A Phase 1a/1b, Open-label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Anti-neoplastic Activity of S095029 (Anti-NKG2A) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triplet Combinations of S095029 and Sym021 and an Anti-HER2 mAb or Anti-EGFR mAbs (Futuximab/Modotuximab) in Patients With Metastatic Gastric or Colorectal Cancers

The purpose of the study is to investigate the safety, tolerability, and preliminary anti-neoplastic activity of S095029 alone and in combination with Sym021 in patients with advanced solid tumor malignancies followed by an expansion phase of triple combinations.
*The study sponsor has made the decision not to move forward to the expansion part of the study due to strategic considerations, unrelated to any safety issues or concerns. The study will be stopped after completion of dose escalation parts 1a and 1b of the study.

开始日期2021-10-15

申办/合作机构

Institut de Recherches Intern Servier

[+1]

NCT04195373

/ Withdrawn临床1期

A Phase I Open-label, Safety Study of Intra-tumoral Application of TMV-018 in Combination With 5-FC or Anti-PD-1 Therapy in Patients With Tumors of the Gastrointestinal Tract

This study aims to determine the safety and tolerability of TMV-018 when given alone or in combination with the prodrug 5-Fluorocytosine (5-FC) or an anti-PD-1 checkpoint inhibitor in patients with gastrointestinal tumors. Furthermore, the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018 shall be determined.

开始日期2020-11-23

申办/合作机构

Themis Bioscience GmbH

[+2]

NCT04672434

/ Completed临床1期

A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym024 (Anti-CD73) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies

The primary purpose of this study is to see if Sym024 is safe and tolerable as monotherapy and in combination with Sym021 in patients with solid tumor malignancies.

开始日期2020-11-19

申办/合作机构

Symphogen A/S

100 项与 Sym-021 相关的临床结果

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100 项与 Sym-021 相关的转化医学

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100 项与 Sym-021 相关的专利（医药）

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项与 Sym-021 相关的文献（医药）

2024-09-20·Nan fang yi ke da xue xue bao = Journal of Southern Medical University

[High RNF7 expression enhances PD-1 resistance of non-small cell lung cancer cells by promoting CXCL1 expression and myeloid-derived suppressor cell recruitment via activating NF-κB signaling].

Article

作者: Zhong, N ; Geng, B ; Sun, Z ; Zhao, W ; Wang, H

OBJECTIVE:

To investigate the mechanism of RNF7 for regulating myeloid-derived suppressor cells (MDSCs) in nonsmall cell lung cancer (NSCLC).

METHODS:

TIMER2.0 database and immunohistochemistry were used to analyze RNF7 expression level and its correlation with immune cell infiltration in non-small cell lung cancer. The impact of RNF7 expression levels on prognosis of lung cancer patients was analyzed using Kaplan-Meier survival analysis. CMT-167 cells with RNF7 overexpression or knockdown were inoculated subcutaneously in C57BL/6 mice, and the mice in RNF7 knockdown group were treated with anti-PD-1 or IgG isotype control 7 days after the inoculation. The tumor tissues were harvested after 30 days for tumor volume measurement, detection of S100A8+A9 and Gr-1 expressions with immunohistochemistry, and analysis of MDSC infiltration. Gene set enrichment analysis (GSEA) was performed to identify the potential pathways regulated by RNF7 in NSCLC. Western blotting and luciferase assays were used to assess the impact of RNF7 on the NF-κB signaling pathway. ELISA and RT-qPCR were used to measure chemokine (C-X-C motif) ligand 1 (CXCL1) expression.

RESULTS:

RNF7 expression was significantly upregulated in NSCLC, and high RNF7 expression levels were associated with poor prognosis of the patients (P < 0.001). TIMER2.0 analysis revealed a positive correlation between RNF7 expression and MDSC infiltration (P < 0.001). GSEA suggested that RNF7 was enriched in the NF-κB signaling pathway. In NSCLC cells, RNF7 knockdown significantly inhibited NF-κB activation and reduced CXCL1 expression. In the tumor-bearing mice, RNF7 overexpression significantly increased MDSC infiltration in the tumor tissue, and RNF7 knockdown obviously reduced MDSC infiltration and enhanced the efficacy of anti-PD-1 therapy.

CONCLUSION:

High expression of RNF7 in NSCLC cells promotes CXCL1 expression by activating the NF-κB signaling pathway, thus leading to the chemotactic recruitment of MDSCs, which contributes to tumor resistance to antiPD-1 therapy.

2020-12-01·Journal of hematology & oncology1区 · 医学

CDK7 inhibitor THZ1 enhances antiPD-1 therapy efficacy via the p38α/MYC/PD-L1 signaling in non-small cell lung cancer

1区 · 医学

ArticleOA

作者: Dong, Xiaorong ; Wu, Gang ; Chen, Yaobing ; Zhou, Xiaoshu ; Xu, Shuangbing ; Zhang, Tao ; Meng, Rui ; Liu, Li ; Hong, Jiaxin ; Zhang, Sheng ; Zhang, Ruiguang ; Wang, Jian ; Tang, Jing ; Lin, Zhenyu ; Zong, Yan ; Yang, Kunyu ; Xu, Yingzhuo

Abstract:

Background:

The cyclin-dependent kinase 7 (CDK7) subunit of TFIIH regulates RNA polymerase-II-based transcription and promotes tumor progression. However, the mechanisms involved in CDK7-mediated immune evasion are unclear in non-small cell lung cancer (NSCLC).

Methods:

RNA silencing and pharmacologic inhibitors were used to evaluate the functions of CDK7/p38α/MYC/PD-L1 axis in cancer cell proliferation and antiPD-1 therapy resistance. Flow cytometry was performed to detect the status of the immune microenvironment after CDK7 inhibition and antiPD-1 therapy in vivo. CD8 depletion antibodies were used to assess the role of CD8+ T cells in combined CDK7 and PD-1 blockade. The associations among CDK7, p38α, MYC, PD-L1, infiltrating T cells, and survival outcomes were validated in two tissue microarrays and public transcriptomic data of NSCLC.

Results:

High CDK7 mRNA and protein levels were identified to be associated with poor prognosis in NSCLC. CDK7 silencing and CDK7 inhibitor THZ1 elicited apoptosis and suppressed tumor growth. Moreover, CDK7 ablation specifically suppressed p38α/MYC-associated genes, and THZ1 inhibited MYC transcriptional activity through downregulating p38α. CDK7 inhibition sensitized NSCLC to p38α inhibitor. Further, THZ1 suppressed PD-L1 expression by inhibiting MYC activity. THZ1 boosted antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with antiPD-1 therapy. The CDK7/MYC/PD-L1 signature and infiltrating T cell status collectively stratified NSCLC patients into different risk groups.

Conclusion:

These data suggest that the combined CDK7 inhibitor THZ1 and antiPD-1 therapy can be an effective treatment in NSCLC.

2019-05-19·mAbs2区 · 医学

Sym021, a promising anti-PD1 clinical candidate antibody derived from a new chicken antibody discovery platform

2区 · 医学

Article

作者: Bouquin, Thomas ; Uhlenbrock, Franziska ; Pedersen, Mikkel W ; Lindsted, Trine ; Kragh, Michael ; Gad, Monika ; Horak, Ivan D ; Fröhlich, Camilla ; Galler, Gunther R ; Dietrich, Nikolaj ; Gjetting, Torben ; Melander, Maria C ; Grandal, Michael M ; Koefoed, Klaus ; Lantto, Johan ; Strandh, Magnus ; Bhatia, Vikram K

Discovery of therapeutic antibodies is a field of intense development, where immunization of rodents remains a major source of antibody candidates. However, high orthologue protein sequence homology between human and rodent species disfavors generation of antibodies against functionally conserved binding epitopes. Chickens are phylogenetically distant from mammals. Since chickens generate antibodies from a restricted set of germline genes, the possibility of adapting the Symplex antibody discovery platform to chicken immunoglobulin genes and combining it with high-throughput humanization of antibody frameworks by "mass complementarity-determining region grafting" was explored. Hence, wild type chickens were immunized with an immune checkpoint inhibitor programmed cell death 1 (PD1) antigen, and a repertoire of 144 antibodies was generated. The PD1 antibody repertoire was successfully humanized, and we found that most humanized antibodies retained affinity largely similar to that of the parental chicken antibodies. The lead antibody Sym021 blocked PD-L1 and PD-L2 ligand binding, resulting in elevated T-cell cytokine production in vitro. Detailed epitope mapping showed that the epitope recognized by Sym021 was unique compared to the clinically approved PD1 antibodies pembrolizumab and nivolumab. Moreover, Sym021 bound human PD1 with a stronger affinity (30 pM) compared to nivolumab and pembrolizumab, while also cross-reacting with cynomolgus and mouse PD1. This enabled direct testing of Sym021 in the syngeneic mouse in vivo cancer models and evaluation of preclinical toxicology in cynomolgus monkeys. Preclinical in vivo evaluation in various murine and human tumor models demonstrated a pronounced anti-tumor effect of Sym021, supporting its current evaluation in a Phase 1 clinical trial. Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; CDR, complementarity determining region; DC, dendritic cell; ELISA, enzyme-linked immunosorbent assay; FACS, fluorescence activated cell sorting; FR, framework region; GM-CSF, granulocyte-macrophage colony-stimulating factor; HRP, horseradish peroxidase; IgG, immunoglobulin G; IL, interleukin; IFN, interferon; mAb, monoclonal antibody; MLR, mixed lymphocyte reaction; NK, natural killer; PBMC, peripheral blood mono-nuclear cell; PD1, programmed cell death 1; PDL1, programmed cell death ligand 1; RT-PCR, reverse transcription polymerase chain reaction; SEB, Staphylococcus Enterotoxin B; SPR, surface Plasmon Resonance; VL, variable part of light chain; VH, variable part of heavy chain.

项与 Sym-021 相关的新闻（医药）

2025-08-27

·博安生物

Boan Biotech Announces 2025 Half-Year Results

Boan Biotech (6955.HK) today announced its 2025 half-year results and latest developments. During the reporting period, the company's total revenue was RMB 393 million, up 8% YoY, and the contribution to this from product sales was RMB 385 million, up 16% YoY. The company has maintained profitability for three consecutive half-year reporting periods and currently holds over RMB 1 billion in cash reserves. The strong cash position and healthy cash flow laid a solid foundation for Boan Biotech to accelerate innovation going forward. Building momentum for growth by expanding the product portfolio Boan Biotech has four products approved for marketing. Three of them generated a combined sales growth of 16% in the first half of this year. The solid growth was driven by the company’s sophisticated commercial operation system, including a nationwide sales network covering 3,000-plus hospitals and other healthcare organizations, an experienced in-house sales & marketing team, and various strategic partners. Boyounuo® Boyoubei® Boluojia® Boyouping® In oncology, the company took advantage of its own sales & marketing team to promote and sell Boyounuo® (bevacizumab injection) and Boluojia® (denosumab injection 120 mg), resulting in the continued expansion of the two products’ coverage in the marketplace. In areas other than oncology, the company worked with Qingdao Conson Pharmaceutical to extend the reach of Boyoubei® (denosumab injection 60 mg). In August 2025, Boyouping® (Dulaglutide Injection), the 4th product of Boan Biotech, was approved for marketing in China. This was also China’s first locally developed dulaglutide injection approved for marketing in the country. The company granted Shanghai Pharmaceutical Co., Ltd. (Shaphar) the exclusive right to commercialize this product in the Chinese mainland, taking advantage of the latter’s integrated sales & marketing expertise across channels and extensive distribution network to accelerate the ramp-up time for the product. In addition, the company’s pipeline also includes several investigational drugs that will be made commercially available soon. For example, BA9101 (aflibercept injection) is under review for its Biologics License Application (BLA) in China, and Boyoubei (denosumab injection 60 mg) and Boluojia (denosumab injection 120 mg) will complete their Phase 3 clinical trials in Europe, the U.S., and Japan soon. The launch of these drugs will further fuel the company’s high-speed growth. Doubling down on innovation to build a competitive edge Boan Biotech’s pipeline currently includes 2 drug candidates with their BLA under review, and 10-plus drug candidates in the clinical or preclinical development stage. With the first cohort of drug candidates being commercialized one after another, the company is able to generate a sustainable cash flow, which can be used to speed up new drug development on an ongoing basis. The company has built a pipeline of innovative drugs standing out from the competition. It pursues an “IO + ADC” strategy for new drug development, with a focus on developing IO 2.0 therapies as well as the next-generation bispecific and dual-toxin antibody-drug conjugates (ADCs). Here are some examples: ● BA1106 (a non-IL-2 blocking anti-CD25 antibody): This is the first innovative anti-CD25 antibody in China to undergo clinical trials for the treatment of solid tumors. A Phase 1 clinical trial of BA1106 as a monotherapy has been completed. A dose-escalation clinical trial of BA1106 in combination with BA1104 (nivolumab injection), a PD-1 inhibitor developed by the company, also began to enroll patients in June 2025. In April 2025, the early results of the Phase 1 clinical trial of BA1106 were presented at the annual meeting of the American Association for Cancer Research (AACR). In the trial, BA1106 was shown to have the potential for treating multiple types of solid tumor and a pharmacodynamic (PD) profile matching its intended mechanism of action. It was shown to be safe and well-tolerated as well. Besides, BA1106 demonstrated a good pharmacokinetics (PK) profile with low immunogenicity, and all of its anti-drug antibody (ADA) assays were negative. ● BA1302 (an anti-CD228 ADC): This is China’s first innovative anti-CD228 ADC under clinical development. A dose-escalation part of Phase-1 clinical trial is currently going on in China using it as a monotherapy. It was granted an Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for treating squamous non-small cell lung cancer (sqNSCLC) and pancreatic cancer, and was cleared by the FDA for clinical trials as well. ● BA1301 (an anti-Claudin18.2 ADC): It is undergoing a dose-expansion part of Phase 1 clinical trial as a monotherapy in China. This drug candidate was also granted an ODD in the U.S. for the treatment of gastric cancer and pancreatic cancer. Furthermore, the company is also accelerating the development of other innovative biologics in the pre-clinical phase, including: ● PR201 (an antibody-cytokine fusion protein targeting PD-1 and IL-2): Developed in house, PR201 was shown to be a potent anticancer agent in multiple tumor models where anti-PD-1/PD-L1 antibodies were ineffective or had a low efficacy. ● PR203 (a bispecific antibody targeting TL1A and IL23): Its targeted indications include inflammatory bowel disease (IBD), psoriasis (PS), and psoriatic arthritis (PSA). ● BA1304 (a bispecific ADC targeting EGFR and B7-H3): Based on site-specific glycan conjugation, it is intended to treat lung cancer, colon cancer, bladder cancer, kidney cancer, esophageal cancer, and other types of cancer. The company is talking with several partners including multinational pharmaceutical companies to speed up the development of the aforementioned high-potential candidates globally. Maximizing the synergy for BD through collaboration across the value chain Boan Biotech is among a small number of Chinese biopharmaceutical companies operating an integrated system to develop, manufacture and sell products on its own. This system enables seamless collaboration across the value chain, which can be translated into powerful productivity and exceptional efficiency. At the same time, the company is actively deepening external operations by building an ecosystem of partners across the realms of development, production, and commercialization. Its aim is to work with exceptional partners around the world to maximize the synergy and achieve win-win results. Empowering new drug development Previous examples of collaboration include granting Joincare the exclusive rights to develop and commercialize BA2101 (a long-acting anti-IL-4Rα monoclonal antibody) for the treatment of respiratory diseases in the Chinese mainland; conducting a Phase 3 clinical trial of BA9101 in China with Ocumension and granting the latter the exclusive right to commercialize this drug in the Chinese mainland; granting Zencore Biologics the non-exclusive right to use Boan Biotech's proprietary BA-HIEXcell® platform to develop stable cell lines in the Chinese mainland; and collaborating with the Hong Kong University of Science and Technology in several frontiers of biomedicine. Increasing productivity Previous examples of collaboration include working closely with Haier Biomedical for digital, automation and AI endeavors, to improve its digital capabilities for manufacturing and quality management. Speeding up global commercialization Previous examples of collaboration include granting Shaphar the right to commercialize Boyouping in the Chinese mainland; granting Qingdao Conson Pharmaceutical the right to commercialize Boyoubei in the Chinese mainland; granting Kexing Biopharm the right to commercialize Boyoubei and Boluojia in Hong Kong and Macao, as well as the right to commercialize BA9101 in markets other than the Chinese mainland, the EU, the U.K., the U.S., and Japan; and joining hands with overseas partners to commercialize Boyounuo, Boyoubei, and Boluojia in Brazil. In addition, Boan Biotech is also talking with partners for the development and commercialization of multiple drugs in different regions abroad. Increasing capacity through smart manufacturing Boan Biotech already has a production capacity that is enough to address the growing demand driven by new product launch and business development. It also leverages smart manufacturing to optimize production processes and upgrade digital production systems. The company has put into place a quality management system conforming to Chinese, American, European, and Japanese standards. The system has been certified by four major internationally recognized standards: ISO 9001, ISO 14001, ISO 45001, and ISO 50001. In addition, its manufacturing facility has passed the GMP inspection by Brazil’s ANVISA resulting in a “no observation” result and the QP audit of the EU. Boan Biotech was on the “List of Provincial Quality Management Examples” in Shandong, and its digital facility was named one of the “Provincial Digital Facilities of the Year in Shandong” for 2024, all in recognition of the company’s outstanding practices in quality management and digital transformation. Driving high-speed growth by achieving multiple milestones In the second half of 2025, Boan Biotech is expected to achieve multiple milestones, including completing clinical trials at different phases for several innovative biologics and achieving breakthroughs for several biosimilars in China and abroad. Here are some examples: ● The dose-escalation part of Phase 1 trial for the combination therapy of BA1106 (a non-IL-2 blocking anti-CD25 antibody) and BA1104 (nivolumab injection) to be completed this year; ● The dose-expansion part of Phase 1 trial of BA1301 (an anti-Claudin18.2 ADC) as a monotherapy to be completed this year. The phased clinical data will be presented at this year’s annual meeting of the European Society for Medical Oncology (ESMO); ● The dose-escalation part of Phase 1 trial of BA1302 (an anti-CD228 ADC) as a monotherapy to be completed this year; ● BA9101 (aflibercept injection), under review for its BLA in China, to be approved for marketing this year; ● Boyounuo (bevacizumab injection), under review for its BLA in Brazil, to be approved for marketing this year; ● The international multicenter Phase 3 clinical trials of Boluojia (denosumab injection 120 mg) and Boyoubei (denosumab injection 60 mg) to be completed in Europe, the U.S., and Japan, with their BLAs to be submitted in the U.K. this year and in the U.S. next year; ● Patient enrollment to be completed for the Phase 3 clinical trial of BA1104 (nivolumab injection) in China this year, with permission from the FDA already granted to waive the need for a Phase 3 clinical trial of it in the U.S. Jiang Hua, Chairlady and Chief Executive Officer of Boan Biotech, said: “The first half of 2025 was our third consecutive half-year reporting period of being in the black. This made us one of a small number of biotech companies to achieve sustained profitability through product sales thanks to our efficient commercialization efforts and our strategy for building a differentiated portfolio. In the future, we will continue to pursue the goal of becoming a leading biopharmaceutical company in the world with a focus on four fronts: the first is to extend the reach of our four existing products, Boyouping in particular, by enhancing our commercial capabilities; the second is to expedite the approval of several core products for launch in China and abroad to drive revenue growth; the third is to ramp up the development of innovative drugs and build a value-added pipeline; and the fourth is to cash in on our innovation and speed up the development of high-potential candidates overseas by building partnerships. We are confident that we will maintain the high-speed growth over the next three years, to deliver better products for our patients and better results for our shareholders.” About Boan Biotech Boan Biotech is a fully-integrated biopharmaceutical company developing, manufacturing, and marketing biologics, with a focus on oncology, autoimmune diseases, ophthalmology, and metabolic diseases. The company's drug discovery activities revolve around multiple platforms: Human Antibody Transgenic Mouse and Phage Display Technology Platform, Bispecific T-cell Engager Technology Platform, ADC Technology Platform and Cell Therapy Platform. Boan Biotech operates across the entire value chain of the industry covering antibody discovery, cell line development, upstream and downstream process development, analytical and bio-analytical method development, technology transfer, non-clinical research, clinical research, regulatory affairs and registration, and commercial production. In the cell therapy field, Boan Biotech focuses on a new generation of enhanced and regulated CAR-T technology, developing safer, more effective, and affordable treatments for patients. Boan Biotech’s portfolio includes four products approved for marketing. Its pipeline includes one investigational drug under review for its marketing application, multiple novel biologics as drug candidates protected for their international intellectual property rights, and biosimilar candidates. In addition to China, the company is also developing biopharmaceutical products in overseas markets, including the U.S., the EU, and Japan. With a differentiated portfolio and well-established commercial capabilities, Boan Biotech operates across the industry’s value chain from research and development to manufacturing and commercialization, laying a solid foundation for long-term, high-quality growth in the future.

抗体药物偶联物AACR会议财报

2025-08-27

·生物谷

癌症还会“绑架”机体的神经系统？！Nature：癌细胞能够主动损害机体周围神经，引发慢性炎症，进而诱导免疫系统“叛变”

来自德克萨斯大学MD安德森癌症研究中心等机构的科学家们通过研究揭示了一种全新的抗癌耐药机制，即癌细胞会主动损伤机体周围的神经从而引发慢性炎症，进而“教唆”免疫系统“叛变”并导致免疫治疗失败。你是否能想象，癌症这一无情的病魔，不仅无情地侵蚀人体器官，还能狡黠地 “操控” 神经系统，进而使免疫治疗这一抗癌利器失去效力？这并非科幻小说中的情节，而是一项前沿科学研究揭示的惊人事实。近日，发表于国际顶尖杂志《Nature》上，题为 “Cancer-induced nerve injury promotes resistance to anti-PD-1 therapy” 的研究报告，由德克萨斯大学 MD 安德森癌症研究中心等全球 30 多家顶尖机构携手合作完成，为我们揭开了全新的抗癌耐药机制 —— 癌细胞能够主动损害机体周围神经，引发慢性炎症，进而诱导免疫系统 “叛变”，最终致使免疫治疗宣告失败。这项意义非凡的研究，不但精准阐释了部分患者对 PD-1 抑制剂治疗无反应的深层原因，更为逆转耐药提供了一系列创新策略。一、神经受伤，免疫治疗就“失灵”？研究人员最初将目光聚焦于“神经周围侵犯”（PNI，Perineural Invasion）这一现象。早在多年前，临床医生便已察觉，当癌细胞包绕或侵入神经时，患者的预后往往不容乐观，尤其是在皮肤鳞癌、黑色素瘤、胃癌等多种癌症类型中，PNI 更是作为显著的 “不良预后指标” 频繁出现。然而，长久以来，神经遭受癌细胞侵犯后究竟发生了何种变化，始终是未解之谜。通过对 56 名接受 PD-1 抑制剂治疗的皮肤癌患者展开深入分析，研究人员惊异地发现，在治疗无响应的患者群体中，高达 50% 存在 PNI 现象；而在治疗有响应的患者里，这一比例仅为 15%。这一数据清晰表明，神经被侵犯的患者，对免疫治疗产生耐药性的可能性显著增加。进一步深入探究后，研究者们发现，这些受侵犯的神经呈现出 “受伤状态”，它们会大量高表达 ATF3 等损伤标志物，仿佛在绝望地发出“SOS”求救信号。由此可见，神经损伤与机体对抗 PD-1 疗法的耐受性之间，存在着直接且紧密的关联。神经损伤或与机体对抗PD-1疗法的耐受性直接相关二、癌细胞如何处心积虑地 “攻击” 神经？为了精准模拟癌细胞侵犯神经的全过程，科学家们在显微镜下对癌细胞与神经的互动进行了实时细致的观察。结果令人大为震惊，癌细胞不仅会迅速贴近神经，还会如同饥饿的老鼠啃咬电线一般，直接 “啃食” 神经外层至关重要的髓鞘。髓鞘作为神经的 “绝缘保护皮”，一旦遭到破坏，神经信号的传递便会大幅变慢，甚至完全中断。研究人员通过严谨的电生理实验有力证实，肿瘤周围的神经确实出现了严重的 “信号故障”。不过，受伤的神经并不会消极地 “坐以待毙”。它们会立即启动自身的自我修复程序，同时释放出 IL-6 和干扰素等炎症因子，急切地召唤免疫细胞前来救援。这本是机体正常的自我修复反应，然而在肿瘤这一特殊环境中，这一反应却被癌细胞巧妙地 “利用”，成为了癌细胞进一步作恶的 “帮凶”。三、慢性炎症：免疫系统的“特洛伊木马” 随着肿瘤不断生长扩大，越来越多的神经遭到侵犯，炎症反应也逐渐从最初的 “急性修复” 模式，悄然转变为 “慢性破坏” 模式。在这一过程中，大量的免疫抑制细胞，如 M2 型巨噬细胞、耗竭性 T 细胞等，会被源源不断地招募到肿瘤周围。令人遗憾的是，这些免疫细胞不但不会对癌细胞发起攻击，反而会 “劝退” 那些本应发挥抗癌作用的免疫细胞。这一过程就如同一场精心策划的 “特洛伊木马” 行动，神经发出的求救信号，竟被癌细胞恶意篡改成了 “召集免疫抑制部队” 的指令。研究人员借助先进的空间转录组学技术，直观清晰地展示了这种 “神经 - 免疫共谋” 现象。在神经受伤的区域，免疫抑制标志物显著升高，更为糟糕的是，这种抑制状态会迅速扩散至整个肿瘤微环境，使得肿瘤得以在免疫逃逸的道路上越走越远。四、逆转耐药：从“断神经”到“阻断信号” 令人振奋的是，研究人员并未仅仅满足于机制的阐释，而是进一步勇敢地探索逆转耐药的有效方法。他们尝试了多种极具创新性的策略： 1. 手术切断神经（去神经术）：这一策略旨在从物理层面阻止癌细胞继续 “骚扰” 神经，切断癌细胞与神经之间的不良联系，从而为后续治疗创造有利条件。 2. 基因敲除 ATF3：通过精准的基因编辑技术，使神经无法发出损伤信号，从根源上阻断癌细胞利用神经损伤信号作恶的途径。 3. 阻断 IL-6 或干扰素受体：通过药物干预，切断炎症信号的传递路径，阻止免疫抑制细胞被大量招募，进而恢复肿瘤微环境中的免疫平衡。令人惊喜的是，这些策略均取得了一致的积极结果：只要成功中断 “神经损伤 - 炎症” 这条关键通路，就能显著恢复 PD-1 抑制剂的治疗疗效。特别是在动物模型实验中，联合使用抗 PD-1 + 抗 IL-6R 抗体，能够显著抑制肿瘤的生长，为癌症治疗带来了新的希望曙光。五、启示与展望这项研究不仅揭示了一种全新的耐药机制，更开辟了一个新兴领域：“癌症神经免疫学”（Cancer Neuroscience）；它提醒我们，癌症不是一个孤立的“肿块”，而是一个系统性疾病，能操控人体的神经网络和免疫系统。未来研究人员还将进一步研究检测神经损伤标志物（比如ATF3）来预测免疫治疗响应，同时开发针对神经-免疫轴的新型药物并结合神经调节与免疫治疗来实现“双通路”抗癌。这项研究告诉我们，抗癌之战远不止“细胞打细胞”那么简单，其涉及神经、免疫、炎症等多重网络，更像是一场“信息战”。（生物谷Bioon.com）参考文献： Baruch, E.N., Gleber-Netto, F.O., Nagarajan, P. et al. Cancer-induced nerve injury promotes resistance to anti-PD-1 therapy. Nature (2025). doi：10.1038/s41586-025-09370-8

免疫疗法

2025-08-22

·德琪医药

Antengene Announces 2025 Interim Financial Results

// ▶The Phase I/II CLINCH study of ATG-022 (CLDN18.2 antibody-drug conjugate) demonstrated promising results, showing robust clinical efficacy and a favorable safety profile in patients with gastric/gastroesophageal junction adenocarcinoma across high, low, and ultra-low CLDN18.2 expression levels. Supported by these results, ATG-022 was granted a Breakthrough Therapy designation by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA). ▶The Phase I/II STAMINA study of ATG-037 (Oral CD73 small molecule inhibitor) is progressing smoothly. The latest data show particularly encouraging efficacy in the CPI-resistant melanoma subgroup, with an objective response rate (ORR) of 36.4%, a disease control rate (DCR) of 100%, including 1 CR and 3 partial responses (PRs). In the CPI-resistant non-small cell lung cancer (NSCLC) subgroup, the ORR was 21.4%, the DCR was 71.4%, including 3 PRs. ▶Expanding its pipeline’s therapeutic area to autoimmune diseases, Antengene released the preclinical data of ATG-201, a CD19 x CD3 TCE with steric hindrance masking technology. In non-human primate (NHP) models, repeated dosing of ATG-201 surrogate at 1mpk, 3mpk, and 6mpk was well tolerated and associated with very low cytokine release. ATG-201 is expected to enter clinical development in Q4 2025. ▶In the first half of 2025, XPOVIO® generated a revenue of RMB 53.2 million, which rose sharply by 70.6% period-over-period. In addition to the rapid revenue growth, the company’s operational efficiency continued to improve, with sales and administrative expenses declining by 34.0% and 32.8% year-over-year, respectively. Shanghai and Hong Kong, PRC, August 22, 2025 — Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK) today announced its interim results for the period ending June 30, 2025, along with an update highlighting some of its recent achievements. Dr. Jay Mei Antengene’s Founder, Chairman, and CEO "In the first half of 2025, Antengene delivered a series of milestone achievements. Our core mid/late-stage clinical asset, ATG-022, was granted a Breakthrough Therapy designation by the NMPA based on its outstanding clinical data that demonstrated efficacy across all CLDN18.2 expression levels. This underscores ATG-022’s distinctive characteristics as a potential backbone therapy for the treatment of gastric cancer. Moreover, ATG-037 has also exhibited compelling best-in-class potential in clinical studies, with encouraging efficacy data in patients with CPI-resistant melanoma and NSCLC. During the reporting period, we disclosed the preclinical data of ATG-201 (CD19 x CD3 TCE with masking via steric hindrance) in NHP models. ATG-201 is being developed for the treatment of autoimmune diseases and is expected to enter clinical development in Q4 2025. On the commercialization and operational front, XPOVIO® delivered a robust 70.6% period-over-period revenue growth, while sales and administrative expenses declined significantly year-over-year, validating the effectiveness of our two-pronged strategy that centers around innovation and operational efficiency. Looking ahead, we will strive to accelerate the development and commercialization of our key assets, in efforts to deliver breakthrough therapies to patients worldwide and generate sustainable long-term value for our investors." Business Updates Key Clinical Assets ▶ATG-022(CLDN18.2 Antibody-Drug Conjugate) -Updated Data from the Ongoing Phase I/II CLINCH Study: ATG-022 demonstrated significant clinical efficacy and a favorable safety profile in patients with gastric/gastro-esophageal junction adenocarcinoma across high, low, and ultra-low CLDN18.2 expression levels. In patients with moderate-to-high CLDN18.2 expression (IHC 2+ > 20%), the 2.4 mg/kg dose cohort achieved an objective response rate (ORR) of 40% (12/30), including 1 complete response (CR), with a disease control rate (DCR) of 90% (27/30), a median progression-free survival (mPFS) of 6.97 months, a 6-month PFS rate of 51.1%, a 9-month overall survival (OS) rate of 82.7%, and a 12-month OS rate of 66.2%. The 1.8 mg/kg dose cohort achieved an ORR of 40% (10/25), including 1 CR, and a DCR of 84% (21/25). Low and ultra-low CLDN18.2 expressors (IHC 2+ ≤ 20%) who were treated at the efficacious dose range of 1.8-2.4 mg/kg achieved an ORR of 33.3% (6/18), including 1 CR, and a DCR of 50% (9/18). To date, three patients in the study have achieved CR during treatment, with one case of CR observed in each of the three cohorts (i.e., both dose levels in the CLDN18.2 moderate-to-high expressor cohorts and the CLDN18.2 low and ultra-low expressor cohort). -Breakthrough Therapy Designation: ATG-022 was granted a Breakthrough Therapy designation by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the treatment of patients with CLDN18.2-positive, HER2-negative unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have received at least two prior lines of therapy. -Advancing Clinical Development in Gastric Cancer Across First- to Third-Line Settings: Antengene is currently conducting a Phase II dose-expansion study of ATG-022 in the Mainland of China and Australia. The company will continue to advance the clinical development of ATG-022 in gastric cancer in first- to third-line settings, including first-line treatment with ATG-022 in combination with pembrolizumab and chemotherapy (CAPOX/FOLFOX); second-line treatment with ATG-022 in combination with pembrolizumab; and third-line treatment with ATG-022 monotherapy. This strategy covers patients with a wide spectrum of CLDN18.2 expression levels, including moderate-to-high expressors (2+ >20%) and low and ultra-low expressors (2+ ≤20%). In addition, the ongoing clinical study includes a basket trial cohort including multiple tumor types. In preliminary data from patients with a certain subtype of gynecologic tumor, all 7 evaluable patients achieved tumor shrinkage, indicating significant clinical potential of ATG-022 in other CLDN18.2-positive tumors. Currently, this cohort continues to enroll patients. ▶ATG-037 (Oral CD73 Small Molecule Inhibitor) -Updated Data from the Ongoing Phase I/II STAMINA Study: Following the initiation of a global clinical collaboration with MSD, Antengene is evaluating ATG-037 in combination with the anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in patients with checkpoint inhibitor (CPI)-resistant melanoma and non-small cell lung cancer (NSCLC). As of July 24, 2025, data from 25 evaluable patients (11 with melanoma and 14 with NSCLC) showed an ORR of 28% (7/25) and a DCR of 84% (21/25). The melanoma subgroup with majority of patients with double resistance to both anti-PD-1 and anti-CTLA-4 antibodies demonstrated particularly notable efficacy, with an ORR of 36.4%, a DCR of 100%, including 1 CR and 3 partial responses (PRs). In the NSCLC subgroup, the ORR was 21.4%, the DCR was 71.4%, including 3 PRs. It is worth noting that the responses demonstrated impressive durability, with 1 patient in CR demonstrated durable response and has been on the trial for over 32 months, 2 patients with durable PR and has been on the trial for over 15 months, and 1 patient with stable disease (SD) has been on the trial for over 28 months. These data highlight the durable antitumor activity of this combination regimen in CPI-resistant patients. The Phase II STAMINA dose optimization and dose expansion study is currently progressing smoothly in China and Australia. ▶ATG-031 (CD24-targeting macrophage activator) -Ongoing PERFORM study: ATG-031 is the first-in-class humanized anti-CD24 monoclonal antibody that has entered clinical trials for cancer treatment in the U.S. ATG-031 works by blocking the CD24-Siglec10 pathway and enhancing macrophage-mediated phagocytosis of cancer cells. Key study sites of ATG-031 include MD Anderson Cancer Center at the University of Texas, University of California, San Francisco (UCSF), University of Colorado, and Yale Cancer Center, four renowned cancer centers in the U.S. The Phase I PERFORM study is progressing in the U.S. The TCE Platform and Preclinical/Pre-IND Assets ▶A TCE Platform Featuring Steric Hindrance Masking: AnTenGager™ TCE is a proprietary “2+1” TCE technology platform featuring “2+1” bivalent binding for low-expressing targets, steric hindrance masking, and proprietary CD3 sequences with fast on/off kinetics to minimize cytokine release syndrome (CRS) and enhance efficacy. These characteristics support the platform’s broad applicability across autoimmune diseases, solid tumors and hematological malignancies indications. Antengene is seeking a range of collaborations with its global partners for AnTenGager™ TCE, through platform access, co-development, and out-licensing to accelerate the development of TCE therapeutics and maximize the value of the technology platform. ▶ATG-201 (CD19 x CD3 TCE): ATG-201 is a novel “2+1” CD19-targeted T-cell engager developed on the AnTenGagerTM TCE platform for the treatment of autoimmune diseases. Preclinical data showed that in NHP models, the repeated dosing of ATG-201 surrogate at 1mpk, 3mpk, and 6mpk dose levels was well tolerated and associated with very low cytokine release. Furthermore, this surrogate antibody can mediate complete B cell depletion in peripheral blood, spleen and lymph nodes. ATG-201 is poised to enter clinical development in Q4 2025. ▶Antengene will continue to advance the development of other preclinical programs, including ATG-106 (CDH6 x CD3 TCE) for the treatment of ovarian cancer and kidney cancer, ATG-110 (LY6G6D x CD3 TCE) for the treatment of microsatellite stable (MSS) colorectal cancer, and ATG-112 (ALPPL2 x CD3 TCE) for the treatment of gynecologic tumors and lung cancer. Commercialized Product ▶Mainland of China: In July 2025, XPOVIO® received approval for its third indication in the Mainland of China, bringing a new treatment option to patients with multiple myeloma (MM) who have received at least one prior therapy. Among the three approved indications of XPOVIO®, two have already been included in China’s National Reimbursement Drug List (NRDL), including XPOVIO® monotherapy for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) and XPOVIO® in combination with dexamethasone for the treatment of R/R MM. ▶Taiwan Market: In February 2025, XPOVIO® received national reimbursement approval in Taiwan market, making it the fifth APAC market to secure reimbursement coverage after mainland of China, South Korea, Australia, and Singapore. ▶ASEAN Markets: In March 2025, XPOVIO® was approved in Indonesia. To date, XPOVIO® has been approved for multiple indications in ten countries and regions across the APAC region. Highlights of Financial Results Revenue From Product Sales Rose Sharply by 70.6% Period-over-Period With the steady expansion of its commercial footprint across the Asia-Pacific markets, XPOVIO® generated a sales revenue of RMB 53.2 million in the first half of 2025, which rose sharply by 70.6% period-over-period. Along with the rapid revenue growth, the company’s operational efficiency continued to improve, with sales and administrative expenses declining by 34.0% and 32.8% year-over-year, respectively, demonstrating excellent cost control. Strong Cash Reserves Securing the Execution of Long-Term Strategies As of the end of the reporting period, the company held RMB 794 million in cash and bank balances, which is sufficient to support existing key programs to the proof-of-clinical-concept stage, securing the execution of the company’s long-term strategies. To learn more about the 2025 interim financial results, please see the full announcement in the “Investor Relations” section on the company’s website. About Antengene Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK) is a global, R&D-driven, commercial-stage biotech company focused on developing first-in-class/best-in-class therapeutics for diseases with significant unmet medical needs. Its pipeline spans from preclinical to commercial stages and includes several in-house discovered programs, including ATG-022 (CLDN18.2 ADC), ATG-037 (oral CD73 inhibitor), ATG-101 (PD-L1 × 4-1BB bispecific antibody), ATG-031 (CD24-targeting macrophage activator), and ATG-042 (oral PRMT5-MTA inhibitor). Antengene has also developed AnTenGager™, a proprietary T cell engager 2.0 platform featuring “2+1” bivalent binding for low-expressing targets, steric hindrance masking, and proprietary CD3 sequences with fast on/off kinetics to minimize cytokine release syndrome (CRS) and enhance efficacy. These characteristics support the platform’s broad applicability across autoimmune diseases, solid tumors and hematological malignancies indications. To date, Antengene has obtained 31 investigational new drug (IND) approvals in the U.S. and Asia, and submitted new drug applications (NDAs) in 11 Asia Pacific markets. Its lead commercial asset, XPOVIO® (selinexor), is approved in the Mainland of China, Taiwan China, Hong Kong China, Macau China, South Korea, Singapore, Malaysia, Thailand, Indonesia and Australia. Forward-looking statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, please see the other risks and uncertainties described in the Company’s Annual Report for the year ended December 31, 2024, and the documents subsequently submitted to the Hong Kong Stock Exchange.

100 项与 Sym-021 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
晚期恶性实体瘤	临床1期	美国	Adir SRL	2021-10-15
晚期恶性实体瘤	临床1期	加拿大	Adir SRL	2021-10-15
胆管癌	临床1期	美国	Symphogen A/S	2020-10-12
胆管癌	临床1期	加拿大	Symphogen A/S	2020-10-12
胆管癌	临床1期	法国	Symphogen A/S	2020-10-12
胆管癌	临床1期	西班牙	Symphogen A/S	2020-10-12
Vater壶腹癌	临床1期	美国	Symphogen A/S	2020-10-12
Vater壶腹癌	临床1期	加拿大	Symphogen A/S	2020-10-12
Vater壶腹癌	临床1期	法国	Symphogen A/S	2020-10-12
Vater壶腹癌	临床1期	西班牙	Symphogen A/S	2020-10-12

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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


ASCO2024	N/A	复发性头颈部鳞状细胞癌 PD-L1 positive (CPS≥1)	89	anti-PD-1 (irAEs)	廠壓淵餘蓋淵遞壓製範(糧願窪壓鏇構顧鑰憲簾) = 10% 蓋範製夢鑰選簾觸壓鬱 (鹹淵鬱簾膚鑰鑰窪齋鬱 ) 更多	积极	2024-05-24
				anti-PD-1 (non-irAEs)
ASCO2023	N/A	黑色素瘤	86	Anti-PD-1 antibody plus ipilimumab therapy	鑰鹽壓遞製鑰餘願衊鏇(艱廠鬱願繭糧醖築顧築) = 鬱壓齋積構觸鏇膚簾築壓範淵廠蓋齋積醖遞蓋 (築襯齋鏇廠簾齋積淵淵 ) 更多	积极	2023-05-31
NCT03489343 \| NCT03311412 \| NCT03489369 (ESMO2020)	临床1期	肿瘤转移 \| 晚期恶性实体瘤 \| 淋巴瘤	-	Sym021	夢齋選襯鏇齋壓鑰獵構(壓淵窪餘鑰鏇鏇窪襯範) = Sym021, Sym022 and Sym023 alone and Sym021 in combination with either Sym022 or Sym023 were well tolerated with AE profiles typical of immune checkpoint inhibitors 窪醖遞顧鏇鹹齋夢網齋 (鏇糧醖齋窪築顧範願鹹 )	-	2020-09-20
				Sym022
AUA2020	N/A	泌尿生殖系统肿瘤 HLA-I genotypes \| HLA-C genotypes \| KIR ligands ... 更多	51	anti-PD-1 drugs (HLA-A2 supertype)	廠簾鹹憲齋鹹醖餘鬱齋(衊簾範鬱糧壓膚衊獵醖) = 繭積憲醖齋鑰衊衊夢積積鏇衊淵衊夢鏇廠鹹鏇 (襯簾襯網鬱衊簾夢觸構 )	-	2020-04-01
				anti-PD-1 drugs (Patients without HLA-A2 supertype)	廠簾鹹憲齋鹹醖餘鬱齋(衊簾範鬱糧壓膚衊獵醖) = 壓醖艱築餘範願獵醖構積鏇衊淵衊夢鏇廠鹹鏇 (襯簾襯網鬱衊簾夢觸構 )
ASCO2017	N/A	转移性黑色素瘤	-	aPD1	築獵夢選艱範淵簾顧獵(膚製糧願繭淵製築糧襯) = 獵鬱鏇醖襯夢獵鏇膚窪憲淵鏇製觸艱蓋襯構鑰 (獵製鹹艱觸醖顧淵選簾 ) 更多	-	2017-05-30
				aPD1 + IPI	簾獵觸衊築餘觸獵醖襯(觸範範膚簾艱範鬱獵窪) = 夢鏇鹹簾製蓋鬱壓淵遞製製鹹蓋夢願衊鑰獵願 (憲壓蓋憲獵壓窪網顧製 ) 更多
ASCO2017	N/A	转移性黑色素瘤	64	aPD1 + aCTLA4	衊襯鹽廠築蓋繭觸餘網(蓋積觸淵顧壓餘醖襯構) = One death from irAEs occurred related to Toxic Epidermal Necrolysis (TEN) 蓋築衊網憲憲願齋鏇膚 (鏇蓋簾築範選範蓋衊齋 ) 更多	积极	2017-05-30