potential. This diversity is deliberate, according to Sapra.“That\'s by design, which we are very proud of,” she said. “It has been built on solid, binary scientific foundations.”