Ariceum Therapeutics GmbH

225Ac-Satoreotide is a first-in-class somatostatin receptor 2 antagonist targeting extensive stage small cell lung cancer and is the first antagonist labelled with 225Ac to enter clinical development Satoreotide expressed a superior pharmacokinetic profile relative to DOTA-TATE with a higher pre-clinical anti-tumour efficacy, irrespective of radionuclide used 100% survival with a single dose of 30 kBq 225Ac-satoreotide but not with 225Ac-DOTA-TATE BERLIN, Oct. 22, 2024 /PRNewswire/ -- 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 '225Ac-SSO110 induces long-lasting anti-tumour responses in contrast to 225Ac-DOTA-TATE and 161Tb-DOTA-TATE in the treatment of SSTR2-positive tumour xenografts', details the anti-tumour efficacy of different radiolabelled satoreotide antagonists (225Ac, 161Tb, 177Lu-labelled SSO110) versus respective DOTA-TATE agonists (225Ac- and 161Tb-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 225Ac-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, 225Ac-satoreotide, is multiple times more potent than SSTR2 agonist, 225Ac-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 212Pb 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 225Ac-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: 225Ac-SSO110 induces long-lasting anti-tumour responses in contrast to 225Ac-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, 177Lu-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 . 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 WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Novel iodine radiolabelled PARP inhibitor (rPARPi) entering clinical development in Phase 1 trial to assess safety and early efficacy Dose escalation study followed by expansion cohorts in recurrent glioblastoma with potential to move into primary glioblastoma BERLIN, July 25, 2024 /PRNewswire/ -- 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 has commenced a Phase 1 first-in-human clinical trial (CITADEL-123) of 123I-ATT001, its Iodine-123 labelled PARP inhibitor, in patients with recurrent glioblastoma. The trial opened at University College London Hospitals (UCLH) and will assess the safety and early efficacy of Ariceum's radiotherapeutic candidate, ATT001. UCLH consultant medical oncologist, Dr Paul Mulholland, designed the trial and is also chief investigator of the study. Ariceum is the first company to sponsor a clinical trial of Auger therapy for recurrent glioblastoma, an aggressive form of brain cancer with a high unmet medical need. The initiation of the Phase 1 clinical trial follows Ariceum's submission of a Clinical Trial Authorisation (CTA) application to the UK's Medicines and Healthcare products Regulatory Agency (MHRA) in December 2023 and subsequent approval received from the MHRA in February 2024. The trial has commenced at UCLH, with other sites due to open in the UK and EU later this year. The dose escalation study will be followed by expansion cohorts at a recommended dose in monotherapy and in combination with other therapies in recurrent glioblastoma, with the potential to move into primary glioblastoma. Manfred Rüdiger, Chief Executive Officer at Ariceum Therapeutics, said: "The start of this clinical trial marks a significant clinical milestone for Ariceum's targeted radionuclide therapy, ATT001, especially so soon after receiving approval from the MHRA. We are very pleased to have begun the trial and hope it will bring a much-needed therapy to patients affected by glioblastoma, an aggressive and devastating form of brain cancer." Germo Gericke, Chief Medical Officer at Ariceum Therapeutics, commented: "Recurrent glioblastoma is a very challenging brain cancer with currently no cure and limited treatment options. Ariceum's radiotherapeutic, ATT001, has demonstrated promising pre-clinical results as a potential treatment for patients. We hope to achieve further favourable results in the clinic from our continued collaboration with the team at UCLH, led by Dr Paul Mulholland." Dr Paul Mulholland, who leads the Glioblastoma Research Group at the UCL Cancer Institute, added: "We have been working with Ariceum Therapeutics for some years to develop this study. It will allow us to deliver a low level of radioactivity directly into the tumour of patients with recurrent glioblastoma. I'm very pleased that this clinical trial is now opening." ATT001 delivers its radioisotope payload, Iodine-123, in a highly targeted way to cancer cells expressing PARP, an enzyme they use to repair their DNA. This radioisotope emits low energy Auger electrons, which deposit their energy over short distances, making them particularly useful for causing lethal damage to cancer cells while sparing healthy tissue. An additional benefit of using Iodine-123 is that this isotope is more widely available than others, being produced in a cyclotron. Ariceum in parallel is also exploring 123I-ATT001 in other solid tumour indications, as PARP is a validated target, highly expressed in several other cancers. Notes to Editors 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, 177Lu-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, 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), which is slated to enter clinical development in 2024. 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 . SOURCE Ariceum Therapeutics

最近几年，靶向放射性药物（targeted radiopharmaceuticals）赛道势头火热，吸引大型制药公司和投资者纷纷涌入。 与其他癌症疗法相比，放射性药物有其独特的优势。这类药物通过“粉碎”DNA达到杀伤肿瘤细胞的目的，这种作用机制最大限度地减少了耐药性，并带来了丰富的联合治疗机会，特别是与免疫疗法的联合。此外，放射性药物是真正能够实现诊疗一体化的药物，在使用治疗性同位素之前或者同时，可以使用诊断性同位素确定患者的肿瘤位置和治疗情况，这种方法改善了患者选择及给药准确性。靶向放射性药物还扩大了可成药靶点的范围，一些放射性同位素非常有效，即使是低表达的靶点也可能吸引足够的放射性分子来摧毁癌细胞。 这些优势，叠加诺华两款明星靶向放射性药物——Lutathera和Pluvicto强大的疗效数据及市场表现，触发了这一赛道数十亿美元的biotech收购（下表），其中包括了核药赛道全球领导者诺华的多次加码。 尽管靶向放射性药物的开发仍有多项挑战需要克服，例如，由于不可阻挡的放射性衰变，放射性药物很难生产及配送，因此确保可靠的同位素供应并非易事；此外，产业下游缺乏核医学专家和治疗设施来管理放射性药物，一些医院在管理放射性生物废物方面也面临挑战，但靶向放疗的发展为改善癌症治疗带来了全新的机会。 靶向放射性药物（也被称为放射性配体疗法、RDC等）与ADC同属偶联药物，结构相似，一般包含四部分：放射性同位素（radioisotope）、螯合剂（chelator，负责稳定或“笼化”放射性核素，以防止核素在到达目的地之前伤及无辜）、靶向配体（负责精准识别和结合肿瘤靶点）及连接子（linker，负责连接靶向配体和螯合剂）。这样的结构为开发者提供了巨大的创新空间。越来越多的公司和机构开始研究多种排列及组合。 “创造一款好的靶向放射性药物，与其说是科学，不如说是艺术。”Advanced Accelerator Applications前CMO Germo Gericke说道（2017年，诺华以39亿美元的价格收购Advanced Accelerator Applications，获得了放射性配体药物Lutathera和相关技术平台）。 β核素之外 诺华的Lutathera和Pluvicto分别于2018年和2022年获得批准，两者都使用了同位素lutetium-177以产生β粒子。在晚期疾病患者的III期试验中，Lutathera和Pluvicto相对于标准治疗显著提高了总生存期。最近，在NETTER-2试验中，Lutathera联合octreotide一线治疗新诊断的胃肠胰神经内分泌肿瘤（GEP-NET）将死亡或进展风险降低了72%。Pluvicto同样收获了好消息：在化疗前使用，使放射学无进展生存期增加了一倍以上。诺华预计将在2024年申请额外批准Pluvicto治疗早期疾病。预计Pluvicto每年的最高销售额将超过20亿美元。 诺华现在希望将这些药物以及更广泛的放射性药物产品线扩展到更多的肿瘤和疾病阶段。一些其他公司也同样看到了靶向放射性药物赛道的机会，近两年，多家公司获得了最新融资。 许多下一代放射性药物采用了发射α粒子的放射性核素。α粒子具有传能线密度（Linear Energy Transfer，LET）高、电离辐射效应大、细胞杀伤效率高和射程短的特点，通常在组织中穿透距离约40-100 μm（<10个细胞直径）。α粒子的高LET可使肿瘤细胞核中的DNA双螺旋链断裂而引起细胞凋亡，并且所需放射性剂量较低，数个穿过细胞核的α粒子足以杀死细胞，且由于射程短，不会伤害附近的健康细胞（β粒子LET远低于α粒子，但穿透力高于α粒子，其在生物组织中可穿透几百个细胞，发挥交叉火力效应，可破坏并消灭邻近的癌细胞）。对β放射性治疗药物产生“抗性”的患者可能会受益于α放射性治疗药物。 一些与Lutathera和Pluvicto具有相同靶点的α放射性治疗药物目前取得了不错的开发进展，例如RayzeBio公司（已被BMS收购）靶向SSTR2的RYZ101（核素为actinium-225，III临床）、Fusion Pharmaceuticals公司（已被AZ收购）靶向PSMA的FPI-2265（核素也为actinium-225，II/III期临床 ）。actinium-225（Act-225）也在拜耳、Convergent Therapeutics和Actinium Pharmaceuticals的临床项目中发挥作用。此外，诺华最新收购Mariana Oncology，也收获了基于Act-225的先导项目MC-339。 α粒子的另一个优势在于它能够利用免疫系统，这对于持久的抗癌效果至关重要。用任何一种电离辐射照射肿瘤细胞都会产生新抗原，这可能会使肿瘤对免疫疗法敏感。与低能的β粒子相比，α粒子的短程高能量打击使其成为更好的新抗原“产生器”。 α放射性治疗药物的另一个潜在优势是方便：接受Lutathera或Pluvicto治疗的患者必须在治疗后至少一周内远离孕妇和儿童，因为Lu-177的半衰期为一周，并且会发出β和γ射线，这两种射线都比α粒子传播得更远。 据医药魔方NextPharma®数据库，虽然目前还没有使用Act-225或Pb-212的靶向α放射性药物获批上市，但已有超70个管线在研，其中20多个项目已经进入临床开发阶段。 “尽管业界对α放射性药物展现出巨大的热情，但目前的人类数据并不多。” MSKCC的Jason Lewis教授警告说。在不久前的ASCO年会上，强生公布了其基于Act-225的前列腺癌候选药物JNJ-69086420的I期数据，结果显示，57例接受治疗的患者中，有4名患者因治疗相关不良事件而死亡，同时在先前接受了大量治疗的患者中，出现了“深刻而持久”的反应。 “对于Act-225来说，长期的安全性仍然没有定论。”Germo Gericke说道。 α同位素之战：Act-225 or Pb-212 一个与Act-225相关的主要担忧是刺激衰变：该同位素衰变成几个“子”同位素，释放出更多的α射线。这可能会增加效力，但如果这些“子”同位素逃离肿瘤环境，也可能带来安全风险。RayzeBio在2023年发布了RYZ101剂量学亚研究的成像数据，表明大部分α辐射仍留在肿瘤内。虽然令人放心，但这些数据仅来自少数患者。此外，Act-225及其子代仅在其衰变链的某些点释放成像(γ)射线，因此其活动难以精确测量。 lead (Pb)-212另一种受行业追捧的发射α粒子的放射性核素，其衰变链更“干净”，只发射一个α粒子，因此杂散辐射的风险更小。它还可以与适合成像的发射γ射线的同位素Pb-203配对。在成像和治疗中使用相同的元素可以确保匹配的生物分布。使用不同的元素意味着你不知道你看到的(吸收)模式是否与治疗完全相同。不过，Pb-212 11小时的半衰期给物流和运输带来了巨大的挑战。Act-225需要超过10天的时间才能衰减到初始数量的一半，但这给废物管理带来了更大的负担。 Pb-212的支持者认为，其快速衰变带来的短暂高能冲击可能增强了这种同位素使免疫系统敏感的能力。由于Pb-212的清除速度很快，肿瘤浸润淋巴细胞可以聚集在一起发挥作用，而不会像使用Act-255那样受到长期辐射的损害。有临床数据显示，单次注射Perspective Therapeutics的MC1R靶向黑色素瘤候选药物（[212Pb]VMT01）后，肿瘤浸润淋巴细胞（包括CD8 T细胞）显著增加，该候选药物也正在与BMS的PD-1抗体Opdivo联合进行测试。 临床前研究显示，将一系列靶向放射性药物与检查点抑制剂相结合，总生存期获得改善，但相关临床数据还不完善。 核素供应也影响了Act-225与Pb-212的竞争。几年前，Pb-212比Act-225更难获得，这也帮助解释了为什么基于Act-225的候选药物进展更快。后来，形势发生了变化。生产Act-225需要专门的设备，如回旋加速器或核反应堆，需要一个单独的供应链，BMS和RayzeBio的III期试验RYZ101最近因Act-225短缺而推迟。开发商们正在疯狂签订供应协议，一些公司则选择直接收购相关供应商。Pb-212供应方面，包括Orano Med、Perspective和Artbio在内的公司已经开发了自己内部（in-house）的Pb-212生成方法。 FDA似乎对于α放射性药物持开放态度。2024年2月，RadioMedix和Orano Med基于Pb-212的GEP-NET候选药物AlphaMedix（II期临床）成为首个获得FDA突破性疗法认定的靶向α 放射疗法。FDA还授予了Perspective Therapeutics基于Pb-212的神经内分泌肿瘤候选药物（I/IIa期临床）快速通道资格认定。 进化的配体设计 过去几年，靶向放射性药物的配体设计也在不断发展。 Convergent Therapeutics的联合创始人兼CSO Neil Bander解释说：“我们需要将同位素半衰期与靶向药物的动力学相匹配。”衰变较慢的同位素更适合于停留时间较长的配体，比如抗体;寿命较短的小分子或小肽更适合与快速衰变的同位素匹配。 配体和靶点如何相互作用也影响同位素的选择。举例来说，Convergent的II期前列腺癌候选药物（225Ac-J591，靶向PSMA）将全尺寸抗体rosopatamab与缓慢衰减的Act-225连接起来。由于靶向PSMA会内化抗体及其偶联核素，因此，Act-225的多步衰变链更有可能被控制。 全尺寸的抗体特异性强，但尺寸及持久力可能是一个缺点：放射性同位素不应该停留太久。相对较小的肽结合了抗体的特异性及靶向亲和力，同时具有更强的肿瘤细胞穿透性及更快的清除。现在，很多公司在尝试定制肽，以实现靶点亲和力、肿瘤穿透、载荷负载能力及清除特性的最佳组合。其中，限制肾脏积累尤为重要：肾脏倾向于重吸收氨基酸，这有可能导致放射性同位素的积累。包括3B在内的公司已经找到了避免肾脏吸收肽的方法（FAP靶向肽技术），肽可以通过尿液排出体外。该公司的技术已经授权给Fusion、Debiopharm和诺华。其他一些肽设计也在发展，包括大环肽（比线性肽具有更好的稳定性和药代动力学，代表性公司PeptiDream与诺华也达成了合作，被诺华收购的Mariana Oncology也在开发大环肽）、双环肽（代表性公司Bicycle Therapeutics已经吸引了拜耳和诺华等公司）等。 小分子在放射性疗法的复兴中也占有一席之地。Radionetics正在探索靶向GPCR的小分子与同位素的结合。公司生物学高级副总裁Ana Kusnetzow说：“小分子与多肽之间的差距正在缩小。” 更多靶点 随着同位素和靶向配体的发展，用于靶向放射性药物开发的靶点范围也不断扩大，远远超出了SSTR2和PSMA。 在许多癌症中表达的FAP引起了制药界的兴趣。FAP并不存在于癌细胞本身，而是存在于周围的组织中。诺华肿瘤开发全球主管Jeff Legos表示，杀死真正的癌细胞“可能需要一些交叉火力”。他认为Lu-177的远距离β射线是理想选择。2022年，诺华从Clovis Oncology收购了基于Lu-177的FAP靶向资产，目前处于I/II期临床。 Ariceum正在开发一种靶向PARP的放射性药物，用于治疗复发性胶质母细胞瘤。由于PARP恰好位于细胞DNA的顶部，所以短范围的辐射是理想的选择。这类辐射也会降低损伤大脑中邻近神经元的风险。Ariceum将PARP抑制剂(本身是一种有效的抗癌药物) 附着在放射性碘-123上，碘-123可以发射超短程俄歇电子（Auger electrons）和γ射线。PARP酶位于俄歇辐射的范围内，并且在DNA损伤时会上调。因此，以辐射损伤DNA应该会导致更多的PARP表达和更多的同位素结合，就像一个连锁反应。该公司计划于2024年6月在英国开始I期试验。 俄歇电子是无辐射跃迁引起的低能电子，其作用范围远低于α粒子与β粒子，可直接定位病灶部分而不损伤周围的细胞。迄今为止，工业界对俄歇电子的兴趣不如α粒子与β粒子。但伦敦国王学院放射生物学专家Samantha Terry认为，俄歇电子可能在未来的治疗中占有一席之地。虽然俄歇电子不太可能对大肿瘤有帮助，但可以对最顽固的癌细胞进行有针对性的“最后一击”，清除癌症的最后残余。 在放射性药物管线中，还有很多其他靶点，如Carbonic anhydrase IX（代表性项目：TLX250）、GRPR（代表性项目：177Lu-NeoBOMB1、212Pb-DOTAM-GRPR1）、CXC4（代表性项目：90Y-pentixather）、KLK2（代表性项目：JNJ-69086420）、nectin 4、glypican-3、melanocortin 1 receptor、delta-like ligand 3等。 Orano Med的CEO Julien Dodet说：“这可能只是一个开始。α辐射如此强大，以至于只需要少数分子到达癌细胞就可以消灭它。这有望大大拓宽潜力靶点的范围，包括低表达的靶点。” 障碍 尽管已有一些下一代放射性药物获批上市，但这类疗法也将面临一些独特的“后勤”挑战。同位素供应、大规模生产、在同位素衰变时间内交付给患者都需要相当的专业知识、设施和协调。诺华的4个放射性药物生产基地使其每年可以生产25万剂Pluvicto。但即使是这家资源丰富的制药巨头也面临着产能挑战。用一位生物技术公司CEO的话说，其他规模较小的开发商希望诺华可以“铺设一条其他人可以驾驶的高速公路”。 不过，诺华当前只销售两种下一代放射性药物，都使用相同的放射性同位素。其他的放射性同位素则需要不同的配送和处理基础设施。例如，使用短寿命Pb-212的产品必须在靠近治疗中心的地方生产，并且由于发射强烈的γ射线，需要大量的屏蔽。医院和治疗中心必须将基于Act-225的产品废物储存100天（根据指南要求安全的同位素储存至少达10个半衰期），病人可能需要在医院待更长时间。 另一个复杂的问题是，放射性药物必须由训练有素的核医学医生管理。这类医生目前资源并不充分。Lutathera和Pluvicto的成功吸引了更多的受训者，但是肿瘤学家和核医学专家之间需要协调是另一个挑战（他们可能在不同的site或机构工作）。 一些公司，如Y-mAbs正在开发可能有助于解决这些问题的方法。Y-mAbs的两步骤放射性药物技术授权自MSKCC和MIT，用基于抗体的四聚体“预涂”肿瘤细胞，这些四聚体结合靶点，然后分解。未结合的片段被迅速排出体外，结合的组分就像“分子魔术贴”一样，吸引在第二步中递送的螯合剂-同位素复合物。第一步的预涂工作由肿瘤学家操作，因为不涉及放射性。第二步需要核医学专家操作，过程将比Lutathera所需的5或6小时输液更快，因为只涉及“笼化”的放射性同位素。此外，由于大部分配体复合物在同位素注入之前就被排出体外，因此放射性预计不会持续太久。“对于Lutathera，配体-螯合剂在工厂与Lu-177结合，并以偶联物的形式运输。在我们的病例中，这种组装发生在病人体内。”Y-mAbs CEO Michael Rossi说道。 Y-mAbs的基于Lu-177的GD2（存在于一系列转移性肿瘤中）靶向项目目前处于I期临床，用于治疗小细胞肺癌、黑色素瘤和肉瘤。 新的治疗支柱 下一波获批放射性药物可能会与Lutathera或Pluvicto采用同样的靶点和/或同位素，但有逐步的改进，如更方便的剂量，疗效的改善等。 除此之外，该领域的支持者正押注使用更广泛放射性同位素、配体和靶点，治疗更广泛疾病类型和阶段的新型放射性药物。产业参与者们认为，下一代放射性药物可能会成为肿瘤治疗的新支柱。 2013–2026全球核医学市场预测 据Evaluate预测，到2026年，放射性药物疗法的年销售额预计将超过60亿美元。算上诊断试剂，这个数字要翻了一番。这就是投资者不断涌入的原因。同位素供应商及放射性药物开发商ITM本月刚刚宣布完成1.88亿欧元最新融资，去年6月5日，该公司也宣布了2.55亿欧元的融资。 未来，携带Act-225或Pb-212的放射性药物的获批将为这个已经因投资者兴趣、并购和许可交易而高涨的领域提供进一步的动力。 “这仍然是一个年轻的行业，未来还有更多机会。” 3B Pharmaceuticals的核医学和成像负责人Christiane Smerling说道。 备注：文中图表均来自Nature。 参考资料： [1]Precision radiation opens a new window on cancer therapy（来源：Nature） [2]《放射性体内治疗药物临床评价技术指导原则》 Copyright © 2024 PHARMCUBE. 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