Phase 0/1 Theragnostic Study in Patients With Metastatic Castration Resistant Prostate Cancer in Need of Salvage Therapy, Selected by 18F-PSMA-PET Imaging and Treated by Alpha-therapeutic Radioligand 212Pb-NG001

The purpose of this study is to evaluate the imaging feasibility and safety of 212Pb-NG001.

开始日期2023-03-06

申办/合作机构

ARTBIO, Inc.初创企业

100 项与 212Pb-NG001 相关的临床结果

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100 项与 212Pb-NG001 相关的转化医学

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100 项与 212Pb-NG001 相关的专利（医药）

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项与 212Pb-NG001 相关的文献（医药）

2005-07-01·Environmental toxicology and pharmacology3区 · 环境科学与生态学

Inhibition of collagen and DNA biosynthesis by a novel amidine analogue of chlorambucil is accompanied by deregulation of β1-integrin and IGF-I receptor signaling in MDA-MB 231 cells

3区 · 环境科学与生态学

Article

作者: Bielawska, Anna ; Palka, Jerzy ; Bielawski, Krzysztof ; Sienkiewicz, Pawel

A novel amidine analogue of chlorambucil N-(2-(4-(4-bis(2-chloroethyl)aminophenyl)butyryl)aminoethyl)-5-(4-amidinophenyl)-2-furanecarboxamide hydrochloride (AB(1)), and the parent drug were compared for their effects on collagen and DNA synthesis in breast cancer MDA-MB 231 cells. IC(50) values for chlorambucil and its amidine analogue for collagen synthesis were found to be about 44 and 19μM, respectively. Increased ability of AB(1) to suppress the protein synthesis, compared to chlorambucil, was found to be related to an inhibition of prolidase activity and expression. The phenomena were probably a result of disruption of β(1)-integrin and the insulin-like growth factor-I (IGF-I) receptor mediated signaling caused by this compound. Expression of β(1)-integrin receptor, as well as focal adhesion kinase pp125(FAK) (FAK), growth-factor receptor-bound protein 2 (GRB2), son of sevenless protein 1 (Sos1) and phosphorylated mitogen activated protein kinases (MAPK), extracellular-signal-regulated kinase 1 (ERK(1)) and kinase 2 (ERK(2)) but not Src and Shc proteins was significantly decreased in cells incubated for 24h with 10μM AB(1), compared to controls. Chlorambucil in the same conditions did not evoke any changes in expression of all these signaling proteins, as shown by Western immunoblot analysis. In addition, AB(1) revealed a higher antiproliferative activity than chlorambucil, accompanied by a stronger down-regulation of IGF-I receptor expression. The results were confirmed by [(3)H]thymidine incorporation assay. Incubation of the cells with 10μM AB(1) for 12 and 24h contributed to a decrease in DNA synthesis by about 33 and 46% of the control values, respectively, while in case of chlorambucil by about 23 and 29%, respectively. These data suggest that the amidine analogue of chlorambucil (AB(1)) disturbs MDA-MB 231 cell metabolism more potently than does the parent drug, chlorambucil. The mechanism of this phenomenon may be due to its stronger suppression of β(1)-integrin and IGF-I receptor signaling.

Cancers

Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001

Article

作者: Bruland, Øyvind Sverre ; Stenberg, Vilde Yuli ; Tornes, Anna Julie Kjøl ; Nilsen, Hogne Røed ; Revheim, Mona-Elisabeth ; Juzeniene, Asta ; Larsen, Roy Hartvig

This study aimed to determine the influence of cellular PSMA expression, radioligand binding and internalization, and repeated administrations on the therapeutic effects of the PSMA-targeting radioligand 212Pb-NG001. Cellular binding and internalization, cytotoxicity, biodistribution, and the therapeutic efficacy of 212Pb-NG001 were investigated in two human prostate cancer cell lines with different PSMA levels: C4-2 (PSMA+) and PC-3 PIP (PSMA+++). Despite 10-fold higher PSMA expression on PC-3 PIP cells, cytotoxicity and therapeutic efficacy of the radioligand was only 1.8-fold better than for the C4-2 model, possibly explained by lower cellular internalization and less blood-rich stroma in PC-3 PIP xenografts. Mice bearing subcutaneous PC-3 PIP xenografts were treated with 0.2, 0.4, and 0.8 MBq of 212Pb-NG001 that resulted in therapeutic indexes of 2.7, 3.0, and 3.5, respectively. A significant increase in treatment response was observed in mice that received repeated injections compared to the corresponding single dose (therapeutic indexes of 3.6 for 2 × 0.2 MBq and 4.4 for 2 × 0.4 MBq). The results indicate that 212Pb-NG001 can induce therapeutic effects at clinically transferrable doses, both in the C4-2 model that resembles solid tumors and micrometastases with natural PSMA expression and in the PC-3 PIP model that mimics poorly vascularized metastases.

项与 212Pb-NG001 相关的新闻（医药）

2024-11-14

·PipelineReview

ARTBIO to Enter into Licensing and Research Partnership with 3B Pharmaceuticals to Advance a First-in-Class Alpha Radioligand Therapy for Solid Tumors

Partnership combines ARTBIO’s AlphaDirect™ platform for 212 Pb-based alpha radioligand therapies with 3B Pharmaceuticals’ expertise in peptide radioligand therapy discovery and development ARTBIO gains exclusive global license for highly novel program close to clinical development addressing first in class target in solid tumor indications with high unmet need CAMBRIDGE, MA, USA and BERLIN, Germany I November 14, 2024 I ARTBIO, Inc. (ARTBIO), a clinical-stage radiopharmaceutical company developing a new class of targeted alpha radioligand therapies (ARTs), and 3B Pharmaceuticals GmbH (3BP), a private biotechnology company developing targeted radiopharmaceutical drugs and diagnostics for oncology indications, today announced a worldwide, exclusive license and research agreement to develop an advanced preclinical stage first-in-class peptide ART for the treatment of solid tumors. This partnership extends ARTBIO’s pipeline with the addition of a highly differentiated program focused on a novel, first-in-class target that is optimal for 212 Pb-based alpha radioligand therapy. 212 Pb has an ideal clinical profile well suited to this program due to a short half-life and single alpha emission that delivers maximal energy into tumors. “In-licensing this first-in-class program from 3BP speaks to our mission to expand beyond prostate cancer and create a whole new class of therapies that can improve outcomes for patients with many types of cancer,” said Emanuele Ostuni, Ph.D., CEO of ARTBIO. “We can achieve this goal by addressing targets novel to radioligand therapies. By partnering 3BP’s proven track record in peptide discovery with our leadership in 212 Pb ART development, we believe we can unlock an important new target and deliver much-needed patient benefit.” The program has promise across a range of solid tumor indications where patients have a high need for alternatives and for which radioligand therapies are not currently in clinical use or advanced development. ARTBIO will advance the licensed program through clinical development, starting in 2025, with both companies contributing their respective expertise to optimize the therapy’s profile. “By combining our unique and innovative discovery platforms, we’re redefining treatment paradigms for solid tumors,” said Dr. Ulrich Reineke, Managing Director of 3BP. “Our shared vision and complementary contributions will accelerate the development of this potentially transformative treatment for patients with solid tumors.” About ARTBIO ARTBIO is a clinical-stage radiopharmaceutical company redefining cancer care by creating a new class of alpha radioligand therapies (ARTs). The unique ARTBIO approach selects the optimal alpha-precursor isotope ( 212 Pb) and tumor-specific targets to create therapeutics with the potential for highest efficacy and safety. The company’s AlphaDirect™ technology, a first-of-its-kind 212 Pb isolation method, enables a distributed manufacturing approach for the reliable production and delivery of ARTs. ARTBIO is advancing multiple pipeline programs with lead program AB001 currently in first-in-human trials. ARTBIO is shaped by a long-standing scientific legacy with nearly a century of pioneering work in radiation therapy conducted at the University of Oslo and Norway’s Radium Hospital. For more information, visit www.artbio.com , and follow us on LinkedIn and Twitter . About 3B Pharmaceuticals 3B Pharmaceuticals GmbH is a German biotechnology company developing innovative therapeutic and diagnostic radiopharmaceuticals for oncology applications. Using its dedicated technology platform 3BP developed a broad pipeline of novel compounds addressing innovative as well as established drug targets to deliver diagnostic and therapeutic radioisotopes to tumors. The company’s mission is to advance the standard of care in precision oncology through innovative nuclear medicine solutions that address unmet medical needs. For more information on 3B Pharmaceuticals, visit www.3b-pharma.com . SOURCE: ARTBIO

引进/卖出放射疗法

2024-11-14

·PRNewswire

ARTBIO to Enter into Licensing and Research Partnership with 3B Pharmaceuticals to Advance a First-in-Class Alpha Radioligand Therapy for Solid Tumors

Partnership combines ARTBIO's AlphaDirect™ platform for 212Pb-based alpha radioligand therapies with 3B Pharmaceuticals' expertise in peptide radioligand therapy discovery and development ARTBIO gains exclusive global license for highly novel program close to clinical development addressing first in class target in solid tumor indications with high unmet need CAMBRIDGE, Mass. and BERLIN, Nov. 14, 2024 /PRNewswire/ -- ARTBIO, Inc. (ARTBIO), a clinical-stage radiopharmaceutical company developing a new class of targeted alpha radioligand therapies (ARTs), and 3B Pharmaceuticals GmbH (3BP), a private biotechnology company developing targeted radiopharmaceutical drugs and diagnostics for oncology indications, today announced a worldwide, exclusive license and research agreement to develop an advanced preclinical stage first-in-class peptide ART for the treatment of solid tumors. This partnership extends ARTBIO's pipeline with the addition of a highly differentiated program focused on a novel, first-in-class target that is optimal for 212Pb-based alpha radioligand therapy. 212Pb has an ideal clinical profile well suited to this program due to a short half-life and single alpha emission that delivers maximal energy into tumors. "In-licensing this first-in-class program from 3BP speaks to our mission to expand beyond prostate cancer and create a whole new class of therapies that can improve outcomes for patients with many types of cancer," said Emanuele Ostuni, Ph.D., CEO of ARTBIO. "We can achieve this goal by addressing targets novel to radioligand therapies. By partnering 3BP's proven track record in peptide discovery with our leadership in 212Pb ART development, we believe we can unlock an important new target and deliver much-needed patient benefit." The program has promise across a range of solid tumor indications where patients have a high need for alternatives and for which radioligand therapies are not currently in clinical use or advanced development. ARTBIO will advance the licensed program through clinical development, starting in 2025, with both companies contributing their respective expertise to optimize the therapy's profile. "By combining our unique and innovative discovery platforms, we're redefining treatment paradigms for solid tumors," said Dr. Ulrich Reineke, Managing Director of 3BP. "Our shared vision and complementary contributions will accelerate the development of this potentially transformative treatment for patients with solid tumors." About ARTBIO ARTBIO is a clinical-stage radiopharmaceutical company redefining cancer care by creating a new class of alpha radioligand therapies (ARTs). The unique ARTBIO approach selects the optimal alpha-precursor isotope (212Pb) and tumor-specific targets to create therapeutics with the potential for highest efficacy and safety. The company's AlphaDirect™ technology, a first-of-its-kind 212Pb isolation method, enables a distributed manufacturing approach for the reliable production and delivery of ARTs. ARTBIO is advancing multiple pipeline programs with lead program AB001 currently in first-in-human trials. ARTBIO is shaped by a long-standing scientific legacy with nearly a century of pioneering work in radiation therapy conducted at the University of Oslo and Norway's Radium Hospital. For more information, visit , and follow us on LinkedIn and Twitter. About 3B Pharmaceuticals 3B Pharmaceuticals GmbH is a German biotechnology company developing innovative therapeutic and diagnostic radiopharmaceuticals for oncology applications. Using its dedicated technology platform 3BP developed a broad pipeline of novel compounds addressing innovative as well as established drug targets to deliver diagnostic and therapeutic radioisotopes to tumors. The company's mission is to advance the standard of care in precision oncology through innovative nuclear medicine solutions that address unmet medical needs. For more information on 3B Pharmaceuticals, visit . ARTBIO Media Contact Marites Coulter Tel: +1 415 819 2214 Email: [email protected] 3B Pharmaceuticals Media Contact Dr. Jan Michel Director Finance & Corporate Development Tel.: +49 (30) 6392-4317 Fax.: +49 (30) 6392-4316 E-mail: [email protected] SOURCE ARTBIO WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

引进/卖出放射疗法

2024-11-01

·同写意

被引进和被并购的：Big Pharma涌向“核”战场

中国核药产业创新链盟将举办对接交流会系列活动之“中国新药向‘核’处去”，遴选“一线一流”专家共研核药未来，助力产业创新与发展。诺华对放射性药物的执着，早已不是什么行业秘辛。年初，当一大波制药高管抛出进军ADC的畅想，诺华是少有的“逆行者”。而近期，通过将旗下Advanced Accelerator Applications（AAA）诊断部门以2.24亿美元售价转让西门子医疗，诺华有望获得更大的药物布局空间。值得注意，诺华跨入“蓝海”的一个重要节点，就是在2017年斥资39亿美元收购AAA，获得Lutathera等资产。后来的故事，几乎可以形容为，诺华以一己之力撑高市场天花板。 Lutathera在2023年贡献了6.05亿美元销售额，另一款放射性药物Pluvicto的营收，则达到9.8亿美元。今年前九个月，Pluvicto总销售额同比增长47%达到10.4亿美元，诺华，同时也是整个放射性药物行业，正式迎来“重磅炸弹”级别的产品。对于一众苦于“专利悬崖”的MNC，这无疑是不可错过的新机会。事实上，经过这些年的酝酿，市场早已从诺华、拜耳这样的初代玩家，逐渐过渡到更加多元的生态。一波Biotech的兴起，也为交易盛世提供了土壤。包括政府拨款，资金池肉眼可见地增加着。例如，欧盟的“地平线欧洲”计划已向成百上千的高校、研究机构和药企提供了30亿欧元的支持，突破性创新方向之一，就纳入放射性药物。小“核”才露尖尖角，而今“上车”犹可期。泼天富贵，正在砸来。 1 MNC，跑步进场放射性药物可以精确地摧毁癌细胞，这是它想象空间的起点，但问题是，使用靶向放射性同位素治疗癌症并非易事。自1941年，业界就在尝试如何将放射性同位素与生物分子结合，靶向人体内的特定器官、组织或细胞。起初，放射性药物长期被限制在诊断领域。不过随着关注的增加，它们的潜力在治疗领域得到释放。诺华是最先察觉到这种治疗机会的巨头之一。并且，除了Pluvicto和Lutathera之外，这家药企还在通过一系列交易，拓宽自己的统治版图。 5月，诺华开价17.5亿美元，收购了一家尚处于临床前开发阶段的Biotech Mariana。Mariana拥有一个放射性药物平台，涵盖靶向配体。据介绍，这些配体可以更好地靶向肿瘤，并迅速从体内清除以降低毒性，以及释放α和β粒子的有效载荷。而整个行业的风向变动，发生在2023年。正如诺华那样，礼来、BMS纷纷下重金，尝试在放射性药物领域建立影响力。 BMS在2023年底完成了41亿美元收购案。被买下的RayzeBio，管线包括正在针对不同癌症进行III期和II期试验的RYZ101，以及其他早期候选药物。 “新手”礼来，似乎也更加急切地补齐短板。2023年，通过一笔14亿美元的收购，该Big Pharma算是真正下场。礼来肿瘤学部门总裁Jacob Van Naarden称，他们并将收购Point Biopharma视为“投资开发多种治疗癌症的放射性药物的开始”。到今年，礼来先后宣布了两项资产开发合作。其中，7月与Radionetics Oncology签订的投资协议，预付了1.4亿美元，让其获得以10亿美元的价格收购该Biotech的选择权。 2024年至今，Big Pharma阵营的另一大并购案，来自阿斯利康。四年前，阿斯利康与Fusion Pharma达成开发合作，这份关系在今年3月升级，前者选择以约20亿美元的价格直接收购后者。分析指出，放射性药物的专业性，意味着MNC不能像其他领域的Biotech资产交易那样，只买下药物，然后抛弃公司的其他部分。也就是说，接下来，这个领域或许会有更多Big Pharma从单纯的管线引进转向完整的并购。赛诺菲可能是下一个大买家。最近，它开始涉足放射性药物领域，与RadioMedix达成了一项价值3.56亿美元的许可协议。 2 下半场的“香饽饽” 与MNC的跑步进场相对，在此创新的Biotech孤军奋战。对于Biotech来说，问题是，资本寒冬的大背景下，怎样才能“嫁入豪门”？下面的五家明星公司，某种程度可以提供一些答案。 01 Aktis Oncology 渴望获得放射性药物的礼来，于5月与Aktis Oncology签署了一项价值6000万美元的合作协议，从而获得该Biotech的靶向抗癌药物。该交易的潜在里程碑和特许权使用费，可能会达到11亿美元。 9月底，Aktis还获得一笔1.75亿美元的超额认购B轮融资，凸显业界对该领域的兴趣。此轮融资由RA Capital Management领投，RTW Investments和Janus Henderson Investors共同领投。其他参与者，包括BMS、礼来，以及默沙东旗下风险基金MRL Ventures Fund。 Aktis使用发射α粒子精准治疗癌症，同时避免副作用。其主要管线，针对尿路上皮癌和其他癌症。其中，AKY-1189是一种靶向Nectin-4的微蛋白α放射性结合物，正在开发用于治疗实体肿瘤。虽然这家Biotech目前拥有充足的现金——其首席执行官Matthew Roden称公司手头有3亿美元——但随着投资方中活跃的三家Big Pharma追逐身影，Aktis估计很快就会再次成为新闻焦点。 02 ARTBIO ARTBIO于去年6月成立，正在利用α前体同位素（Pb212）和肿瘤特异性靶标，开发一类新型放射性配体疗法。尽管成立时间不长，ARTBIO已手握一项进入临床试验阶段的资产。针对前列腺癌的AB001，也正在挪威开展进入临床之前的最后测试。 2023年12月，由Third Rock Ventures和一家未公开的医疗基金共同领投的A轮融资，给ARTBIO筹集了9000万美元。从那时起，这家Biotech就不断签署协议，以加强供应和制造。 5月的另一笔交易，是ARTBIO与另一家临床阶段Biotech Fog Pharma合作，利用双方的平台（AlphaDirect和Helicon），开发α粒子放射性配体疗法。 03 Nucleus RadioPharma 区别于直接开发开发疗法，Nucleus RadioPharma主要为放射性药物提供集成制造和供应链服务。 Nucleus的平台已经吸引了阿斯利康的投资，后者于6月参与A+轮融资。财务细节尚未披露，但这家Biotech在一年前由GE Health和Eclipse领投的A轮融资中筹集了5600万美元，当时A轮融资超额认购。据悉，最新的融资预计将用于Nucleus在美国各地建立多个新制造工厂，其中包括位于梅奥诊所附近的一家工厂（梅奥诊所也是A轮融资的参与者）。额外的资金，则会投向开发、制造和分销放射性药物的技术。 04 PeptiDream 诺华曾多次与日本Biotech PeptiDream合作，以扩充其放射性药物管线。今年4月，两家公司重新达成了一项合作，总金额超过27亿美元。而最早的联手，可追溯到2010年。当然，诺华并不是PeptiDream的唯一伙伴。该公司还与罗氏旗下的Genentech，以及礼来、默沙东达成了协议，潜在里程碑金额总计达数十亿美元。 PeptiDream的秘诀是什么？据该公司称，其肽发现平台系统可以找到基于大环肽的新药，非常快速地针对任何感兴趣的生物靶点进行筛选。PeptiDream声称，成功率高达95%。该技术由东京大学授权，并在公司内部进行了优化。值得注意的是，该公司广泛的管线由其他合作伙伴提供支持，包括Biohaven和RayzeBio。它们大多数都用于抗肿瘤，但也有例外。PeptiDream唯一内部开发项目是一种肌肉生长抑制素抑制剂，专注于开发针对肥胖和其他肌肉疾病的放射配体。 05 RadioMedix 9月，赛诺菲找到了跟诺华、BMS、礼来在放射性药物领域展开竞争的理想合作伙伴。赛诺菲与RadioMedix和Orano Med达成开发协议，以获得神经内分泌肿瘤候选药物，为此要支付1亿欧元的预付款，以及2.2亿欧元的销售里程碑付款和特许权使用费。该交易的重点是AlphaMedix，这是一种利用铅-212Pb治疗癌症的靶向放射性配体疗法。RadioMedix和Orano Med正在针对神经内分泌肿瘤患者对该候选药物进行II期临床试验，预计今年将公布结果。 RadioMedix还拥有另外两个临床项目和一些处于临床前测试阶段的早期资产。除了治疗药物，这家Biotech还开发用于诊断和监测癌症的放射性药物，并具备从开发到制造的能力。主要参考资料： 1.市值8000亿美元的礼来，在下一盘大棋；同写意 2.ADC的逆行者：诺华“独醒”，核药正劲；同写意 3.Why is pharma going gaga for radiopharmaceuticals?；pharmaphorum 4.5 Radiopharma Biotechs to Watch for Potential Buyouts；BioSpace 同写意媒体矩阵，欢迎关注↓↓↓

放射疗法抗体药物偶联物并购

100 项与 212Pb-NG001 相关的药物交易

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