A Multi-center Phase 2 Study of Neoadjuvant Immunotherapy in Combination With the Anti-GDF-15 Antibody Visugromab (CTL-002) for the Treatment of Muscle Invasive Bladder

This is a multi-center, stratified and single-blinded Phase 2 study of neoadjuvant immunotherapy in combination with the antiGDF15 antibody visugromab (CTL-002) for the treatment of subjects with MIBC set to undergo radical Cystectomy (RC)/Re-TURBT who cannot receive or refuse to receive cisplatin-based chemotherapy.

开始日期2023-09-06

申办/合作机构

CatalYm GmbH

NCT04725474

/ Active, not recruiting临床1/2期

A Phase 1/2, FIH, Two-part, Open-label Clinical Trial of Intravenous (IV) Administration of CTL-002 Given as Monotherapy and/or in Combination With an Anti-PD-1 Checkpoint Inhibitor in Subjects With Advanced-stage, Relapsed/Refractory Solid Tumors (The "GDFATHER"-Trial: GDF-15 Antibody-mediaTed Human Effector Cell Relocation).

The Phase 1 part (Part A) is a dose escalation study of IV visugromab (CTL-002, a monoclonal antibody neutralizing GDF-15) as monotherapy and in combination with an approved checkpoint inhibitor (CPI) in patients with advanced solid tumors.
Enrolment into the Ph 1 part is completed.
The Phase 2 parts (Part B) are cohort expansions with visugromab (CTL-002) in combination with a defined CPI at a fixed dose into seven different solid tumor indications.

开始日期2020-12-09

申办/合作机构

CatalYm GmbH

100 项与维苏格罗单抗相关的临床结果

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100 项与维苏格罗单抗相关的转化医学

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100 项与维苏格罗单抗相关的专利（医药）

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项与维苏格罗单抗相关的文献（医药）

2025-01-30·Nature

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours

Article

作者: Trojan, Jörg ; Vilalta-Lacarra, Anna ; Fettes, Petra ; Richly, Heike ; Akdemir, Julia ; Chun, Felix Kyoung Hwan ; Gajewski, Thomas F ; Hackl, Hubert ; Racca, Fabricio ; Esteban-Villarrubia, Jorge ; Rössler, Bernhard ; Reis, Henning ; Torres-Jiménez, Javier ; Bargou, Ralf ; Lloyd, Peter ; Wild, Peter ; Trajanoski, Zlatko ; Alonso, Guzman ; Landa-Magdalena, Ana ; Auckenthaler, Alexandra ; Hermann, Frank ; Schuler, Martin ; Schuberth-Wagner, Christine ; Gjorgjioska, Ana ; Rodriguez Ruiz, Maria-Esperanza ; König, David ; Koster, Kira-Lee ; Foerster, Friedrich ; Melero, Ignacio ; Goebeler, Maria-Elisabeth ; Auer, Marlene ; Saavedra, Omar ; Koll, Florestan J ; Machacek, Matthias ; Dutta, Aradhana ; Gromke, Tanja ; Fridman, Wolf H ; Galle, Peter R ; de Miguel Luken, Maria ; Soto-Castillo, Juan José ; Eggenschwiler, Corinne ; Liebig, Mara ; Sanduzzi-Zamparelli, Marco ; Dummer, Reinhard ; Garralda, Elena ; Hess, Dagmar ; Läubli, Heinz ; Rüschoff, Josef ; da Silva, Antonio ; Tereshchenko, Anastasiia ; Rüdiger, Manfred ; Eggermont, Alexander M M ; Calvo, Emiliano ; L'Huillier, Phil ; Haake, Markus ; Fortuny, Marta ; Koch, Christine ; Klar, Kathrin ; Gogolla, Falk ; Moreno, Irene ; Sayehli, Cyrus ; Joerger, Markus ; Sabat, Paula ; Oberoi, Arjun ; Hernando-Calvo, Alberto ; Schmitt, Andreas M ; Reichhardt, Daniela ; Schöniger, Sandra ; Lichtenegger, Felix S ; Ramelyte, Egle ; Zink, Carina ; de Velasco, Guillermo ; Martín-Liberal, Juan ; Reig, Maria ; Wischhusen, Jörg ; Leo, Eugen

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment¹. Yet, response rates are still limited, and tumour progression commonly occurs². Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity. Recently, growth differentiation factor 15 (GDF-15), a cytokine that is abundantly produced by many cancer types, was shown to interfere with antitumour immune response. In preclinical cancer models, GDF-15 blockade synergistically enhanced the efficacy of anti-PD-1-mediated checkpoint inhibition³. In a first-in-human phase 1-2a study (GDFATHER-1/2a trial, NCT04725474 ), patients with advanced cancers refractory to anti-PD-1 or anti-PD-L1 therapy (termed generally as anti-PD-1/PD-L1 refractoriness) were treated with the neutralizing anti-GDF-15 antibody visugromab (CTL-002) in combination with the anti-PD-1 antibody nivolumab. Here we show that durable and deep responses were achieved in some patients with non-squamous non-small cell lung cancer and urothelial cancer, two cancer entities identified as frequently immunosuppressed by GDF-15 in an in silico screening of approximately 10,000 tumour samples in The Cancer Genome Atlas database. Increased levels of tumour infiltration, proliferation, interferon-γ-related signalling and granzyme B expression by cytotoxic T cells were observed in response to treatment. Neutralizing GDF-15 holds promise in overcoming resistance to immune checkpoint inhibition in cancer.

2015-07-01·Arteriosclerosis, thrombosis, and vascular biology1区 · 医学

Choline Transporter-Like Protein-2

1区 · 医学

Article

作者: Santoso, Sentot ; Werth, Silke ; De Meyer, Simon F. ; Tjahjono, Yudy ; Bayat, Behnaz ; Berghöfer, Heike ; Sachs, Ulrich J. ; Deckmyn, Hans

Objective—:

In contrast to other antibodies involved in transfusion-related acute lung injury, anti–HNA-3a antibodies are incapable of inducing direct neutrophil activation and seem to interact with endothelial cells (ECs) primarily. In animal studies, anti–HNA-3a-mediated transfusion-related acute lung injury could be precipitated in the absence of neutrophils, but was stronger when neutrophils were present. In a different context the target protein of these antibodies, choline transporter-like protein-2 (CTL-2), was reported to interact with a protein of the inner ear carrying 2 von Willebrand factor (VWF) A-domains. These observations prompted us to investigate whether VWF might be involved in anti–HNA-3a-mediated neutrophil activation, and whether signaling via CD11b/CD18 is involved, as in various other experimental settings.

Approach and Results—:

Cell adhesion demonstrated specific binding of CTL-2 to VWF. Immunoprecipitation analysis of CTL-2/CD11b/CD18 coexpressing cells indicated that anti–HNA-3a colocalizes CTL-2 and CD11b/CD18 when VWF is present. Functional studies revealed that anti–HNA-3a-mediated neutrophil agglutination is an active, protein kinase C-dependent and partially Fc-dependent process. Agglutination and the production of reactive oxygen species seem to require the formation of a trimolecular complex between the target antigen (CTL-2), CD11b/CD18 and VWF. In line with these observations, anti–HNA-3a induced less severe transfusion-related acute lung injury and less neutrophil recruitment to the alveolar space in VWF knockout mice.

Conclusions—:

We introduce CTL-2 as a new binding partner for VWF. Interaction of neutrophils with VWF via CTL-2 allows anti–HNA-3a to induce signal transduction via CD11b/CD18, which leads to neutrophil activation and agglutination. In transfusion-related acute lung injury, this mechanism may further aggravate endothelial leakage.

项与维苏格罗单抗相关的新闻（医药）

2025-07-01

·药研网

GDF15崛起：能否成为继PD-1、GLP-1之后的“超级靶点”？

阅读导览前言GDF15靶点简介GDF15介导的信号通路“一靶多病”的治疗潜力GDF15在研格局总结与展望前言癌症恶病质（Cancer Cachexia）是一种常见且高度致残的癌症并发症，典型表现包括体重显著下降、骨骼肌丧失、食欲减退以及体力活动能力减弱，严重影响患者生活质量与生存预后。然而，长期以来该领域缺乏有效治疗手段。近日，《新英格兰医学杂志》发表了一项关于Ponsegromab（珀塞古单抗）的II期临床研究结果，为这一临床难题带来了新的突破。Ponsegromab是一种靶向GDF15的单克隆抗体，通过阻断GDF15通路，有望改善癌症恶病质相关的体重和肌肉流失，初步数据显示其在提高患者体重、改善食欲和身体功能方面表现出积极疗效，为癌症患者带来新的治疗希望。图源：The New England journal of MedicineGDF15靶点简介生长分化因子15（GDF15），又称巨噬细胞抑制细胞因子（MIC-1），是一种应激诱导型分泌蛋白，以25 kDa二聚体形式循环，由两个含112个氨基酸的多肽链经二硫键连接组成。GDF15在正常生理条件下表达水平较低，主要在肝、肾、心、肺等器官受到损伤或细胞应激时上调表达。近年来研究发现，GDF15在炎症调节、组织修复、代谢紊乱和细胞应激等生理及病理过程中均发挥关键作用，且其表达可由多种应激因子（如细胞损伤、氧化应激、抗糖尿病药物二甲双胍等）诱导上升。Figure.Structure of GDF-15. [2]GDF15介导的信号通路GDF15通过与其唯一已知受体GFRAL（胶质细胞源性神经营养因子家族α样受体）结合，形成配体-受体复合物，并招募辅助受体RET，从而激活一系列下游信号通路，包括RET、AKT、ERK和PLC-γ1等通路。该受体主要表达于延髓的孤束核区，GDF15-GFRAL通路因此在调控食欲、能量代谢、体重控制等方面发挥重要作用，并在心血管疾病、非酒精性脂肪肝等代谢类疾病中展现出潜在干预价值。Figure. Intracellular signaling pathways.[3]吉满生物基于前沿研究与市场需求，创新推出GDF15药物研发全流程解决方案，涵盖稳定表达细胞系、高灵敏度报告基因细胞系及高纯度抗体蛋白产品系列，为抗体药物体外药效评估提供精准工具，高效助力临床前研究及IND申报。（咨询吉满客服联系同微信：18916119826）“一靶多病”的治疗潜力肿瘤免疫逃逸：破解“冷肿瘤”的新钥匙GDF15在肿瘤微环境中高表达，抑制树突状细胞成熟、T细胞活化及浸润，帮助肿瘤逃避免疫监视。其“胎盘式免疫屏障”机制也被肿瘤细胞利用，导致免疫治疗耐药。靶向GDF15有望打破免疫抑制，增强PD-1/PD-L1疗法效果，为冷肿瘤患者提供新解法。改善癌症恶病质的潜力靶点GDF15是癌症恶病质的驱动因子之一。这类代谢综合征在50%~80%的癌症患者中出现，表现为厌食、体重骤降、肌肉和脂肪萎缩，严重影响生存质量和治疗耐受性。当前，靶向抗体GDF15的单抗Ponsegromab等正在开发，已显示出改善体重和身体功能的初步效果，为肿瘤支持治疗提供新路径。肥胖与糖尿病：继GLP-1后的中枢减重新靶点2017年前后，医学界发现了GDF15在肥胖治疗领域的潜力，礼来、诺和诺德和强生三家制药巨头同时在Nature Medicine明确指出GFRAL是GDF15的高亲和力受体，在减少摄食和降低体重机制中发挥着核心作用。这是科学家们首次确定GDF15调节体重的核心机制和关键受体，为肥胖和Ⅱ型糖尿病的治疗提供了绝佳的靶点。2023年6月28日，加拿大McMaster大学Dr. Gregory Steinberg课题组的王冬冬博士领导的GDF15研究项目在Nature上发表成果，系统阐释了GDF15通过提高肌肉能量消耗发挥减重作用的机制。Figure.连接GDF15与GFRAL和肾上腺素能受体的生物回路的机制图，以在热量限制期间维持肌肉的能量消耗[4]NAFLD与心血管疾病：炎症与代谢调控新窗口GDF15在非酒精性脂肪肝中可改善肝脏代谢、减轻炎症；同时作为心血管事件的应激标志物，也具备早期诊断与干预潜力，正在成为慢病管理领域的新焦点。GDF15靶点在研格局在全球范围内，GDF-15靶向药物的开发还处于较早期阶段，药物类型以单抗为主，最高临床阶段为临床II期，包括CatalYm的Visugromab、辉瑞的ponsegromab，NGM Bio的NGM120。数据来源：药研网辉瑞抗GDF15单抗Ponsegromab去年9月，辉瑞在欧洲肿瘤内科学会（ESMO）年会上公布Ponsegromab在临床II期研究中的积极结果：在所有测试的剂量中，ponsegromab组均达到了体重相对于基线的变化，与安慰剂相比，在12周时评估的最高剂量下体重平均增加5.6%；ponsegromab在所有剂量水平下均被认为安全且耐受性良好的，而且在测试的最高剂量下，患者食欲和恶病质症状、身体活动和肌肉质量较基线有所改善。按照辉瑞此前披露的计划，Ponsegromab预计在2025年推进III期临床试验；2022年底，Ponsegromab在国内也获批临床，成为国内首款获批临床的GDF15单抗。CatalYm的VisugromabVisugromab可中和肿瘤衍生的GDF-15，是一种局部作用的免疫抑制剂，可促进免疫疗法耐药性。此前在2024年ASCO年会上公布了1期临床研究结果，使用 Visugromab 中和 GDF-15 可逆转关键的癌症耐药机制，通过重新激活免疫细胞和肿瘤浸润来恢复有效的抗肿瘤反应。Visugromab 在临床1期试验中已展现出良好的安全性，目前正在针对多种实体瘤适应症开展临床2期研究。劲方医药GDF15/IL-6双抗GFS202AGFS202A为拮抗性双特异性抗体，是全球首个恶病质双抗疗法及GDF15/IL-6双抗产品，也是国内首个进入临床的恶病质靶向疗法及GDF-15抗体类药物。今年3月，劲方医药宣布，GFS202A针对肿瘤恶病质前期及恶病质期患者开展一项开放标签、多中心的I期临床研究试验申请获得国家药品监督管理局批准。此外，针对GDF-15靶点的其他药物类型有纳米抗体、融合蛋白、重组蛋白和小分子化药，适应症多为肥胖。其中由美国强生开发小分子药物JNJ-9090处于临床1期阶段，这是一款GDF-15调节剂，其作用机制主要是通过激活GFRAL受体来促进产热和脂解。这些靶向GDF-15的临床前阶段药物种类丰富，也为未来的药物研发提供了积极的信号。总结及展望GDF15凭借其在免疫调节与代谢控制中的“双重功能”，正在成为肿瘤治疗、代谢疾病干预和慢性病控制的共同靶点。从癌症免疫耐药与恶病质，到肥胖、糖尿病和NAFLD，靶向GDF15不仅打通了多个疾病路径，也为未来多靶点协同治疗打开全新窗口。随着Ponsegromab等靶向药物推进临床，GDF15有望成为“免疫+代谢”精准医学新时代的关键分子。吉满生物吉满生物基于前沿研究与市场需求，创新推出GDF15药物研发全流程解决方案，涵盖稳定表达细胞系、高灵敏度报告基因细胞系及高纯度抗体蛋白产品系列。产品列表数据展示GM-C06718 H_GDF15 Reporter 293 Cell Line使用Recombinant Human GDF-15蛋白激活验证结果H_GDF15 Reporter 293 Cell Line使用Recombinant Human GDF-15蛋白激活验证结果GM-C19363 Mouse_GDF15 Reporter 293 Cell Line使用Recombinant Mouse GDF-15蛋白激活验证结果GM-C28579 H_GDF15 Reporter 293 DDX35TM Cell Line使用Recombinant Human GDF-15蛋白各代次稳定性验证结果H_GDF15 Reporter 293 DDX35TM Cell Line使用Recombinant Human GDF-15蛋白高低代次三重复验证结果GM-87627RP Human GDF15 Protein; His Tag ELISA验证联系我们吉满生物(Genomeditech)成立于2011年，是专业从事生物科技服务和前沿技术研发的高新技术企业。吉满生物专注为生物药开发赋能，自主创立了国内知名的细胞系品牌-DDXCELL，目前已布局近400个热门靶向药靶点，超1000株现货单克隆细胞系，涵盖GPCR、细胞因子、免疫检查点、TAA等多领域，做到进口细胞的国产替代。此外，吉满生物还可在药物研发进程中提供一系列抗体、蛋白产品，旨在为客户提供高效的研发工具和解决方案!扫码咨询扫码找现货参考文献：1. Dufour I, Bindels LB, Goffin E. Ponsegromab for the Treatment of Cancer Cachexia. N Engl J Med. 2025 Mar 6;392(10):1035. doi: 10.1056/NEJMc2500502. PMID: 40043243.2. Delrue, C., et al., Growth differentiation factor 15 (GDF-15) in kidney diseases. Adv Clin Chem, 2023. 114: p. 1-46.3. Adela, R. and S.K. Banerjee, GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective. J Diabetes Res, 2015. 2015: p. 4908424. Wang, D., Townsend, L.K., DesOrmeaux, G.J. et al. GDF15 promotes weight loss by enhancing energy expenditure in muscle. Nature 619, 143–150 (2023). https://doi.org/10.1038/s41586-023-06249-45. Groarke JD, Crawford J, Collins SM, Lubaczewski S, Roeland EJ, Naito T, Hendifar AE, Fallon M, Takayama K, Asmis T, Dunne RF, Karahanoglu I, Northcott CA, Harrington MA, Rossulek M, Qiu R, Saxena AR. Ponsegromab for the Treatment of Cancer Cachexia. N Engl J Med. 2024 Dec 19;391(24):2291-2303. doi: 10.1056/NEJMoa2409515. Epub 2024 Sep 14. PMID: 39282907.6. https://www.esmo.org/oncology-news/inhibition-of-gdf-15-with-ponsegromab-results-in-increased-weight-gain-and-overall-activity-level-and-reduced-cancer-cachexia-symptoms7. https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.25138. https://mp.weixin.qq.com/s/Nh4ShQqQx-U_-CphXoskgg

临床申请免疫疗法临床2期

2025-05-13

·CPHI制药在线

金笔奖|冉冉升起的新兴靶点——GDF15

关注并星标CPHI制药在线在2024 ESMO大会上发布、同步发表于《新英格兰医学杂志》（The New England Journal of Medicine）的一项重要研究结果显示，辉瑞的创新疗法ponsegromab 的II 期临床研究达到了主要终点，即与安慰剂相比，接受ponsegromab治疗的癌症恶液质和GDF-15水平升高患者的体重与基线相比发生了显著变化。在较高用药剂量下可使癌症恶病质患者在12周内恢复约5.6%的体重，食欲、身体活动量和骨骼肌质量均有所改善。Ponsegromab是一种针对GDF15（生长分化因子-15）的单克隆抗体。GDF15是一种蛋白质，研究发现它在恶病质等病症中起到了关键作用。辉瑞在此领域的研究并非首次亮相，但此次的进展令人瞩目。根据辉瑞的计划，将推进Ponsegromab进入三期临床试验，这意味着这款药物可能会成为一种能够治疗癌症恶病质的突破性疗法。早在2022年，Ponsegromab注射液就获CDE临床实验默示许可，适应症为癌症相关恶液质，以及成人患者心力衰竭。这是国内首款获批IND的GDF15单抗。免疫耐药及恶病质潜力靶点：GDF-15癌症相关厌食/恶病质综合征(cancer-related anorexia/cachexia syndrome, CACS)是指癌症患者在患病过程中不可控制的体重减轻，其症状包括厌食，肌肉量和脂肪组织减少引起的体重减轻。每年全球癌症死亡人数的一半（约820万人）归因于最常与恶病质相关的癌症，如胰腺癌（33万人死亡），食道癌（40万），胃癌（72万），肺癌（159万），肝（75万）和结肠直肠癌（69万）。研究表明，没有体重减轻的癌症患者有更好的预后推估，有效的治疗手段能够大大增加癌症患者的存活几率。根据FortuneBusinessInsights，2019年全球癌症恶病质市场规模为20.2亿美元，预计到2032年将达到37.6亿美元，预测期内复合年增长率为5.0%。此外，全球范围内恶性肿瘤患者患病率不断上升，恶病质患病率也不断增加，对其有效治疗需求激增，推动市场增长。肿瘤恶病质的临床治疗主要为营养干预和药物干预。共识仅推荐改善患者食欲的孕激素类似物、糖皮质激素以及中医药辅助治疗。截至目前，FDA尚未批准任何药物用于肿瘤恶病质的治疗。研发端，全球首个治疗肿瘤恶病质药物阿那莫林anamorelin（日本小野制药）已于2021年在日本上市，是一种选择性GHS-R1a（促生长激素释放激素受体）激动剂，目前仍为肿瘤恶病质靶向治疗的研究热点。除阿那莫林外，治疗肿瘤恶病质的创新药管线主要聚焦被称为“厌食激素”的生长分化因子15（GDF15）。GDF-15是一种应激诱导细胞因子，可与后脑中的神经胶质细胞衍生的神经营养因子家族受体α样蛋白（GFRAL）结合。GDF-15-GFRAL通路已成为厌食症和体重调节的主要调节因子，并与恶病质的发病机制有关。研究表明GDF-15水平升高与体重和骨骼肌质量下降以及癌症患者的力量和生存率下降有关，以上这些因素凸显了GDF-15是潜在的治疗靶点。另外，GDF15也被认为是抗肿瘤T细胞活性的负调节因子，与抑制免疫反应有关，并阻止了T细胞被招募到肿瘤微环境中。同时，肿瘤在其微环境中表达并释放大量的GDF-15，这使它能够避免被循环免疫细胞识别并产生抗肿瘤免疫反应。因此，抑制GDF15也是克服癌症标准治疗和免疫治疗（如检查点抑制剂）耐药的重要靶点。GDF-15靶点相关的药物可以通过以下途径治疗肿瘤：减少癌症相关恶病质的发生和发展，提高癌症生存期和生活质量；干扰DC的激活和成熟；减少树突状细胞对T细胞的诱导和激活作用；阻断有效的免疫细胞外渗和肿瘤浸润；抑制T细胞和NK细胞对肿瘤细胞的杀伤作用；通过产生和增强调节性T细胞的功能，在肿瘤组织中诱发免疫抑制。初见曙光截至目前，全球范围内尚未有GDF15靶点相关药物获批上市，处于临床阶段的药物数量也较少。除Ponsegromab外，开发用于克服免疫耐药及恶病质处于临床活跃阶段的仅有CatalYm的Visugromab和AVEO的Rilogrotug两款药物。值得一提的是，国内劲方医药研发的GDF15/IL-6双抗GFS202A IND也于近日获批，不久将开展1期临床，首选适应症为肿瘤恶病质（恶性肿瘤）。GFS202A有望通过双靶点协同机制提升疗效，并同时缓解炎症反应、降低抗癌治疗相关副作用。CatalYm公司VisugromabVisugromab是一款人源化的单克隆抗体，旨在中和肿瘤产生的GDF15来抵消免疫抑制机制，增强免疫细胞对肿瘤的浸润，改善DC细胞对T细胞的激活，增强T细胞和NK细胞的肿瘤杀伤作用。目前已进入到2期临床研究当中。在2024年ASCO年会上，CatalYm报告了其正在进行的“GDFATHER”1/2a期试验的随访结果。数据显示，Visugromab与抗PD-1抗体nivolumab联合治疗，在非小细胞肺癌（NSCLC）、尿路上皮癌（UC）或肝细胞癌（HCC）的抗PD-1/PD-L1复发/难治性患者中，获得了深度和持久的抗肿瘤活性，包括几个完全反应。AVEO的RilogrotugAV-380是AVEO 首款靶向GDF15 的高效人源化抑制性 IgG1 抗体，用于治疗癌症恶病质。临床前数据显示，恶病质作为一种复杂的代谢综合征，抑制GDF15可诱导分解代谢转向合成代谢，这表明AV-380抑制GDF15可能逆转恶病质的影响。目前正在进行针对癌症患者的 1b 期临床试验。在2023年9月底于爱丁堡召开的第七届癌症恶病质会议（7th Cancer Cachexia Conference）上，AVEO公布了Rilogrotug临床1b期剂量递增研究的方案，拟探索在标准治疗（SOC）中加入Rilogrotug是否会为转移性恶病质患者带来额外的临床获益。参考来源 1.Groarke JD, Crawford J, Collins SM, Lubaczewski S, Roeland EJ, Naito T, Hendifar AE, Fallon M, Takayama K, Asmis T, Dunne RF, Karahanoglu I, Northcott CA, Harrington MA, Rossulek M, Qiu R, Saxena AR.Ponsegromab?for the Treatment of Cancer Cachexia.N Engl J Med. 2024 Sep 14. doi: 10.1056/NEJMoa24095152.Groarke JD, Crawford J, Collins SM, Lubaczewski SL, Breen DM, Harrington MA, Jacobs I, Qiu R, Revkin J, Rossulek MI, Saxena AR.Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design.J Cachexia Sarcopenia Muscle. 2024 Jun;15(3):1054-1061 作者简介：@江湖之远，男，暨南大学药物化学专业硕士，曾在多家国内药企从事肿瘤新药学术推广工作，关注国内外肿瘤新药研发动态，专注于肿瘤新药领域耕耘。END【企业推荐】领取CPHI & PMEC China 2025展会门票来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

临床申请临床2期临床3期临床1期

2025-04-25

·Business Wire

CatalYm to Present New Data Demonstrating GDF-15 Blockade Enhances Efficacy of Antibody-Drug Conjugates at AACR 2025

MUNICH--(BUSINESS WIRE)--CatalYm today announced the presentation of the first preclinical data demonstrating that the company’s clinical-stage antibody visugromab can improve the anti-tumor activity of antibody-drug conjugates (ADCs). The data will be presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place in Chicago, IL, April 25-30, 2025. The poster will highlight the potential of targeting Growth Differentiation Factor 15 (GDF-15) to enhance the activity and overcome resistance to ADC therapies, which are increasingly used as frontline treatments in several solid tumor indications. The full abstract is available on the AACR Annual Meeting website. The study showed that several clinically validated ADCs, including topoisomerase I and microtubule inhibitor-based regimens, consistently triggered GDF-15 expression, suggesting a potential resistance mechanism to ADC therapy. Across in vitro and in vivo models of multiple solid tumor types, ADC treatment induced GDF-15 release from tumor cells, leading to elevated serum levels and reduced ADC efficacy. Combining ADC treatment with GDF-15 neutralization improved anti-tumor responses, resulting in reduced tumor growth and enhanced infiltration and activation of T cells and myeloid cells in the tumor microenvironment. “We are building a broader understanding of GDF-15 as a key resistance mechanism activated by targeted approaches like ADCs as well as the leading immunotherapies like PD-1 inhibitors,” said Christine Schuberth-Wagner, PhD, Chief Scientific Officer at CatalYm. “By blocking GDF-15, visugromab restores anti-tumor immune activity and enhances treatment efficacy, underscoring its potential as a versatile combination partner across a broad spectrum of cancer therapies beyond immunotherapies.” “ADCs continue to demonstrate potent and specific therapeutic impact, nevertheless resistance is a significant challenge for long-term patient benefit. In addition to our Phase 2 clinical development program, CatalYm will continue to investigate how our GDF-15 neutralizing antibody visugromab can create a novel path to address cancer resistance effectively,” added Scott Clarke, Chief Executive Officer at CatalYm. The preclinical findings build on clinical evidence from the GDFATHER-1/2a trial (GDF-15 Antibody-mediaTed Human Effector T Cell Relocation Phase 1/2a Trial; NCT04725474), that was recently published in Nature. The data show that visugromab induces deep and durable responses in patients with relapsed or refractory solid tumors who had progressed on prior anti-PD-1/PD-L1 therapies. In addition to restoring anti-tumor immune responses, visugromab also demonstrated the potential to mitigate cancer-associated cachexia. CatalYm is currently conducting a broad, global Phase 2b clinical development program for visugromab, evaluating its effectiveness in earlier treatment lines of non-squamous non-small-cell lung cancer and hepatocellular carcinoma, as well as neoadjuvant treatment in urothelial cancer in combination with standard of care. Poster details Session title: “PO.IM01.03 - Antibodies and Antibody-Drug Conjugates” Abstract title: “GDF-15 neutralization enhances the therapeutic activity of antibody-drug conjugates” Abstract number: 4777/13 Location: Section 36 Date and time: April 29, 2025, 9:00 AM – 12 PM CT/ 4:00 PM – 7:00 PM CEST About Visugromab Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by re-enabling immune cell activation, proliferation and induction of interferon-γ. About CatalYm CatalYm is developing visugromab, a first-in-class anti-GDF-15 antibody, in solid tumors and other indications. In its first-in-human Phase 1/2a study, visugromab demonstrated durable anti-tumor efficacy with long-lasting objective responses in relapsed and refractory metastatic solid tumor patients in combination with anti-PD-1 treatment. In addition, data from the same study demonstrated that visugromab can significantly counteract the effects of cachexia in these patients. This data was recently published in Nature and presented at the International Conference on Sarcopenia, Cachexia & Wasting Disorders. CatalYm is now advancing visugromab into multiple Phase 2b studies. Founded in 2016 and based in Munich, Germany and San Francisco, USA, CatalYm is backed by leading international investors including Canaan Partners, Bioqube Ventures, Forbion, Omega Funds, Gilde Healthcare, Jeito Capital, Novartis Venture Fund, Vesalius, Brandon Capital, Bayern Kapital, BioGeneration Ventures, and Coparion.

临床2期免疫疗法临床结果AACR会议抗体药物偶联物

100 项与维苏格罗单抗相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
转移性非小细胞肺癌	临床2期	美国	CatalYm GmbH	2025-07-30
转移性非鳞状非小细胞肺癌	临床2期	美国	CatalYm GmbH	2025-07-30
肌层浸润性膀胱癌	临床2期	意大利	CatalYm GmbH	2023-09-06
实体瘤	临床2期	-	CatalYm GmbH	2022-03-01
晚期癌症	临床2期	德国	CatalYm GmbH	2020-12-09
晚期癌症	临床2期	西班牙	CatalYm GmbH	2020-12-09
晚期癌症	临床2期	瑞士	CatalYm GmbH	2020-12-09
晚期恶性实体瘤	临床2期	德国	CatalYm GmbH	2020-12-09
晚期恶性实体瘤	临床2期	西班牙	CatalYm GmbH	2020-12-09
晚期恶性实体瘤	临床2期	瑞士	CatalYm GmbH	2020-12-09

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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


NCT04725474 (GDFATHER, BusinessWire) 人工标引	临床1/2期	肝细胞癌 \| 实体瘤 \| 非鳞状非小细胞肺癌 ... 更多	-	visugromab (non-squamous NSCLC)	鹽遞艱夢蓋憲鑰糧繭夢(獵鹹築製遞醖衊壓鹽選) = 構齋膚襯顧範壓遞築積鹹積蓋蓋窪獵築範獵夢 (憲膚願觸製製蓋築衊觸 ) 更多	积极	2024-12-11
NCT04725474 (GDFATHER, BusinessWire) 人工标引	临床1/2期	肝细胞癌 \| 实体瘤 \| 非鳞状非小细胞肺癌 ... 更多	-	visugromab (UC)	鹽遞艱夢蓋憲鑰糧繭夢(獵鹹築製遞醖衊壓鹽選) = 鏇壓網製範艱襯淵鹹築鹹積蓋蓋窪獵築範獵夢 (憲膚願觸製製蓋築衊觸 ) 更多	积极	2024-12-11
NCT04725474 (GDFATHER, Biospace) 人工标引	临床1/2期	肝细胞癌 \| 非小细胞肺癌 \| 尿路上皮癌	-	Visugromab + Nivolumab	糧觸鹽醖築鏇獵齋構願(壓憲觸鏇鏇鏇構獵願積) = 鑰積積顧衊醖鬱構齋鬱製選積憲齋願積鑰顧鏇 (憲遞築醖獵蓋艱蓋願積 )	积极	2024-06-02
NCT04725474 (GDFATHER, Biospace) 人工标引	临床1/2期	肝细胞癌 \| 非小细胞肺癌 \| 尿路上皮癌	-	Visugromab + Nivolumab (NSCLC)	淵蓋窪醖鏇築願膚蓋選(憲艱範醖製觸鹹憲選膚) = 構窪觸憲鬱遞壓選蓋網餘鹽齋鹹簾築鬱夢壓鹽 (簾積鬱壓鏇鏇夢廠夢淵 )	积极	2024-06-02
NCT04725474 (GDFather, ASCO2024) 人工标引	临床2期	肝细胞癌 \| 非小细胞肺癌 \| 尿路上皮癌	87	Visugromab 10 mg/kg + Nivolumab 240 mg Q2W	蓋醖繭鬱齋艱鬱觸網鹽(簾壓鏇願淵選醖夢鹽製) = 壓憲夢選積製膚網積構廠廠醖鹽窪繭衊鬱鑰觸 (鑰夢糧糧膚觸夢膚廠壓 ) 更多	积极	2024-05-24
NCT04725474 (GDFather, ASCO2024) 人工标引	临床2期	肝细胞癌 \| 非小细胞肺癌 \| 尿路上皮癌	87	Visugromab 10 mg/kg + Nivolumab 240 mg Q2W (NSCLC)	-	积极	2024-05-24
NCT04725474 (GDFATHER-2, Biospace) 人工标引	临床2期	晚期非小细胞肺癌 \| 尿路上皮癌 PD-L1 Positive	27	Visugromab+nivolumab (NSCLC)	顧窪淵壓窪選網製鬱網(壓獵構襯膚積壓網鹽廠) = 衊廠積鏇築鹽範鏇齋鹽製廠鑰壓鏇選簾選網構 (廠衊鬱衊憲夢窪繭鑰遞 )	积极	2023-12-06
NCT04725474 (ESMO_IO2023)	临床2期	实体瘤 \| 非小细胞肺癌 \| 膀胱癌 PD-L1+	114	Visugromab 10 mg/kg + Nivolumab 240 mg	襯積襯網艱築構鹹蓋壓(餘憲網顧積膚膚鏇夢衊) = 蓋顧築網壓觸壓淵範製憲鑰糧蓋鏇襯網鹹醖製 (選憲選鹽鹽壓網顧廠廠 )	积极	2023-12-06
NCT04725474 (GDFATHER, ASCO 12023 \| ASCO 22023) 人工标引	临床2期	实体瘤	79	Nivolumab 240 mg+visugromab 10 mg/kg	齋顧範鑰製蓋艱積積鹽(糧鑰願選蓋醖鑰願膚繭) = 顧廠夢膚衊衊鑰鹽鹽範網鹽窪鹽窪選簾齋鬱餘 (膚憲製鬱選範蓋憲獵鬱 ) 更多	积极	2023-05-31
NCT04725474 (GDFATHER-1, ESMO2022) 人工标引	临床1期	复发性实体肿瘤	25	CTL-002 0.3-20 mg/kg+Nivolumab	醖夢製願蓋餘鑰蓋憲積(遞蓋築鑰積衊餘齋夢選) = 餘製壓憲夢壓網廠鹽齋衊廠獵淵餘鹹糧繭繭衊 (鑰鹽餘鬱襯衊築願夢鑰 ) 更多	积极	2022-09-10