预约演示

更新于：2025-05-07

Siglec-10

更新于：2025-05-07

基本信息

别名

MGC126774、PRO940、sialic acid binding Ig like lectin 10

+ [8]

简介

Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid (By similarity). The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, seems to act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules (PubMed:11284738, PubMed:12163025). Involved in negative regulation of B-cell antigen receptor signaling. The inhibition of B cell activation is dependent on PTPN6/SHP-1 (By similarity). In association with CD24 may be involved in the selective suppression of the immune response to danger-associated molecular patterns (DAMPs) such as HMGB1, HSP70 and HSP90 (By similarity). In association with CD24 may regulate the immune repsonse of natural killer (NK) cells (PubMed:25450598). Plays a role in the control of autoimmunity (By similarity). During initiation of adaptive immune responses by CD8-alpha(+) dendritic cells inhibits cross-presentation by impairing the formation of MHC class I-peptide complexes. The function seems to implicate recruitment of PTPN6/SHP-1, which dephosphorylates NCF1 of the NADPH oxidase complex consequently promoting phagosomal acidification (By similarity).

关联

项与 Siglec-10 相关的药物

ONC-841

靶点

Siglec-10

作用机制

Siglec-10拮抗剂

在研机构

OncoC4, Inc.

原研机构

OncoC4, Inc.

在研适应症

晚期恶性实体瘤 [+1]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

AK-007

靶点

Siglec-10

作用机制

Siglec-10拮抗剂

在研机构

Allakos, Inc.

原研机构

Allakos, Inc.

在研适应症

炎症 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

CN114656523

专利挖掘

靶点

Siglec-10

作用机制-

在研机构

南京市第一医院

原研机构

南京市第一医院

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

项与 Siglec-10 相关的临床试验

NCT06352359

/ Recruiting临床1期

Safety, Pharmacokinetics (PK), and Efficacy of ONC 841 in Advanced Solid Tumors

This is a Phase I open label, dose-escalation study of intravenous (IV) infusion of ONC-841 as a single agent in patients with advanced/metastatic solid tumors. The study will evaluate seven dose levels of ONC-841 starting from 0.03 mg/kg to 30 mg/kg.

开始日期2024-08-23

申办/合作机构

OncoC4, Inc.

NCT06219499

/ Withdrawn临床1期

A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Immunogenicity and Pharmacokinetics of ONC-841 When Administered Intravenously in Healthy Adult Subjects

The Phase 1 study is a randomized, double-blind, placebo-controlled, single ascending dose, multi-cohort study. The study will evaluate 5 dose levels of the investigational product, in 5 cohorts of 8 healthy volunteers per cohort. In each cohort, 6 volunteers will receive the investigational product and 2 volunteers will receive placebo.

开始日期2024-06-01

申办/合作机构

OncoC4, Inc.

NCT04060407

/ Withdrawn临床1/2期

Phase Ib/II Study Combining CD24Fc With Checkpoint Inhibitors for Patients With Metastatic Melanoma

This is a phase Ib/II clinical trial to test safety and efficacy of combining CD24Fc with ipilimumab and nivolumab to decrease irAE, with built-in interim analyses, and safety and response stopping rules.

开始日期2021-06-15

申办/合作机构

OncoImmune, Inc.

[+2]

100 项与 Siglec-10 相关的临床结果

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100 项与 Siglec-10 相关的转化医学

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0 项与 Siglec-10 相关的专利（医药）

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159

项与 Siglec-10 相关的文献（医药）

2025-07-01·European Journal of Pharmacology

Erythromycin repurposing for hepatocellular carcinoma treatment: Targeting CD24 to enhance anti-tumor immunity

Article

作者: Guo, Sheng ; Sun, Yuanli ; Wang, Kangle ; Zhang, Yongxi ; Yang, Zishan ; Geng, Jiaxin ; Zhao, Tiesuo ; Dong, Xiaoyu ; Wei, Tian ; Chen, Zhihan ; Jia, Huijie ; Jia, Xiaolong ; Qian, Li ; Shao, Mingguang

Hepatocellular carcinoma (HCC) is a malignant tumor, making up about 90% of all primary liver cancers and ranking as a top cause of cancer mortality globally. With the severe side effects of conventional radiotherapy and chemotherapy, there's an ongoing quest for less toxic treatment options. CD24, a highly glycosylated membrane surface protein, plays a role in cancer cell adhesion and metastasis. Its overexpression is associated with poor prognosis in cancer patients. By binding to Siglec-10 on macrophages, CD24 helps tumor cells dodge the immune system. Targeting CD24 expression on is seen as a promising approach to cancer therapy. This study investigated the potential of repurposing the old drug erythromycin to regulate CD24 and its anti-HCC effect. The results investigated that erythromycin didn't significantly impact liver cancer cell growth, movement, or death. However, it effectively inhibited CD24 expression after treatment, and the effect that can be reversed with a proteasome inhibitor MG132. Further study showed erythromycin not only reduced CD24 expression but also slowed tumor growth, triggered cell death, and altered the balance of proteins involved in cell proliferation and migration in vivo. Importantly, it altered the immune environment within tumors and boosted the presence of immune cells that fight cancer including the infiltration increase of M1 macrophages and T lymphocytes in tumor tissues and the decrease of M2 macrophages. The research confirmed that erythromycin enhanced the anti-tumor immune response in HCC-bearing mice by reducing CD24 expression, providing a novel strategy for the clinical development of HCC treatments.

2025-04-01·Journal for ImmunoTherapy of Cancer

Targeted release of a bispecific fusion protein SIRPα/Siglec-10 by oncolytic adenovirus reinvigorates tumor-associated macrophages to improve therapeutic outcomes in solid tumors

Article

作者: Zhang, Yenan ; Zou, Peng ; Wei, Min ; Xu, Chuning ; He, Bohao ; Wei, Jiwu ; Wu, Mengdi ; Dong, Jie

BackgroundThe pleiotropic roles of tumor-associated macrophages (TAMs) render them attractive targets in antitumor drug development. CD47/SIRPα (signal regulatory protein alpha) and CD24/Siglec-10 (sialic acid-binding immunoglobulin-like lectin 10) signaling pathways have been found to suppress macrophage phagocytosis of malignant cells. Systemic blockade of CD47/SIRPα has shown severe side effects. Intratumoral delivery of a CD47 inhibitor by oncolytic viruses (OVs) may circumvent this hurdle.MethodsTo identify the characteristics of recombinant adenovirus (AdV)-SIRPα/Siglec-10, we conducted CCK8 assay, quantitative PCR, western blot, competitive binding assay, in vitro cytotoxicity assay, ELISA and phagocytosis assay. We investigated the antitumor immune responses of AdV-SIRPα/Siglec-10 using flow cytometry, various tumor-bearing mouse models, humanized tumor-bearing mouse models, immune cell depletion, RNA sequencing, and in vitro T cell activation assay.ResultsHere, we developed a novel AdV encoding a fusion protein composed of the extracellular domains of murine or human SIRPα and Siglec-10 (SIRPα/Siglec-10), termed AdV-mSS or AdV-huSS. The SIRPα/Siglec-10 was effectively secreted by cells infected with AdV-mSS and functioned as a dual blocker of CD47 and CD24, thereby significantly enhancing macrophage phagocytosis. In a series of tumor models, including subcutaneous and ascitic H22 hepatocellular carcinoma (HCC), subcutaneous Hepa1-6 HCC, MC38 colorectal carcinoma, and Lewis lung carcinoma, AdV-mSS treatment markedly enhanced antitumor efficacy. Mechanistically, AdV-mSS reprogrammed TAMs toward an antitumor phenotype and enhanced the expression of major histocompatibility complex (MHC)-I/II, promoting CD8+T cell proliferation and activation. Depletion of either macrophages or CD8+T cells abrogated the antitumor efficacy of AdV-mSS. Similarly, in a humanized LM3 HCC mouse model, AdV-huSS significantly inhibited tumor growth and prolonged survival.ConclusionsDual SIRPα/Siglec-10 inhibitor delivered intratumorally by AdV not only reinvigorated the TAM-CD8+T cell axis but also potentially reduced the risk of off-target effects. Further investigation of AdV-huSS in patients with cancer is warranted in the near future.

2025-04-01·Journal of Biological Chemistry

The molecular basis of immunosuppression by soluble CD52 is defined by interactions of N-linked and O-linked glycans with HMGB1 box B

Article

作者: Moh, Edward S X ; Packer, Nicolle H ; Goddard-Borger, Ethan ; Bandala-Sanchez, Esther ; Harrison, Leonard C ; DeBono, Nicholas J ; Fadda, Elisa ; D'Andrea, Silvia ; Zenaidee, Muhammad A

Human soluble CD52 is a short glycopeptide comprising 12 amino acids (GQNDTSQTSSPS) which functions as an immune regulator by sequestering the pro-inflammatory high mobility group box protein 1 (HMGB1) and suppressing immune responses. Recombinant CD52 has been shown to act as a broad anti-inflammatory agent, dampening both adaptive and innate immune responses. This short glycopeptide is heavily glycosylated, with a complex sialylated N-linked glycan at N3 and reported O-linked glycosylation possible on several serine and threonine residues. Previously we demonstrated that specific glycosylation features of CD52 are essential for its immunosuppressive function, with terminal α-2,3-linked sialic acids required for binding to the inhibitory SIGLEC-10 receptor leading to T-cell suppression. Using high resolution mass spectrometry, we have further characterized the N- and O-linked glycosylation of Expi293 recombinantly produced CD52 at a glycopeptide and released glycan level, accurately determining glycan heterogeneity of both N- and O-linked glycosylation, and localizing the site of O-glycosylation to T8 with high confidence and direct spectral evidence. This detailed knowledge of CD52 glycosylation informed the construction of a model system, which we analyzed by molecular dynamics simulations to understand the mechanism of recognition and define interactions between bioactive CD52, HMGB1 and the SIGLEC-10 receptor. Our results confirm the essential role of glycosylation, more specifically hyper-sialylation, in the function of CD52, and identify at the atomistic level specific interactions between CD52 glycans and the Box B domain of HMGB1 that determine recognition, and the stability of the CD52/HMGB1 complex. These insights will inform the development of synthetic CD52 as an immunotherapeutic agent.

项与 Siglec-10 相关的新闻（医药）

2025-05-03

·小药说药

肿瘤免疫中的Siglec受体及其靶向治疗

-01-引言在过去十年中，以免疫检查点抑制剂和细胞疗法为形式的癌症免疫治疗改善了许多患者的治疗和预后。尽管如此，大多数癌症仍然对目前批准的癌症免疫疗法具有耐药性。需要新的方法和合理的组合来克服这些阻力。最新的研究表明，肿瘤微环境中含唾液酸聚糖的唾液酸与肿瘤浸润免疫细胞上唾液酸结合免疫球蛋白样凝集素（Siglec）受体之间的相互作用可能代表一个新的免疫检查点和癌症免疫治疗的潜在新靶点。-02-一、Siglec受体及信号通路Siglecs是一类与含唾液酸的聚糖结合的受体家族。大多数Siglec受体是抑制性的，目前发现 15 种人源和 9 种鼠源的Siglec 分子。Siglec受体可进一步分为序列保守的受体和与CD33相关的快速进化受体。Siglec-1、Siglec-2（CD22）、Siglec-4和Siglec-15属于保守家族；Siglec-3（CD33）、Siglec-5、Siglec-6、Sigleg-7、Siglec8、Siglec-9、Sigle-c-11、Siglec-XII、Siglec-14和Siglec-16属于快速演化的CD33相关Siglecs受体。根据细胞内信号结构域的不同，Siglec受体也可分为抑制型、激活型和非信号型。Siglec-11、Siglec-14和Siglec-15属于激活型Siglec受体，而Siglec-1和Siglec-4没有直接的免疫调节细胞内结构域。所有其他人类Siglec受体在本质上都是抑制性的。Siglec 家族属于一次穿膜的Ⅰ型膜蛋白，在结构上具有非常典型和保守的结构特征，其穿膜区由 2 ～17 个胞外 Ig 结构域组成，N 端由一个结合唾液酸的V-set Ig 结构域和一定数目的 C2-set Ig 结构域组成。抑制性Siglec受体细胞内含有免疫受体酪氨酸抑制基序（ITIM）和免疫受体开关基序（ITSM）的结构域，可以通过SHP1和SHP2磷酸酶的参与调节细胞内信号。因此，抑制性Siglecs可以与PD-1/PD-L1类似的作用方式抑制免疫细胞激活。激活型Siglec受体具有带正电荷氨基酸的跨膜结构域，当CRD与唾液酸聚糖配体结合时，该跨膜结构区介导DAP12的招募，DAP12包含免疫受体酪氨酸基激活基序（ITAM），并可传递激活信号。-03- 二、癌症相关Siglec配体的表达许多研究报告了癌症和肿瘤微环境中唾液酸聚糖的表达变化，肿瘤细胞通常是高唾液酸化的，产生免疫细胞上抑制性Siglec受体的配体。例如，由于唾液酸转移酶ST3GAL1和ST3GAL4的过表达，胰腺导管腺癌（PDAC）肿瘤细胞显示出唾液酸化增加。PDAC细胞的唾液酸化被髓系细胞上的Siglec-7和Siglec-9识别，并使单核细胞向促瘤巨噬细胞极化。同样，Siglec-9配体的上调已在人类结直肠癌、前列腺癌、乳腺癌和非小细胞肺癌中得到证实。通过全基因组筛查，已确定唾液酸化CD43是Siglec-7的高度特异性配体，抑制NK细胞介导的K562白血病细胞杀伤。LGALS3BP已被证明是几种Siglecs（包括Siglec-9）的分泌型癌相关配体，可抑制中性粒细胞活化。CD24在许多癌症中过表达，并通过与Siglec-10在肿瘤相关巨噬细胞（TAM）上的相互作用，成为某些卵巢癌和乳腺癌中免疫逃避的主要机制。此外，可溶性CD52同样与T细胞上的Siglec-10结合，据报道在自身免疫性疾病中抑制T细胞。-04-三、Siglec受体对癌症免疫细胞的影响Siglec受体广泛表达于免疫系统的不同细胞上。已证明，不同免疫细胞上的唾液酸聚糖配体和Siglec受体之间的功能相关相互作用有助于在癌症背景下建立免疫抑制微环境。固有免疫细胞，特别是巨噬细胞，高表达几种不同的Siglec受体，包括Siglec-3、Siglec-5、Siglec-7、Siglec9、Siglec-10、Siglec/14和Siglec-15。最近证明，唾液酸聚糖对胰腺癌细胞的Siglec-7和Siglec-9结合可诱导促肿瘤巨噬细胞表型。。此外，已经表明，癌细胞上的唾液酸化CD24与TAM上的Siglec-10相互作用可以抑制吞噬作用。巨噬细胞上的Siglec-15也被证明可以抑制T细胞介导的抗肿瘤免疫。树突状细胞是抗肿瘤免疫反应的重要介质，与免疫治疗的成功密切相关。最近的研究进一步表明Siglec受体在经典树突状细胞（cDC）上的作用。已证明DC上的小鼠Siglec-G可以调节抗原处理；此外，小鼠体内的Siglec-E被证明参与了抗原摄取和向CD4+T细胞的递呈。在小鼠模型系统中，抗原的唾液酸化可通过Siglec-E诱导耐受性调节性T细胞。人单核细胞衍生树突状细胞上的唾液酸聚糖通过Siglec-7和Siglec-9抑制免疫细胞激活。唾液酸聚糖还可诱导DC和CD8+T细胞之间的高亲和力相互作用。NK细胞是重要的先天性淋巴细胞。几组研究表明，NK细胞上的Siglec-7和Siglec-9可与癌症相关唾液酸聚糖作用，参与抑制抗肿瘤免疫激活。将合成唾液酸聚糖插入肿瘤细胞的细胞膜能够剂量依赖性地抑制NK细胞介导的杀伤和脱颗粒。最近的工作进一步证明Siglec-7与多发性骨髓瘤细胞上的唾液酸化PSGL-1相互作用，能够抑制NK细胞介导的骨髓瘤细胞杀伤。此外，在肾癌细胞中，神经节苷脂Siglec-7配体的过表达抑制NK细胞活化；唾液酸化MUC16结合人Siglec-9并抑制卵巢癌中的NK细胞。除了影响髓系细胞和其他先天免疫细胞外，唾液酸聚糖-Siglec相互作用也影响癌症的适应性免疫系统。研究发现，Siglec-9在癌症患者血液和肿瘤浸润性T细胞中上调，其在肿瘤特异性耗竭的PD-1+T细胞上表达。肿瘤细胞上Siglec-9配体的减少显著诱导T细胞介导的效应器功能和肿瘤细胞杀伤。在T细胞急性激活后，Siglec-5和Siglec-10也被发现上调，并可能影响抗肿瘤免疫。总之，唾液酸聚糖与Siglec受体的相互作用已被证明通过诱导肿瘤相关巨噬细胞的促癌表型、抑制NK细胞和中性粒细胞活化、减少DC成熟和抗原提呈以及抑制T细胞反应，有助于免疫抑制肿瘤微环境。-05-四、针对唾液酸聚糖-Siglec的药物开发近几年以来，作为肿瘤抗原的Siglec受体一直是治疗癌症的重要靶点。Siglec-2（CD22）在许多B细胞恶性肿瘤中表达，抗体偶联药物（ADCs）已成功用于靶向肿瘤细胞，如inotuzumab ozogamicin治疗复发性急性淋巴细胞白血病。靶向Siglec-2和CD19的CAR-T细胞也被开发用来治疗复发性弥漫性大细胞B细胞淋巴瘤或急性淋巴细胞白血病患者。此外，靶向Siglec-3的ADC也在开发和测试当中。除了作为一种直接的肿瘤相关性抗原，Siglec受体及其唾液酸聚糖配体也可以作为靶向激活免疫细胞对抗肿瘤。Siglec受体可以被高亲和力抗体阻断，类似于PD-1/PD-L1和CTLA-4的免疫检查点抑制剂。阻断性抗体NC318以Siglec-15为靶点，目前正在进行一项对晚期非小细胞肺癌患者联合使用pembrolizumab的临床研究（NCT04699123）。Siglec-7和Siglec-9是提高NK细胞抗肿瘤活性的潜在靶点，一项使用Siglec-7和-9阻断性抗体的临床前研究证明了在小鼠模型中的抗肿瘤功效，阻断抑制性Siglec受体可支持免疫抑制微环境中TAM的复极，增加抗肿瘤巨噬细胞的吞噬作用。此外，肿瘤细胞上CD24与肿瘤相关巨噬细胞上Siglec-10之间的相互作用被认为是增强巨噬细胞吞噬作用的新治疗靶点。另一种方法是使用针对特定糖类的阻断性抗体。最近的一项研究表明，抗神经节苷脂GD2的抗体可以通过抑制巨噬细胞上GD2与Siglec-7的结合来提高抗肿瘤免疫，从而通过进一步增加吞噬作用来增强CD47阻断的效果。此外，降低肿瘤细胞和肿瘤微环境中的唾液聚糖密度是一种替代策略。可以开发新的唾液酸生物合成抑制剂，以改善癌症免疫治疗。在小鼠模型中，使用2-脱氧-D-葡萄糖抑制肿瘤细胞的N-糖基化可增加CAR-T细胞介导的杀伤作用和疗效。使用酶降低肿瘤中唾液酸聚糖的密度也被证明可以增强抗肿瘤免疫治疗，与抗HER2抗体trastuzumab偶联的细菌唾液酸酶，目前正在首次人体临床试验。-06-结语癌症免疫治疗的改进需要开发新的方法。Siglec受体及其与唾液酸聚糖配体的相互作用是改善癌症免疫治疗的一个潜在的新型免疫检查点。在过去的几年里，已经进行了一些临床前和临床研究，支持了针对Siglec受体的药物开发。以唾液酸聚糖-Siglec轴为靶点的癌症免疫治疗显示出良好的潜力。参考资料：1.Siglec receptors as new immune checkpoints in cancer. Mol Aspects Med.2022 Aug 7;101112.公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

免疫疗法细胞疗法临床研究

2025-04-15

·PipelineReview

Pheast Therapeutics Announces First Patient Treated in Phase 1 Clinical Trial of PHST001 for Patients with Advanced Solid Tumors

REDWOOD CITY, CA, USA I April 14, 2025 I Pheast Therapeutics , a private biotechnology company developing novel therapies to unleash the power of macrophages on aggressive, difficult-to-treat cancers, today announced that the first patient has been treated in its Phase 1 clinical trial evaluating PHST001, an anti-CD24 macrophage checkpoint inhibitor, in patients with advanced solid tumors. “The start of this Phase 1 trial is an important milestone for Pheast and for the advancement of next generation macrophage checkpoint therapies,” said Roy Maute, Ph.D., Cofounder and CEO, Pheast Therapeutics. “We believe PHST001 has the potential to provide new treatment options for patients, particularly in cancers where other immunotherapies have not been effective.” The multicenter, open-label Phase 1 study will enroll up to 80 patients with advanced relapsed and/or refractory solid tumors (ClinicalTrials.gov Identifier: NCT06840886 ). The study’s primary objectives include evaluating safety and tolerability of PHST001 and establishing the recommended Phase 2 dose, with secondary endpoints assessing pharmacokinetics and early signs of anti-tumor activity. Raphaël Rousseau, M.D., Ph.D., Chief Medical Officer, Pheast Therapeutics, said, “PHST001 has demonstrated robust activity across tumor types and a favorable safety profile in preclinical studies. Furthermore, these data suggest that PHST001 may overcome tumor immune evasion through a differentiated approach to macrophage activation. We are pleased to have initiated this study as a first step in understanding the clinical potential of PHST001 to improve patient outcomes across multiple cancer types.” Irving Weissman, M.D., scientific co-founder of Pheast Therapeutics added, “CD24 is a key mechanism that tumors use to evade macrophage-mediated immune responses. PHST001 was developed based on foundational research into this pathway, and I’m encouraged to see this science progressing into the clinic. It’s a meaningful step toward harnessing the full potential of the innate immune system in cancer.” Preclinical data presented at SITC 2024 highlight PHST001’s potential across multiple cancer types, and its differentiation as a novel macrophage checkpoint inhibitor uniquely designed to target all glyco-variants of CD24. By binding CD24 with high affinity and specificity, PHST001 promotes macrophage-induced phagocytosis in a variety of cancer cell types and significantly shrinks tumors in in vivo models. Additionally, PHST001 has a favorable pharmacokinetic profile in non-human primates and does not induce immune-mediated toxicity in in vitro studies. About CD24 CD24 is a cell surface protein that plays a key role in tumor immune evasion by engaging Siglec-10, an inhibitory receptor on macrophages. This interaction suppresses macrophage-mediated clearance of cancer cells, allowing tumors to escape destruction by the innate immune system. CD24 was identified as a novel macrophage checkpoint through foundational work by Dr. Amira Barkal, principal founder of Pheast. Along with other co-founders, Drs. Irving Weissman, Ravi Majeti, and Roy Maute, Pheast’s research opened the door to therapeutic strategies targeting CD24 to drive innate immune responses against cancer. About PHST001 PHST001 is an anti-CD24 macrophage checkpoint inhibitor designed to overcome immune suppression in the tumor microenvironment. CD24 is highly expressed by many human cancers, including ovarian and triple negative breast cancer (TNBC), and high expression of CD24 is a negative prognostic factor in multiple cancer indications. Pheast has engineered PHST001 to be a best in class antibody designed to induce macrophages to phagocytose cancer cells and initiate a powerful immune response. About Pheast Therapeutics Pheast is a clinical-stage immuno-oncology company focused on activating the innate immune system in the fight against cancer. Founded as a spinout from Stanford University and led by scientific experts in innate immunity and cancer immunotherapy, Pheast is developing novel therapies for some of the most difficult-to-treat and aggressive cancers. Pheast is backed by leading life sciences investors, Catalio Capital Management and ARCH Venture Partners. For more info, visit Pheast.com and connect on LinkedIn . SOURCE: Pheast Therapeutics

临床1期免疫疗法

2025-03-21

·德琪医药

德琪医药公布2024年全年业绩：自研产品迈入关键期，多市场营收加速放量

中国上海和香港，2025年3月21日–德琪医药（6996.HK）今日公布公司截至2024年12月31日的全年业绩以及近期取得的多项重要里程碑。梅建明德琪医药创始人、董事长兼首席执行官 “2024年对德琪医药而言是意义非凡的一年，我们在临床开发、产品研发和商业化方面均取得了令人振奋的突破性进展。正在中国大陆和澳大利亚进行II期研究的Claudin 18.2抗体偶联药物ATG-022展现出极具差异化的临床治疗潜力，不仅在Claudin 18.2中高度表达的胃癌患者中显示了疗效，还为低表达和极低表达的患者带来了前所未有的临床获益。我们自研的具有空间位阻遮蔽效应的AnTenGager™ TCE 2.0更是彰显出强大的创新实力，临床前研究表明AnTenGager™在安全性方面显著优于第一代TCE平台，并具备覆盖实体瘤、血液瘤以及自免领域的潜力。我们将面向全球合作伙伴开放基于该平台的多种合作模式，最大化释放平台价值。基于该平台研发的ATG-201（CD19 x CD3 TCE 2.0）预计将于2025下半年进入临床。在临床开发和创新研发高歌猛进的同时，我们的商业化成绩同样精彩纷呈。已上市产品希维奥®国际化进程显著加快，在中国大陆新增获批第2项适应症并迅速进入医保，成功纳入韩国和台湾市场医保体系，并在马来西亚、泰国、印度尼西亚相继获批上市。截至目前，希维奥®已在亚太市场的10个国家和地区获批上市，并被纳入其中5个市场的医保。公司现持有现金9亿余元人民币，即便在不考虑后续收入的情况下，也足以保障公司未来三年的运营。我们满怀信心的期待与大家分享2025年的更多进展，即将到来的便是将于AACR 2025上展示的AnTenGager™ TCE 2.0的最新研究成果。” Claudin 18.2 ADC临床价值显著多款产品蓄势待发 ▶ATG-022（Claudin 18.2 抗体偶联药物 ADC）独特的治疗潜力：ATG-022是一款高度差异化的产品，它在广泛的Claudin 18.2（CLDN18.2）表达水平下均有效，具有独特的治疗潜力。临床数据显示，ATG-022不仅可以有效靶向作用于CLDN18.2高表达的胃癌患者，还能有效作用于CLDN18.2低表达和极低表达的肿瘤。此外，ATG-022在安全性方面表现更优，无累积毒性，且与其他处于相似临床开发阶段的CLDN 18.2 ADC药物相比，剂量限制性毒性和重度不良反应显著减少。ATG-022还获得了美国食品药品管理局（FDA）授予的2项孤儿药资格认定（ODD），分别用于治疗胃癌和胰腺癌。正在进行的CLINCH研究：截至2024年11月22日，剂量扩展阶段的21例CLDN 18.2表达IHC 2+ ≥ 20%的胃癌患者的总体缓解率（ORR）为42.9%，疾病控制率（DCR）为95.2%（9例达到部分缓解[PR]，其中8例PR确定；11例达到疾病稳定[SD]）。另有10例CLDN 18.2表达IHC 2+ < 20%的胃癌患者接受了1.8 – 2.4 mg/kg有效剂量的治疗，ORR为30.0%（1例获得完全缓解 [CR]，2例获得PR，所有PR/CR全部确定并是CLDN 18.2表达IHC 2+ < 5%），DCR为50.0%。已获得CR的患者显示了持久缓解，并截至数据截止日已参与研究超过14个月。目前，II期CLINCH研究正在中国和澳大利亚顺利开展中。 ▶其它临床阶段产品 ATG-037（CD73小分子抑制剂）：ATG-037在临床前研究中显示了克服 “弯钩效应” 的能力，而 “弯钩效应” 可限制疗效并常见于抗CD73抗体药物的治疗。公司已与默沙东达成一项全球临床合作，并正在抗PD-1耐药的黑色素瘤和非小细胞肺癌（NSCLC）患者中对ATG-037联合抗PD-1药物KEYTRUDA®（帕博利珠单抗）进行评估。公司在2024年欧洲肿瘤内科学会（ESMO）大会上以Mini Oral形式公布临床数据。截至2024年11月27日的最新数据，在26例抗PD-1耐药且接受了联合帕博利珠单抗治疗的疗效可评估患者中，有9例NSCLC患者和11例黑色素瘤患者。当周，这些患者的ORR为35%，DCR为85%。这些数据表明，ATG-037在剂量爬坡阶段已显示逆转抗PD-1耐药的潜力。目前，II期STAMINA剂量优化和扩展阶段研究正在中国和澳大利亚顺利开展中。 ATG-031（抗CD24单抗）：ATG-031是首款在美国进入肿瘤临床研究的人源抗CD24单克隆抗体。ATG-031可通过阻断CD24-Siglec10信号通路，增强由巨噬细胞介导的肿瘤细胞吞噬。ATG-031的主要研究单位包括美国的4个知名癌症中心，分别是德州大学MD安德森癌症中心、加州大学旧金山分校、科罗拉多大学和耶鲁大学癌症中心。目前，I期PERFORM研究正在美国顺利开展中。极具前景并具有空间位阻遮蔽效应的 AnTenGager™ TCE 2.0 ▶第二代TCE平台：AnTenGager™ TCE 2.0是德琪医药自主研发的具有空间位阻遮蔽效应的“2+1”TCE，可通过诱导疾病相关抗原（DAA）依赖的T细胞结合和激活，在实现较强的活性的同时降低发生CRS的风险。相较于第一代TCE平台，AnTenGager™ TCE 2.0具有更高的安全性，并具备覆盖实体瘤、血液瘤以及自身免疫性疾病领域的潜力。此外，AnTenGager™ TCE 2.0具有更长的半衰期，可以减少给药频率，提高临床便利性。公司将继续推进AnTenGager™ TCE 2.0的开发。 ▶全球化合作：公司将面向全球合作伙伴开放AnTenGager™ TCE 2.0平台合作，通过平台技术授权、共同开发、产品授权三种合作模式，加速赋能TCE治疗行业生态，最大程度释放平台价值。 ▶ATG-201（CD19 x CD3 TCE 2.0）：ATG-201是AnTenGager™ TCE 2.0下的一款用于治疗B细胞相关的自身免疫疾病的新型“2+1”CD19靶向的T细胞衔接器。临床前研究中，ATG-201已显示出较对照药物更强的B细胞清除，以及更低的细胞因子释放。公司预计ATG-201将于2025年下半年进入临床。 ▶德琪医药将继续推进其他临床前资产的开发，这些资产包括可靶向作用于MTAP-null肿瘤的选择性PRMT5抑制剂ATG-042、用于治疗卵巢癌和肾癌的ATG-106（CDH6 x CD3 TCE 2.0）、以及用于治疗微卫星稳定 (MSS) 结直肠癌的ATG-110（LY6G6D x CD3 TCE 2.0）等。加速“出海”步伐覆盖10个亚太市场 ▶中国大陆：2024年7月，希维奥®在中国大陆获批第2项适应症，为中国DLBCL患者带来新选择。同年11月，该适应症被纳入医保。截至目前，希维奥®在中国累计获批的两项适应症均已被纳入国家医保目录，医保覆盖人群进一步扩大。 ▶韩国：2024年6月，希维奥®在韩国获得医保批准，于2024年7月1日起正式生效。同年10月，希维奥®在韩国新增第3项适应症获批上市。公司正为希维奥®的更多适应症获得韩国医保收录做努力。 ▶台湾市场：2025年2月，希维奥®在台湾市场获得医保批准。这是继中国大陆、韩国、澳大利亚和新加坡之后，公司在第5个亚太市场实现对于希维奥®的医保覆盖。 ▶东盟市场：2024年8月至今，希维奥®陆续在马来西亚、泰国、印度尼西亚这3个东盟市场获批上市，公司在亚太市场的商业化布局大幅推进。至此，希维奥®已在亚太市场的10个国家和地区获批用于治疗多项适应症。现金储备充裕保障各项战略目标实现截至2024年12月31日，公司持有现金和银行结余9亿余元人民币，即便在不考虑后续融资的情况下，也足以为公司未来三年的发展和企业运营提供坚实保障。如需了解2024年财务业绩的更多详情，请查阅公司官网“投资者关系”一栏中的完整公告。关于德琪医药德琪医药有限公司（简称“德琪医药”，香港交易所股票代码：6996.HK）是一家以研发为驱动，并已进入商业化阶段的生物制药领先企业，以“医者无疆，创新永续”为愿景，德琪医药专注于血液及实体肿瘤领域的同类首款和同类最优疗法的早期研发、临床研究、药物生产及商业化，致力于通过提供突破性疗法，改善全球患者生活质量。自2017年以来，德琪医药现已建立起一条拥有9款从临床延展至商业化阶段的肿瘤药物资产研发管线，其中，6款产品具有全球权益，3款产品具有亚太权益。公司已在美国及多个亚太市场获得31个临床批件（IND），并在11个亚太市场递交了新药上市申请（NDA）。目前，希维奥®（塞利尼索片）已获得中国大陆、中国台湾、中国香港、中国澳门、韩国、新加坡、马来西亚、泰国、印度尼西亚和澳大利亚的新药上市批准。前瞻性陈述本文所作出的前瞻性陈述仅与本文作出该陈述当日的事件或资料有关。除法律规定外，于作出前瞻性陈述当日之后，无论是否出现新资料、未来事件或其他情况，我们并无责任更新或公开修改任何前瞻性陈述及预料之外的事件。请细阅本文，并理解我们的实际未来业绩或表现可能与预期有重大差异。本文内有关任何董事或本公司意向的陈述或提述乃于本文刊发日期作出。任何该等意向均可能因未来发展而出现变动。有关这些因素和其他可能导致未来业绩与任何前瞻性声明存在重大差异的因素的进一步讨论，请参阅我们截至2024年12月31日的公司年报中描述的其他风险和不确定性，以及之后向香港证券交易所提交的文件。

抗体药物偶联物孤儿药上市批准财报AACR会议