A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients With Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors

This study aims to determine the safety and the recommended phase II dose of RYZ101 (actinium-225 labelled DOTA-octreotate (225Ac-DOTATATE)) in participants with refractory and relapsing multiple myeloma (MM) that have received at least 3 prior lines of myeloma therapy. Participants will be selected based on somatostatin receptor (SSTR) positivity assessed by gallium-68 labelled DOTA-octreotate (68Ga-DOTATATE) PET/CT. The response to 225Ac-DOTATATE therapy will also be assessed in the target study population.

开始日期2024-10-01

申办/合作机构

Jules Bordet Institute

[+1]

NCT06590857 / Recruiting临床1/2期

Phase 1b/2 Open-label Trial of 225Ac-DOTATATE (RYZ101) Alone and in Combination with Pembrolizumab in Subjects with Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)-negative, Locally Advanced and Unresectable or Metastatic Breast Cancer Expressing Somatostatin Receptors (SSTRs) and Progressed After Antibody-drug Conjugates And/or Chemotherapy (TRACY-1)

Phase 1b/2 open-label trial of 225Ac-DOTATATE (RYZ101) alone and with pembrolizumab in subjects with ER+, HER2-negative unresectable or metastatic breast cancer expressing SSTRs.

开始日期2024-07-19

申办/合作机构

Rayzebio, Inc.初创企业

NCT05595460 / Recruiting临床1期

Phase 1b Single Arm, Open-label Trial of RYZ101 in Combination With Carboplatin + Etoposide + Atezolizumab in Subjects With Somatostatin Receptor Expressing (SSTR+) Extensive Stage Small Cell Lung Cancer (ES-SCLC)

This study aims to determine the safety, preliminary antitumor activity, and pharmacokinetics (PK) of RYZ101 in combination with standard of care (SoC) therapy consisting of carboplatin + etoposide + atezolizumab in untreated subjects with somatostatin receptor expressing (SSTR+) ES-SCLC.

开始日期2022-10-10

申办/合作机构

Rayzebio, Inc.初创企业

100 项与 RYZ-101 相关的临床结果

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100 项与 RYZ-101 相关的转化医学

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100 项与 RYZ-101 相关的专利（医药）

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项与 RYZ-101 相关的文献（医药）

2024-07-01·RADIOLOGY

Dotatate PET/CT and ²²⁵Ac-Dotatate Therapy for Somatostatin Receptor–expressing Metastatic Breast Cancer

Article

作者: Atzen, Sarah ; VanderMolen, Louis A. ; Ulaner, Gary A. ; Ferreira, Denis ; Li, Gary

Background Somatostatin receptors, and specifically somatostatin receptor type 2 (SSTR2), have primarily been associated with neuroendocrine tumors and have revolutionized the imaging and therapy of patients with these tumors. SSTR2 is expressed on other tumors at lower prevalence. Purpose To evaluate the potential of SSTR2-targeted imaging and therapy in patients with breast cancer. Materials and Methods In a preclinical experiment, SSTR2 expression was assessed in tissue microarrays of breast cancer samples using H-score analysis. H-scores higher than 50 (0-300 scale) were considered positive. Then, a prospective phase 2 clinical trial of SSTR2-targeted tetraazacyclododecane tetraacetic acid octreotate (Dotatate) PET/CT was performed in participants with biopsy-proven estrogen receptor (ER)-positive breast cancer from January to August 2023. A positive Dotatate PET/CT scan was defined as tumors with a Krenning score of 3 (avidity greater than liver) or 4 (avidity greater than spleen). The proportion of positive scans and the 95% CI were calculated. One participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET/CT result underwent treatment with SSTR2-targeted actinium 225 (²²⁵Ac) Dotatate. Results Preclinical microarrays demonstrated that 63 of 123 ER-positive breast cancer tissue samples (51% [95% CI: 42, 60]) but only 22 of 121 ER-negative breast cancer tissue samples (18% [95% CI: 12, 26]) were enriched for SSTR2 (P < .001). Thirty female participants (mean age, 66 years ± 15) with metastatic ER-positive breast cancer were accrued to the phase 2 SSTR2-targeted imaging trial and underwent Dotatate PET/CT. Dotatate PET/CT demonstrated that nine of 30 participants (30% [95% CI: 15, 49]) had tumors with Krenning scores of 3 or 4, indicating strong SSTR2 expression. SSTR2-targeted therapy with alpha-emitting ²²⁵Ac-Dotatate resulted in a near complete response in a heavily pretreated participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET result. Conclusion Molecular imaging targeting SSTR2 and radioligand therapy with SSTR2-targeted ²²⁵Ac-Dotatate enables a new therapeutic option for patients with metastatic breast cancer. Clinical trial registration no. NCT05880394 © RSNA, 2024 See also the editorial by Lin and Choyke in this issue.

2024-06-01·Clinical nuclear medicine

Efficacy and Safety of 225Ac-DOTATATE in the Treatment of Neuroendocrine Neoplasms With High SSTR Expression

Article

作者: Yang, Hongyu ; Li, Hongmei ; Yang, Xiqun ; Chen, Yue ; Zhang, Yu ; Feng, Yue

Purpose:

We aimed to evaluate the efficacy and safety of 225Ac-DOTATATE targeted α therapy (TAT) in various neuroendocrine neoplasms (NENs) with high somatostatin receptor (SSTR) expression.

Patients and Methods:

This single-center prospective study included 10 patients with histologically diagnosed NENs that exhibited increased SSTR expression on 68Ga-DOTATATE PET/CT imaging. All patients received 225Ac-DOTATATE TAT. The primary end points were molecular imaging–based response and disease control rate (DCR), measured using the slightly modified Positron Emission Tomography Response Criteria in Solid Tumors 1.0. The secondary end points were adverse event profiles and clinical responses. The adverse event profile was determined according to the Common Terminology Criteria for Adverse Events version 5.0. Clinical response was assessed using the EORTC QLQ-C30 v3.0 (European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire version 3.0).

Results:

A molecular imaging–based partial response was observed in 40% of all patients, SD in 40%, PD in 20%, and DCR in 80%. The DCR was 83.3% (5/6) in patients who were previously treated with 177Lu-DOTATATE. According to the EORTC QLQ-C30 v3.0 score, most symptoms improved after 225Ac-DOTATATE treatment, with only diarrhea showing no improvement. Grade III/IV hematological, kidney, and liver toxicities were not observed. The median follow-up time was 14 months (7–22 months), and no deaths were reported.

Conclusions:

This initial study suggests that 225Ac-DOTATATE is a potentially promising option for treating NENs with elevated SSTR expression, with an acceptable toxicity profile and well-tolerated adverse effects.

2024-05-01·European journal of hospital pharmacy : science and practice

¹⁷⁷Lu-Dotatate administration using an infusion pump or a peristaltic pump: comparison of two methods

Article

作者: Deshayes, Emmanuel ; Fersing, Cyril ; Rubira, Léa ; Donzé, Charlotte ; Santoro, Lore ; Kotzki, Pierre Olivier ; Viarasakd, Malissone

OBJECTIVES:

¹⁷⁷Lu-oxodotreotide (Lutathera) is an intravenous peptide receptor radionuclide therapy to treat unresectable metastatic digestive neuroendocrine tumours. The recommended method for Lutathera administration is gravity infusion; however, other appropriate and safe techniques are possible. This work compares two infusion methods from a medico-economic, radiation protection, efficiency and practicality point of view.

METHODS:

Two infusion methods were studied, either involving a volumetric infusion pump (method 1) or a peristaltic pump (method 2). For each method, the mean residual activity per vial and the mean injection time were compared. Occupational radiation exposure was measured. The cost of initial equipment and consumables for one administration was determined. Feedback from operators and past incidents during injections were collected through a survey.

RESULTS:

Three operators performed 219 Lutathera injections over 70 months: 60.7% (133) with method 1 and 39.3% (86) with method 2. After infusion, the mean residual activity in vial was 124.3±16.9 MBq with method 1 and 80.9±19.3 MBq with method 2 (34.9% decrease). The average administration time was 41±7.2 min with method 1 and 39±8.5 min with method 2. Occupational exposures obtained with both methods were very low and quite similar. Method 1 required an initial investment of 1165.8 US$ plus 4.0 US$ of supplies for each administration. Initial investment for method 2 was comparable (1261.4 US$) but supplies cost per administration was higher (12.5 US$). Two major incidents were recorded with method 1 and none with method 2. From operators' experience, method 2 felt safer and more suitable.

CONCLUSIONS:

Method 2 appeared to be convenient and secure, despite a higher cost per injection. It could also be applied to new radioligand therapies such as ¹⁷⁷Lu-PSMA or ²²⁵Ac-Dotatate.

115

项与 RYZ-101 相关的新闻（医药）

2024-11-06

·同写意

巨头重注核药赛道

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。随着诺华三季报的披露，Pluvicto在今年前三季度中取得10.41亿美元的营收，成为全球首款销售额突破10亿美元的核药产品。Pluvicto的火爆，也让核药成为各大MNC的重点布局方向。虽然核药已经拥有近百年历史，但却始终不温不火，直到RDC药物的出现，让才其重新成为肿瘤治疗领域的重要方向。与ADC原理类似，RDC也是将精准靶向分子和强力杀伤因子用连接臂偶联在一起而设计开发的一种药物形态。图：RDC结构示意图，来源：招商证券与其他小分子靶向药物或ADC药物相比，RDC药物的放射性核素不需要与细胞直接接触，Linker在起效过程中不需要断裂，提高了RDC药物在体内的稳定性和安全性。同时，由于核素通过辐射方式杀伤癌细胞，在辐射半径内，肿瘤细胞即使没有相应抗原，也能通过交叉火力效应杀伤更多肿瘤细胞，从而具有更好的抗耐药性。 RDC药物的优势以及核药在医学诊断、治疗中独特的作用让全球核药市场迅速升温。根据Precedence Research预测，2023年全球核医学市场规模为106.5亿美元，预计到2033年将超过314.4亿美元。尤其是Pluvicto销售额的持续爆发，更是验证了核药的成功路径。时代大势面前，各大MNC均在核药赛道频频加码，诺华、礼来、阿斯利康、BMS、赛诺菲频频通过投资、并购增加自身在核药领域的筹码。一场关于MNC的“核”竞赛早已悄然开启。 1 诺华：当之无愧的龙头坐拥Pluvicto这个重磅核药产品，诺华无愧是当今世界最大的核药赢家。诺华对于核药的布局，最早要追溯到2017年。诺华斥资60亿美元先后收购了法国创新药公司AAA（Advanced Accelerator Applications）和美国生物制药公司Endocyte，并以此为基础，将核素药物作为其四大技术平台之一。可以说，诺华是最早将核药技术上升到公司核心战略的MNC巨头。 2018年，诺华从AAA公司获得的首款RDC药物Lutathera得到FDA批准上市，用于治疗SSTR阳性的胃肠胰神经内分泌肿瘤患者，成为首款FDA批准的放射性配体疗法，开启了RDC靶向治疗的新时代。尽管获批的仅是市场很小的罕见病适应症，但Lutathera上市依然取得了不俗的销售成绩，上市第一年就取得了1.67亿美元的销售额，第二年营收额就增至4.41亿美元。不过，受疫情及适应症影响，Lutathera的营收在2020年-2022年陷入停滞，2023年才重新恢复增长。今年前9个月，Lutathera收获了5.34亿美元营收。图：Lutathera营收一览，来源：锦缎研究院 Lutathera仅算是诺华在核药领域的小试牛刀，2022年3月获批上市的Pluvicto才是真正的重磅产品。Pluvicto被FDA批准用于治疗去势抵抗性转移前列腺癌患者（mCRPC）。与Lutathera不同，Pluvicto针对的前列腺癌是男性第二大癌种。2023年，美国新发病人数约28.83万人，存量患者高达334万人，市场空间巨大。果然在上市后，Pluvicto不负众望的取得营收高增长。在产能受限的情况下，首年销售额就达到了2.71亿美元，2023年继续放量，全年销售额9.8亿美元，增长261%。今年前9个月，Pluvicto的营收就已经突破10亿美元大关，毫无疑问是最成功的核药产品。 Pluvicto和Lutathera的成功商业化，让诺华继续加大在核药领域的布局。通过一系列的投资及授权合作，诺华获得了大量早期研发管线，并从中选择有潜力的管线进行临床研发。目前，诺华已经有8个核药管线，包括2个上市产品和6个处于临床1期的管线。图：诺华RLT管线，来源：公司官网在核药逐渐火热的2024年，诺华也没有停止扩张的步伐。4月底，诺华与PeptiDream签署了总价值约29亿美元的合作协议，共同开发多款大环肽靶向偶联核药；5月初，又以10亿美元预付款以及7.5亿美元的潜在里程碑付款收购Mariana Oncology，以加强放射性配体疗法的布局。内部不断拓展已上市产品适应症，外部持续高效BD的战略下，诺华将核药领域变成自己的主场，希望以绝对领先的地位长期领跑该赛道。 2 拜耳：核药领域先行者拜耳在核药领域的布局虽然不及诺华，但也是较早布局核药赛道的MNC之一。早在2009年，拜耳就与Algeta联合开发Xofigo（氯化镭223），并于2013年获批上市，用于治疗晚期骨转移型去势抵抗性前列腺癌。拜耳也顺势以29亿美元的重金买下了Algeta，拿下了Xofigo的所有权益。自2013年上市后，Xofigo销售额便稳步上升，2017年达到4.71亿美元。但Xofigo仍属于传统放射性治疗药物，市场空间有限，2017年-2020年销售额分别为4.08亿欧元、3.51亿欧元、3.03亿欧元和2.62亿欧元，逐年下滑。尽管Xofigo并没有成为一款大药，但拜耳并未停止核药领域的布局，只不过与诺华全面重注核药赛道不同，拜耳更专注于开发靶向α粒子的疗法。与177Lu等发射的β粒子相比，α粒子在组织中生效的距离更短，但是在有效距离内对细胞的杀伤效果更强。 2021年的时候，拜耳大手笔收购Noria Therapeutics和PSMA Therapeutics，获得了一款靶向PSMA的小分子α粒子疗法的开发权益，这是一种基于锕-225的放射性核素疗法，此次收购扩展了拜耳的靶向α疗法（TAT）的肿瘤学产品组合。 2023年5月，拜耳又以4500万美元的预付款以及潜在高达17亿美元的里程碑付款，与Bicycle Therapeutics达成一项战略合作协议，双方将利用Bicycle的合成肽技术，在肿瘤学领域合作开发、制造和商业化RDC。目前拜耳共有7个处于临床前阶段和2个处于早期临床阶段（BAY 3546828、BAY 3563254）的RDC在研。图：拜耳核药领域布局，来源：公司官网 3 礼来：加速布局核药在减肥药和阿尔兹海默症均取得突破的礼来，亦在最近两年连续重金投入核药赛道。礼来关注核药赛道很早，早在2006年和2009年，就参与了分子成像公司Avid Radiopharmaceuticals的B轮和D轮融资，并在2010年以8亿美元收购了该公司。但此后礼来在核药领域就没有什么大的动作了。直到2023年，礼来开始加码核药赛道。先是在9月参与了Mariana Oncology 1.75亿美元的B轮融资（这家放射性药物研发公司在今年5月被诺华以10亿美元收购）；10月，礼来宣布将以14亿美元收购核药生物技术公司Point Biopharma，标志着礼来正式进军核药领域。 Point是一家放射性疗法制药公司，拥有一系列正在开发的临床和临床前阶段放射性配体疗法，用于治疗癌症。核心资产包括已处于临床III期的一款针对转移性去势抵抗性前列腺癌 (mCRPC) 的靶向PSMA的疗法PNT2002，以及下一代放射性配体疗法技术平台和相应的核药供应链。图：Point管线布局，来源：新浪医药通过这笔交易，礼来获得了核药研发、生产、制造和商业化的全产业链条，甚至可直接与诺华展开竞争。今年礼来在核药领域再度加码。先是5月与Aktis Oncology达成合作协议，以6000万美元的预付款，以及高达11亿美元的额外里程碑付款和销售特许权使用费，获得在全球范围内开发由Aktis发现的、针对礼来选定的一系列明确靶标的放射性药物和诊断产品的权利。而后又在6月与Radionetics Oncology达成战略合作，共同推进靶向GPCR的新型小分子放射性药物的研发，用于治疗广泛的实体瘤。同时，礼来向其注入1.4亿美元的前期资金，并获得了收购Radionetics的排他权，潜在收购款为10亿美元。礼来在核药领域的一系列举措，意味着其正在积极扩大其在核药领域的研发管线，未来或将在该领域有更大举动。 4 阿斯利康：24亿美元收购阿斯利康得以进入核药赛道，完全源于小规模一次投资。 2020年11月，阿斯利康与Fusion Pharmaceuticals达成合作，开发和商业化下一代α发射放射性药物和治疗癌症联合疗法。虽然这笔交易只有500万美元的首付款和4000万美元的里程碑付款，但此次交易为阿斯利康进入放射性药物领域提供了一个切入点。今年3月，阿斯利康就宣布耗资24亿美元收购了Fusion，并获得其4款在研放射性药物，包括FPI-2265、FPI-1434、FPI-2068和FPI-2059。其中FPI-2265是一款针对前列腺特异性膜抗原（PSMA）的靶向药物，用于治疗转移性去势抵抗性前列腺癌（mCRPC），II期临床试验结果表明，FPI-2265 对既往接受过大量治疗的进展性 mCRPC 患者有疗效，包括既往接受过基于177Lu放射配体疗法的患者。 5月7日，阿斯利康FPI-2265启动了一项II/III期临床研究，旨在评估 FPI-2265 在既往接受过 177Lu-PSMA-617或其它177Lu-PSMA放射性疗法治疗的PSMA阳性转移性去势抵抗性前列腺癌（mCRPC）患者中的安全性和有效性。此外，在买下Fusion三个月后，6月，阿斯利康再次投资核药CDMO公司Nucleus RadioPharma，开始布局核药产能。阿斯利康在核药领域布局虽然才刚刚开始，但一出手就是24美元的大手笔，毫不掩饰其在核药赛道的野心。 5 赛诺菲、BMS、罗氏除上述跨国药企外，布局核药的MNC队伍仍在不断扩大。今年9月，赛诺菲宣布，与RadioMedix和Orano Med达成总额超3.2亿欧元的独家许可协议，将共同开发基于同位素铅（lead）的放射性配体疗法（RLT）用于癌症治疗，首次进军核药领域。紧接着10月，赛诺菲又发布公告称，将与Orano Med共同投资一家新实体，专注于基于铅-212（²¹²Pb）α发射同位素的下一代放射性配体疗法（RLT）的发现、设计和临床开发，赛诺菲将进行3亿欧元的股权投资，占新实体约16%的股权。另一方面，BMS在2023年12月宣布以41亿美金收购成立仅三年多的核药公司RayzeBio。RayzeBio是一家处于临床阶段的放射性药物疗法（RPT）公司，在锕系元素放射性药物治疗领域处于领先地位，拥有多个潜在的“First-in-Class”和“Best-in-Class”药物开发项目。通过此次收购，BMS获得了一项胃肠胰神经内分泌肿瘤（GEP-NET）和广泛期小细胞肺癌（ES-SCLC）的临床RPT项目、多项临床前资产以及位于印第安纳州的GMP生产设施以及基于α核素的差异化放射性药物技术平台和多款在研创新产品，包括RYZ101、RYZ801等创新靶向核药。罗氏在核药的布局并不多，2023年9月，罗氏旗下的基因泰克（Genentech）与PeptiDream达成合作协议，共同发现和开发新型大环肽-放射性同位素偶联药物。为此，基因泰克付出了4000万美元预付款以及未来可能高达10亿美元的里程碑付款。这笔交易为罗氏切入核药赛道提供了很好的机会。概括而论，Pluvicto的爆发让MNC看到了核药赛道的机遇。相信随着越来越多MNC的入局，这个赛道必将在未来成为医药主流赛道之一。2024年，即是核药的爆发“元年”。同写意媒体矩阵，欢迎关注↓↓↓

抗体药物偶联物并购

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

2024-10-22

·PipelineReview

Ariceum Therapeutics Presents Outstanding Data on its First-in-Class Radiopharmaceutical Drug 225Ac-Satoreotide at the European Association of Nuclear Medicine 2024

BERLIN, Germany I October 22, 2024 I Ariceum Therapeutics (Ariceum), a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, today announces that it presented data on its proprietary radiolabelled peptide SS0110 (satoreotide), a first-in-class antagonist of the somatostatin receptor 2 (SSTR2), at this year’s European Association of Nuclear Medicine (EANM) Annual Conference , held in Hamburg, Germany from 19-23 October 2024. The Top-Rated Oral Presentation (TROP) entitled ‘ 225 Ac-SSO110 induces long-lasting anti-tumour responses in contrast to 225 Ac-DOTA-TATE and 161 Tb-DOTA-TATE in the treatment of SSTR2-positive tumour xenografts’ , details the anti-tumour efficacy of different radiolabelled satoreotide antagonists ( 225 Ac, 161 Tb, 177 Lu-labelled SSO110) versus respective DOTA-TATE agonists ( 225 Ac- and 161 Tb-labelled DOTA-TATE) in mice engrafted with SSTR2 positive xenografts of small cell lung cancer (SCLC) and pancreatic cancer using clinically relevant associated dose ranges. Results demonstrate that 225 Ac-satoreotide shows the strongest anti-tumoural effect in vivo at a low single dose when evaluating satoreotide and DOTA-TATE radiolabelled with different radionuclides. Irrespective of the radionuclides used, satoreotide demonstrated a higher pre-clinical anti-tumour efficacy when compared to DOTA-TATE which was less potent and required increased dose levels. Satoreotide was well tolerated across all dose levels and with all used radionuclides. These comparisons between satoreotide and DOTA-TATE will facilitate and guide further clinical development of satoreotide across multiple indications expressing SSTR2, such as SCLC, pancreatic cancers and Merkel Cell Carcinoma (MCC). Previous comparisons between satoreotide and DOTA-TATE demonstrated that antagonist, 225 Ac-satoreotide, is multiple times more potent than SSTR2 agonist, 225 Ac-DOTA-TATE, signifying a durable complete response in standard murine xenograft models of SCLC in animal models, versus tumour growth delay. Ariceum had previously shown at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting 2024 that 212 Pb was not seen to be more potent than Lutetium or Terbium but caused more side effects and hence was not further pursued. Manfred Rüdiger, Chief Executive Officer at Ariceum Therapeutics, said: “These results provide strong evidence for satoreotide and its potential to clinically outperform SSTR2 targeting agonists, by demonstrating significantly better efficacy in tumour growth control, up to complete tumour eradication depending on isotope used. In addition, when a single dose of 30 kBq 225 Ac-satoreotide was administered, we observed high frequency of complete durable responses and 100% survival which strongly supports further clinical development for the treatment of SCLC, MCC and other cancers.” Details of the oral presentation are as follow: Title: 225 Ac-SSO110 induces long-lasting anti-tumour responses in contrast to 225 Ac-DOTA-TATE and 161Tb-DOTA-TATE in the treatment of SSTR2-positive tumour xenografts Presenting Author: Prachi Desai, Scientist at Ariceum Therapeutics Session Number: 1204 Session Title: M2M Track – TROP Session: Radiopharmaceutical Sciences + Translational Molecular Imaging & Therapy Committee: From Radionuclide to Clinical Translation Oral Presentation Date & Time: Tuesday 22 October 2024, 09:00 AM – 09:10 AM CEST Abstract Authors: Prachi Desai, Manuel Sturzbecher-Hoehne, Dennis Mewis, Manfred Ruediger & Anika Jaekel of Ariceum Therapeutics Session Date & Time: Tuesday 22 October 2024, 08:00 AM – 09:30 AM CEST Location: Session Hall X1-X4 Abstracts are available in the September edition of Springer’s European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI) abstract book here and on the Ariceum website here . About Ariceum Therapeutics Ariceum Therapeutics (Ariceum) is a private, clinical stage radiopharmaceutical company focused on the diagnosis and precision treatment of certain neuroendocrine and other aggressive, hard-to-treat cancers. The name Ariceum is an anagram of ‘Marie Curie’ whose discovery of radium and polonium have been huge contributions to finding treatments for cancer. Ariceum’s lead targeted systemic radiopharmaceutical product, 177 Lu-satoreotide tetraxetan (“Satoreotide”), is an antagonist of the somatostatin type 2 (SSTR2) receptor which is overexpressed in neuroendocrine tumours (NETs) and some aggressive cancers such as small cell lung cancer (SCLC), or Merkel Cell Carcinoma (MCC), all of which have few treatment options and poor prognosis. Satoreotide is being developed as a ‘theranostic’ pair for the combined diagnosis and targeted radionuclide treatment of these tumours. Ariceum is also developing a radiolabelled PARP-inhibitor (ATT001), currently in Phase 1 clinical development under the trial name CITADEL-123. ATT001 was part of the acquisition of Theragnostics Ltd which was closed in June 2023. Ariceum Therapeutics, launched in 2021, acquired all rights to Satoreotide from Ipsen. Ipsen remains a shareholder in the Company. Ariceum is headquartered in Berlin, with operations in Germany, Switzerland, Australia, United Kingdom and United States of America and with activities currently across the globe. Ariceum is led by a highly experienced management team and supported by specialist investors including EQT Life Sciences (formerly LSP), HealthCap, Pureos Bioventures, Andera Partners and Earlybird Venture Capital. For further information, please visit www.ariceum-therapeutics.com . About European Association of Nuclear Medicine (EANM) The European Association of Nuclear Medicine (EANM) is a non-profit organization that promotes nuclear medicine and aims to improve public health. The EANM’s mission is to advance nuclear medicine through personalized healthcare, innovation in diagnosis and treatment, and raising awareness of nuclear medicine SOURCE: Ariceum Therapeutics

临床1期并购寡核苷酸

100 项与 RYZ-101 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
类癌	临床3期	美国	Rayzebio, Inc.初创企业	2022-03-24
类癌	临床3期	比利时	Rayzebio, Inc.初创企业	2022-03-24
类癌	临床3期	巴西	Rayzebio, Inc.初创企业	2022-03-24
类癌	临床3期	加拿大	Rayzebio, Inc.初创企业	2022-03-24
类癌	临床3期	法国	Rayzebio, Inc.初创企业	2022-03-24
类癌	临床3期	荷兰	Rayzebio, Inc.初创企业	2022-03-24
类癌	临床3期	西班牙	Rayzebio, Inc.初创企业	2022-03-24
功能性内分泌肿瘤	临床3期	美国	Rayzebio, Inc.初创企业	2022-03-24
功能性内分泌肿瘤	临床3期	比利时	Rayzebio, Inc.初创企业	2022-03-24
功能性内分泌肿瘤	临床3期	巴西	Rayzebio, Inc.初创企业	2022-03-24

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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


NCT05595460 (WCLC2024) 人工标引	临床1期	广泛期小细胞肺癌	10	RYZ101+carboplatin + etoposide + atezolizumab	網鑰鹹餘顧醖繭鏇築繭(艱遞範鑰廠廠鬱構衊獵) = G1 decreased appetite, G2 dehydration, G1 diarrhea, G1 fatigue, G2 influenza-like illness, G2 nausea, G2 neutrophil count decrease, G1 vomiting 夢鏇選鏇夢鹹觸醖廠艱 (艱壓夢構選憲鏇觸襯醖 ) 更多	积极	2024-09-08
SNMMI2024	N/A	胃肠胰神经内分泌肿瘤	-	RYZ101 120 kBq/kg	糧廠鏇鏇遞鏇壓衊窪餘(餘鏇顧憲襯壓蓋鹹範醖) = 52.9% 顧簾顧積餘遞築憲顧鹽 (積繭選鹽夢鹹餘衊製鬱 ) 更多	-	2024-06-09
NCT05477576 (ACTION-1, ASCO2024) 人工标引	临床1期	SSTR阳性胃肠胰神经内分泌肿瘤 SSTR2	17	RYZ101	鬱獵鹹築築範觸餘鏇淵(艱憲觸遞願觸壓網艱觸) = 膚齋艱餘築觸積鏇觸鹽遞築憲繭窪壓顧淵範鏇 (觸築齋醖艱築範襯膚膚 ) 更多	积极	2024-05-24
NCT05477576 (ACTION-1, ESMO2023) 人工标引	临床1期	胃肠胰神经内分泌肿瘤 SSTR positive	17	RYZ101 120kBq/kg	衊鹹觸醖鹽壓廠蓋蓋齋(簾鹽獵蓋簾積遞糧選鑰) = 艱選衊鹹壓願壓衊衊顧簾壓糧繭築鏇網蓋觸鹹 (鑰築築齋鑰繭壓築夢醖 ) 更多	积极	2023-10-22
NCT05477576 (ACTION-1, ASCO2023) 人工标引	临床1期	SSTR2阳性胃肠胰神经内分泌肿瘤 SSTR2 Expression	9	RYZ101	構蓋壓艱遞襯憲構壓積(選觸構鏇製襯鹽夢鬱衊) = 選廠鹽壓膚範餘觸齋淵顧糧淵築網醖襯壓餘築 (衊鏇夢衊築膚鏇憲範鬱 ) 更多	积极	2023-05-31
SNMMI2022	N/A	胃肠胰神经内分泌肿瘤	-	225Ac-DOTATATE TAT	衊構餘繭餘獵蓋廠製醖(遞鹹鹹蓋獵積蓋憲膚夢) = Malignant ascites was noted in 14, resulting in 11 deaths 觸衊憲遞鹽鑰廠窪夢鏇 (遞衊選網獵鬱淵製鹽鏇 ) 更多	-	2022-08-08
SNMMI2022	N/A	胃肠胰神经内分泌肿瘤	-	177Lu-DOTATATE		-	2022-08-08
SNMMI2021	N/A	胃肠胰神经内分泌肿瘤	-	225Ac-DOTATATE	顧獵壓廠襯鹹願積夢鬱(繭鬱廠鑰簾築淵遞壓艱) = No grade 3 renal or hepatotoxicities were observed. No other unexpected longer-term adverse events were observed with 225Ac-DOTATATE therapy 觸夢簾簾網顧繭夢簾鑰 (繭鹹糧製鬱膚艱餘顧觸 ) 更多	-	2021-05-18