To learn about the safety and effects of an investigational drug called nirogacestat when given to participants with a desmoid tumor/aggressive fibromatosis

开始日期2024-11-26

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT05949099

/ Recruiting临床2期IIT

Phase II Study of Cryoablation and Nirogacestat for Desmoid Tumor

The primary purpose of this protocol is Systemic therapy with oral study agent, nirogacestat, followed by a single cryoablation procedure.

开始日期2023-08-15

申办/合作机构

Stanford University

[+1]

NCT05573802

/ Recruiting临床1/2期IIT

A Phase 1/2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administrated in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma

This is a phase 1/2, open-label study designed to assess the safety and clinical activity of different belantamab mafodotin doses in combination with lenalidomide, dexamethasone and nirogacestat in patients with transplant ineligible newly diagnosed multiple myeloma.
This will be a 2-part study. In part 1 participants will be enrolled in one cohort to receive belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat and will determine the recommended phase 2 dose (RP2D) to be further evaluated for safety and clinical activity in the dose expansion cohort. The RP2D dose will be used in future studies in the transplant-ineligible newly diagnosed multiple myeloma (NDMM) setting. In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 of the study will also evaluate an alternative dose modification guideline for corneal adverse events (AEs).
Overall, approximately 36 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is enrolled (follow-up period range: 3-4 years). The estimated accrual period will be 12 months, corresponding to an approximate total study duration of 4 years.

开始日期2023-07-14

申办/合作机构

Hellenic Society of Cardiology

[+1]

100 项与硝加司他相关的临床结果

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100 项与硝加司他相关的转化医学

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100 项与硝加司他相关的专利（医药）

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项与硝加司他相关的文献（医药）

2025-05-30·Current Oncology

Evaluating Management of Extra-Abdominal Desmoid Fibromatosis: A Retrospective Analysis of Treatments, Outcomes and Recurrence Patterns.

Article

作者: Saraf, Vidhi ; Triplicane Dwarakanathan, Hariharan ; Gupta, Sanjay ; Mahendra, Ashish ; Al-Abri, Al-Muaayad ; Nixon, Ioanna ; Vaughan, Sarah

Background: Desmoid fibromatosis (DF) is a rare, locally aggressive soft tissue tumour with unpredictable clinical behaviour. Historically, treatment has involved surgery; however, contemporary guidelines, such as those from the Desmoid Tumour Working Group, advocate active surveillance. This article reviews current perspectives on DF, focusing on epidemiology, pathogenesis, treatment strategies, emerging research directions and cost effectiveness based on our experience at the West of Scotland Musculoskeletal Oncology Service, Glasgow Royal Infirmary (GRI). Methodology: We reviewed 101 patients diagnosed with desmoid fibromatosis between 2010 and 2024. A review of patient records was conducted to gather information on demographics, date of diagnosis, prior treatment, treatment initiation, intervention types, imaging intervals, follow-up duration, recurrence rate for surgery and other intervention, and discharge timelines. All data was systematically organized and analyzed to assess our outcomes. Results: Out of 101 patients with DF in the study, 66% were females. The most common site of primary tumour was lower extremity (39.6%) followed by near equal distribution in upper extremity and trunk. Out of the total cases, 72 (71.2%) were successfully managed with active surveillance involving serial imaging and clinical reviews in accordance with European guidelines. A total of 22 patients (21%) received treatment: 10 underwent surgery alone, 2 had surgery combined with radiotherapy, 8 received only radiotherapy, 1 was treated with hormonal therapy and 1 participated in a trial with Nirogacestat. Of the seven remaining patients, six had unplanned surgery outside followed by active surveillance at GRI. One patient was on alternative treatment modality, homeopathy. The average number of MRI scans per patient was 3.11, with many patients requiring significantly more imaging. MRI surveillance varies significantly in desmoid tumours due to their heterogeneous behaviour. Active or symptomatic tumours often require more frequent scans (every 3-6 months), while stable cases may need only imaging annually or just clinical monitoring. Recurrence was noted in eight patients, all of which were related to prior surgery. The total combined cost of imaging and appointments exceeds £6500 per patient in active surveillance. Conclusions: We conclude that most patients with desmoid fibromatosis in our cohort were effectively treated with active surveillance, consistent with current European guidelines. Surgical management of desmoid fibromatosis in our cohort is historic and has shown a significant recurrence risk. Our study proposes a revised follow-up protocol that significantly reduces costs without compromising on patient care. We suggest a two-year surveillance period for stable disease with patient-initiated return to reduce unnecessary clinic visits, imaging and healthcare costs.

2025-04-21·CANCER INVESTIGATION

Clinical Challenges and Evolving Treatments in Desmoid Fibromatosis: A Single Institution Experience

Article

作者: Gitelis, Steven ; Butler, Zachary ; Tasse, Jordan ; Yu, Austin ; T Blank, Alan ; Honore, Lesly ; Demetrious, Matthew ; Unson, Gabrielle

Desmoid tumor (DT), also known as desmoid fibromatosis, is a rare, locally proliferative tumor characterized by an overgrowth of myofibroblastic cells. Due to the varied clinical presentation of DT, there are a multitude of treatment options. This study provides our institutional experience in characterizing and treating DT as well as patient outcomes. A retrospective review was performed for 49 patients diagnosed with DT. Patient demographics, tumor characteristics, treatment characteristics, and tumor recurrence were reported. We reported our institution's treatment trends over time, relative risk analysis for surgery, as well as univariate analysis for recurrence. Thirty-seven patients received surgery with an overall recurrence rate of 29.7% (11/37). In total, ten patients received medical therapy including tamoxifen/sulindac (n = 7), nirogacestat (n = 1), and sorafenib (n = 2). One patient has been followed with active surveillance. Relative risk for surgery and tumor recurrence was not significantly correlated with race, gender, location, or large tumor size > 5 cm. Four patients treated with medical therapy experienced tumor reduction and symptomatic improvement. Management of DT includes many surgical and non-surgical options. We noted a similar recurrence rate in patients who received surgical treatment to what has been reported in the literature roughly 33%. We also noted effective tumor control in patients receiving medical therapy. As such, surgery can be utilized in situations with well-demarcated DT which can be removed en bloc, while utilizing medical therapy for highly invasive tumors.

2025-04-01·NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural basis of human γ-secretase inhibition by anticancer clinical compounds

Article

作者: Lu, Xiaoli ; Shi, Yigong ; Zhou, Rui ; Lei, Jianlin ; Yan, Chuangye ; Liu, Hao ; U, Kaicheng ; Huang, Jing ; Li, Haotian ; Guo, Xuefei

Aberrant activation of Notch signaling, mediated by the Notch intracellular domain (NICD), is linked to certain types of cancer. The NICD is released through γ-secretase-mediated cleavage of the Notch receptor. Therefore, development of a γ-secretase inhibitor (GSI) represents an anticancer strategy. Here we report the cryo-electron microscopy structures of human γ-secretase bound individually to five clinically tested GSIs (RO4929097, crenigacestat, BMS906024, nirogacestat and MK-0752) at overall resolutions of 2.4-3.0 Å. Three of the five GSIs are in active anticancer clinical trials, while nirogacestat was recently approved. Each of these GSIs similarly occupies the substrate-binding site of presenilin 1 but shows characteristic differences in detailed recognition pattern. The size and shape of the binding pocket are induced by the bound GSI. Analysis of these structural features suggest strategies for modification of the GSI with improved inhibition potency.

214

项与硝加司他相关的新闻（医药）

2025-07-02

·GBIHealth

医保局启动2025年医保谈判和商业健康创新药目录调整工作

药械追踪No.1 / 武田低IgA含量即用型免疫球蛋白GAMMAGARD LIQUID ERC在美获批2025年6月30日，武田宣布，GAMMAGARD LIQUID ERC（人免疫球蛋白输注液）获得美国食品药品监督管理局（FDA）批准，作为替代疗法用于治疗两岁及以上人群的原发性免疫缺陷。GAMMAGARD LIQUID ERC是一种即用型免疫球蛋白输注液，临床使用时无需复溶，可通过静脉或皮下给药，有望减轻用药负担。其10%溶液中IgA含量≤2µg/mL，是目前唯一一款低IgA含量的即用型免疫球蛋白溶液。GAMMAGARD LIQUID ERC预计将于2026年在美国商业上市，随后将于2027年在欧盟上市；其在欧盟已获得批准，商品名为DEQSIGA。->点击文末阅读原文，解锁完整双语新闻企业动态No.1 / 德国默克完成对SpringWorks的收购，对价34亿美元2025年7月2日，德国默克宣布完成对SpringWorks Therapeutics, Inc.（简称“SpringWorks”）的收购，对价34亿美元（约30亿欧元）。这是2025年迄今全球生物制药领域规模最大的并购交易之一。双方此前于2025年4月28日宣布达成最终协议。此次业务合并将助推默克的营收增长，并预计到2027年将提升默克的每股摊薄前收益（EPS pre）。SpringWorks的产品组合包含两款极具创新性的罕见肿瘤治疗药物。一款是Ogsiveo（nirogacestat），这是一种口服γ分泌酶抑制剂，也是FDA批准的首个成人硬纤维瘤治疗药物；另一款是Gomekli（mirdametinib），这是一种口服小分子MEK抑制剂，已获FDA批准用于治疗无法完全切除的患有1型神经纤维瘤病（NF1）且伴有症状性丛状神经纤维瘤（PN）的成人和儿童患者。Gomekli和Ogsiveo分别于2025年5月和6月获得欧洲药品管理局（EMA）人用药品委员会（CHMP）积极意见推荐批准。SpringWorks的产品组合将补充默克的罕见肿瘤业务管线，目前默克还拥有与和誉医药合作开发的腱鞘巨细胞瘤（TGCT）疗法pimicotinib，该产品已在中国提交上市申请。->点击文末阅读原文，解锁完整双语新闻No.2 / 镁信健康拟赴港交所上市近日，镁信健康递交招股书，拟赴香港联交所上市。镁信健康是目前中国最大的医药多元支付平台。公司致力于解决患者、保司与药企面临的筹资与支付挑战，助力推动中国医疗支付体系变革。公司拥有自研AI中枢mind42.ai、医疗供应链多元支付平台MediTrust Rx以及商保医师网络MediTrust Healthcare三大核心产品，依托AI技术为保司、药企及患者提供了智能化的解决方案。截至2024年12月31日，镁信健康已经累计服务了约160万名患者、超过90家保司以及超140家药企。公司2022~2024年业绩持续增长，年度收入分别为10.69亿元、12.55亿元和20.35亿元。->点击文末阅读原文，解锁完整双语新闻行业政策No.1 / 医保局启动2025年医保谈判和商业健康创新药目录调整工作2025年7月1日，国家医保局发布《2025年国家基本医疗保险、生育保险和工伤保险药品目录及商业健康保险创新药品目录调整工作方案（征求意见稿）》以及《2025年国家基本医疗保险、生育保险和工伤保险药品目录及商业健康保险创新药品目录调整申报指南（征求意见稿）》，并修订完善了《谈判药品续约规则》，于7月7日前向社会公开征求意见。2025年制定第一版商业健康保险创新药品目录，主要纳入超出保基本定位、暂时无法纳入基本目录，但创新程度高、临床价值大、患者获益显著的创新药，推荐商业健康保险、医疗互助等多层次医疗保障体系参考使用。满足以下条件之一的协议期内谈判药品，可以纳入常规目录管理：①非独家药品（以国家药监部门批准的同通用名药品数量为准），截至目录调整当年 6 月30 日（含），下同；②截至目录调整当年12月31 日，连续纳入目录“协议期内谈判药品部分”时间达到8年的药品。以2025年目录调整为例（截至2025年12月31日），2017年至2024年谈判新增的药品，纳入目录的时间分别为8年、7年、6年、5年、4年、3年、2年、1年。目录外新药申报进入医保谈判和目录内续约的规则与往年基本一致，其中条件①2020年1月1日（含，下同）至2025年6月30日（含，下同）期间，经国家药监部门批准上市的新通用名药品和⑤2025年6月30日前，经国家药监部门批准上市的罕见病治疗药品，可单独申报商保创新药目录或同时申报商保创新药目录、基本目录。参与商保创新药目录调整的专家主要通过相关部门、行业学协会、商业保险公司和省级医保部门、人力资源社会保障部门推荐。续约规则也与往年一致，从2025年起，调整支付范围的药品且连续在谈判药品目录中不够4年的独家药，药品销售额上限开始调整为往年的1.5倍，即纳入支付范围的药品费用预算年均增加值3亿元（含）以内的（往年为2亿元），按简易续约阶梯降价调整；年均增加值在3~15亿元（含）之间，支付标准的下调比例增加2%。年均增加值在15~30亿元（含）之间，支付标准的下调比例增加4%。年均增加值在30~60亿元（含）之间，支付标准的下调比例增加6%。年均增加值在60亿元以上的，支付标准的下调比例增加10%。截至目录调整当年12月31日，连续纳入目录“协议期内谈判药品部分”达到或超过4年的品种，其支付标准的下调比例在前述计算值基础上减半。->点击阅读原文，解锁完整双语新闻全球医疗情报领导者解锁隐藏在数据中的商业潜力关于 G B I”自从2002年成立以来，GBI始终以技术为驱动，为药企、器械及行业相关服务商提供贯穿生命周期的全球药品市场竞争数据、全球行业资讯、HCPs洞察、全国医疗器械数据等商业信息与洞察，助力企业在进行战略布局和决策时，脱颖而出。历经20余年的深耕细作GBI已成为95%以上跨国药企、国内头部药企、咨询与投资机构等医疗圈灯塔用户值得信赖的长期合作伙伴。联系我们投稿 | 发稿 | 媒体合作▶ olivia.xu@generalbiologic.com数据库 | 咨询服务 | 资讯追踪▶ 点击左下“阅读原文”完成表单填写点击阅读原文，解锁完整双语新闻

并购申请上市上市批准免疫疗法

2025-06-22

·动脉网

管线覆盖ADC和RLT，这家创新药企总融资近6亿美元！

2025年1月，Immunome完成1.5亿美元融资，此轮融资将推动核心管线的临床转化。3月，Immunome宣布靶向ROR1的ADC（抗体-偶联药物）IM-1021完成I期临床试验首例患者给药。其核心产品管线Varegacestat（AL102）Ⅲ期RINGSIDE试验也已完成入组，预计2025年下半年公布顶线数据。Immunome的核心竞争力是快速抗体筛选与精准递送技术。高效、精准且安全性高的治疗优势突破了传统癌症治疗中“脱靶损伤”与研发周期过长的行业瓶颈。这家临床阶段的靶向肿瘤学公司已累计融资5.989亿美元、21轮资本加持——成立17年的Immunome，凭什么让投资者持续买单？01利用天然抗体解决脱靶损伤的精准性难题传统化疗与放疗的局限性在于其作用机制缺乏特异性，药物或辐射在攻击癌细胞的同时会无差别损伤快速分裂的健康细胞（如骨髓、消化道细胞），导致患者免疫力下降、脱发等严重副作用。这种攻击对人体健康组织损伤率高达60%。以胰腺癌为例，传统放疗虽能缩小肿瘤，但患者容易出现消化道溃疡等严重并发症。据塔夫茨药物开发研究中心数据，开发一款新药平均耗时10年、耗资26亿美元左右，且90%以上候选药物的临床表现会因脱靶或毒性问题而以失败告终。传统抗体筛选需要从数万种化合物中“大海捞针”，肿瘤药物研发普遍面临周期长、成本高的挑战。Immunome的优势在于其独特的ADC研发管线思路。它通过新型拓扑异构酶抑制剂HC74载荷与差异化靶点选择瞄准了实体瘤与血液瘤的未满足需求。同时，Immunome的管线布局兼具平衡性与前瞻意识。通过ADC与RLT（放射性配体疗法）双管齐下的方式减少靶点失败风险，提高商业效益。在了解核心管线之前，我们首先要厘清其核心技术，包括抗体筛选到精准递送的两大技术基石：MemoryB平台和Targeted Effector平台。● Memory B细胞技术：从患者体内“借力”的抗体发现平台MemoryB细胞杂交瘤技术平台经过样本提取、细胞融合、抗体筛选三个流程：首先，平台从患者血液或肿瘤组织中分离出记忆B细胞，这些细胞因接触过肿瘤抗原而天然携带抗肿瘤抗体信息；然后将记忆B细胞与骨髓瘤细胞融合，形成杂交瘤细胞，使其具备无限增殖能力；最后通过高通量筛选技术，从杂交瘤细胞中筛选出针对特定肿瘤抗原的高效抗体。相较于传统疗法，这一突破提高了抗体亲和力与特异性。对于耐药性患者而言，药物递送效果会逐步减弱。耐药性肿瘤往往通过基因突变或表观遗传改变产生新抗原（Neoantigens），这些抗原在传统疗法中难以被靶向。Immunome的MemoryB细胞杂交瘤技术直接从患者体内提取记忆B细胞，这些细胞天然携带针对肿瘤特异性抗原的抗体信息。因此尤其适用于耐药肿瘤和罕见靶点。● Targeted Effector：放疗剂量提升5倍的“制导系统”Immunome的Targeted Effector平台通过模块化设计解决了肿瘤治疗的核心矛盾——如何在最大化药物杀伤力的同时避免脱靶损伤。该平台能够根据不同靶点特性适配最优的效应分子与递送策略。对于需要强效细胞杀伤的靶点，平台可调用拓扑异构酶抑制剂HC74等毒素载荷，并通过半胱氨酸定点偶联技术实现药物抗体比，同时维持稳定性；而对于实体瘤微环境等复杂场景，则切换至放射性核素策略，利用碘苯基白蛋白结合域延长药物循环时间，使肿瘤组织暴露量显著提升。传统ADC受限于内化效率低的靶点难以成药，而Targeted Effector通过辐射旁杀效应覆盖周边细胞，使原本不可成药的基质靶点FAP转化为有效靶标。其次是连接子技术：蛋白酶可裂解连接子确保毒素仅在肿瘤细胞内释放，pH敏感型连接子则针对肿瘤微酸环境激活。如IM-1021的蛋白酶敏感linker仅在肿瘤细胞内释放毒素，降低脱靶毒性。这些特性是IM-3050在胶质瘤模型中单次给药即实现肿瘤消退的关键原因。从研发效率看，团队完成新靶点抗体筛选后可直接调用经过验证的效应器模块进行组装。FAP配体到IM-3050的管线开发仅耗时11周，而传统放射性药物开发平均需9个月。除了研发效率的提升，该平台通过“配体-效应分子”复合物实现精准治疗，利用小分子配体实现抗体级靶向性，精准递送放射性同位素或细胞毒素，使177Lu-FAP的肿瘤辐射剂量较传统放疗提升5倍，同时减少健康组织损伤。该平台还具有强大的可拓展性。单个靶点验证后（如FAP-RLT），可快速切换至类似靶点。其次，ADC+RLT双路径并行的平台优势即使当某一类靶点临床失败时，平台技术也可迅速转向其他方向。02ADC先行，多靶点管线协同发展Immunome目前有三款产品管线进入临床阶段。核心管道项目是varegacestat（原AL102），一种γ分泌酶抑制剂。IM-1021（ROR1 ADC）和IM-3050（RLT）。● Varegacestat （AL102）：针对罕见肉瘤的口服靶向药硬纤维瘤是一种罕见肉瘤，美国约5500-7500名患者面临无有效系统治疗的困境。Immunome的AL102（Varegacestat）是一款口服γ分泌酶抑制剂，通过阻断NOTCH通路抑制肿瘤生长。其机制核心在于抑制γ分泌酶对Notch受体的切割，阻止致癌性Notch胞内结构域（NICD）的释放与核转位，从而截断下游促生存基因（如HES1、MYC）的激活。针对手术难根治、化疗无效的硬纤维瘤，Ⅱ期试验显示1.2mg每日剂量组客观缓解率（ORR）达64%，显著优于历史对照（化疗ORR<10%）。此外，通过优化γ分泌酶亚型选择性，将卵巢功能障碍风险降至55.6%（同类药物nirogacestat为75%），规避了传统Notch抑制剂常见的胃肠道毒性。● IM-1021（ROR1 ADC）：双倍载药量克服实体瘤耐药性实体瘤的耐药性本质上是肿瘤细胞在基因组不稳定性驱动下，通过多重机制逃避药物杀伤的过程。针对在非小细胞肺癌（NSCLC）、三阴性乳腺癌（TNBC）等癌种中高表达的ROR1（受体酪氨酸激酶），Immunome开发了IM-1021（靶向ROR1的 ADC）。该药物采用DAR8（通过在抗体上稳定连接8个毒素，实现“高载药量”与“稳定性”的平衡，载药量是传统ADC的2倍）设计，搭载TOP1抑制剂HC74载荷，兼具旁杀效应与优化的抗体亲和力。此款药物已于2025年一季度完成I期首例患者给药，起始剂量2mg/kg。临床前数据显示，其在TNBC（MDA-MB-468）和NSCLC PDX（人源肿瘤异种移植模型）中可实现完全缓解（CR），且与默克同类药物MK-2140相比耐受性更优，未来计划扩展至弥漫大B细胞淋巴瘤（DLBCL）等适应症。除了临床阶段产品，IM-1617、IM-1335 和 IM-1340，均为临床前ADC，靶向多种实体肿瘤中表达的未公开靶点。● IM-1617：激活“冷肿瘤”免疫应答的双功能ADCIM-1617针对传统免疫疗法失效的“冷肿瘤”设计。冷肿瘤（Cold Tumor）指免疫细胞（尤其杀伤性T细胞）无法浸润或活化的肿瘤类型。这类肿瘤微环境中缺乏免疫细胞浸润，且充满抑制性细胞（如Treg、M2型巨噬细胞）和抑制因子（如TGF-β、IL-38）。传统免疫疗法失效是因为PD-1抗体这类药物需要依赖预先存在的T细胞才能起效，但冷肿瘤里T细胞要么进不去，进去了也会被免疫抑制因子干扰。IM-1617的聪明之处在于创新性地融合了TLR7/8激动剂载荷。这款ADC通过靶向肿瘤特异性抗原CLDN18.2，将免疫刺激因子精准递送至胃癌及胰腺癌病灶内部，打破免疫抑制微环境。临床前数据显示，药物在诱导肿瘤细胞凋亡的同时，激活了肿瘤浸润性T细胞和树突细胞，将“冷肿瘤”转化为对PD-1抑制剂敏感的“热肿瘤”。● IM-1335：破解小细胞肺癌耐药难题的DLL3瞄准小细胞肺癌患者治疗后的快速复发困境，IM-1335采用双表位抗体靶向DLL3（一种在多种恶性肿瘤中特异性表达的细胞表面蛋白，尤其在神经内分泌肿瘤中扮演关键角色）的膜近端结构域。该设计有效阻断Notch信号反馈激活——这种机制正是导致化疗及Tarlatamab耐药的关键因素。其搭载的新型拓扑异构酶抑制剂HC74经脑部富集改造，穿透血脑屏障的能力提升5倍，对脑转移灶展现出强效清除力。在循环肿瘤细胞模型中，单次给药即可清除99%的DLL3阳性肿瘤干细胞。● IM-1340：克服HER2耐药谱系的智能化抗体药物针对HER2阳性乳腺癌的继发性耐药问题，IM-1340通过三重机制突破传统ADC局限。其抗体能同时结合HER2受体结构域Ⅱ与Ⅳ，有效阻断曲妥珠单抗无法抑制的HER2-HER3异源二聚体形成。连接子采用肿瘤微环境pH敏感设计，仅在酸性肿瘤组织中释放强效载荷AS269。创新的“旁杀效应增强剂”更促使药物扩散至低HER2表达细胞。在携带HER2 L755S/T798I双重耐药突变的模型中，IM-1340使肿瘤逐步消退且6个月内无复发，这种对耐药突变谱系的广谱覆盖能力，为晚期乳腺癌患者带来长期生存新希望。03RLT助力，克服肿瘤微环境屏障难题除了ADC药物，RLT（放射配体疗法）也是Immunome公司重点推进的研发方向。其核心管线是IM-3050。在实体瘤治疗中，肿瘤微环境屏障是一大核心难题。这一屏障由癌相关成纤维细胞（CAFs）、免疫抑制因子及肿瘤细胞异质性共同构成，传统药物往往难以突破。常见的化疗药物在实体瘤中的响应率常低于20%，而抗体药物因分子量过大也难以穿透基质层。Immunom的RLT疗法通过精准靶向——长效循环——辐射协同三步对这一屏障实现了精准摧毁。以IM-3050为例，它通过结合177-Lu同位素与白蛋白结合域，克服了传统ADC靶向FAP内化率低的缺陷。首先是精准靶向。他们瞄准了癌相关成纤维细胞（CAFs）表面特异性高表达的FAP蛋白（这种靶点在75%实体瘤中显著富集），团队开发的先导化合物IM-3050展现出超强结合力（Kd<1 pM），这种结合作用让药物像磁铁般精准吸附在肿瘤微环境的核心构筑者上。然后是药物持久循环问题。研究人员通过独创的碘苯基白蛋白结合域改造技术，成功将药物血浆暴露量（AUC）提升至竞品的20倍（70,531 vs. 3,862 h•ng/mL），同时将半衰期延长至6小时。这种改造让更多有效成分能够突破屏障在肿瘤组织持续积累。最后是辐射协同机制。其搭载的177Lu核素持续释放高能β射线，在精准清除FAP阳性CAFs细胞的同时，凭借2mm辐射半径形成强大的“旁杀效应”可同步摧毁周边肿瘤细胞，瓦解了肿瘤赖以生存的微环境生态。2025年第一季度，Immunome已提交IM-3050的IND（研究性新药申请），计划下半年启动I期试验。临床前研究显示，单剂量治疗可使U87MG胶质瘤模型肿瘤消退，且未观察到严重不良反应、安全性良好。04ADC老将掌舵，即将迎来实验室到市场的“惊险一跃”Immunome的竞争力也源于复合型人才团队。2024年，新任CEO ClaySiegall博士的加入标志着Immunome的战略转型，计划在2026年前推动至少两款管线进入Ⅱ期临床，并通过技术授权合作扩大全球市场覆盖。他曾主导多款ADC药物的商业化，具有从技术验证到临床转化的丰富经验。首席科学官JackHiggins博士深耕抗体工程领域，将MemoryB细胞平台的抗体筛选周期压缩至传统方法的1/3，显著加速管线迭代。首席技术官PhilTsai凭借在Moderna的技术运营背景，推动TargetedEffector平台的商业落地。Immunome团队研发的商业价值有目共睹。至今，Immunome累计融资5.989亿美元，共经历21轮融资。具体情况如下表：但Immunome的融资结构并不均衡。其中，Post-IPO融资占比超70%。新增股份会降低现有股东的持股比例，现有股东的权益面临被稀释风险。生物医药创新长周期、高投入的行业特性让很多中小型Biotech面临生存难关。Crunchbase数据显示，2024年Immunome 收入为904万美元。虽然公司收入依然呈现下滑趋势（同比下降 35.5%），但相较2023年亏损收窄。如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。文中如果涉及企业信息和数据，均由受访者向分析师提供并确认。动脉网，未来医疗服务平台

抗体药物偶联物临床1期细胞疗法临床2期

2025-06-20

·FiercePharma

Europe's CHMP gives thumbs up to ExCellThera's blood cancer cell therapy Zemcelpro

Europe’s Committee for Medicinal Products for Human Use has recommended marketing authorization for ExCellThera’s novel cell therapy Zemcelpro in certain blood cancer patients. In a first for the bloc, Europe’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for a new type of stem cell transplant therapy for certain blood cancer patients. The marketing endorsement was awarded to ExCellThera’s Zemcelpro and covers a recommended approval in adults with blood cancers that require an allogeneic hematopoietic stem cell transplantation (HSCT) following myeloablative conditioning for whom no other type of suitable donor cells is available.Zemcelpro contains stem cells from a donor’s umbilical cord blood, some of which have been grown and multiplied, the European Medicines Agency (EMA) said in a press release on the decision. By boosting the number of cells, Zemcelpro makes the stem cells from a small cord blood unit more effective, the European regulator explained. For several blood cancers—including leukemias, which are detected in the blood; lymphomas, which are found in the lymph nodes; and myelodysplastic syndrome and myelomas, which are diagnosed in the bone marrow—the only current curative treatment option is allogeneic HSCT. This type of transplant involves using donated stem cells to replace the patient’s bone marrow cells to form new marrow that produces healthy blood cells. The CHMP based its Zemcelpro recommendation on pooled analysis of two single-arm trials that included 25 patients. The studies found that 84% of patients who received Zemcelpro achieved neutrophil engraftment, when donor stem cells establish themselves in the recipient’s bone marrow and produce the white blood cells known as neutrophils within a median span of 20 days.Some 10,000 new blood cancer cases requiring bone marrow transplant crop up in Europe each year, ExCellThera estimates. Many of these patients do not have access to suitable donor cells largely because of the unavailability of matched donors, the company explained. ExCellThera said it expects to gain marketing authorization from the EMA in roughly two months' time. After winning an endorsement from the CHMP, prospective medicines must go before the European Commission for a final approval verdict.ExCellThera also plans to file for approval of Zemcelpro in the U.S., U.K. and other countries. Madrigal’s Rezdiffra among others gaining CHMP nodsThe committee has also given a thumbs up to Madrigal’s Rezdiffra for the treatment of adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), a disease where fat cells accumulate in the liver causing chronic inflammation. If the drug gains marketing authorization, it would become the first treatment in the EU for the condition. Fifteen months ago, Rezdiffra became the first drug approved for MASH in the U.S. Also making the grade this month was Teva blockbuster Austedo for patients with moderate-to-severe tardive dyskinesia. The FDA approved the treatment in the indication eight years ago. Tardive dyskinesia is an irreversible movement disorder characterized by repetitive and uncontrollable movements of the tongue, lips, face, trunk and extremities and can be caused by medications used to treat mental health or gastrointestinal conditions.Meanwhile, Pfizer spinout SpringWorks Therapeutics has picked up a CHMP nod for Ogsiveo in adults with progressing desmoid tumors, which are marked by noncancerous soft tissue growths in the limbs and abdomen that often cause severe pain and disfigurement. The FDA approved Ogsiveo in the same indication in 2023.Also gaining a positive recommendation from the CHMP was Partner Therapeutics’ Imreplys for the treatment of patients exposed to myelosuppressive doses of radiation with hematopoietic sub-syndrome of acute radiation syndrome. The medicine is known as Leukine in the U.S. where it was approved in 2018. CHMP signs off on label expansions for 6 drugsAside from new approval recommendations, the CHMP has also endorsed labeled expansions for a half-dozen established medicines. The committee gave a thumbs up to Ipsen’s Cabometyx as a second-line treatment for patients with unresectable or metastatic, well differentiated extra-pancreatic (epNET) and pancreatic (pNET) neuroendocrine tumors. The FDA signed off Cabometyx in the indication three months ago. The treatment, which has been on the market since 2016, brought home sales of $1.8 billion last year.Also winning CHMP recommendations were Johnson & Johnson blockbusters Darzalex, for smoldering multiple myeloma, and Imbruvica, for patients with previously treated mantle cell lymphoma who would be eligible for autologous stem cell transplant. AbbVie partners with J&J on Imbruvica.The committee further signed off on expansions for GSK’s lupus treatment Benlysta, Bayer’s prostate cancer drug Nubeqa and Sanofi’s multiple myeloma medicine Sarclisa. CHMP opens re-examination of Lilly’s KisunlaElsewhere, fifteen months after giving a thumbs down to Eli Lilly’s Alzheimer’s disease treatment Kisunla in March of last year, the CHMP will give the medication a second look. The regulator said that it re-opened its examination of Kisunla on June 2. The FDA signed off on Kisunla in July of last year, opening up competition with Eisai and Biogen’s Alzheimer's rival Leqembi.

上市批准细胞疗法临床结果

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KEGG	Wiki	ATC	Drug Bank
D10960 D11453	-	-	DB12005

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适应症	国家/地区	公司	日期
侵袭性纤维瘤病	美国	Springworks Therapeutics, Inc.	2023-11-27

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适应症	最高研发状态	国家/地区	公司	日期
角膜疾病	临床2期	希腊	GSK Plc	2023-07-14
多发性骨髓瘤	临床2期	希腊	GSK Plc	2023-07-14
卵巢颗粒细胞瘤	临床2期	美国	Springworks Therapeutics, Inc.	2022-08-30
卵巢颗粒细胞瘤	临床2期	加拿大	Springworks Therapeutics, Inc.	2022-08-30
卵巢颗粒细胞瘤	临床2期	波兰	Springworks Therapeutics, Inc.	2022-08-30
晚期乳腺癌	临床2期	美国	Pfizer Inc.	2015-02-03
晚期乳腺癌	临床2期	匈牙利	Pfizer Inc.	2015-02-03
晚期乳腺癌	临床2期	意大利	Pfizer Inc.	2015-02-03
晚期乳腺癌	临床2期	波兰	Pfizer Inc.	2015-02-03
晚期乳腺癌	临床2期	西班牙	Pfizer Inc.	2015-02-03

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ESMO_SRC2025	N/A	侵袭性纤维瘤病 familial adenomatous polyposis (FAP)	13	Nirogacestat 150 mg BID	餘糧糧餘鬱鹽鹽壓餘餘(襯觸鏇糧鑰齋糧壓窪築) = 選襯顧壓簾選鏇衊簾糧遞鹹遞艱窪願選壓選簾 (鏇夢願顧衊淵夢鑰顧築 ) 更多	积极	2025-03-21
NCT03785964 (DeFi, ESMO_SRC2025)	临床3期	侵袭性纤维瘤病	70	Nirogacestat	構壓糧鹹築鹹窪選觸醖(築鏇淵鹹遞醖夢窪積蓋) = 製憲網繭襯鬱夢窪蓋觸鏇願蓋構夢壓襯願艱製 (齋醖構積窪餘觸繭憲膚 ) 更多	积极	2025-03-20
NCT03785964 (DeFi, ASCO_GI2025)	临床3期	腺瘤性结肠息肉病 \| 侵袭性纤维瘤病	142	Nirogacestat 150 mg	齋餘衊膚壓獵獵窪構壓(窪範鏇繭憲觸觸觸獵膚) = diarrhea was the most frequently reported adverse event 餘範獵網艱壓顧獵鏇選 (製糧醖糧鑰願襯鬱築簾 ) 更多	积极	2025-01-23
				Placebo
NCT03785964 (DeFi, GlobeNewswire) 人工标引	临床3期	侵袭性纤维瘤病	142	Nirogacestat 150 mg	鬱簾顧鑰襯齋獵選襯選(憲壓鏇醖鬱築餘鬱選獵) = 願衊選蓋獵獵廠淵廠簾選繭顧構醖網範鹹繭糧 (獵鬱構膚鏇簾齋膚鹹膚 ) 更多	积极	2024-11-07
				Placebo	-
NCT03785964 (DeFi, ASCO2024) 人工标引	临床3期	侵袭性纤维瘤病 APC Mutation	29	NirogacestatNirogacestat 150 mg	鬱醖艱襯壓鬱網鬱範鏇(夢窪繭齋餘憲製蓋蓋壓) = 夢願選製壓鬱製蓋襯鬱淵觸鬱觸築選廠範製鬱 (蓋衊選廠範製齋網憲願 ) 更多	积极	2024-05-24
				Placebo	鬱醖艱襯壓鬱網鬱範鏇(夢窪繭齋餘憲製蓋蓋壓) = 鑰廠觸範範積網鑰鬱艱淵觸鬱觸築選廠範製鬱 (蓋衊選廠範製齋網憲願 ) 更多
NCT03785964 (DeFi, ASCO2024) 人工标引	临床3期	侵袭性纤维瘤病 CTNNB1	142	Nirogacestat 150 mg	鹹積廠憲顧築願餘蓋簾(窪衊繭膚遞選艱鏇壓餘) = 夢觸遞築範網簾壓憲範獵廠餘範窪餘選鬱鏇鏇 (遞醖鹹憲糧夢鑰獵繭獵, 0.11 ~ 0.70) 更多	积极	2024-05-24
				Nirogacestat	鹹積廠憲顧築願餘蓋簾(窪衊繭膚遞選艱鏇壓餘) = 餘艱獵艱蓋糧膚範選獵獵廠餘範窪餘選鬱鏇鏇 (遞醖鹹憲糧夢鑰獵繭獵, 0.13 ~ 0.80) 更多
NCT03785964 (DeFi, ESMO_SRC2024) 人工标引	临床3期	纤维瘤	144	Nirogacestat (niro) 150 mg	鏇襯壓願選廠膚範鏇鹽(構網製選夢鬱構顧憲鹽) = 艱鹹鏇鑰選艱鹽製憲糧築糧糧壓醖艱觸鏇膚艱 (鬱鑰遞範鏇餘鬱齋餘範 )	积极	2024-03-15
				Placebo	鏇襯壓願選廠膚範鏇鹽(構網製選夢鬱構顧憲鹽) = 遞鹹襯遞築築網齋憲獵築糧糧壓醖艱觸鏇膚艱 (鬱鑰遞範鏇餘鬱齋餘範 )
NCT03785964 (DeFi, FDA) 人工标引	临床3期	侵袭性纤维瘤病	142	OGSIVEO	獵網鏇鏇構醖構選糧齋(獵憲繭襯鹽壓遞壓餘糧) = 壓鹽顧鹽遞積壓觸製淵鑰構壓製積鹽遞夢廠糧 (餘夢憲憲獵範網淵觸壓 ) 更多	积极	2023-11-27
				Placebo	獵網鏇鏇構醖構選糧齋(獵憲繭襯鹽壓遞壓餘糧) = 構壓膚積壓鏇遞鏇鑰齋鑰構壓製積鹽遞夢廠糧 (餘夢憲憲獵範網淵觸壓, 8.4 ~ NR) 更多
NCT03785964 (DeFi , Biospace) 人工标引	临床3期	侵袭性纤维瘤病	142	Nirogacestat	觸製鏇積廠壓艱淵襯顧(繭鬱壓鏇遞獵鑰窪鬱網) = Nirogacestat significantly improved mean physical functioning score from baseline per the GODDESS DTIS PF domain compared with placebo at the pre-specified time point. The GODDESS DTIS PF domain captures varying degrees of vigorous and moderate daily activity, including moving and reaching. 遞淵襯衊淵憲製積網獵 (構繭憲構憲憲襯簾憲積 ) 更多	积极	2023-11-01
				Placebo
NCT03785964 (DT/AF, ASCO 12023 \| ASCO 22023) 人工标引	临床3期	侵袭性纤维瘤病	122	Nirogacestat	繭鹹鹹衊簾積蓋鑰窪簾(範艱鹽艱網遞鬱簾憲網) = 遞繭顧願簾築繭鏇夢憲鏇鹹築齋醖鏇窪糧壓築 (夢鬱夢壓壓鹽蓋網獵蓋, –100.0 ~ 517.2) 更多	积极	2023-05-31
				Placebo	繭鹹鹹衊簾積蓋鑰窪簾(範艱鹽艱網遞鬱簾憲網) = 選餘艱齋願憲淵襯願獵鏇鹹築齋醖鏇窪糧壓築 (夢鬱夢壓壓鹽蓋網獵蓋, –88.6 ~ 441.7) 更多