AZD0754

AstraZeneca’s dealmaking in the cell and gene therapy space shows no signs of slowing. On Tuesday, the pharma agreed to spend up to $1.2 billion to acquire Chinese cell therapy company Gracell, its sixth such deal in the past year. The acquisition fills in some gaps in AstraZeneca’s cell therapy pipeline, adding a clinical-stage CAR-T therapy in development for haematologic cancers and autoimmune diseases. The pharma also gains Gracell’s FasTCAR platform, which is intended to significantly shorten manufacturing time, enhance T cell fitness, and improve efficacy.A bit of a latecomer to the CGT space, AstraZeneca began adding to its portfolio in earnest late last year with the $320-million takeout of Neogene and its T-cell receptor (TCR) candidates for solid tumours. The pharma has since signed a $2-billion deal with Quell Therapeutics to develop regulatory T (Treg) cell therapies for autoimmune diseases; acquired a slate of preclinical gene therapies from Pfizer for up to $1 billion; and last month, formed a broad strategic alliance with Cellectis to use its TALEN gene editing platform and manufacturing capabilities to develop cell and gene therapy products.AstraZeneca also partnered this month with AbelZeta Pharma to co-develop C-CAR031, an autologous, armoured GPC3-targeted CAR-T therapy for liver cancer that’s based on a novel construct designed by the pharma. AstraZeneca’s only wholly owned and internally developed cell therapy programme is AZD0754, a preclinical TGF-beta-armoured CAR-T targeting STEAP2, which is overexpressed in prostate cancer. Under the deal terms, AstraZeneca will acquire Gracell at $2.00 per share, plus a milestones-based non-tradable contingent value right of $0.30 per share, for a total deal value of $1.2 billion. The combined price is an 86% premium to Gracell's close on December 22.Early MM data, eyes on lupusThe most prominent asset AstraZeneca gains is Gracell’s lead candidate, GC012F, a BCMA/CD19 dual-targeted CAR-T in a Phase Ib/II multiple myeloma (MM) trial.At the December American Society of Hematology (ASH) meeting, Gracell presented data from an investigator-initiated trial of GC012F to treat newly diagnosed, high-risk MM. In 22 patients, GC012F demonstrated a 100 percent overall response rate, with 21 patients achieving stringent complete response with a median follow-up of 18.8 months. Although positive, KOLs told FirstWord Pharma they weren’t overwhelmed by the data. To displace the market-leading BCMA-targeted CAR-T for MM, Johnson & Johnson’s Carvytki (ciltacabtagene autoleucel), both high response rate and quick manufacturing are needed.AstraZeneca will also have an opportunity to explore GC012F’s potential in autoimmune diseases. Gracell was cleared by the FDA in November to start a trial of GC012F in systemic lupus erythematosus (SLE). This shift was validated by data presented by a German academic group at ASH, which found impressive responses treating SLE patients with a CD19-targeting CAR-T. Gracell’s pipeline also includes three preclinical dual-targeted CAR-Ts for haematological malignancies, and one CAR-T in development for solid tumours that targets Claudin-18.2, a protein expressed in gastrointestinal cancers.

11 月 9 日，阿斯利康公布了 Q3 及前 9 个月业绩，Q3 收入 114.92 亿美元，同比 +6%（以 CER 计，下同），前三季度收入 337.87 亿美元（+4%）。排除新冠产品，前三季度和 Q3 分别获得 15% 和 13% 的增长。阿斯利康 2023 前三季度总体营收情况截图来自：阿斯利康官网（下文如无额外提及，均为同一来源）分地区来看，中国地区 Q3 收入 14.52 亿美元，同比 +1%；前三季度收入 44.95 亿美元，同比 +6%。阿斯利康 2023 前三季度分地区营收及增长（排除新冠产品）分治疗领域来看，肿瘤和 CVRM 继续以 20% 和 19% 的同比增速领衔。阿斯利康 2023 前三季度分地区营收及增长销售额 TOP10 相比前一季度无变化，达格列净、度伐利尤单抗、Ultomiris 这些关键产品都保持在 40% 以上的同比增速，达格列净今年全年销售额可能超越奥希替尼，成为阿斯利康 TOP1 的扛把子产品；BTK 抑制剂阿克替尼也保持有 26% 的增速。阿斯利康 2023 前三季度 TOP10 产品及销售额具体来看关键产品们。对于奥希替尼，AZ 希望它有能力覆盖到每一位 EGFRm 患者，针对 I-III 期可切除、III 期不可切除、1L 转移性疾病状态都有关键 III 期临床开展，还开始了广泛的联合疗法探索。阿可替尼的新处方份额上在 BTK 抑制剂中也处于领先地位，高于同领域 FIC 产品伊布替尼和潜在 BIC 泽布替尼。IO 产品在 Imfinzi/Imjudo 的 56% 高增长率之下，双抗管线正在积极推进，PD-1/CTLA-4 双抗 volrustomig 已展现有意疗效，还有 4 项 III 期临床布局。ADC 已经成为 MNC 必争之地，AZ 作为最早以独到眼光引进第一三共 Enhertu 的企业，更是如此。除与第一三共合作的 2 款之外，还有 5 条 ADC 管线在开发，3 条为完全自主研发，2 条引进自中国企业康诺亚和礼新。AZ 特别介绍了合作康诺亚的 CLDN18.2 ADC AZD0901 的早期数据。CGT 也是最近大热，阿斯利康的 CAR-T 项目 AZD7003 正在 I 期临床开发中，此外还有 AZD0754 和 AZD6422。生物制药领域，以 Farxiga 为首，对慢性肾病、心衰、高血压领域广泛覆盖。2023Q4~2024 潜在里程碑如下：发生在 Q3 的管线移除：同日，阿斯利康还公布了 2 则积极信息：Imfinzi 联用贝伐珠单抗的 EMERALD-1 研究在肝癌患者中达到了 PFS 主要终点；联手国内诚益生物，以 1.85 亿美元首付款 + 18.25 亿美元里程碑引进 GLP-1RA 小分子，直攻肥胖症和心血管疾病。在交易新闻稿中，对这一产品的开发方向看起来更注重肥胖症和心血管疾病，这也与这类药物当前发展大势一致。GLP-1 赛道主流的两大开发方向在双靶点激动剂和小分子药物，而 AZ 今年 Q1 终止了已处于 IIb/III 期阶段的每日一次 GLP-1R/GCGR 双重激动剂 Cotadutide，转而开发每周一次给药的同类产品 AZD9550；本次又引进小分子 GLP-1RA，今年也可谓是动作频频，双管齐下，力争在此赛道也分一杯羹。封面来源：企业 Logo免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：加一PR 稿对接：微信 insightxb投稿：微信 insightxb；邮箱 insight@dxy.cn多样化功能、可溯源数据……Insight 数据库网页版等你体验点击阅读原文，立刻解锁！