100 mCi of [177Lu]Ludotadipep, the dose determined in the phase 1 clinical trial (FC705-1), was administered repeatedly up to 6 times at intervals of 8 weeks (±2 weeks) to patients with metastatic castration resistant prostate cancer (mCRPC) in order to assess the safety and efficacy.

开始日期2022-10-30

申办/合作机构

FutureChem Co., Ltd.

NCT05458544

/ Recruiting临床1/2期

A Phase 1 Open-label, Dose-finding Multi-center Trial of [177Lu]Ludotadipep in Metastatic Castration-resistant Prostate Cancer Patients, Followed by an Open-label, Repeat Dose, Multi-center Phase 2a Trial to Assess Safety and Efficacy

Phase 1: The objective of the Phase 1 part of the clinical trial is to verify safety and tolerability (dose-limiting toxicity [DLT], maximum tolerated dose [MTD]) of a single 3.7 Giga-Becquerel (GBq) dose with the potential for one dose level de-escalation to 2.775 GBq if necessary, to determine the recommended [177Lu]Ludotadipep dose for use in the Phase 2a part of the trial.
Phase 2a: The objective of the Phase 2a part of the trial is to evaluate safety and efficacy for repeated administration of the recommended [177Lu]Ludotadipep dose. The Recommended Phase 2 dose (RP2D) will be based on the study results from the Phase 1 trial in South Korea upon consultation with the FDA.

开始日期2022-09-01

申办/合作机构

FutureChem Co., Ltd.

NCT04509557

/ Completed临床1期

[177Lu]Ludotadipep Treatment in Patients With Metastatic Castration-resistant Prostate Cancer: Phase I Clinical Trial.

The study aims to evaluate the stability and efficacy after administration of [177Lu]Ludotadipep in patients with metastatic castration resistant prostate cancer (mCRPC), with dose-escalation applied to determine the appropriate dose.

开始日期2020-10-14

申办/合作机构

FutureChem Co., Ltd.

100 项与 177Lu-Ludotadipep 相关的临床结果

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100 项与 177Lu-Ludotadipep 相关的转化医学

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100 项与 177Lu-Ludotadipep 相关的专利（医药）

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项与 177Lu-Ludotadipep 相关的文献（医药）

2024-12-01·European Journal of Nuclear Medicine and Molecular Imaging

[177Lu]Lu DOTATOC PRRT with PARP inhibitors in small cell lung cancer

作者: Masala, Salvatore ; Scaglione, Mariano ; Piscopo, Leandra ; Klain, Michele

2024-01-01·Korean journal of radiology

Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With [¹⁷⁷Lu]Ludotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer

Article

作者: Boo, Sun Ha ; Lee, Ji Youl ; Park, Chansoo ; Moon, Hyong Woo ; Ha, Seunggyun ; O, Joo Hyun ; Yoo, Ie Ryung ; Chi, Dae Yoon

OBJECTIVE:

¹⁷⁷Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [¹⁷⁷Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC).

MATERIALS AND METHODS:

Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [¹⁷⁷Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [¹⁷⁷Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organ- and tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1.

RESULTS:

Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq.

CONCLUSION:

[¹⁷⁷Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

2023-04-01·BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Evaluation of PSMA target diagnostic PET tracers for therapeutic monitoring of [177Lu]ludotadipep of prostate cancer: Screening of PSMA target efficiency and biodistribution using [18F]DCFPyL and [68Ga]PSMA-11

Article

作者: Kil, Hee Seup ; Oh, Keumrok ; Lee, Kyongkyu ; Lee, Yong Jin ; Kim, Chul Hee ; Chi, Dae Yoon ; Lee, Kyo Chul ; Kim, Min Hwan

We have compared the similarity of the in vivo distribution of the prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging agents [¹⁸F]DCFPyL, [⁶⁸Ga]galdotadipep, and [⁶⁸Ga]PSMA-11. This study is designed for a further selection of a PSMA-targeted PET imaging agent for the therapeutic evaluation of [¹⁷⁷Lu]ludotadipep, our previously developed prostate-specific membrane antigen (PSMA)-targeted prostate cancer therapeutic radiopharmaceutical. In vitro cell uptake was performed to evaluate the affinity to PSMA using PSMA + PC3-PIP, and PSMA- PC3-flu was used for the study. MicroPET/CT 60 min dynamic imaging and biodistribution were performed at 1, 2, and 4 h after injection. Autoradiography and immunohistochemistry were performed to evaluate the PSMA + tumor target efficiency. In the microPET/CT image, [⁶⁸Ga]PSMA-11 showed the highest uptake in the kidney among all three compounds. [¹⁸F]DCFPyL and [⁶⁸Ga]PSMA-11 showed similar patterns of in vivo biodistribution and high tumor targeting efficiency, similar to those of[⁶⁸Ga]galdotadipep. All three agents showed high uptake in tumor tissue on autoradiography, and PSMA expression was confirmed by immunohistochemistry. Thus, [¹⁸F]DCFPyL or [⁶⁸Ga]PSMA-11 can be used as a PET imaging agent to monitor [¹⁷⁷Lu]ludotadipep therapy in prostate cancer patients.

项与 177Lu-Ludotadipep 相关的新闻（医药）

2024-10-10

·PRNewswire

Metastatic Castration-Resistant Prostate Cancer Clinical Trial Pipeline Appears Robust With 90+ Key Pharma Companies Actively Working in the Therapeutics Segment | DelveInsight

Metastatic Castration-Resistant Prostate Cancer (mCRPC) refers to prostate cancer that has spread (metastasized) to other parts of the body and continues to progress despite treatments that lower testosterone levels (androgen deprivation therapy or ADT) major pharmaceutical companies are heavily investing in research and development of new treatments, including immunotherapy (e.g., sipuleucel-T) and targeted therapies, which are seen as the next frontier in treating mCRPC. The use of precision medicine to identify genetic profiles in patients has further expanded the potential for targeted treatment. LAS VEGAS , Oct. 10, 2024 /PRNewswire/ -- DelveInsight's ' Metastatic Castration-Resistant Prostate Cancer Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline mCRPC therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the mCRPC pipeline domain. Key Takeaways from the Metastatic Castration-Resistant Prostate Cancer Pipeline Report DelveInsight's mCRPC pipeline report depicts a robust space with 90+ active players working to develop 100+ pipeline therapies for mCRPC treatment. Key mCRPC companies such as Regeneron Pharmaceuticals, AstraZeneca, Hinova Pharmaceuticals, Zenith Epigenetic, Eli Lilly and Company, Astellas Pharma, Seagen, Pfizer, Progenics Pharmaceutical, Molecular Insight Pharmaceuticals, Bayer, Accutar Biotechnology Inc, Hinova Pharmaceuticals, Forma Therapeutics, Inc., HALDA THERAPEUTICS INC., Tavanta Therapeutics, Lantheus, Pfizer, AB Science, Syntrix Pharmaceuticals, Exelixis, Laekna Therapeutics Shanghai Co. Ltd., Cardiff Oncology, Ipsen, Norroy Bioscience, Astellas Pharma, Novartis, Johnson & Johnson, Tempest Therapeutics, and others are evaluating new mCRPC drugs to improve the treatment landscape. Promising mCRPC pipeline therapies such as REGN 4336, Capivasertib, Deutenzalutamide, ZEN003694, Abemaciclib, Enfortumab vedotin, Talazoparib, I-131-1095, Pelgifatamab corixetan, AC176, HP518, FT-7051, HLD-0915, TAVT-45, PNT2002, Mevrometostat, Masitinib, SX-682, XL092, LAE001, Onvansertib, Tazemetostat, 177Lu-NYM032, PRL-02, 225 Actinium PSMA 617, ARX51, TPST-1120, and others are under different phases of mCRPC clinical trials. In October 2024, Curium announced that it had entered into a strategic partnership with PDRadiopharma Inc, a wholly-owned subsidiary of PeptiDream, for the clinical development, regulatory filing, and commercialization in Japan of 177Lu-PSMA-I&T and 64Cu-PSMA-I&T. The two agents 177Lu-PSMA-I&T and 64Cu-PSMA-I&T target prostate-specific membrane antigen (PSMA) expressed on prostate cancer cells and are being investigated for prostate cancer treatment and diagnostics. In July 2024, the US FDA granted fast-track designation to the prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical 225Ac-FL-020 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). In July 2024, Merck and Orion Corporation announced the mutual exercise of option providing Merck global exclusive rights to Opevesostat, an investigational CYP11A1 inhibitor, for the treatment of Metastatic Castration-Resistant Prostate Cancer. In July 2024, the US FDA granted fast-track designation to the antibody-drug conjugate (ADC) BNT324/DB-1311 to potentially treat patients with unresectable advanced or metastatic castration-resistant prostate cancer (mCRPC) whose disease had progressed on or after standard systemic regimens. In July 2024, FutureChem announced that the FC-705 has received orphan drug designation from the Ministry of Food and Drug Safety (MFDS) for the treatment of prostate cancer. In June 2024, CAR T-Cell Therapy demonstrated promising results for mCRPC according to Phase I trial results. In January 2024, Lava Therapeutics announced that it has signed a clinical trial collaboration and supply agreement with Merck to evaluate its prostate cancer therapy LAVA-1207 as a combination treatment with MSD's Keytruda (pembrolizumab). In July 2024, Blue Earth Therapeutics announced the signing of a clinical research collaboration with University College London (UCL). The collaboration is centered on a Phase I/II trial designed to evaluate the safety, tolerability, radiation dosimetry, and antitumor activity of the 225Ac-rhPSMA-10.1 in men with metastatic castrate-resistant prostate cancer who have previously responded to lutetium 177 (177Lu)-PSMA therapy. Request a sample and discover the recent advances in mCRPC treatment drugs @ Metastatic Castration-Resistant Prostate Cancer Pipeline Report The mCRPC pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage mCRPC drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the mCRPC clinical trial landscape. Metastatic Castration-Resistant Prostate Cancer Overview Metastatic castration-resistant prostate cancer (mCRPC) is an advanced stage of prostate cancer that continues to grow and spread despite hormone therapy aimed at lowering testosterone levels. The term "metastatic" refers to cancer spreading to other parts of the body, such as the bones, lymph nodes, or distant organs, while "castration-resistant" indicates that the cancer no longer responds to treatments that reduce testosterone, a key driver of prostate cancer growth. mCRPC is typically more aggressive and challenging to treat than earlier stages of prostate cancer. The causes of mCRPC stem from genetic and environmental factors. Genetic mutations in the androgen receptor pathway can make cancer cells less dependent on testosterone, allowing them to thrive even under hormone-suppressing treatments. Environmental factors like diet, lifestyle, and exposure to certain chemicals may also contribute to the development and progression of prostate cancer. Symptoms of mCRPC often include pain in bones, fatigue, difficulty urinating, weight loss, and general weakness. As the cancer spreads, it can impair the function of other organs, depending on the site of metastasis. Diagnosis of mCRPC usually involves a combination of tests, including prostate-specific antigen (PSA) blood tests, imaging studies like CT scans, MRIs, or bone scans, and sometimes biopsies to confirm the spread and resistance to treatment. Treatment options for mCRPC are more complex and may include newer hormonal therapies (e.g., abiraterone, enzalutamide), chemotherapy (docetaxel or cabazitaxel), immunotherapy (e.g., sipuleucel-T), or targeted therapies such as PARP inhibitors. Bone-targeting therapies, radiation, and palliative care can also be used to manage symptoms and improve the quality of life. Treatment is typically tailored to the individual based on the extent of the disease and the patient health. Find out more about mCRPC treatment drugs @ Drugs for Metastatic Castration-Resistant Prostate Cancer Treatment A snapshot of the mCRPC Pipeline Drugs mentioned in the report: Learn more about the emerging mCRPC pipeline therapies @ Metastatic Castration-Resistant Prostate Cancer Clinical Trials Metastatic Castration-Resistant Prostate Cancer Therapeutics Assessment The mCRPC pipeline report proffers an integral view of the mCRPC emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Metastatic Castration-Resistant Prostate Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous Therapeutics Assessment By Molecule Type: Small molecule, Cell therapy, Peptides, Polymer, Small molecule, Gene therapy Therapeutics Assessment By Mechanism of Action: Androgen receptor degradation enhancers, Antibody-dependent cell cytotoxicity, Proto-oncogene protein c-akt inhibitors, Androgen receptor antagonists, Bromodomain and extraterminal domain protein inhibitors, Cyclin-dependent kinase 4 inhibitors, Cyclin-dependent kinase 6 inhibitors, Ionizing radiation emitters, PPAR alpha antagonists. Key Metastatic Castration-Resistant Prostate Cancer Companies: Regeneron Pharmaceuticals, AstraZeneca, Hinova Pharmaceuticals, Zenith Epigenetic, Eli Lilly and Company, Astellas Pharma, Seagen, Pfizer, Progenics Pharmaceutical, Molecular Insight Pharmaceuticals, Bayer, Accutar Biotechnology Inc, Hinova Pharmaceuticals, Forma Therapeutics, Inc., HALDA THERAPEUTICS INC., Tavanta Therapeutics, Lantheus, Pfizer, AB Science, Syntrix Pharmaceuticals, Exelixis, Laekna Therapeutics Shanghai Co. Ltd., Cardiff Oncology, Ipsen, Norroy Bioscience, Astellas Pharma, Novartis, Johnson & Johnson, Tempest Therapeutics, and others. Key Metastatic Castration-Resistant Prostate Cancer Pipeline Therapies: REGN 4336, Capivasertib, Deutenzalutamide, ZEN003694, Abemaciclib, Enfortumab vedotin, Talazoparib, I-131-1095, Pelgifatamab corixetan, AC176, HP518, FT-7051, HLD-0915, TAVT-45, PNT2002, Mevrometostat, Masitinib, SX-682, XL092, LAE001, Onvansertib, Tazemetostat, 177Lu-NYM032, PRL-02, 225 Actinium PSMA 617, ARX51, TPST-1120, and others. Dive deep into rich insights for new drugs for mCRPC treatment, visit @ Metastatic Castration-Resistant Prostate Cancer Drugs Table of Contents For further information on the mCRPC Cancer pipeline therapeutics, reach out @ Metastatic Castration-Resistant Prostate Cancer Treatment Drugs Related Reports Metastatic Castration-Resistant Prostate Cancer Market Metastatic Castration-Resistant Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCRPC companies including AstraZeneca, Merck Sharp & Dohme, Hinova Pharmaceuticals, Pfizer, Astellas Pharma, Modra Pharmaceuticals, AB Science, Eli Lilly and Company, Zr Pharma & GmbH, Bristol-Myers Squibb, Ipsen, Exelixis, Takeda, Janssen Research & Development, Tesaro, Lantheus Holdings, Kintor Pharmaceutical, MacroGenics, Daiichi Sankyo, Madison Vaccines, Novartis, Point Biopharma, Xencor, Essa Pharma, Telix International, Bayer, Arvinas, among others. Metastatic Prostate Cancer Market Metastatic Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key metastatic prostate cancer companies including AstraZeneca, Arvinas, Madison Vaccines, Phosplatin Therapeutics, Hinova Pharmaceuticals, Bristol Myers Squibb, Merck, MacroGenics, Daiichi Sankyo, Seagen, Taiho Pharmaceutical, Modra Pharmaceuticals, Xencor, Point Biopharma, Lantheus Holdings, Zenith Epigenetics, Essa Pharma, Telix Pharmaceuticals, Kintor Pharmaceutical, AB Science, Eli Lilly and Company, Exelixis among others. Metastatic Castration-Sensitive Prostate Cancer Market Metastatic Castration-Sensitive Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCSPC companies including Myovant Sciences, Pfizer, Bayer, Orion, Novartis, AstraZeneca, Pfizer, Janssen, Merck, Eli Lilly, among others. Metastatic Castration-Sensitive Prostate Cancer Pipeline Metastatic Castration-Sensitive Prostate Cancer Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key mCSPC companies, including Myovant Sciences, Pfizer, Bayer, Orion, Novartis, AstraZeneca, Pfizer, Janssen, Merck, Eli Lilly, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

快速通道免疫疗法临床1期临床结果

2024-07-15

·药智网

海外加速布局！「非抗体蛋白偶联」有望成为新一代ADC技术

偶联技术有多火？仅ADC（抗体偶联药物）领域，2017年之后就有超过10款新药获FDA批准上市，时至今日，全球进入临床阶段的ADC药物更是超过500余款，而万物偶联趋势下，这个数字还在无限扩大。偶联药物有多卷？随着DS-8201获批上市，其突出的优势为ADC药物开发提出了更高的标准，也让“差异化偶联创新药”成为主要趋势，部分入局较晚的企业产品还在研就已丧失优势，不得不思考“偶联药物未来又将如何发展”？其实，与最初“魔术子弹概念”时代并没有太大的变化，尽管蛋白质基因工程、化学偶联等技术的持续进步，但偶联药物的发展方向仍主要围绕新的靶抗原、新作用机制的有效载荷、新的抗体和载体形式等方面进行，而最大的不同就在于，偶联药物方向更偏向于了靶向性，即更多具有特异定向作用的结构被用作了小分子毒素等有效载荷的载体。数据来源：公开数据整理在此环境之下，组合用药、精确递药的理念和应用场景进一步扩大，多种新兴偶联技术概念相继涌现，业界也掀起了新兴偶联技术药物研发热潮。差异化之路非抗体蛋白偶联的出现原则上来讲，偶联药物或许并不存在最优组合。 “万物皆可偶联”的核心理念之下，对最优组合的不断探索反而促进了更多创新技术的出现，继ADC爆火之后，PDC、FDC、SMDC、ISAC、RDC、ARC等多种技术如雨后春笋般不断冒出。多样化策略之下，各种创新偶联技术相较传统ADC技术，或多或少都存在自身的核心优势，如PDC较强肿瘤穿透性、更低的免疫原性与更低的生产成本；SMDC工艺简单、安全性较好与安全性较高。而除了抗体、多肽与小分子等常规的靶向分子，近来出现的“非抗体蛋白”也逐渐全新的研究领域。非抗体蛋白偶联药物，即将靶向性蛋白分子与发挥药效的效应分子（比如细胞毒分子，siRNA等）连接在一起，递送效应分子到特定疾病部位发挥作用。其原理上与ADC的机理类似，最大区别就是靶向分子的不同，但相较前者却有着核心的四大优势：免疫副作用更小：蛋白偶联药物的蛋白部分大都来源于人类蛋白，例如重组人甲胎蛋白、重组人转铁蛋白等，相较于抗体、多肽能对人产生较小的免疫副作用。靶点灵活：对靶点的选择相对灵活，很多企业在蛋白部分做了很多创新，例如Aro Biotherapeutics的Centyrins蛋白经过设计后可以与不同肿瘤抗原相结合。原则上可以避开偶联药物较集中的hear2等领域，去尝试更新、更小众的靶点方向。高效：如外泌体偶联药物，可控的、模块化的药物装载与递送，突破了抗体偶联药物（ADC）载药率低、安全性有限的瓶颈，实现了更高效的提升效率。稳定：蛋白偶联药物的结构稳定性一般较高，且具有高效、可控的制药载荷数量。依从性高：可以通过在蛋白中引入半胱氨酸来提高药物的结合率，提高了药物的依从性和便利性。不过，由于蛋白偶联技术总体上处于研究早期阶段，某种程度上其优势性与局限性都尚未研究透彻，后续或可能存在系列变化，但无论如何，从目前市面上相继出现的非抗体蛋白偶联技术来看，其临床优势也可初见端倪。外泌体+转铁蛋白蛋白偶联的两大典型技术路线外泌体偶联药物（EDC） 2021年7月26日，Nature子刊Nature Biomedical Engineering在线刊发了中科院魏炜教授团队联合首都医科大学陶勇教授团队和昆士兰大学余迪教授团队共同署名文章，开发出外泌体偶联VEGF单抗，利用Treg来源的外泌体（rEXS）为载体，通过基质金属蛋白酶（MMP）敏感肽段（cL）连接VEGF抗体（aV)，创建了rEXS-cL-aV体系。后续通过外泌体化学偶联技术，在外泌体上进行可控、可调节的多功能化改造，如构建融合表达特定蛋白和外泌体膜蛋白的质粒，通过转染等方式，让该融合蛋白在外泌体来源细胞中大量表达，使得这些细胞分泌的外泌体能够会携目标融合蛋白。图片来源：参考资料1 最终，将外源性小分子化学药物或生物大分子药物与外泌体偶联结合，形成外泌体偶联药物（EDC），实现高效、稳定、广谱、可控的外泌体模块化药物装载与递送，突破了抗体偶联药物（ADC）载药率低、安全性有限的瓶颈。在该领域上，天津外泌体科技有限公司是国内掌握该技术商业化的领先公司，根据其以往公布的数据显示，其EDC药物装载率可达到92.3%、溶解性提高71.4倍、半衰期提高36.2倍、药峰浓度提高3倍、口服相对生物利用度提升2.6倍；装载Herceptin抗体的外泌体呈现靶向效果相比对照组提升174.5倍，数据着实惊人。至少就目前而言，EDC技术是外泌体领域最具商业化前景的技术，也是最为经典的非抗体蛋白偶联技术。重组人转铁蛋白偶联药物铁蛋白作为一种脱铁蛋白组成的具有大分子结构的糖蛋白，通常情况下是由蛋白质外壳和铁内核两部分组成，在维持机体铁代谢平衡和细胞抗氧化过程中起着关键作用，并且与炎症、血管增生和肿瘤有关。而人工条件下的铁蛋白是具有空腔结构的笼形结构，外部的蛋白质外壳可通过基因和化学修饰增加靶向性，以达到提高递送效率的目的，而空腔机构则可以用于装载药物，实现药物的包载荷递送。图片来源：参考资料2 2005年铁蛋白被成功用于包载递送阿霉素，开启药物递送领域新篇章，之后铁蛋白药物载体（FDC）的概念得以面世，相较ADC等常规偶联药物，其在安全性、渗透性、稳定性与靶向性等方面具有天然优势，尤其是靶向性方面。安全性：铁蛋白是来自生物体内的天然存在蛋白质，毒性低，具有良好的生物降解性和生物相容性，不容易引起排异反应。渗透和滞留性：由于铁蛋白粒径较小，使其易于逃脱网状内皮系统的吞噬，半衰期较长，可在病变部位形成蓄积，增强药效。稳定性：铁蛋白的环境要求低，部分情况分解成亚基后仍能重组恢复笼状结构，在制备和储存工艺上要求简便很多。靶向性：该领域铁蛋白主要优势主要有两者，一者是肿瘤靶向性的基本要求，即肿瘤细胞对铁离子的需求远大于正常细胞，使得肿瘤细胞表面的转铁蛋白受体过度表达；二者是其脑靶向性，由于铁蛋白可跨越血脑屏障，同时转铁蛋白受体在血脑屏障中的表达水平明显高于正常细胞组织，被寄希望于多种中枢神经疾病的药物载体。很明显，就算同属于蛋白偶联药物，在较EDC药物高效、稳定与免疫副作用等相同的优势，不同技术路线的蛋白偶联药物也有着差异化的优势（如FDC的脑靶向性），而随着生物医药基础研究水平的上升，未来也有望诞生更多非抗体蛋白偶联药物，进一步丰富领域优势性的同时，也可以拉高整个市场的天花板。国内空白蛋白偶联药物的蓝海市场就蛋白偶联药物市场而言，尽管近年来受ADC大火所带动，但目前国内外对于该类型药物的研究尚不完善，领域内多项技术仍处于临床早期阶段，相关性报道并不多。数据显示，全球活跃蛋白偶联类临床药物仅有20款，且绝大多数均处于临床前阶段，FutureChe的镥[177Lu]Ludotadipep是目前临床进度最快的管线产品。而就在研药物适应症来看，实体瘤、肺癌、乳腺癌等热门疾病类型的集中度明显更高，但同时部分蛋白偶联药物管线也选择了自免、脓毒症、代谢疾病与神经系统疾病为主要突破点。其中，Aro Biotheraputics的「ABX1100」与Alpha Cancer Technologies的「ACT-903」是目前在研药物中信息披露较全面的品种，也是蛋白偶联药物中具有代表意义的品种。「ABX1100」 ABX1100由ARO利用其Centyrins专利平台技术开发的核心产品，其特色的Centyrin蛋白FF0C具有优异的稳定性和溶解度、包括体积较小、可大肠杆菌生产，免疫原性较低，化学偶联方法与生产方式相对比较简单等优势，特别适合靶向递送寡核苷酸。图片来源：ARO官网与抗体相比，Centyrins在早期内体中含量更高递送速度更快，这可能Centyrins分子量小具有强渗透性优势，这样更多的药物分子能够实现内涵体逃逸从而发挥其作用。作为ARO针对庞贝病的一种全新潜在治疗方法，ABX1100由结合CD71受体的Centyrin与特异性干扰Gys1 mRNA表达的小干扰RNA（siRNA）结合而成，从而降低肌肉组织中Gys1酶的水平和整体活性。在GLP毒理学研究中显示出良好的安全性，肌肉中Gys1 mRNA的持久减少，支持每月或每季度给药的潜力，目前已获得美国食品药品监督管理局颁发的孤儿药资格认定和儿科罕见病资格认定。「ACT-903」 Alpha Cancer Technologies Inc. (ACT）是一家生物制药公司，专注于其特有的重组人α胎蛋白（AFP）平台开发和商业化靶向免疫肿瘤学和免疫调节疗法。图片来源：ACT官网 ACT-903作为ACT公司下一代ADC技术靶向α胎蛋白受体治疗癌症新方法的重要管线，其在2023 ASCO大会上首次亮相，是一种新型甲胎蛋白（AFP)-美坦氨酸偶联物，在一项卵巢异种移植模型试验中，ACT-903四种给药方案下的临床数据进行了对照，并观察其细胞毒性，目前所有治疗组体积缩小与生存期增加上均有明显统计学意义。 ACT-903结合物对肿瘤体积的影响图片来源：ACT官网总研究结果显示，ACT-903在卵巢异种移植模型中的安全性和有效性，以及在患者来源的癌症类器官中观察到的细胞毒性，支持ACT-903进入临床研究。目前ACT已计划在2024年提交ACT-903的研究新药（IND）申请。小结随着ADC药物的越来越火、越来越卷，就连PDC、FDC、SMDC、ISAC、RDC等领域的竞争格局也同样开始不容乐观，稀有标的属性正在逐渐消失，如何在偶联领域形成更差异化的竞争成为行业后续主要的思考方向。但同时，药物研发虽不能盲目跟风，但也不能为了差异化而差异化，应着重考虑临床优势与产业优势，而对于蛋白偶联药物而言，尽管目前各项研究都尚处于早期阶段，但其高效、稳定与特殊靶向性等特点也足够吸引人。或许，随着未来研究的深入，蛋白偶联药物还真有望成为下一代更具潜力的ADC技术。路漫漫其修远兮，吾等仍将上下而求索。参考资料：外泌体的五大商业应用（三）：外泌体偶联药物，精致颜容， 2024年01月14日药物递送（八）——铁蛋白技术，药物递送，2021年10月08日双靶向Centyrin-siRNA偶联物ABX300及其siRNA平台分析，洞见conjugates 2022年06月19日 ALPHA CANCER TECHNOLOGIES PRESENTS NEW DATA FROM ACT-903, AN AFP-MAYTANSINE CONJUGATE, IN ONLINE PUBLICATION AT THE 2023 AMERICAN SOCIETY OF CLINICAL ONCOLOGY (ASCO) ANNUAL MEETING，ACT官网来源 | 博药（药智网获取授权转载）撰稿 | 头孢责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。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

抗体药物偶联物多肽偶联药物

2022-11-18

·BioSpace

Monrol and FutureChem Announced a Clinical Supply Partnership

ISTANBUL & SEOUL--(BUSINESS WIRE)-- Eczacıbaşı-Monrol Nuclear Products Co. (Monrol) is delighted to announce that it has reached an agreement in principal with FutureChem based in Seoul, South Korea, a radiopharmaceutical company, for the clinical supply of radioisotope, Lu-177 n.c.a. (Lutetium-177 non-carrier-added), to support FutureChem’s Investigational New Drug IND-enabling Phase 2 clinical trial with Ludotadipep, 177Lu-FC705 to assess the efficacy and safety for repeated administration of the recommended Ludotadipep dose in patients with metastatic castration resistant prostate cancer (mCRPC). Clinical supply contract signed by two parties on 18th of Oct 2022 in Barcelona. A new supply contract between Monrol and FutureChem will be signed following the commercialization of the product in South Korea and US. Monrol General Manager Aydın Küçük, added: “We are delighted to be working with FutureChem to have a clinical supply agreement to support clinical development program of an innovative radiopharmaceutical product Ludotadipep, 177Lu-FC705 to assess the efficacy and safety in patients with metastatic castration resistant prostate cancer (mCRPC). Collaboration with FutureChem is another example of we continue our mission to improve quality of life for cancer patients and transform patient care for the future.” Dae Yoon Chi, Chief Executive Officer, FutureChem said: “FutureChem is thrilled to be partnering with Monrol, a company with a broad set of offerings to support our development programs and pipeline. We look forward to rolling out the supply of high-quality radioisotopes to our Phase 2a clinical trial patients in US soon. We have a future prospect to expand this partnership, supply of radioisotope, Lu-177 n.c.a. by Monrol for the commercialization of the Ludotadipep, 177Lu-FC705”. ENDS About Monrol Monrol is one of the world’s largest nuclear medicine companies leading innovation for the development and manufacturing of GMP grade radioisotopes and radiopharmaceuticals having headquarters in Istanbul. Monrol is distributing its world-class radiopharmaceutical products portfolio with excellence in global markets. Monrol is a CDMO, providing early development support to its customers as well as offering fully integrated services for today’s nimble, lean, virtual companies effectively taking new product concepts into clinical trials, demonstrating proof of concept and going into first-in-human studies. Monrol is committed to transform and improve patient journey in cancer treatment with its radiopharmaceutical products portfolio distributing to more than 50 countries around the globe. To learn more, visit and LinkedIn. About FutureChem Since its establishment in 1999, FutureChem has led the radiopharmaceuticals industry through research and development. FutureChem is the global forerunner in the production of radiopharmaceutical precursors and compounds, development of remarkable radiopharmaceuticals, and worldwide commercialization of new medicine. FutureChem developed competitive technologies and innovative products with a mission to grow the company into a world-class radiopharmaceuticals enterprise, so to contribute a healthy and happy society, protecting the health of patients. For more information, please visit About FC705 and 177Lu-FC705 2nd generation PSMA-targeted therapeutic radiopharmaceuticals. 177Lu-FC705 belongs to the 2nd generation of albumin binders introduced drugs. Its hydrophilicity is higher than that of other compounds, and has low nonspecific binding. 177Lu-FC705 will have constantly increasing uptake in prostate cancer due to the introduction of albumin binder while it will be rapidly excreted from normal organs. In this regard, 177Lu labeled 177Lu-FC705 can be expected to have high therapeutic effect and very low damage to normal organs. Currently, efficacy of 177Lu-FC705 is being clinically tested in Phase 2 in Korea and 1/2a in US. About n.c.a. Lutetium-177 Lutetium-177 n.c.a is a radioisotope of choice for targeted radionuclide therapy. Lu-177 n.c.a production process enables treatment options that have the potential to improve treatment outcomes for certain cancer patients today and more potential treatment options in future under clinical development. The unique properties of Lu-177 n.c.a. make it a theranostically desirable radioisotope for peptide receptor radionuclide therapy (PRRT) to treat certain cancers like Neuro Endocrine Tumors (NET) and Prostate cancer. N.c.a. Lutetium-177 DMF by Monrol listed by FDA.

临床2期

100 项与 177Lu-Ludotadipep 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
转移性去势抵抗性前列腺癌	临床2期	美国	FutureChem Co., Ltd.	2022-09-01

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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


SNMMI2022	N/A	转移性去势抵抗性前列腺癌	-	Lu-177 Ludotadipep 50 mCi	獵醖觸淵蓋獵蓋憲餘鏇(衊顧齋築繭鹹壓築壓夢) = 壓鬱糧觸獵衊鬱願網遞構願構獵廠襯鬱鹹襯襯 (膚鹽壓壓鏇鹽鬱齋鬱繭 )	-	2022-08-08
				Lu-177 Ludotadipep 75 mCi	獵醖觸淵蓋獵蓋憲餘鏇(衊顧齋築繭鹹壓築壓夢) = 淵網餘顧憲遞鏇襯窪齋構願構獵廠襯鬱鹹襯襯 (膚鹽壓壓鏇鹽鬱齋鬱繭 )
AUA2022	N/A	转移性去势抵抗性前列腺癌 PSMA-expression	20	50 mCi [177Lu]Ludotadipep	襯膚齋醖衊壓網網網鬱(範醖鹽鹽壓構衊網願築) = Only 2 patient complained transient nausea 簾淵蓋顧夢繭製顧選願 (築願製鏇網衊構窪積醖 ) 更多	-	2022-05-01
				75 mCi [177Lu]Ludotadipep