Rituximab

28岁的林女士，近半年总觉得人有点“虚”——容易疲劳、体重莫名下降、还总是低烧、盗汗。本以为是工作压力大，拖着没当回事。直到某天，她无意中摸到左腋下有个小包块，按压不疼，但越来越大，她才决定去医院看看。B超显示：腋窝肿块约3.8×2.5cm，血常规显示贫血、CRP升高、白蛋白偏低。医生建议住院进一步评估。胸腹增强CT提示：纵隔、腹膜后多个淋巴结增大，一时间，“淋巴瘤？”“肿瘤转移？”成了家人最担心的词。最终在全麻下行腋下肿块切除手术。可病理结果却出乎所有人意料：淋巴结增生性病变，符合Castleman病（卡斯特曼病），浆细胞型。这是一种罕见的淋巴结增生性疾病，容易误诊为淋巴瘤或感染性疾病，既非良性肿瘤，也不完全是癌症。林女士的病情进一步检查后，被诊断为多中心性Castleman病（MCD），需长期随访和治疗。什么是卡斯尔曼病Castleman 病（Castleman disease，CD），卡斯尔曼病，又称巨大淋巴结病或血管滤泡性淋巴结增生症。是一种较为少见的淋巴增生性疾病。1956 年由 Benjamin Castleman 首次报道。临床上根据肿大淋巴结分布和器官受累的情况不同，可将 CD 分为单中心型（unicentric CD，UCD） 和多中心型（multicentric CD，MCD）。前者往往仅累及单个淋巴结区域，相关症状较轻，外科治疗效果良好；后者则累及多个淋巴结区域，有较为明显的全身症状，预后较差。临床表现CD是一种罕见的淋巴组织增生性疾病，临床表现多样，轻则无症状，仅表现为淋巴结肿大，重则可引发严重的全身炎症反应和多器官功能障碍。确诊需依赖淋巴结活检，并排除其他疾病。单中心型卡斯尔曼病（UCD）通常仅累及身体某一部位的单个或多个淋巴结，常见于胸部、颈部或腹部。多数UCD患者无明显症状，仅因肿大的淋巴结压迫周围结构引发不适。个别患者可出现低热、乏力、体重减轻、皮疹等轻度系统症状，这些表现通常在病灶切除后缓解。部分患者可能伴有副肿瘤性天疱疮、闭塞性细支气管炎或发育迟缓。多中心型卡斯尔曼病（MCD）表现为多个区域淋巴结肿大，并伴有明显的全身炎症症状，如发热、盗汗、乏力、贫血、水肿、肝脾肿大及肾功能异常。MCD可分为HHV-8阳性型和特发性型（iMCD）。其中iMCD又包括TAFRO亚型和NOS亚型，前者病情进展迅猛，伴血小板减少、水肿、骨髓纤维化和器官肿大，后者则表现相对温和，常伴血小板增多和免疫球蛋白升高。HHV-8相关MCD多见于免疫功能低下者，常合并HIV感染及卡波西肉瘤等。此外，iMCD可能与POEMS综合征、恶性肿瘤或其他免疫紊乱相关联。UCD患者虽然较少出现严重并发症，但应警惕副肿瘤性天疱疮的发生，其为UCD最致命的潜在并发症。诊断Castleman病的诊断较为复杂，因其临床表现多样且与多种常见疾病（如感染、淋巴瘤、自身免疫病）相似，常被误诊或漏诊。确诊通常需结合临床表现、实验室检查、影像学评估以及病理组织学特征，并在排除其他可能疾病后作出。诊断主要依赖以下三类评估：一是淋巴结活检，这是诊断的核心环节。需进行完整的切除性活检，而非细针抽吸或核心活检。镜下典型特征包括退化性或增生性生发中心、滤泡树突状细胞增生、小血管过度增生、浆细胞浸润等。根据组织学特征，Castleman病可分为三型：透明血管型、浆细胞型和混合型。二是实验室检查，用于评估系统性炎症和器官功能情况。常规项目包括全血细胞计数、C反应蛋白（CRP）、红细胞沉降率（ESR）、肝肾功能、白蛋白、免疫球蛋白，以及HIV/HHV-8检测。HHV-8阳性提示HHV-8相关的多中心型Castleman病（MCD）。三是影像学检查，如X光、CT、PET-CT等，用于评估淋巴结分布及活性，辅助判断是否为单中心型（UCD）或多中心型（MCD）。各亚型诊断要点如下：UCD：表现为单一部位淋巴结肿大，多无全身症状，诊断依赖切除淋巴结的病理特征。HHV-8阳性的MCD：具备多发淋巴结肿大、炎症症状、活检显示“Castleman样”病理特征且HHV-8阳性。iMCD（特发性MCD）：需符合两个主要标准（特征性活检病理＋多区域淋巴结肿大）及11个次要标准中至少2项（至少1项为实验室异常），并排除感染、肿瘤和自身免疫病。Castleman病的诊断本质上是排除性诊断，依赖病理证据和系统性临床评估，需多学科合作，以确保准确识别和分类。治疗Castleman病的治疗根据亚型不同而异，主要分为单中心型（UCD）、特发性多中心型（iMCD）和HHV-8相关多中心型（HHV-8 MCD）。1. 单中心型Castleman病（UCD）UCD首选治疗是手术切除受累淋巴结，通常可治愈。若无法手术或复发，依据症状选择治疗：压迫症状可用利妥昔单抗，炎症症状可用抗IL-6治疗（如Siltuximab），必要时辅以放疗。2. 特发性多中心型Castleman病（iMCD）一线治疗为抗IL-6抗体Siltuximab（无此药时用Tocilizumab）。无效时可考虑糖皮质激素、利妥昔单抗、西罗莫司或化疗。部分轻症患者可先观察，重症者或器官功能受损者可联合化疗或短期激素治疗。沙利度胺等免疫调节药也有一定疗效。3. HHV-8相关多中心型Castleman病（HHV-8 MCD）利妥昔单抗是一线治疗，有时需联合抗病毒（如更昔洛韦）或细胞毒化疗。若合并HIV感染，推荐联合抗反转录病毒治疗，但避免使用骨髓抑制较强的药物如齐多夫定。总体上，Castleman病的治疗需根据亚型、症状严重程度及是否合并感染进行个体化方案选择。参考资料：1.Van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018 Nov 15;132(20):2115-2124. doi: 10.1182/blood-2018-07-862334. Epub 2018 Sep 2. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657.3. Liu AY, Nabel CS, Finkelman BS, et al. Idiopathic multicentric Castleman’s disease: a systematic literature review. The Lancet Haematology. 2016;3(4):e163-e175.来源 | 梅斯医学编辑 | wanny神经系统罕见病交流群↓点击下方“阅读原文”，下载梅斯医学APP吧！

▎药明康德编者按：靶向蛋白降解剂（TPD）通过利用细胞自身的蛋白降解系统降解与疾病相关的靶蛋白。由于无需直接抑制靶蛋白的活性，这种治疗模式有望针对许多以往被认为“不可成药”的靶点，因而成为新药开发的热点领域之一。早在近10年前，这项技术刚刚起步时，药明康德就开始布局相关能力和技术，积累了丰富的成功经验，搭建起集发现、合成、分析纯化和测试等能力的一体化赋能平台。目前，该平台已成功支持超过120款TPD分子的开发，其中20余款顺利推进至临床阶段。本文将回顾2025年上半年TPD领域的最新进展。还将介绍药明康德的一体化CRDMO平台如何高效解决TPD药物开发过程中的诸多挑战，在短短12个月内完成IND申报所需的蛋白降解靶向嵌合体（PROTAC）候选药物的制备，并为首次人体临床研究提供临床试验用药。临床进展：首个PROTAC分子3期结果发布，细胞外蛋白降解疗法初步临床数据积极今年3月，辉瑞（Pfizer）和Arvinas联合公布了PROTAC药物vepdegestrant的首个关键性3期临床试验结果。在携带ESR1突变的HR阳性、HER2阴性乳腺癌患者中，vepdegestrant与活性对照相比，将患者的疾病进展或死亡风险降低超过40%（风险比低于0.60）。Arvinas和辉瑞近日已经向美国FDA递交vepdegestrant的新药申请（NDA）。此外，该公司的另一款在研PROTAC疗法ARV-102在1期临床试验中显著降低健康志愿者中枢神经系统（CNS）和外周的LRRK2蛋白水平。这一结果为后续在LRRK2相关神经退行性疾病中的进一步临床研究奠定了基础。Kymera Therapeutics公司的潜在“first-in-class”口服STAT6降解剂KT-621在1期健康受试者的临床试验中也获得积极结果。数据显示，每日一次口服KT-621，在所有高于1.5 mg剂量水平中实现了平均超过90%的血液STAT6降解；在所有≥50 mg的多剂量递增（MAD）组中，更在血液与皮肤中均达成STAT6完全降解。百时美施贵宝（Bristol Myers Squibb）在欧洲血液学协会（EHA）年会上，展示了其靶向蛋白降解平台的最新研究数据，包括其在研口服E3泛素连接酶cereblon调节剂（CELMoD）药物mezigdomide和iberdomide在多发性骨髓瘤（MM）患者中的更新临床研究结果，以及golcadomide在非霍奇金淋巴瘤（NHL）中的研究进展。此外，该公司也公布其潜在“first-in-class”的口服BCL6配体导向降解剂（LDD）BMS-986458在NHL中的初步研究结果。其中，golcadomide联合利妥昔单抗治疗复发/难治性滤泡性淋巴瘤患者展现出显著疗效，总缓解率（ORR）高达94%，完全缓解（CR）率为63%。BMS-986458的初步研究结果显示，在外周血和肿瘤组织中均观察到BCL6快速且持久的降解。从最低剂量起即观察到在弥漫性大B细胞淋巴瘤和滤泡性淋巴瘤患者中的抗肿瘤活性。在21名可评估疗效的患者中，ORR为81%（N=17），CR率为23.8%（N=5）。Biohaven公司开发的靶向蛋白降解剂BHV-1300和BHV-1400近期在早期临床试验中表现出显著降低细胞外蛋白的能力。这两款在研药物均为双特异性分子，一端与靶蛋白结合，另一端与肝细胞表面的去唾液酸糖蛋白受体（ASGPR）结合。ASGPR可介导肝细胞通过内吞作用，将靶蛋白摄入细胞内并降解。临床试验数据显示，BHV-1300和BHV-1400注射入患者体内后，短短数小时内即介导了靶蛋白的快速降解，蛋白水平降幅达到70%~80%，凸显出这类药物迅速的起效速度与临床应用潜力。融资与合作：大药企持续布局分子胶药物在靶向蛋白降解领域，促进蛋白降解的双特异性分子之外，分子胶降解剂通过与单个靶蛋白或E3泛素连接酶结合，即可诱导或稳定它们之间的相互作用，从而实现蛋白降解。这一细分领域近年来不断升温。在2024年，诺华（Novartis）、渤健（Biogen）、辉瑞、武田（Takeda）、卫材（Eisai）与诺和诺德（Novo Nordisk）等多家跨国药企先后签署了单笔数额超过10亿美元的分子胶研发合作协议。进入2025年上半年，分子胶领域的布局热度依然持续。今年5月，基因泰克（Genentech）与Orionis Biosciences达成超过20亿美元的研发合作协议，致力于开发靶向难以成药靶点的小分子单价分子胶药物，用于癌症治疗。此前在今年2月，礼来（Eli Lilly and Company）也与Magnet Biomedicine公司签署一项近13亿美元的合作协议。双方合作的范围不仅涵盖基于分子胶的蛋白降解剂研发，还将探索利用分子胶促进蛋白质之间产生诱导接近和协同作用，精准靶向疾病相关组织的创新作用机制。此外，艾伯维（AbbVie）公司在1月也与Neomorph公司达成超16亿美元的分子胶蛋白降解剂研发合作。与此同时，2025年上半年，多家开发靶向蛋白降解剂的新锐公司也完成新一轮融资。具体融资及合作信息请参见下表：▲2025年上半年靶向蛋白降解领域的融资和研发合作信息（数据来源：公开资料）展望未来，靶向蛋白降解剂有着更为深远的意义。这一领域的权威，丹娜-法伯癌症研究所（Dana–Farber Cancer Institute）的Eric Fischer教授在接受Nature Medicine采访时指出，利用口服小分子药物来降解蛋白质，将改变过去受制于“可成药性”局限的研发模式，使科学家们能更自由地探索哪些靶点真正能够最大程度改变疾病的进程。期待未来有更多蛋白降解药物在临床研究中取得积极进展，造福广大患者。然而，TPD药物的广阔前景也伴随着独特的开发挑战。例如，由于分子量大、结构复杂，PROTAC类分子通常存在溶解度差和药代动力学性质不佳的问题。以下案例展示了药明康德旗下合全药业（WuXi STA）如何与合作伙伴携手，有效应对这些挑战。解决TPD药物开发痛点，加速创新疗法进入临床试验几年前，一家公司因PROTAC分子的生产难题，选择与合全药业合作，希望在14个月内完成候选药物的生产，以支持IND申请及首次人体临床试验。然而，该候选分子的初始合成路线非常复杂，需要多达24个步骤，且最终产率仅为0.3%。此外，PROTAC特定的分子结构进一步增加了产品结晶和纯化难度。同时，由于候选化合物分子量较大且水溶性低，其口服生物利用度只有0.9%。值得注意的是，在合成过程中还有三步涉及使用罕见金属钯（Pd）作为催化剂，这不仅带来潜在安全隐患，更显著提高了生产成本。针对上述问题，合全药业的工艺研发、生物催化及结晶工艺等团队协同攻关，重新设计了一条合成路线，将合成步骤从原来的24步缩减至16步，并在其中两个步骤中用生物催化剂替代了钯催化剂。为攻克结晶难题，团队采用高通量结晶筛选技术，迅速确定了符合纯度与产量要求的结晶工艺，并通过优化大幅提升了生产过程的总产率。这些改进不但极大提高了整体合成工艺的可放大性，也提升了合成效率并降低了成本。与此同时，合全药业的制剂研发团队针对药物口服生物利用度低的问题，进行了全面的生物利用度增强技术筛选，最终选定喷雾干燥制备固体分散体（SDD）技术进行制剂制备。这种技术将难溶药物以无定形状态高度分散在聚合物中，目前已成功应用于多种上市药物的制剂开发中。借助SDD技术，候选化合物药片制剂的口服生物利用度提高了约30倍，为后续临床应用奠定了坚实基础。合全药业一体化CRDMO平台的整合能力，使多个团队能够并行推进原料药与制剂开发，高效协作，加速破解PROTAC分子开发中的难题。最终，团队仅用了12个月就完成了支持IND申请所需的候选药物生产和制剂制备，顺利供应首次人体临床研究用药，比合作伙伴原定时间提前了2个月。作为赋能全球靶向蛋白降解药物开发的重要平台之一，药明康德一体化平台的能力不但涵盖PROTAC，还包括分子胶、以及多种新兴双功能性蛋白降解剂类型。例如，诱导细胞外或细胞膜蛋白进入溶酶体进行降解的溶酶体靶向嵌合体（LYTAC），将抗体与蛋白降解剂偶联产生的蛋白降解剂-抗体偶联药物（DAC），诱导靶蛋白被自噬体吞噬降解的自噬靶向嵌合小分子（AUTAC），以及靶向降解特定RNA的核糖核酸酶靶向嵌合体（RIBOTAC）等。展望未来，药明康德将继续秉持“让天下没有难做的药，难治的病”的愿景，依托全球研发基地与生产网络，以独特的一体化、端到端的CRDMO模式，助力靶向蛋白降解剂的开发，帮助合作伙伴将科学创新转化为惠及全球患者的变革性药物。CRDMO: H1 2025 Review of Targeted Protein Degraders Targeted protein degraders (TPDs) offer a novel therapeutic approach by leveraging the body’s own protein degradation systems to eliminate disease-associated target proteins. This strategy opens new avenues for addressing previously “undruggable” targets. Nearly a decade ago, when this technology was still in its infancy, WuXi AppTec began building relevant capabilities. Since then, the company has established a comprehensive, integrated platform encompassing discovery, synthesis, purification, analysis, and testing. To date, this platform has supported the development of more than 120 TPD molecules, with over 20 advancing to clinical stages. This article summarizes key developments in the TPD landscape during the first half of 2025. It also presents a case study demonstrating how WuXi AppTec’s integrated CRDMO platform efficiently overcomes TPD development challenges, including preparing IND-enabling materials for a proteolysis-targeting chimera (PROTAC) candidate within just 12 months for first-in-human (FIH) trials.Clinical Advances: First PROTAC Phase 3 Results and Progress in Extracellular Protein DegradersIn March 2025, Pfizer and Arvinas jointly announced top-line results from the first-ever Phase 3 clinical trial of a PROTAC therapy—vepdegestrant. In HR+, HER2- breast cancer patients with ESR1 mutations, vepdegestrant reduced the risk of disease progression or death by more than 40% compared to the active control (hazard ratio < 0.60). Arvinas and Pfizer have recently submitted a new drug application (NDA) for the drug.Arvinas' second PROTAC candidate, ARV-102, also showed promise in Phase 1 studies, achieving significant reductions in LRRK2 protein levels in both the central nervous system and peripheral tissues of healthy volunteers—laying the groundwork for future clinical trials in LRRK2-related neurodegenerative diseases.Meanwhile, Kymera Therapeutics reported positive Phase 1 results for KT-621, a potential first-in-class oral STAT6 degrader. Once-daily administration achieved over 90% average degradation of STAT6 in the blood at doses above 1.5 mg. Complete degradation in both blood and skin was observed in all multiple ascending dose (MAD) cohorts at doses ≥50 mg.Bristol Myers Squibb presented its latest research on targeted protein degradation at the European Hematology Association (EHA) 2025 Congress, highlighting progress across its protein degradation platform. This included updated clinical data on its investigational oral cereblon E3 ligase modulators (CELMoDs) mezigdomide and iberdomide in patients with multiple myeloma (MM), as well as developments in the study of golcadomide in non-Hodgkin lymphoma (NHL). Additionally, the company released initial data on BMS-986458, a potential first-in-class oral BCL6 ligand-directed degrader (LDD), in NHL.Among the findings, golcadomide in combination with rituximab demonstrated significant efficacy in patients with relapsed/refractory follicular lymphoma, with an overall response rate (ORR) of 94% and a complete response (CR) rate of 63%. Preliminary results for BMS-986458 showed rapid and sustained degradation of BCL6 in both peripheral blood and tumor tissue. Antitumor activity was observed from the lowest dose levels in patients with diffuse large B-cell lymphoma and follicular lymphoma. Among 21 evaluable patients, the ORR was 81% (N=17), with a CR rate of 23.8% (N=5).Biohaven’s BHV-1300 and BHV-1400 demonstrated rapid and robust reductions in target protein levels—achieving 70–80% decreases within hours. These molecules bind target proteins on one end and the asialoglycoprotein receptor (ASGPR) on the other, thereby facilitating internalization and degradation via endocytosis.Financing and Collaborations: Molecular Glues Attract Major DealsAlongside bifunctional degraders, molecular glues—small molecules that induce or stabilize interactions between E3 ligases and target proteins—continue to draw significant interest. In 2024, multiple major pharmaceutical companies signed R&D deals for molecular glue technologies worth over $1 billion.That momentum has carried into 2025, with several multinational pharmaceutical companies announcing collaborations focusing on molecule glue-based degraders, targeting undruggable targets in oncology, immunology, and more diseases with unmet medical needs. In addition, novel proximity-inducing mechanisms are being explored to target disease-relevant tissues with high precision. In parallel, several emerging companies in the TPD space completed new funding rounds during H1 2025. The potential of targeted protein degradation continues to expand. A recent article in Nature Medicine noted that the ability to degrade proteins with orally available small molecules is fundamentally reshaping drug discovery—liberating scientists from traditional “druggability” constraints and allowing them to focus on the targets that matter most in disease biology. As the field progresses, more TPD therapies are expected to achieve clinical milestones and ultimately bring benefits to patients worldwide.However, the promise of TPDs comes with unique development challenges. For example, due to their large molecular weight and structural complexity, PROTACs often suffer from poor solubility and suboptimal pharmacokinetics. The following case study illustrates how WuXi STA, an integral part of WuXi AppTec, collaborated with a partner to address these challenges effectively.Addressing Key Bottlenecks in TPD Drug DevelopmentSeveral years ago, a biotech company developing a PROTAC candidate faced synthetic challenges and turned to WuXi STA for support. The goal was to complete the production of drug substance and clinical trial material within 14 months to support an IND filing and FIH trial. However, the original synthesis route involved 24 steps and yielded only 0.3%. Crystallization and purification proved difficult due to the compound’s unique structure.Compounding the challenge, the candidate’s high molecular weight and poor solubility resulted in oral bioavailability of just 0.9%. Moreover, three steps in the synthesis relied on a palladium (Pd) catalyst, raising safety concerns and increasing production costs.To resolve these issues, WuXi STA’s process chemistry, biocatalysis, and crystallization teams worked in concert to redesign the synthesis route, reducing the number of steps from 24 to 16 and replacing palladium with biocatalysts in two steps. To tackle crystallization bottlenecks, high-throughput crystallization screening identified suitable conditions that met both purity and yield requirements. These changes significantly improved the scalability and efficiency of the synthetic route while reducing costs.Simultaneously, WuXi STA’s formulation team addressed the low oral bioavailability by exploring a range of enabling technologies and ultimately selected spray-dried dispersion (SDD) to prepare a solid dosage form. SDD disperses poorly soluble compounds in an amorphous state within a polymer matrix and has been successfully used in several approved drugs. With this approach, the candidate’s oral bioavailability improved by approximately 30-fold—supporting further clinical advancement.Thanks to WuXi STA’s integrated CRDMO model, API process development and formulation were advanced in parallel by multiple teams working seamlessly together. Ultimately, they delivered IND-enabling materials and clinical trial materials within just 12 months—two months ahead of schedule.As one of the industry’s leading platforms enabling targeted protein degradation, WuXi AppTec’s integrated services extend beyond PROTACs to a wide array of bifunctional modalities, including:• LYTACs (lysosome-targeting chimeras): for degrading extracellular or membrane proteins via lysosomes• DACs (degrader-antibody conjugates): combining antibodies with protein degraders• AUTACs (autophagy-targeting chimeras): small molecules inducing autophagic degradation• RIBOTACs (ribonuclease-targeting chimeras): targeting and degrading specific RNA sequencesAs targeted protein degradation continues to evolve, WuXi STA remains committed to leveraging its integrated CRDMO platform to empower the development of targeted protein degraders, helping partners translate scientific innovation into transformative medicines for patients around the world.参考资料：[1] Induced proximity pushes beyond protein degraders, as first RIPTAC moves into the clinic. Retrieved May 15, 2025, from https://www-nature-com.libproxy1.nus.edu.sg/articles/d41573-025-00037-7[2] Monte Rosa Therapeutics Announces Fourth Quarter 2024 Financial Results and Provides Corporate Update Including New Clinical Results from MRT-6160 and MRT-2359 Programs. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/03/20/3046104/0/en/Monte-Rosa-Therapeutics-Announces-Fourth-Quarter-2024-Financial-Results-and-Provides-Corporate-Update-Including-New-Clinical-Results-from-MRT-6160-and-MRT-2359-Programs.html[3] Magnet Biomedicine Enters into a Collaboration and License Agreement with Lilly to Discover and Develop Novel Molecular Glue Medicines. Retrieved May 15, 2025, from https://www.prnewswire.com/news-releases/magnet-biomedicine-enters-into-a-collaboration-and-license-agreement-with-lilly-to-discover-and-develop-novel-molecular-glue-medicines-302387756.html[4] AbbVie and Neomorph Announce Collaboration to Develop Molecular Glue Degraders for Oncology and Immunology. Retrieved May 15, 2025, from https://www.prnewswire.com/news-releases/abbvie-and-neomorph-announce-collaboration-to-develop-molecular-glue-degraders-for-oncology-and-immunology-302357741.html[5] Arvinas Presents First-in-Human Data for Investigational Oral PROTAC ARV-102 Demonstrating Blood-Brain Barrier Penetration, and Central and Peripheral LRRK2 Degradation. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/04/04/3055854/0/en/Arvinas-Presents-First-in-Human-Data-for-Investigational-Oral-PROTAC-ARV-102-Demonstrating-Blood-Brain-Barrier-Penetration-and-Central-and-Peripheral-LRRK2-Degradation.html[6] Arvinas and Pfizer Announce Positive Topline Results from Phase 3 VERITAC-2 Clinical Trial. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/03/11/3040386/0/en/Arvinas-and-Pfizer-Announce-Positive-Topline-Results-from-Phase-3-VERITAC-2-Clinical-Trial.html[7] Argobio and the Institut Pasteur launch Enodia Therapeutics: A biotech company with a new approach for Targeted protein Degradation. Retrieved May 15, 2025, from https://www.pasteur.fr/en/press-area/press-documents/argobio-and-institut-pasteur-launch-enodia-therapeutics-biotech-company-new-approach-targeted[8] Biohaven Reports Positive Degrader Data Achieving > 80% Sustained Reductions in Total IgG with Potential First-in-Class BHV-1300. Retrieved May 15, 2025, from https://ir.biohaven.com/news-releases/news-release-details/biohaven-reports-positive-degrader-data-achieving-80-sustained[9] Revolution Medicines Reports First Quarter 2025 Financial Results and Update on Corporate Progress. Retrieved May 15, 2025, from https://ir.revmed.com/node/11636[10] Photys Therapeutics Enters into Exclusive License Agreement with Polymed for Phase 1-Ready IRAK4 Degrader, Furthering its Proximity-based Pipeline and Mission. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/02/20/3029603/0/en/Photys-Therapeutics-Enters-into-Exclusive-License-Agreement-with-Polymed-for-Phase-1-Ready-IRAK4-Degrader-Furthering-its-Proximity-based-Pipeline-and-Mission.html[11] Nurix Licenses a Drug Discovery Program to Sanofi Targeting a Novel Transcription Factor for Autoimmune Diseases. Retrieved May 15, 2025, from https://ir.nurixtx.com/news-releases/news-release-details/nurix-licenses-drug-discovery-program-sanofi-targeting-novel[12] PAQ Therapeutics Announces $39 Million Series B Financing and Initiates Phase 1 Trial to Advance Novel Approach Addressing KRAS-Driven Cancers with High Unmet Need. Retrieved May 15, 2025, from https://www.prnewswire.com/news-releases/paq-therapeutics-announces-39-million-series-b-financing-and-initiates-phase-1-trial-to-advance-novel-approach-addressing-kras-driven-cancers-with-high-unmet-need-302447786.html[13] Fraser Therapeutics Secures $29 Billion Series B from J&J and 8 Others. Retrieved May 15, 2025, from http://prazertx.com/pages/board/view.php?menu_code=477&board_sid=16&data_sid=261&page_num=&skey=&sval=&category_code1=[14] TRIMTECH Therapeutics raises $31M seed funding to advance targeted protein degradation pipeline for treatment of neurodegenerative diseases. Retrieved May 15, 2025, from https://www.businesswire.com/news/home/20250305069531/en/TRIMTECH-Therapeutics-raises-%2431M-seed-funding-to-advance-targeted-protein-degradation-pipeline-for-treatment-of-neurodegenerative-diseases[15] Auron Therapeutics Announces FDA Clearance to Initiate Clinical Development of AUTX-703 and Completion of Series B Financing. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/02/04/3020131/0/en/Auron-Therapeutics-Announces-FDA-Clearance-to-Initiate-Clinical-Development-of-AUTX-703-and-Completion-of-Series-B-Financing.html[16] Advancing targeted protein degraders: leveraging CMC strategies for rapid IND submission and bioavailability solutions. Retrieved May 15, 2025, from https://sta.wuxiapptec.com/wp-content/uploads/2024/10/Advancing-targeted-protein-degraders.pdf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