Iopofosine I-131

▎药明康德编者按：偶联药物通过将与靶蛋白结合的配体与功能性载荷连接，实现向特定组织或细胞精准递送载荷的效果。近年来，这一领域快速发展，据统计，2024年全球启动了284项抗体偶联药物（ADC）临床试验，比2023年增加了100多项，彰显了偶联药物领域的迅猛增长。ADC之外，放射性偶联药物（RDC）、多肽偶联药物（PDC）以及寡核苷酸偶联药物等新兴偶联模式也不断涌现。药明康德旗下WuXi TIDES搭建了为寡核苷酸、多肽及复杂化学偶联药物开发提供一体化服务的CRDMO平台，覆盖从药物发现、CMC开发及商业化生产的全生命周期，尤其借助药明康德在化学业务方面的丰富经验，为赋能新一代偶联疗法奠定了坚实基础。本文将盘点2025年上半年偶联领域的最新进展，并介绍WuXi TIDES一体化CRDMO平台赋能多肽偶联药物开发的能力。抗体偶联药物：三款新药获批上市，多项超10亿美元合作达成2025年上半年，三款创新ADC获得监管机构批准上市。阿斯利康（AstraZeneca）与第一三共（Daiichi Sankyo）联合开发的Datroway获批，用于治疗无法切除或转移性HR阳性、HER2阴性乳腺癌成人患者。这款靶向Trop2的ADC曾被行业媒体Evaluate列为潜在重磅疗法。今年5月，FDA批准艾伯维（AbbVie）靶向c-Met的抗体偶联药物Emrelis上市，用于治疗c-Met蛋白高度表达的局部晚期或转移性非鳞状非小细胞肺癌（NSCLC）成年患者。恒瑞医药的HER2靶向ADC瑞康曲妥珠单抗获得批准，单药治疗存在HER2激活突变且既往接受过至少一种系统治疗的不可切除的局部晚期或转移性NSCLC成人患者。此外，ADC领域在2025年上半年达成了多项授权许可与研发合作，多项交易数额超过10亿美元。这体现了业界对ADC治疗模式的重视及对创新ADC开发技术的持续关注。除了靶点开发、连接子及载荷方面的创新外，利用双特异性抗体开发的双特异性ADC也正在成为下一代ADC设计的重要探索方向。▲2025年上半年ADC领域部分许可和研发合作信息（数据来源：公开资料）放射性偶联药物：诺华重磅药再获FDA批准，潜在“first-in-class”药物获突破性疗法认定RDC通过将放射性同位素与靶向特定组织的配体偶联，将放射性物质精准递送到肿瘤组织，同时最大限度减少对健康组织的损害。这一领域近年来增长迅速，据统计，2024年启动的RDC临床试验超过30项，与5年前相比增长了3倍。2025年，诺华的重磅RDC疗法Pluvicto再次获得FDA批准，用于治疗PSMA阳性转移性去势抵抗性前列腺癌患者。近日公布的3期临床试验结果显示，它在治疗PSMA阳性激素敏感性前列腺癌患者时，也显示出具有临床意义和统计学显著性的放射学无进展生存期获益。此外，Cellectar Biosciences开发的潜在“first-in-class”疗法iopofosine I 131近日获得FDA授予的突破性疗法认定，用于治疗复发/难治性华氏巨球蛋白血症（WM）。该药物将磷酸酯与放射性同位素偶联，能够特异性结合癌细胞表面的特定脂质区域。在治疗WM的2期临床试验中，其总缓解率达83.6%。ITM Isotope Technologies开发的基于多肽偶联的靶向RDC疗法177Lu-edotreotide，在治疗胃肠胰神经内分泌肿瘤的3期临床试验中也达到主要终点，该公司预计今年提交新药申请（NDA）。虽然RDC在早期肿瘤成像和治疗方面均展现巨大潜力，但其药物结构复杂，通常由靶向配体、连接子、螯合剂和放射性同位素组成。其生产过程需要多学科的专业技术支持。药明康德综合性的放射性药物发现平台整合了多肽发现和放射性药物开发能力，提供包括多肽合成、螯合剂合成、放射性标记、成像、药理学研究和监管申报支持等完善的服务。一体化平台让多个团队并行攻坚、高度协作，帮助合作伙伴快速推动RDC项目，节省宝贵的开发时间。药明康德旗下WuXi TIDES CRDMO平台目前正在赋能各类偶联药物开发，覆盖多种疾病领域。持续创新，多家偶联药物新锐完成融资2025年上半年，偶联药物领域的多家新锐陆续完成融资，为持续推动这一治疗模式的创新提供了强劲动力。在抗体偶联药物领域，Callio Therapeutics完成了1.87亿美元的A轮融资。这家公司致力于开发能够同时携带两种不同载荷的双载荷ADC，以进一步增强药物的治疗效力。映恩生物于今年3月在港交所完成约2.1亿美元的首次公开募股（IPO）。该公司独特的双特异性抗体偶联药物平台，利用双特异性抗体精准驱动药物载荷的靶向递送。基于该平台开发的EGFR/HER3靶向ADC药物是该公司与Avenzo Therapeutics达成的超12亿美元授权协议的核心。在放射性偶联药物领域，AdvanCell公司于上半年完成1.12亿美元的C轮融资。该公司基于Pb212的靶向α粒子放射性疗法ADVC001具有“best-in-class”潜力，目前正在1/2期临床试验中用于治疗转移性前列腺癌患者。此外，该公司今年还与礼来公司达成研发合作协议，共同开发针对多种癌症类型的创新靶向α粒子疗法。在多肽偶联药物领域，ProteinQure公司于今年5月完成1100万美元的A轮融资。该公司利用先进的人工智能（AI）和机器学习技术，设计并优化包含非天然氨基酸的创新多肽偶联药物。其主打在研疗法PQ203是一款靶向SORT1的潜在“first-in-class”多肽偶联药物，预计在今年下半年启动首个人体临床试验。该公司表示，这将是全球首款进入临床开发阶段的AI设计多肽偶联药物。▲2025年上半年偶联药物领域部分投融资活动（数据来源：公开资料）回顾2025年上半年，偶联药物领域在新药获批、临床进展、授权合作以及投融资方面都取得了可圈可点的进展。期待随着偶联技术的持续创新和优化，催生更多造福患者的突破。WuXi TIDES团队将继续利用其一体化的CRDMO平台赋能偶联药物的开发，帮助合作伙伴将科学创新早日转化成让全球患者获益的疗法。H1 2025 Review of Conjugated Therapeutics: Three Novel ADCs Gained Regulatory ApprovalsConjugated drugs enable the precise delivery of therapeutic payloads to specific tissues or cells by linking target-binding ligands with functional payloads. In recent years, this field has advanced rapidly. According to a recent report, 284 antibody-drug conjugate (ADC) clinical trials were initiated globally in 2024—over 100 more than were initiated in 2023. Alongside ADCs, new conjugated modalities have also gained momentum, including radionuclide drug conjugates (RDCs), peptide-drug conjugates (PDCs), and oligonucleotide-drug conjugates. This growing momentum underscores the expanding potential of conjugated therapeutics in addressing a broad range of diseases.Backed by extensive experience in chemistry and integrated drug development expertise, WuXi TIDES is supporting next-generation conjugated therapies. As an integral part of WuXi AppTec, WuXi TIDES has built an integrated CRDMO platform focused on oligonucleotides, peptides and related synthetic conjugates. This platform simplifies TIDES drug development by providing all discovery, CMC development and the entire manufacturing supply chain under one roof.Antibody-Drug Conjugates: Three Novel ADC Approvals and Multiple Billion-Dollar DealsIn H1 2025, three novel ADCs received their first regulatory approvals in key markets. Datroway (datopotamab deruxtecan), jointly developed by AstraZeneca and Daiichi Sankyo, was approved for the treatment of adults with unresectable or metastatic HR-positive, HER2-negative breast cancer. In May, AbbVie’s Emrelis (telisotuzumab vedotin), a c-Met-targeting ADC, received approval for treating adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with high c-Met expression. Also in May, the HER2-targeting trastuzumab rezetecan, developed by Hengrui Pharma, was approved for the treatment of adult patients with unresectable locally advanced or metastatic NSCLC harboring activating HER2 mutations who have previously received at least one systemic therapy.Moreover, multiple licensing and R&D collaborations exceeding $1 billion were signed in the ADC field in early 2025, underscoring the industry's strong interest in ADCs. Radionuclide Drug Conjugates: Indication Expansion for Pluvicto and a Breakthrough Therapy DesignationRDCs link radioactive isotopes to tissue-targeting ligands to deliver radioactivity precisely to tumors while minimizing harm to healthy tissues. The field has grown rapidly, with more than 30 RDC clinical trials initiated in 2024—three times the number from five years ago.In March 2025, Novartis’ blockbuster RDC, Pluvicto, received indication expansion for earlier use before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Recently released Phase III data also demonstrated significant radiographic progression-free survival benefits in PSMA-positive hormone-sensitive prostate cancer.In addition, Cellectar Biosciences’ potential first-in-class RDC iopofosine I 131 received FDA Breakthrough Therapy Designation for relapsed/refractory Waldenström’s macroglobulinemia (WM). This drug links a phospholipid ether to a radioactive isotope, selectively binding to lipid-rich domains on cancer cells. In its Phase II study for WM, the overall response rate reached 83.6%. Meanwhile, ITM Isotope Technologies’ peptide-conjugated RDC, 177Lu-edotreotide, met primary endpoints in a Phase III trial for gastroenteropancreatic neuroendocrine tumors, with a New Drug Application (NDA) expected this year.Although RDCs have demonstrated potential in early tumor imaging and treatment, their complex drug structures—typically composed of a targeting ligand, linker, chelator, and radionuclide—require multidisciplinary technical expertise for development and manufacturing. WuXi AppTec offers a comprehensive radiopharmaceutical discovery platform that combines peptide discovery with radiopharmaceutical development, covering peptide synthesis, chelator synthesis, radiolabeling, imaging, pharmacology studies, and regulatory filing support. This integrated model enables parallel, highly collaborative efforts across multiple teams, helping partners accelerate RDC programs and save valuable development time.Additionally, WuXi TIDES offers an integrated CRDMO platform with extensive experience in chemical synthesis, supporting the development of various conjugated drugs across multiple disease areas.Sustained Innovation: Emerging Players Secure New Financing In the first half of 2025, several emerging companies in the conjugated drug space secured new financing, providing a strong foundation for continued innovation in this rapidly evolving modality.Within the ADC segment, companies developing dual- or multi-payload or dual-targeting ADC technologies are capturing growing investor interest. Dual- or multi-payload ADCs are designed to deliver combinations of cytotoxic agents and maximize therapeutic benefit. Meanwhile, bispecific ADCs are engineered to enhance tumor selectivity over healthy cells.In the RDC field, targeted alpha-particle therapies (TAT) continue to emerge as a focal point. TAT leverages the unique properties of alpha particles—such as high linear energy transfer (LET) and short tissue penetration—to deliver potent cytotoxic effects to cancer cells while minimizing damage to surrounding healthy tissue.In the peptide-drug conjugate (PDC) space, some emerging companies are designing innovative PDCs incorporating non-natural amino acids. A potentially first-in-class PDC is expected to enter first-in-human trials in the second half of the year. In summary, the first half of 2025 has seen remarkable progress in the conjugated drug field across new drug approvals, clinical milestones, strategic partnerships, and financing activity. As innovation and optimization in conjugation technologies advance, the field is poised for even more breakthroughs that promise to benefit patients worldwide. WuXi TIDES remains committed to harnessing its fully integrated CRDMO platform to support the development of conjugated drugs—empowering partners to accelerate the translation of scientific innovation into transformative therapies.参考资料：[1] Case Study: PDC Drug R&D and Manufacturing in 9 Months. Retrieved June 3, 2025, from https://tides.wuxiapptec.com/resources/case-study-pdc-drug-rd-and-manufacturing-in-9-months/[2] 创新多肽偶联药物达3期临床主要终点，今年递交新药申请https://mp.weixin.qq.com/s?__biz=MzAwMDA5NTIxNQ==&mid=2650107324&idx=2&sn=420318d4250bf582588e9e861ca14748&chksm=831934ebc8f5e0a7a1322e83abb62c211eac8fc564211e02881a8e3f6ef8cc23fe51d138ecbc#rd[3] Novartis Pluvicto™ demonstrates statistically significant and clinically meaningful rPFS benefit in patients with PSMA-positive metastatic hormone-sensitive prostate cancer. Retrieved June 3, 2025, from https://www.novartis.com/news/media-releases/novartis-pluvictotm-demonstrates-statistically-significant-and-clinically-meaningful-rpfs-benefit-patients-psma-positive-metastatic-hormone-sensitive-prostate-cancer[4] Global Oncology Trends 2025. Retrieved June 3, 2025, from https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/global-oncology-trends-2025[5] Bicycle Therapeutics Announces Poster Presentations at the 2025 ASCO Annual Meeting. Retrieved June 17, 2025, from https://investors.bicycletherapeutics.com/news-releases/news-release-details/bicycle-therapeutics-announces-poster-presentations-2025-asco[6] New Real-World Data support effectiveness and tolerability of Pepaxti in heavily pretreated Multiple Myeloma patients. Retrieved June 17, 2025, from https://oncopeptides.com/en/media/press-releases/new-real-world-data-support-effectiveness-and-tolerability-of-pepaxti-in-heavily-pretreated-multiple-myeloma-patients/免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Good Tolerability and Robust Tumor Uptake were Observed in TNBC Animal Models Auger Emitters Offer the Potential Benefit of Enhanced Cytotoxicity, Safety and Ease-of-Use June 24, 2025 -- Cellectar Biosciences, Inc. (Nasdaq: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery and development of drugs for the treatment of cancer, today announced that the company has submitted a protocol with the U.S. Food and Drug Administration (FDA) for a Phase 1b Dose Finding study of its Auger emitting radiopharmaceutical, CLR 125, for the treatment of relapsed TNBC. CLR 125 is an iodine-125 Auger-emitting drug candidate targeting solid tumors, such as triple negative breast, lung and colorectal cancers. “Building on the promising preclinical results with CLR 125, we have submitted a Phase 1b dose-finding study protocol to the FDA for the treatment of triple-negative breast cancer, including metastatic disease. This study leverages the unique potential ability of our PLE to deliver iodine-125 directly to the nucleus and mitochondria, which is designed to achieve potent activity while minimizing the risk of adverse effects due to its limited transmission range,” said Jarrod Longcor, Cellectar’s chief operating officer. “Initiating this Phase 1b study is a significant milestone and an important step toward evaluating the safety and optimal dosing of CLR 125 in patients, ultimately providing a potential new treatment option for those afflicted by this challenging disease.” The proposed Phase 1b dose finding study in relapsed TNBC will utilize imaging to determine tumor uptake to evaluate three doses of CLR 125 (32.75 mCi for 4 cycles, 62.5 mCi for 3 cycles, and 95 mCi for 2 cycles) with four doses per cycle in 15 patients per arm. The primary endpoint of the study will be to determine the recommended Phase 2 dose and dosing regimen and will also evaluate safety and tolerability, as well as initial response assessment (RECIST and progression-free survival). “The integration of our PDC-targeted delivery platform with a precision-driven, Auger-emitting isotope represents a powerful therapeutic combination with the potential to deliver significant clinical benefit across a range of solid tumors, including TNBC. Our confidence in CLR 125 is grounded in its molecular similarity to iopofosine I 131, our PDC designed to provide targeted delivery of iodine-131 (radioisotope), for which we have evidence supporting proof-of-concept and tolerability in a Phase 2 clinical trial,” said James Caruso, chief executive officer of Cellectar. “Leveraging dosimetry imaging to measure drug delivered directly to tumors is expected to provide early proof-of-concept of the appropriate dose.” Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptors, progesterone receptors, and HER2 protein expression. This lack of common therapeutic targets makes TNBC particularly challenging to treat, with limited options beyond chemotherapy. TNBC tends to grow and spread more quickly than other breast cancer types and disproportionately affects younger women and those of African descent. In the U.S., approximately 12% of breast cancer diagnoses are TNBC.1 Studies suggest that approximately 25% (40,540) of TNBC cases relapse after standard treatments like surgery, chemotherapy, and radiation.2 Due to its high recurrence rate and poor prognosis, there is a critical need for innovative, targeted therapies to improve outcomes for patients facing this difficult diagnosis.3 Cellectar Biosciences is a late-stage clinical biopharmaceutical company focused on the discovery and development of proprietary drugs for the treatment of cancer, independently and through research and development collaborations. The company’s core objective is to leverage its proprietary Phospholipid Drug Conjugate™ (PDC) delivery platform to develop the next-generation of cancer cell-targeting treatments, delivering improved efficacy and better safety as a result of fewer off-target effects. The company’s product pipeline includes: iopofosine I 131, a PDC designed to provide targeted delivery of iodine-131 (radioisotope), for which the FDA has granted Breakthrough Therapy Designation; CLR 121225, an actinium-225 based program being targeted to several solid tumors with significant unmet need, such as pancreatic cancer; and CLR 121125, an iodine-125 Auger-emitting program targeted in other solid tumors, such as triple negative breast, lung and colorectal, as well as proprietary preclinical PDC chemotherapeutic programs and multiple partnered PDC assets. In addition, iopofosine I 131 has been studied in Phase 2b trials for relapsed or refractory multiple myeloma (MM) and central nervous system (CNS) lymphoma, and the CLOVER-2 Phase 1b study, targeting pediatric patients with high-grade gliomas, for which Cellectar is eligible to receive a Pediatric Review Voucher from the FDA upon approval. The FDA has also granted iopofosine I 131 six Orphan Drug, four Rare Pediatric Drug and two Fast Track Designations for various cancer indications. 1 Source: Triple-negative breast cancer recurrence: Outlook and treatment 2 Source: Triple-Negative Breast Cancer Recurrence After Mastectomy 3 Source: National Cancer Institute The content above comes from the network. if any infringement, please contact us to modify.