排名前五的靶点	数量

DLL3(δ样蛋白-3)	1
TRPV6(瞬态电压感受器阳离子通道亚族V成员6)	1
MSLN(间皮素)	1
SSTR(生长抑素受体)	1
GRPR(胃泌素释放肽前体受体)	1

关联

项与 Orano Med LLC 相关的药物

212Pb-AR-RMX

靶点

SSTR

作用机制

SSTR调节剂 [+1]

在研机构

Orano Med LLC [+1]

原研机构

Orano Med SAS

在研适应症

生长抑素受体阳性神经内分泌肿瘤

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期-

212Pb-DOTAM-GRPR1

靶点

GRPR

作用机制

GRPR拮抗剂 [+1]

在研机构

Orano Med LLC

原研机构

Orano Med LLC

在研适应症

乳腺癌 [+5]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期-

Pb-BCY20603

靶点

MMP14

作用机制

MMP14抑制剂

在研机构

Orano Med LLC [+1]

原研机构

Bicycle Therapeutics Plc [+1]

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

项与 Orano Med LLC 相关的临床试验

NCT05283330

/ Recruiting临床1期

A Phase 1 Open-Label Dose Escalation and Expansion Study to Determine the Safety, Tolerability, Dosimetry, and Preliminary Efficacy of ²¹²Pb-DOTAM-GRPR1 in Adult Subjects With Recurrent or Metastatic GRPR-expressing Tumors

A Phase 1 SAD/MAD dose escalation and expansion study to determine the safety and effectiveness of ²¹²Pb-DOTAM-GRPR1 in subjects with various GRPR-expressing Tumors

开始日期2022-12-22

申办/合作机构

Orano Med LLC

NCT05153772

/ Active, not recruiting临床2期

A Phase 2 Open Label Study to Evaluate the Safety and Effectiveness of 212Pb-DOTAMTATE in Subjects With Somatostatin Receptor Expressing Neuroendocrine Tumors

Multicenter Phase 2 study of 212Pb-DOTAMTATE enrolling adult subjects with positive somatostatin positive neuroendocrine tumors with either no prior history of peptide receptor radionuclide therapy (PRRT naive) or prior history of peptide receptor radionuclide therapy (Previous PRRT)

开始日期2021-12-21

申办/合作机构

RadioMedix, Inc.

[+1]

NCT03466216

/ Unknown status临床1期

A Phase 1, Non-Randomized, Open-Label, Dose Escalation, Single-Center Study to Determine the Safety, Bio-distribution, and Preliminary Effectiveness of AlphaMedix™ in Adult Subjects With SSRT(+) NETs.

AlphaMedix™ (²¹²Pb-DOTAMTATE) is a radiotherapeutic drug indicated in subjects with unresectable, metastatic somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs). Because 212Pb is an in vivo generator of alpha particles, it is particularly suitable for SSTR therapy applications.
This drug addresses an unmet need in the field of peptide receptor radionuclide therapy (PRRT) for NETs. Substitution of an alpha emitter (²¹²Pb) for the beta emitters currently being used (i.e., 177Lu or 90Y) will provide significantly higher Linear Energy Transfer (LET) and a shorter path length. Higher LET particles should cause more tumor cell death. Shorter path length should result in less collateral damage of the normal tissue and therefore less side effects for subjects receiving the drug.

开始日期2018-02-05

申办/合作机构

RadioMedix, Inc.

[+1]

100 项与 Orano Med LLC 相关的临床结果

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0 项与 Orano Med LLC 相关的专利（医药）

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项与 Orano Med LLC 相关的文献（医药）

2025-04-21·Cancer Research

Abstract 339: Development of 212Pb-based Radio-DARPin therapy (RDT) for the treatment of mesothelin (MSLN)-positive solid tumors

作者: Villemagne, Denis ; Croset, Amelie ; Fernandez, Henri ; Schatzmann, Aaron ; Müller, Mischa ; Riesenberg, Stefanie ; Steiner, Daniel ; Goubier, Anne ; Iss, Chloe ; Wong, Amy ; Herzog, Christel ; Lekishvili, Tamara ; Pina, Nicole ; Walter, Justin ; Stallons, Tania ; Domke, Clara ; Blunschi, Jacqueline ; Paladino, Maria ; Saidi, Amal ; Buffet, Delphine ; Torgue, Julien ; Rojas, Federico ; Wullschleger, Stephan ; Abduli, Liridon ; Kaufmann, Yvonne ; Tselempi, Eleni

Radioligand therapies have emerged as promising treatment modality for certain cancers. This therapeutic approach relies on a suitable tumor-targeting moiety labelled with a radioactive payload to allow the delivery of the radionuclide to cancer cells with high specificity. Due to its expression profile in tumor vs healthy tissues, MSLN is an attractive protein for targeted therapies. MSLN is a GPI-anchored membrane protein which is overexpressed in many tumor types, including ovarian cancer and pancreatic adenocarcinoma. Therapeutic approaches targeting MSLN have encountered obstacles due to the high levels of its proteolytically cleaved soluble form (sMSLN), which can sequester anti-MSLN therapeutics and potentially diminish their efficacy. To circumvent this caveat, we sought to generate a Designed Ankyrin Repeat Protein (DARPin) that binds to a membrane proximal epitope of MSLN and therefore avoids binding to sMSLN. Thanks to their small size and high affinity, DARPins are ideal vectors for targeted radiotherapies, dubbed as Radio-DARPin therapies (RDT). As radioactive payload we used 212Pb, an alpha particle-emitting radionuclide with a short half-life and a favorable decay profile which allows high energy deposition on tumor in a short time frame. Herein we report for the first time the development and initial preclinical characterization of our anti-MSLN 212Pb-RDT approach. In vitro assays revealed that the membrane proximal MSLN targeting DARPin specifically interacts with MSLN expressed on cancer cells with high affinity, and cell binding was not affected by the presence of sMSLN. The DARPin was then labelled with 212Pb and its preclinical pharmacokinetic and biodistribution profile was evaluated in MSLN-expressing xenograft tumor models. In these tumor bearing mice, the anti-MSLN 212Pb Radio-DARPin demonstrated substantial uptake into MSLN-positive tumors, while other organs only showed limited accumulation. We designed an approach to specifically target MSLN expressed on cancer cells employing DARPin technology combined with 212Pb. Our early preclinical results indicative of a favorable biodistribution profile of the 212Pb labelled MSLN DARPin motivate further development of this RDT for the treatment of patients with MSLN-positive solid tumors.Citation Format:Stephan Wullschleger,Amal Saidi,Delphine Buffet,Tania Stallons,Stefanie Riesenberg,Amy Wong,Maria Paladino,Federico Rojas,Mischa Müller,Christel Herzog,Justin Walter,Denis Villemagne,Yvonne Kaufmann,Nicole Pina,Henri Fernandez,Tamara Lekishvili,Eleni Tselempi,Jacqueline Blunschi,Liridon Abduli, Chloe Iss,Amelie Croset,Clara Domke,Aaron Schatzmann,Anne Goubier,Julien Torgue,Daniel Steiner. Development of 212Pb-based Radio-DARPin therapy (RDT) for the treatment of mesothelin (MSLN)-positive solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 339.

2025-04-21·Cancer Research

Abstract 346: MP0712, the first anti-DLL3 212Pb radio-DARPin (RDT) candidate for targeted radiotherapy of small cell lung cancer (SCLC)

作者: Kaufmann, Yvonne ; Abduli, Liridon ; Wullschleger, Stephan ; Steiner, Daniel ; Lekishvili, Tamar ; Wong, Amy ; Blunschi, Jacqueline ; Pina, Nicole ; Torgue, Julien ; Rantanen, Jitka ; Goubier, Anne ; Tselempi, Eleni ; Mettier, Madlaina ; Malvezzi, Francesca ; Stallons, Tania ; Lizak, Christian ; Schatzmann, Aaron ; Saidi, Amal ; Reichen, Christian ; Croset, Amelie ; Rojas, Federico ; Riesenberg, Stefanie

AbstractRadioligand therapy has shown strong clinical potential for the treatment of certain neuroendocrine and prostate tumors. Nevertheless, effective strategies in various cancer types are currently restricted by the lack of appropriate targeting agents for suitable tumor-associated antigens. Not expressed in healthy tissue, DLL3 is one of these promising targets highly upregulated in SCLC and other high-grade neuroendocrine tumors. Herein we present preclinical results of our DLL3-targeting 212Pb-based Radio-DARPin Therapeutic (RDT) combining the advantages of a small protein-based delivery vector and the short-lived alpha particle-emitting radioisotope 212Pb. Designed Ankyrin Repeat Proteins (DARPins) are a class of binding proteins with high specificity and affinity that can be generated against a broad range of tumor targets. Leveraging the learnings from our DARPin platform optimization allowed us to achieve efficient tumor uptake and penetration, while limiting exposure of healthy tissues. Our Radio-DARPin platform was optimized to effectively reduce DARPin uptake to kidneys, a major drawback of all small-size polypeptide vectors. This can be addressed by engineering the DARPin scaffold surface in conjunction with half-life extension (HLE) through serum albumin binding. 212Pb is a radioisotope with a short half-life of 11h and a favorable decay chain, allowing high energy deposition on tumor in a short time frame. By combining 212Pb with a HLE anti-DLL3 DARPin candidate, we aimed to generate a targeted RDT with high efficacy and a favorable safety profile. After several screening rounds of anti-DLL3-binding DARPins combined with HLE in mice, MP0712 was selected as lead candidate for further development. This molecule showed specific binding to lung cancer cells in vitro (∼2nM on NCI-H82 ± HSA) and high affinity to human DLL3 (0.2nM by Surface Plasmon Resonance). MP0712 biodistributions were assessed in different mouse xenograft tumor models, matching clinically relevant DLL3 expression levels or overexpression of DLL3, and reached tumor:kidney ratios >2. Double xenografted mouse models showed selective uptake in DLL3-expressing tumors compared with tumors not expressing DLL3, confirming high target specificity of MP0712. The anti-tumor activity of MP0712 in different mouse xenograft tumor models showed promising efficacy. MP0712 led to tumor stabilization and significant effects on tumor versus necrotic tissue. In NCI-H82 tumors, median survival duration increased up to 3-fold with MP0317 compared with the buffer control. MP0712 also showed a favorable safety profile in vivo up to 30µCi. These preclinical results support our 212Pb-based RDT against DLL3 as a promising treatment option for SCLC, with encouraging in vivo antitumor activity and a good safety profile for our first DLL3-targeting 212Pb-RDT candidate for further development into the clinic.Citation Format:Amelie Croset, Amal Saidi, Francesca Malvezzi, Tania Stallons, Madlaina Mettier, Amy Wong, Jitka Rantanen, Federico Rojas, Stephan Wullschleger, Eleni Tselempi, Yvonne Kaufmann, Tamar Lekishvili, Stefanie Riesenberg, Nicole Pina, Jacqueline Blunschi, Liridon Abduli, Christian Reichen, Christian Lizak, Aaron Schatzmann, Anne Goubier, Julien Torgue, Daniel Steiner. MP0712, the first anti-DLL3 212Pb radio-DARPin (RDT) candidate for targeted radiotherapy of small cell lung cancer (SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 346.

2025-03-01·Journal of Nuclear Medicine

Side-by-Side Comparison of the In Vivo Performance of [²¹²Pb]Pb-DOTAMTATE and Other SSTR2-Targeting Compounds

Article

作者: Wong, Amy G ; Torgue, Julien J ; Soysal, Ugur ; Schatzmann, Aaron T ; Stallons, Tania A ; Saidi, Amal

There are numerous versions of octreotide and octreotate, including DOTAMTATE, DOTATATE, JR11, and lead-specific chelator (PSC)-PEG2-TOC. These peptides, which can be either analogs or antagonists, are used in nuclear medicine for diagnostic imaging or targeted radionuclide therapy of neuroendocrine tumors that are positive for somatostatin receptors (SSTRs). Despite their structural and targeting similarities, they have distinct properties and clinical uses. We aimed to perform an extensive preclinical comparison of all these somatostatin analogs with ²¹²Pb, directly studying their pharmacokinetic properties in tumors overexpressing SSTR2. Methods: All SSTR2 analogs were manufactured with the DOTAM, PSC, or DOTA chelators for appropriate comparison after radiolabeling with ²¹²Pb. Chelation, quantification, and pharmacokinetics were compared side by side in AR42J-tumor-bearing animals. Results: These findings highlight the superior chelation efficiency and faster kinetics of DOTAM and then DOTA compared with the PSC. We also discovered a superior tumor-to-kidney area under the curve ratio for [²¹²Pb]Pb-DOTAMTATE over other SSTR2-targeting peptides when radiolabeled with ²¹²Pb. Conclusion: Taken together, the results indicates that [²¹²Pb]Pb-DOTAMTATE has favorable tumor retention and a more favorable dosimetry profile, which is crucial for targeted α-therapy in treating SSTR2-positive neuroendocrine tumors.

项与 Orano Med LLC 相关的新闻（医药）

2024-10-21

·药明康德

3.2亿欧元合作后再加3亿欧元，赛诺菲加码突破性疗法开发

赛诺菲（Sanofi）宣布与Orano Med公司签署协议，携手抗击罕见癌症，并加速下一代放射性配体药物的开发。根据协议，赛诺菲将向Orano Med进行3亿欧元的股权投资。基于Orano Med的专业知识及其放射性配体药物研发管线，赛诺菲与Orano Med将共同专注于基于铅-212同位素的α粒子放射性配体疗法的发现、设计和临床开发。该协议是继赛诺菲宣布与Orano Med和RadioMedix达成数额高达3.2亿欧元的独家许可协议之后的又一进展。今年9月达成的合作主要聚焦于后期临床项目AlphaMedix，该项目目前正在2期临床试验中接受评估，用于治疗无法切除或转移性、进展性表达生长抑素受体的神经内分泌肿瘤（NET）成年患者。 AlphaMedix是一种基于α粒子的靶向疗法，由用铅-212放射性同位素标记的生长抑素受体靶向肽复合物组成，可在患者体内产生α粒子攻击肿瘤。美国FDA已经授予AlphaMedix突破性疗法认定（BTD），用以治疗未接受过肽受体放射性疗法的胃肠胰神经内分泌肿瘤（GEP-NET）患者。AlphaMedix之外，Orano Med的研发管线中还包括治疗前列腺癌、乳腺癌、小细胞肺癌以及其它实体瘤的放射性配体疗法。靶向α粒子治疗基于一个简单的概念：将生物制品靶向癌细胞的能力与α粒子的短程且高能量细胞杀伤能力相结合，将放射性同位素引导至表达特定靶点的癌细胞，即使这些细胞已扩散至全身。这一独特的作用机制旨在破坏或摧毁癌细胞，同时将对周围健康细胞的影响降至最低。参考资料： [1] Sanofi and Orano join forces to develop next-generation radioligand medicines. Retrieved October 17, 2024, from https://ml-eu.globenewswire.com/Resource/Download/97afe504-1735-4fd8-8593-89645b944aba 内容来源于网络，如有侵权，请联系删除。

突破性疗法放射疗法

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药物(靶点)	适应症	全球最高研发状态

212Pb-AR-RMX ( SSTR )	生长抑素受体阳性神经内分泌肿瘤更多	临床2期
212Pb-DOTAM-GRPR1 ( GRPR )	非小细胞肺癌更多	临床1期
Pb-BCY20603 ( MMP14 )	肿瘤更多	临床前
212 Pb-trastuzumab ( HER2 )	晚期前列腺癌更多	临床前
DLL3(Molecular Partners) ( DLL3 )	实体瘤更多	临床前