An International Multicentre, Open-Label First in Human Phase I/II Study to Evaluate the Safety, Tolerability, Biodistribution and Antitumour Activity of 177Lu-3BP-227 for the Treatment of Subjects With Solid Tumours Expressing Neurotensin Receptor 1

This study was conducted to advance new treatment for patients with metastatic or locally advanced cancers expressing Neurotensin receptor 1 (NTSR1). This study was the first time the investigational drug called 177Lu-3BP-227 was administered to patients under controlled conditions of a clinical study.
The purpose of this study was to evaluate how safe the investigational drug is as well to verify how well it is tolerated by patients after several intravenous administrations. In addition, the effect of the study drug on tumoral lesions and how it distributes throughout the body and at which rate it is removed from the body was evaluated. Since 177Lu-3BP-227 is a radio-labelled drug, it also measured how the emitted radiation is distributed throughout the body (dosimetry).
The study consisted of a phase I dose escalation part. The study originally planned to include a phase II study however due to early termination (not due to safety concerns) the study did not progress to phase II and was stopped during phase I. For the phase I dose escalation part, it was anticipated that approximately 30 subjects will be included, in up to six escalation steps. No expansion cohorts were implemented.

开始日期2018-05-03

申办/合作机构

Ipsen SA

100 项与 IPN-01087(3B Pharmaceuticals GmbH) 相关的临床结果

登录后查看更多信息

100 项与 IPN-01087(3B Pharmaceuticals GmbH) 相关的转化医学

登录后查看更多信息

100 项与 IPN-01087(3B Pharmaceuticals GmbH) 相关的专利（医药）

登录后查看更多信息

项与 IPN-01087(3B Pharmaceuticals GmbH) 相关的文献（医药）

2022-07-20·Bioconjugate chemistry

Examination of Charge Modifications of an Endolysosomal Trapping Inhibitor in an Antagonistic NTSR1-Targeted Construct for Colon Cancer

Article

作者: Muilenburg, Kathryn M. ; Zheng, Cheng ; Garrison, Jered C. ; Zhang, Wenting ; Allen, Sadie ; Fan, Wei ; Alshehri, Sameer

Many low-molecular weight targeted radiotherapeutics (TRTs) are capable of rapidly achieving exceptional tumor to non-target ratios shortly after administration. However, the low tumor residence time of many TRTs limits therapeutic dose delivery and has become the Achilles heel to their clinical translation. To combat the tumor efflux of these otherwise promising agents, we have previously presented a strategy of equipping low-molecular weight TRTs with irreversible cysteine cathepsin inhibitors (e.g., E-64 analogues). These inhibitors are capable of forming irreversible adducts with cysteine proteases within the endolysosomal compartments of cells. Using these endolysosomal trapping agents (ETs), the receptor-targeted constructs are able to increase tumor retention and, thus, deliverable therapeutic doses. In this study, we examine this approach in the development of agents targeting the neurotensin receptor subtype 1 (NTSR1), a receptor overexpressed in numerous cancers. Using an antagonistic NTSR1-targeting vector, we explore the impact of charge modification of the ETs on the in vitro and in vivo biological performance of the constructs using HT-29 colon cancer models. Four ETs (based on the epoxysuccinyl peptide E-64) with various charge states were synthesized and incorporated into the structures of the NTSR1-targeted antagonist. These four ¹⁷⁷Lu-labeled, ET-enhanced, NTSR1-targeted agents (¹⁷⁷Lu-NA-ET1-4), along with the structurally analogous ¹⁷⁷Lu-3BP-227, currently in clinical trials, underwent a battery of in vitro assays using HT-29 xenograft colon cancer cells to examine their NTSR1 binding, internalization and efflux, inhibition, and adduct formation properties. The biodistribution profile of these constructs was studied in an HT-29 mouse model. Charge modification of the terminal carboxylic acid and arginine of the ETs had deleterious effects on inhibition kinetics and in vitro adduct formation. Contrastingly, deletion of the arginine resulted in a modest increase in inhibition kinetics. Incorporation of ETs into the NTSR1-targeted agents was well-tolerated with minimal impact on the in vivo NTSR1 targeting but resulted in increased renal uptake. This study demonstrates that the ETs can be successfully incorporated into antagonistic NTSR1-targeted constructs without compromising their adduct formation capabilities. Based on these results, further exploration of the endolysosomal trapping approach is warranted in NTSR1- and other receptor-targeted antagonistic constructs.

2018-05-01·Journal of nuclear medicine : official publication, Society of Nuclear Medicine1区 · 医学

¹⁷⁷Lu-3BP-227 for Neurotensin Receptor 1–Targeted Therapy of Metastatic Pancreatic Adenocarcinoma: First Clinical Results

1区 · 医学

Article

作者: Wiessalla, Stefan ; Kulkarni, Harshad R ; Baum, Richard P ; Klette, Ingo ; Singh, Aviral ; Smerling, Christiane ; Osterkamp, Frank ; Reineke, Ulrich ; Schuchardt, Christiane

Neurotensin receptor 1 (NTR1) is overexpressed in ductal pancreatic adenocarcinoma, which is still one of the deadliest cancers, with a very poor prognosis. Eligible patients were offered salvage radiopharmaceutical therapy with the novel NTR1 antagonist ¹⁷⁷Lu-3BP-227. Methods: Six patients with confirmed ductal pancreatic adenocarcinoma who had exhausted all other treatment options received ¹⁷⁷Lu-3BP-227 for evaluation of NTR1 expression in vivo. Three patients received treatment activities of 5.1-7.5 GBq. Results: Administration of ¹⁷⁷Lu-3BP-227 was well tolerated by all patients. The kidneys were identified as the dose-limiting organ. The most severe adverse event was reversible grade 2 anemia. One patient achieved a partial response and experienced significant improvement of symptoms and quality of life. This patient survived 13 mo from diagnosis and 11 mo from the start of ¹⁷⁷Lu-3BP-227 therapy. Conclusion: This initial report provides clinical evidence of the feasibility of treatment of ductal pancreatic adenocarcinoma using ¹⁷⁷Lu-3BP-227.

2017-06-01·Journal of nuclear medicine : official publication, Society of Nuclear Medicine1区 · 医学

Proof of Therapeutic Efficacy of a ¹⁷⁷Lu-Labeled Neurotensin Receptor 1 Antagonist in a Colon Carcinoma Xenograft Model

1区 · 医学

Article

作者: Pethe, Anette ; Smerling, Christiane ; Stöber, Franziska ; Osterkamp, Frank ; Amthauer, Holger ; Stiebler, Marvin ; Reineke, Ulrich ; Goldschmidt, Jürgen ; Schulz, Jörg ; Noriega, Mercedes ; Lukas, Mathias ; Rohracker, Martin ; Höhne, Aileen

Increased expression of neurotensin receptor 1 (NTR1) has been shown in a large number of tumor entities such as pancreatic or colon carcinoma. Hence, this receptor is a promising target for diagnostic imaging and radioligand therapy. Using the favorable biodistribution data of the NTR1-targeting agent ¹¹¹In-3BP-227, we investigated the therapeutic effect of its ¹⁷⁷Lu-labeled analog on the tumor growth of NTR1-positive HT29 colon carcinoma xenografts. Methods: 3BP-227 was labeled with ¹⁷⁷Lu. To assess its biodistribution properties, SPECT and CT scans of HT29-xenografted nude mice injected with ¹⁷⁷Lu-3BP-227 were acquired, and ex vivo tissue activity was determined. To evaluate therapeutic efficacy, 2 groups of mice received the radiopharmaceutical in a median dose of either 165 MBq (129-232 MBq, n = 10) or 110 MBq (82-116 MBq, n = 10), whereas control mice were injected with vehicle (n = 10). Tumor sizes and body weights were monitored for up to 49 d. Renal function and histologic morphology were evaluated. Results: Whole-body SPECT/CT images allowed clear tumor visualization with low background activity and high tumor-to-kidney and -liver ratios. Ex vivo biodistribution data confirmed high and persistent uptake of ¹⁷⁷Lu-3BP-227 in HT29 tumors (19.0 ± 3.6 vs. 2.7 ± 1.6 percentage injected dose per gram at 3 and 69 h after injection, respectively). The application of ¹⁷⁷Lu-3BP-227 resulted in a distinct delay of tumor growth. Median tumor doubling time for controls was 5.5 d (interquartile range [IQR], 2.8-7.0), compared with 17.5 d (IQR, 5.5-22.5 d) for the 110-MBq and 41.0 d (IQR, 27.5-55.0) for the 165-MBg group. Compared with controls, median relative tumor volume at day 23 after injection was reduced by 55% (P = 0.034) in the 110-MBq and by 88% (P < 0.01) in the 165-MBq group. Renal histology and clinical chemistry results did not differ between radiotherapy groups and controls, suggesting absence of therapy-induced acute renal damage. Conclusion: These data demonstrate that the novel NTR1-targeting theranostic agent 3BP-227 is an effective and promising candidate for radioligand therapy, with a favorable preliminary safety profile and high potential for clinical translation.

项与 IPN-01087(3B Pharmaceuticals GmbH) 相关的新闻（医药）

2024-04-23

·药融圈

强生早期投资，阿斯利康最终174亿收购的核药Fusion

▲5月30-31日第八届广州生物医药创新者峰会扫码立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。2023年年底，又一家制药巨头（百时美施贵宝）宣布以每股62.50美元的现金收购RayzeBio（RayzeBio是一家成立于2020年的临床阶段的放射性药物治疗公司），总股本价值约为41亿美元。就在前几个月，深耕糖尿病和肥胖代谢领域的礼来宣布收购了放射性疗法公司POINT Biopharma，早在十年前，德国药企拜耳就已经布局核药赛道，并推出了FDA和EMA批准的唯一一个α粒子放射治疗药物，诺华更是推出了多个治疗用RDC（放射性核素偶联药物）（通过收购整合开发），阿斯利康、默沙东和强生等跨国药企也通过股权投资、技术引进多种方式切入该领域。据Technavio发布的《2023-2027年全球放射性药物市场》的最新市场研究报告统计，从2021 年到2026 年，全球放射性药物市场规模预计将增加43.7 亿美元。图源Technavio之前药融圈分享过多篇核药企业长文：深耕60多年的Lantheus以及市值翻几十倍的Telix Pharmaceuticals。今天想和朋友们分享一家被多个制药巨头青睐的加拿大制药公司Fusion pharmaceuticals，让我们一起看看他的吸引力到底在何处。从药融云数据库获悉，总部位于加拿大（安大略省）的Fusion pharmaceuticals（以下简称Fusion）成立于2014年，是一家临床阶段的生物制药公司，致力于开发下一代放射性药物作为治疗癌症的精密药物。该公司开发了靶向Alpha疗法（Targeted Alpha Therapies，TAT）平台，以及公司专有的Fast-Clear™连接子技术，使其能够将发射α粒子的同位素与抗体和其他靶向分子连接起来，以选择性地将疗法传递给肿瘤。药融云数据www.pharnexcloud.com：融资情况本文稿件完稿于2024年1月17日，以下内容或非最新。属于完成稿件2个月之后3月19日，阿斯利康宣布收购该公司，价值为24亿美元（约合174亿人民币）（基于生产能力、产品管线前景与协同）。双方最早合作始于2020年。Fusion由Valliant博士创立，但这并不是Valliant博士第一次与放射性药物打交道，在创立公司之前，Valliant博士曾创立了一个放射性药物研究中心CPDC (the Centre for Probe Development and Commercialization)，专注于发现、开发和分发下一代分子成像探针。自成立以来，该公司总融资五轮，2017年融资两轮（除以上统计的A轮融资外，2017年9月A+轮融资2100万美元；强生的JJDC在2017年领投了Fusion），2019年进行了B轮融资，金额达到1.05亿美元，2020年6月通过IPO在纳斯达克上市，此次融资1.25亿美元。同时在2020年11月与阿斯利康合作开发和商业化用于治疗癌症的下一代α发射放射性药物和联合疗法。Fusion专有的Fast-Clear连接子技术促进了不与癌细胞特异性结合的医用同位素的快速排泄，与扩大治疗窗口的商业技术相比，Fast-Clear连接子技术（分子和医用同位素之间的“连接器”）旨在以更快的速度清除更多的医用同位素。鉴于Fast-Clear连接子技术的强大功能和多功能性，Fusion正在将该技术应用于一系列分子和分子类别（抗体、小分子等）。研发管线除了目前开展到临床试验2期的一个管线以及开展到临床试验1期的两个管线外，Fusion其余管线均处于发现和临床前研究阶段，以下是研发管线的详细进展情况：FPI-2265FPI-2265是一种靶向PSMA（前列腺特异性膜抗原）的靶向α疗法（TAT），用于治疗疾病进展的mCRPC（转移性去势抵抗性前列腺癌）患者。2024年1月4日，Fusion宣布已与FDA就其提交的FPI-2265的临床试验2/3期方案达成一致，更新后的开发计划包括临床试验2期剂量优化导入，临床试验2期研究预计将于2024年第二季度启动，并于2024年底完成入组，公司将寻期与FDA举行临床试验2期研究结束会议，根据临床试验2期数据的分析确定临床试验3期给药方案，预计将于2025年开始临床试验3期研究。Fusion还在寻求机会，通过FPI-2265和奥拉帕尼的组合将候选疗法推向更早期的治疗线，预计将在2024年上半年启动联合试验。2023年2月，Fusion获得了FPI-2265的临床试验2期研究（TATCIST试验）的IND（新药临床研究审批），TATCIST试验旨在评估该药在患有mCRPC（转移性去势抵抗性前列腺癌）且疾病进展的患者中的疗效，包括对PSMA靶向放射性药物不敏感的患者，以及使用基于镥-177的PSMA放射性药物（如诺华的Pluvicto）进行预处理的患者。根据迄今为止报道的文献和TATCIST数据，已知每8周给药100 kBq/kg是一种安全且有效的剂量方案，为了进一步优化FPI-2265的获益/风险比，Fusion将探索具有更高给药频率的替代方案，同时保持累积剂量和总治疗持续时间相同，要评估的其他方案包括每4周50 kBq/kg的剂量和每6周75 kBq/kg的剂量。主要终点是安全性和PSA（前列腺特异性抗原）水平下降≥50%的患者比例，关键次要终点为ORR（客观缓解率）和rPFS（影像学无进展生存期）。FPI-1434FPI-1434是一种抗体偶联放射性药物，旨在靶向表达IGF-1R（IGF-1R是一种在许多肿瘤类型上过表达的受体）癌细胞并递送发射α的医用同位素，利用FastClear接头将靶向IGF-1R的人类单克隆抗体与锕225（一种强大的α发射同位素，具有理想的半衰期和衰变链特性）连接起来。目前正处于临床试验1期，计划完成并进一步评估队列2的结果，召开安全审查委员会（SRC）会议以评估新出现的数据，预计在2024年年中分享有关数据和FPI-1434开发计划的更多细节。药融云数据库：药物基本信息2023年6月，Fusion报告了冷/热给药方案队列1中3名患者15 kBq/kg的结果，在队列1中，观察到冷/热给药通常耐受性良好，没有与治疗相关的SAE（严重不良事件）或DLT（剂量限制性毒性）。冷抗体给药前显示出改善肿瘤摄取，同时也降低了在仅热给药组中观察到的血液学毒性。来自冷/热给药组的两名经过大量预处理的患者接受了三个和五个周期的治疗，两人都表现出持久的稳定疾病的最佳反应。正在进行的FPI-1434的临床试验1期研究中，队列2的早期发现令人鼓舞。迄今为止，在25 kBq/kg剂量队列中未观察到DLT。三分之二的患者完成了DLT期，一名胰腺癌患者因疾病进展而停止治疗，一名接受重度治疗的尤因肉瘤患者在单次25 kBq/kg剂量的FPI-1434后显示出抗肿瘤活性，第二位患者接受了四个周期的治疗，并表现出疾病稳定作为最佳反应。总的来看，FPI-1434耐受性良好，在25 kBq/kg剂量水平下，无DLT和短暂的1级或更少的血小板减少。基于FPI-1434的作用机制和临床前研究的数据，Fusion还评估了FPI-1434与检查点抑制剂以及DNA损伤修复抑制剂（DDRI）的组合潜力，其中包括聚（ADP-核糖）聚合酶（PARP）抑制剂。第一项计划的研究是评估FPI-1434与默沙东的抗PD-1疗法Keytruda（帕博利珠单抗）联合治疗表达IGF-1R的实体瘤患者。FPI-2059FPI-2059是一种靶向神经降压素受体1（NTSR1）的小分子放射性药物，在多种实体瘤中过表达，包括胰腺导管腺癌、结直肠癌、头颈部鳞状细胞癌、胃癌、尤文斯肉瘤和神经内分泌分化前列腺。目前正在开发作为各种实体瘤的靶向α疗法。FPI-2059基于一种以前称为IPN-1087 和3BP-227 的化合物，该化合物之前已在研究者赞助的研究和临床试验1期研究中作为发射β的放射性药物进行研究，Fusion于2021年收购了该资产，并使用锕-225将其转化为发射α的放射性药物。FPI-2068是一种双特异性IgG的靶向α疗法（TAT），旨在将锕225递送至共表达EGFR和cMET的各种实体瘤。EGFR和cMET是经过验证的癌症靶点，在多种肿瘤类型中共表达，包括头颈部鳞状细胞癌、非小细胞肺癌、结直肠癌和胰腺导管腺癌。当前正在与阿斯利康根据合作协议共同开发。2023年10月12日，Fusion表示在临床前研究中，FPI-2068在结直肠和肺肿瘤异种移植小鼠模型中显示出抗肿瘤功效，单剂量给药FPI-2068导致肿瘤消退时间延长。此外，FPI-2068引起 DNA损伤反应（DDR）通路的激活以及细胞凋亡，表明细胞机制无法修复由α辐射诱导的DNA 损伤，这与提出的主要作用机制一致。财务状况2022财年，根据与阿斯利康的合作协议收入146万美元，上年同期为144万美元；研发费用为5890万美元；一般和行政费用为3060万美元；年度净亏损约为8760万美元。截至2023年9月30日的前三季度合作收入为207万美元；研发费用为4946万美元；一般和行政费用为2357万美元；净亏损6672万美元。第三季度为研发费用1460万美元，而2022年同期为1660万美元。这一下降主要是由于公司停止了FPI-1966项目的临床开发，导致该项目相关活动的减少，以及FPI-1434的临床试验1期的制造相关成本的降低，部分被FPI-2265的临床试验2期项目费用所抵消。一般和行政费用为680万美元，而2022年同期为740万美元，下降的主要原因是公司和专利相关法律费用的减少。报告净亏损1730 万美元，或每股0.25 美元，而2022 年同期净亏损2400 万美元，或每股0.55 美元。截至2023年9月30日，Fusion的现金、现金等价物和投资约为2.87 亿美元，其中计入公司市场股票发行计划下约6500 万美元的后续销售收益以及公司现有债务融资项下预计提取的1500万美元。Fusion预计，其现金、现金等价物和投资将足以为公司的运营费用和资本支出需求提供资金到2025年第四季度。参考：NMPA/CDE；药融云数据，www.pharnexcloud.com；FDA/EMA/PMDA；相关公司公开披露（除标注外，正文图片均来自企业官网）；https://fusionpharma.com/；RBC Capital Markets,https://www.rbccm.com/en/;https://www.thepaper.cn/newsDetail_forward_25897530；https://www.prnewswire.com/news-releases/radiopharmaceuticals-market-size-to-grow-by-usd-4-37-billion-from-2021-to-2026--actinium-pharmaceuticals-inc-bayer-ag-bracco-spa-bwx-technologies-inc-and-more-among-the-key-companies-in-the-market---technavio-302011756.html；https://www.ccnta.cn/article/3810.html；https://news.bms.com/news/details/2023/Bristol-Myers-Squibb-Adds-Premier-Radiopharmaceutical-Platform-with-Acquisition-of-RayzeBio/default.aspx；https://www.thepaper.cn/newsDetail_forward_25897530；等等。以下为5月大湾区广州核药、ADC、多肽小分子峰会推荐，与上文无关。

并购放射疗法IPO临床3期抗体药物偶联物

2024-03-26

·药智网

百亿核药赛道「再起风云」

核药领域再造大单，百亿核药赛道的全球版图再生大变。核药Biotech“卖身”MNC，又增一员。核药为何成为交易热点？01 为何是Fusion ？英国制药巨头阿斯利康3月19日表示，将以超过 20 亿美元价格收购总部位于加拿大哈密尔顿的 Fusion Pharmaceuticals，后者是一家专注于癌症靶向放射治疗的公司。阿斯利康将向 Fusion 预付 20 亿美元现金，预付款和最大潜在或有价值付款的总计交易价值约达24亿美元。Fusion是一家临床阶段的肿瘤学公司，专注于开发作为精准药物的下一代核药。作为靶向α粒子疗法的行业领导者，Fusion利用一种能放射α粒子的医学同位素，将靶向癌细胞的抗体与α粒子“绑定”在一起，精准狙击癌细胞。α放射性同位素与其它常见的医用射线的对比见图1。图1. α粒子与β，γ粒子和X-射线的区别图片来源：Fusion PharmaceuticalsFusion 的管线资产相对于目前已经投入使用的核药具有多种潜在优势，包括：·使用α粒子辐射增强肿瘤杀伤能力；·针对多种靶标；·跨多种肿瘤类型的广泛适用性；·耐受性和治疗窗口增加；·多种作用机制联合利用，包括直接损伤DNA和 α 粒子介导的增强抗肿瘤免疫反应；·225Ac 的主要作用机制是诱导多个双链 DNA 断裂，直接损伤细胞；·225Ac的第二种机制可能会扩大α粒子的有效直接细胞杀伤范围，被称为旁观者效应（Bystander Effect）。这种效应对于杀死癌细胞的总体功效与直接 DNA 断裂一样重要；·第三种潜在的作用机制是通过α辐射破坏肿瘤细胞。临床前研究显示，被破坏的肿瘤细胞释放出肿瘤相关抗原，从而激活肿瘤部位的 T 细胞。Fusion实现放射性物质与配体连接的技术平台称作Fast-Clear™，实现放射性治疗剂在精准递送之后的linker的快速切割裂解，并释放放射性治疗剂。Fusion管线内目前有3款专属临床资产（图2），还有几款合作开发的项目。图2. Fusion Pharmaceuticals管线资产图图片来源：Fusion·FPI-2265：Fusion 的主导项目 FPI-2265 目前处于II期临床TATCIST 2，其小分子候选药物225Ac-PSMA I&T针对前列腺癌中表达的 PSMA（前列腺特异性膜抗原）。TATCIST 2 临床试验评估病情进展的转移性去势抵抗性前列腺癌 (mCRPC) 患者，包括未接受过 PSMA 靶向核药治疗的患者，以及已接受过177Lu 的 PSMA 核药（例如Pluvicto™）治疗的患者。·FPI-1434： [225Ac]-FPI-1434是一款放射性同位素-抗体偶联物，将 α 粒子递送至癌细胞。FPI-1434将225Ac与癌症生物标志物 IGF-1R （胰岛素样生长因子1受体）的抗体通过Fast-Clear™ 联接产生。IGF-1R 是在多种类型的癌细胞中发现的成熟肿瘤靶标。FPI-1434目前处于针对实体瘤的I期临床。·FPI-2059：FPI-2059 是一种小分子放射性偶联物的靶向 α 疗法，针对各种实体瘤。FPI-2059 靶向神经降压素受体 1 (NTSR1)，NTSR1 是癌症治疗的一个有希望的靶点，在多种实体瘤中过度表达。FPI-2059 将小分子药物IPN-1087 与225Ac结合起来。02 核药为何成为交易热点？近年来，核药领域吸引了几十亿美元的生物制药投资。诺华正在对不同肿瘤类型的不同疗法进行十多项试验，希望将其获批的前列腺癌治疗 Pluvicto 扩展到早期治疗系列。诺华在2017和2018年两年里令人略感惊讶地斥60亿美元巨资收购了两家开发核药的初创公司，激发了行业对该领域的热情。诺华重金求药的回报非常丰厚。Pluvicto 于 2022年3月在美国获得批准，用于治疗前列腺特异性膜抗原 (PSMA) 阳性、既往接受过治疗的转移性去势抵抗性前列腺癌患者。2023年，Pluvicto 带来了9.8亿美元的收入，比2022年增长了262%。2023年第四季度，Pluvicto 贡献2.73亿美元的销售额，同比增长53%。去年，礼来公司以超过10亿美元的价格收购了 Point Biopharma，获得了一款同样针对前列腺癌的主导药物。而百时美施贵宝则以超过40亿美元的价格收购了 RayzeBio，后者同样是专攻放射性肿瘤药物开发的公司。为何核药的开发在肿瘤学领域引发制药巨头们的关注？主要由其潜在的优势决定：·生物学效应：核药通过释放的放射线与肿瘤细胞相互作用，造成DNA双链断裂、细胞凋亡、氧化应激等生物学效应，导致肿瘤细胞的死亡或增殖受限。这种生物学效应对肿瘤组织具有高度选择性，因为肿瘤细胞通常具有较高的代谢活性和较少的修复能力，相对于正常组织更容易受到辐射损伤。·靶向治疗：核药可以通过将放射性同位素连接到靶向分子（如抗体或配体）上，实现对肿瘤的精准治疗。这些靶向分子能够特异性地结合到肿瘤细胞表面的靶标上，使放射性同位素更加精准地定位到肿瘤细胞，减少对正常组织的损伤。·局部治疗：核药可以通过局部给药方式（如直接注射或放射性粒子植入）将放射性同位素直接送达到肿瘤组织中，实现局部治疗效果。这种局部治疗方式可以减少对周围正常组织的伤害，并且可以在肿瘤组织中释放高剂量的辐射，以杀死或破坏肿瘤细胞。·系统性治疗：核药也可以通过静脉注射等方式进行系统性给药，使其能够在全身范围内散布到肿瘤部位，实现全身性的治疗效果。这种系统性治疗方式适用于一些无法局部治疗的情况，或者需要治疗全身性转移的肿瘤。·精准放疗：核药可以实现对肿瘤的精准放疗，即通过放射性同位素释放的能量，直接破坏肿瘤细胞的DNA或细胞结构，从而杀死或破坏肿瘤细胞。这种精准放疗可以最大限度地减少对周围正常组织的伤害，并且可以提高治疗的局部控制率。·放疗剂量计算：核药的治疗效果与施加的辐射剂量密切相关。因此，在治疗计划中需要精确计算适当的放射剂量，以实现对肿瘤的有效治疗，同时最小化对周围正常组织的损伤。放疗剂量计算通常考虑了肿瘤的大小、位置、代谢活性等因素，并结合了生物效应模型，以确定最佳的放射剂量分配方案。·个性化治疗：核药的选择和治疗方案通常会根据患者的个体特征和肿瘤的生物学特性进行个性化调整。这可能涉及到对肿瘤的分子生物学特征进行分析，以确定最适合的靶向治疗方案，或者结合其他治疗模式（如化疗、手术等）进行综合治疗。03 结语核药的发展和商业化前景备受关注。尽管核药面临着技术挑战、安全性和副作用问题以及监管审批流程的严格要求，但随着科学技术的不断进步和临床研究的深入，核药仍然被视为一个前景广阔的领域。未来，随着更多核药的研发和上市，以及对其临床应用的进一步探索，相信核药将会为癌症治疗带来新的突破和可能性，为患者提供更多的治疗选择，并为癌症治疗领域的发展做出更大的贡献。Ref.Fusion Pharmaceuticals pipeline.Joseph, A. As targeted radiation field heats up, AstraZeneca to pick up Fusion Pharmaceuticals in $2 billion deal. STAT. 19. 03. 2024.Hopkins, C. Novartis' Pluvicto Sales Grew 53 Percent in Q4, Closing in on Blockbuster Status in 2023. Precision Medicine Online. 31. 01. 2024.DeAngelis, A. In the fight against cancer, it’s boom times for radiopharmaceuticals. STAT. 08. 11. 2023.声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 晨曦转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是昨天最受欢迎的文章哦

放射疗法并购临床2期临床1期临床结果

2023-04-21

·PipelineReview

Fusion Pharmaceuticals Announces Presentation of Preclinical Data Supporting FPI-2059 and Leading Targeted Alpha Therapy Platform at AACR Annual Meeting

FPI-2059 induces tumor growth inhibition in colorectal tumor model TEM-1 and EGFRvIII demonstrate potential as TAT targets HAMILTON, Canada and BOSTON, MA, USA I April 19, 2023 I Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, today announced the presentation of preclinical data that provide further support of its clinical stage FPI-2059, a neurotensin receptor 1 (NTSR1) targeted alpha therapy (TAT), and additional preclinical development programs. The Company presented these data in three poster presentations at the American Association for Cancer Research (AACR) Annual Meeting. "These data highlight the strong scientific rationale supporting clinical development of FPI-2059, demonstrating that targeting NTSR1 with the tumor killing power of actinium-225 has the potential to induce suppression in solid tumors. We are pleased to be progressing FPI-2059 in our ongoing Phase 1 study," said Fusion Chief Scientific Officer Christopher Leamon, Ph.D. "With our discovery platform, the Fusion team has quickly and efficiently developed TATs for various targets and progressed to multiple clinical programs. The data presented on exploratory targets, such as EGFRvIII and TEM-1, show the ability of our TATs to impact hard to treat cancers." Data from preclinical studies of FPI-2059, a small molecule TAT designed to deliver actinium-225 to tumor sites expressing NTSR1, a protein expressed in gastrointestinal, prostate, pancreatic ductal adenocarcinoma (PDAC) and multiple other cancers, were presented in a poster presentation titled, "NTSR1-targeted alpha therapeutic [Ac-225]-FPI-2059 induces growth inhibition in a preclinical colorectal tumor model". Outcomes of the study demonstrate robust FPI-2059 tumor uptake and dose-dependent tumor growth inhibition and therapeutic efficacy in a preclinical colorectal tumor model. These data provide further evidence supporting the clinical development of FPI-2059, which is currently being evaluated in a Phase 1 study for the treatment of solid tumors expressing NTSR1. Data from additional preclinical studies highlight the potential of tumor endothelial marker 1 (TEM-1) and epidermal growth factor receptor variant 3 (EGFRvIII) as targets for actinium-225 labelled TATs. In sarcoma xenograft models, TEM-1-targeted alpha therapy demonstrates strong dose-dependent and target level-dependent efficacy with no apparent toxicity. In glioblastoma multiforme (GBM) models, EGFRvIII-targeted alpha therapy demonstrates therapeutic efficacy as a single agent and in combination with standard of care. Further, EGFRvIII-targeted alpha therapy demonstrates efficacy in models with both leaky and intact blood-brain tumor barriers, suggesting that even low tumor uptake has potential anti-tumor effect. Copies of the poster presentations can be found at: https://fusionpharma.com/fusion-scientific-presentations/ following the conclusion of the AACR Annual Meeting. About FPI-2059 FPI-2059 is a small molecule radiopharmaceutical targeting neurotensin receptor 1 (NTSR1) which is overexpressed in multiple solid tumors, including pancreatic ductal adenocarcinoma, colorectal, squamous cell carcinoma head & neck, gastric, Ewings sarcoma, and neuroendocrine differentiated prostate. FPI-2059 is based upon a compound previously referred to as IPN-1087 and 3BP-227 that had previously been studied in investigator sponsored studies and a Phase 1 clinical trial as a beta-emitting radiopharmaceutical. Fusion acquired the asset in 2021 and converted it to an alpha emitting radiopharmaceutical using actinium-225. The diagnostic analogue which uses indium-111 in place of actinium-225 is referred to as FPI-2058. About Fusion Fusion Pharmaceuticals is a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines. Fusion connects alpha particle emitting isotopes to various targeting molecules to selectively deliver the alpha emitting payloads to tumors. Fusion's clinical portfolio includes: FPI-2265 targeting prostate specific membrane antigen (PSMA) for metastatic castration resistant prostate cancer currently in a Phase 2 trial; FPI-1434 targeting insulin-like growth factor 1 receptor currently in a Phase 1 trial; FPI-1966, targeting the fibroblast growth factor receptor 3 (FGFR3), currently in a Phase 1 trial; and FPI-2059, a small molecule targeting neurotensin receptor 1 (NTSR1), currently in a Phase 1 trial. In addition to a robust proprietary pipeline, Fusion has a collaboration with AstraZeneca to jointly develop novel targeted alpha therapies (TATs) and combination programs between Fusion's TATs and AstraZeneca's DNA Damage Response Inhibitors (DDRis) and immuno-oncology agents. The Company recently received IND clearance for the first novel TAT under the collaboration, which targets EGFT-cMET. Fusion has also entered into a collaboration with Merck to evaluate FPI-1434 in combination with Merck's KEYTRUDA® (pembrolizumab) in patients with solid tumors expressing IGF-1R. To support Fusion's growing pipeline of TATs, the Company has signed strategic actinium supply agreements with TRIUMF, Niowave, Inc. and BWXT Medical. SOURCE: Fusion Pharmaceuticals

临床1期AACR会议临床2期临床申请

100 项与 IPN-01087(3B Pharmaceuticals GmbH) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
骨癌	临床2期	欧洲	Zentralklinik Bad Berka GmbH	2018-05-03
结直肠癌	临床2期	欧洲	Zentralklinik Bad Berka GmbH	2018-05-03
尤文肉瘤	临床2期	欧洲	Zentralklinik Bad Berka GmbH	2018-05-03
胃肠道间质瘤	临床2期	欧洲	Zentralklinik Bad Berka GmbH	2018-05-03
头颈部肿瘤	临床2期	欧洲	Zentralklinik Bad Berka GmbH	2018-05-03
胰腺导管癌	临床2期	欧洲	Zentralklinik Bad Berka GmbH	2018-05-03
胰腺导管癌	临床2期	法国	Ipsen SA	2018-05-03
鳞状细胞癌	临床2期	欧洲	Zentralklinik Bad Berka GmbH	2018-05-03
胃癌	临床2期	欧洲	Zentralklinik Bad Berka GmbH	2018-05-03
晚期癌症	临床1期	美国	Ipsen SA	2018-05-03

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03525392 (CTgov)	临床1期	骨癌 \| 胰腺导管腺癌 \| 头颈部鳞状细胞癌 ... 更多	14	177Lu-3BP-227 (Cohort 1: 177Lu-3BP-227 2.5 GBq)	顧繭醖廠艱獵獵願窪鹽(夢窪糧淵鬱廠鑰憲蓋鬱) = 範範夢淵齋膚糧艱膚願範繭夢願繭壓範鹹遞鹹 (窪艱蓋築夢製餘築餘憲, 鑰淵顧淵餘窪齋遞醖醖 ~ 構製壓衊遞艱夢顧範網) 更多	-	2023-12-12
				177Lu-3BP-227 (Cohort 2: 177Lu-3BP-227 4.0 GBq)	顧繭醖廠艱獵獵願窪鹽(夢窪糧淵鬱廠鑰憲蓋鬱) = 願選選獵夢選壓繭齋糧範繭夢願繭壓範鹹遞鹹 (窪艱蓋築夢製餘築餘憲, 鏇範鑰製積築簾築製夢 ~ 鏇觸願範醖窪鹽淵製選) 更多