Lutetium Dotatate LU-177

2025年5月6日——基石药业（股票代码：2616.HK），一家专注于抗肿瘤药物研发的创新驱动型生物医药企业，今日宣布，本公司在2025年美国癌症研究协会（AACR）年会上，以壁报形式公布研发管线2.0重磅产品CS5005（SSTR2抗体药物偶联物 [ADC]）的临床前研究结果。生长抑素受体2（SSTR2）是一类G蛋白偶联受体（GPCR），在神经内分泌肿瘤（NETs）、神经内分泌癌（NECs）以及小细胞肺癌（SCLC）等多种实体瘤中过表达。其肿瘤选择性表达的特性使其成为肿瘤精准靶向治疗的研究热点。CS5005是一款同类首创、靶向SSTR2的ADC，由基石药业专有的高亲和力及高选择性的抗SSTR2抗体、亲水性的β葡萄糖醛酸连接子以及高效的拓扑异构酶I抑制剂Exatecan构成。在临床前研究中，CS5005表现出抗原依赖性的强效肿瘤抑制活性，并且不受生长抑素类似物（SSA）联用的影响。此外，CS5005具有出色的稳定性、类似单抗的药代动力学特性，同时在非人灵长类动物的初步毒理研究中表现出良好的耐受性。关键亮点CS5005对SSTR2阳性细胞系具有高亲和力，并高效诱导SSTR2在肿瘤细胞上的内吞。CS5005与食蟹猴SSTR2阳性细胞呈现交叉反应；同时可高选择性结合SSTR2而非其他同家族的SSTR蛋白。CS5005在体外试验中表现出抗原依赖的强效细胞毒性，同时在体内CDX肿瘤模型中展现出显著的肿瘤抑制作用。与配体疗法（如奥曲肽、Lutathera®等）联合用药时，CS5005（SSTR2-DXd）的抗肿瘤活性不受影响，从而避免了针对SSTR2靶向治疗中常见的药物相互作用的问题。体外试验中，相较其他采用经典二肽或四肽连接子的ADC，使用基石药业专有连接子的CS5005表现出较更优的稳定性。CS5005在小鼠动物实验中展现出更优的药代动力学（PK）特性。基于对小细胞肺癌样本的生物信息学分析，同时靶向SSTR2和DLL3可克服肿瘤异质性导致的交叉耐药，并扩大潜在治疗人群范围。CS5005是一款同类首创、靶向SSTR2的ADC，可精准狙击SSTR2阳性肿瘤，如小细胞肺癌、神经内分泌癌、神经内分泌瘤等。分子结构上，CS5005由基石药业专有的高亲和力与高选择性的抗SSTR2抗体、亲水性的β葡萄糖醛酸连接子以及高效的TOP1抑制剂组成。CS5005在体外及体内研究中均展现出令人鼓舞的抗肿瘤活性，将支持其进入IND申报和临床研究阶段。CS5005的自研抗体专利已于2024年上半年注册。CS5008，一款靶向SSTR2/DLL3 双特异性ADC，目前正在临床前开发中，通过同时靶向SCLC、NETs和NECs等疾病中频繁共表达的SSTR2与DLL3，CS5008旨在克服单靶点疗法难以突破的肿瘤异质性治疗瓶颈。壁报信息：【标题】CS5005: A novel SSTR2-targeted antibody-drug conjugate (ADC) with robust anti-tumor activity in preclinical studies【分会场主题】Molecular, Preclinical, and Clinical Endocrinology【编号】4751【时间】美国东部时间4月29日（周二）9:00 AM-12:00 PM【地点】第35区，展板#18关于基石药业基石药业（香港联交所代码: 2616）成立于2015年底，是一家专注于抗肿瘤药物研发的创新型生物制药公司。自成立以来，本公司致力于满足中国和全球患者的殷切医疗需求，并取得了重大进展。迄今为止，本公司已成功上市4款创新药，并获得涵盖9个适应症的16项新药上市申请(NDA)批准。当前研发管线均衡配置了潜在同类首创或同类最优的抗体偶联药物(ADC)、多特异性抗体、免疫疗法及精准治疗药物在内的18款候选药物。同时，基石药业亦拥有一支具有丰富经验和能力的管理团队，覆盖从临床前探索、临床转化、临床开发、药物生产、商务扩展和商业运营等关键环节。如需了解有关基石药业的更多信息，请访问：www.cstonepharma.com。 投资者关系: ir@cstonepharma.com 媒体关系: pr@cstonepharma.com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。本文内所有陈述乃本文章刊发日期作出，可能因未来发展而出现变动。声明：仅供医疗卫生专业人士交流使用。

SUZHOU, China, May 6, 2025 /PRNewswire/ -- CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on anti-cancer therapies, announced today that poster presentations of preclinical data of CS2011 (EGFR/HER3 bispecific antibody), CS5007 (EGFR/HER3 bispecific ADC), CS5005 (SSTR2 ADC) and CS5006 (ITGB4 ADC), key assets in CStone Pipeline 2.0, have been delivered at the 2025 American Association for Cancer Research (AACR) Annual Meeting. Key Highlights: CS2011 (EGFR/HER3 bispecific antibody): EGFR and HER3 are members of the human epidermal growth factor receptor (HER) family and are validated therapeutic targets in advanced solid tumors. EGFR overexpression drives tumor progression in approximately 70% of colorectal cancers (CRC), 60% of lung cancers, and over 90% of head and neck squamous cell carcinomas (HNSCC). Meanwhile, HER3 upregulation frequently emerges as a resistance mechanism to MAPK/PI3K inhibitors, EGFR tyrosine kinase inhibitors (TKIs), and hormone therapies. CS2011 is a bispecific antibody with high binding affinity to both EGFR and HER3. It effectively blocks downstream signaling of both targets, thereby inhibiting tumor growth on EGFR/HER3 positive tumor cells. 1. CS2011 targets almost all HER family signaling except HER2 homodimers, addressing tumor heterogeneity effectively. 2. CS2011 demonstrates potent binding affinity to EGFR and/or HER3 individually and enhanced dual binding affinity to EGFR and HER3 concurrently driven by avidity-based synergy. 3. CS2011 inhibits tumor growth by binding to EGFR and/or HER3-positive tumor cells. 4. CS2011 shows superior in vivo and in vitro anti-tumor activity versus potential major competitors. （1） Compared to anti-EGFR, anti-HER3 and competing bispecific antibody, CS2011 induces faster and deeper internalization in tumor cells across varying EGFR & HER3 expression levels. （2） CS2011 demonstrated potent inhibition of EGFR downstream signaling, comparable to anti-EGFR antibodies, and superior inhibition of HER3-mediated signaling compared to competitive bispecific antibody. （3） CS2011 exhibited robust anti-proliferative activity in tumor cells with diverse EGFR and HER3 expression levels. （4） In in vivo CDX tumor models, CS2011 demonstrated superior tumor-growth inhibition compared to anti-EGFR or anti-HER3 monoclonal antibodies alone and showed comparable efficacy to the combination treatment. 5. CS2011 exhibited a pharmacokinetic (PK) profile comparable to those of monoclonal antibodies in rodents. In summary, CS2011 has demonstrated potent blockage activity on EGFR and HER3 and exhibited synergistic effects on their downstream signaling. It thereby shows the potent tumor growth inhibitory effects in in vitro and in vivo experiments. The patent of CS2011 has been filed in March 2025, and its Investigational New Drug (IND) application is expected to be submitted in the near term. CS5007 (EGFR/HER3 bispecific ADC): CS5007 is a bispecific ADC targeting both EGFR and HER3, developed with CStone's proprietary ADC platform. It is composed of EGFR/HER3 bispecific antibody backbone (CS2011), a hydrophilic β-glucuronide linker and a clinically validated topoisomerase I inhibitor, Exatecan. This integrated approach, featuring precise targeting, optimized linker stability, and proven therapeutic payload, positions CS5007 as a potential best-in-class candidate for precision oncology. 1. CS5007 targets almost all human epidermal growth factor receptor (HER) family signaling except for HER2 homodimers, covering broad tumor types and effectively addressing tumor heterogeneity. 2. CS5007 demonstrated high-affinity binding to EGFR single-positive, HER3 single-positive, and EGFR/HER3 double-positive tumor cells. 3. CS5007 triggered high-rate internalization on tumor cells. 4. CS5007 demonstrated potent, antigen-dependent cytotoxicity against tumor cells in vitro across varying EGFR and HER3 expression levels and showed robust tumor-growth inhibition in CDX models. 5. CS5007 exhibited superior in vitro stability compared to ADCs conjugated with tetrapeptide and dipeptide linkers. After 7 days of incubation in human/monkey serum, it retained approximately 70% of its drug payload, indicating a minimal release rate. 6. CS5007 exhibited comparable pharmacokinetic (PK) profile to those ADCs composed of monoclonal antibodies in rodents. CS5007 demonstrates strong affinity for EGFR- and/or HER3-positive tumor cells and induces efficient internalization. Preclinical studies have shown excellent antitumor activity, favorable safety, and pharmacokinetic profiles. The patent of CS5007 has been filed in March 2025. Preclinical findings support further IND-enabling studies and clinical investigations in various advanced solid tumors. CS5005 (SSTR2 ADC): Somatostatin receptor 2 (SSTR2) is a G protein-coupled receptor (GPCR) that is overexpressed in various solid tumors, including neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and small cell lung cancer (SCLC). Due to its tumor-selective expression profile, SSTR2 has emerged as a promising target in the field of precision oncology. CS5005 is a first-in-class, SSTR2-targeting ADC, composed of CStone's proprietary anti-SSTR2 antibody with high affinity and selectivity, hydrophilic β-glucuronide linker, and potent topoisomerase I inhibitor, Exatecan. In preclinical studies, CS5005 demonstrated potent, antigen-dependent tumor growth inhibition that was not affected by co-administration with SSA-derived therapies. Additionally, CS5005 exhibited superior stability, monoclonal antibody-like pharmacokinetic (PK) properties, and favorable tolerability in preliminary non-human primate toxicity studies. 1. CS5005 demonstrated high affinity to SSTR2-positive cell lines and induced high-rate internalization on tumor cells. 2. CS5005 exhibited cross-reactivity with SSTR2-expressing cells in non-human primates and demonstrated selective binding to SSTR2 with minimal interaction with other SSTRs. 3. CS5005 demonstrated potent antigen-dependent cytotoxic activity against tumor cells in vitro and robust tumor-growth inhibition in CDX tumor model. 4. The antitumor activity of CS5005 (SSTR2-DXd) is not compromised by concomitant ligand-derived treatments (e.g., octreotide, Lutathera®), thereby avoiding drug-drug interference commonly observed with current anti-SSTR2 therapies. 5. CS5005 demonstrated superior in vitro stability due to its proprietary linker, outperforming ADCs conjugated with well-validated dipeptide and tetrapeptide linkers. 6. Superior pharmacokinetic (PK) properties of CS5005 in rodents. 7. Bioinformatics analysis of SCLC samples supports DLL3/SSTR2 dual targeting as a strategy to overcome tumor heterogeneity and expand the treatable patient population. In summary, CS5005 is a first-in-class, SSTR2-targeting ADC designed to selectively eliminate SSTR2-positive tumors, including small cell lung cancer, neuroendocrine carcinoma, and neuroendocrine tumors. It is composed of CStone's proprietary high-affinity, high-selectivity anti-SSTR2 antibody, CStone's proprietary hydrophilic β-glucuronide linker, and potent TOP1 inhibitor payload. CS5005 has demonstrated robust antitumor activity in both in vitro and in vivo studies, supporting its progression toward IND submission and clinical development. The patent of de novo antibody backbone of CS5005 has been filed in the first half of 2024. CS5008, an SSTR2/DLL3 bispecific ADC is under development. By simultaneously targeting SSTR2 and DLL3 that frequently co-express in SCLC, NETs, NECs and others, CS5008 aims to overcome tumor heterogeneity, a challenge faced by mono-specific therapies. CS5006 (ITGB4 ADC): CS5006 is a first-in-class antibody-drug conjugate (ADC) targeting the novel antigen integrin β4 (ITGB4), developed using CStone's proprietary ADC platform. Leveraging an internally developed machine learning-based bioinformatics algorithm alongside rigorous in-house experimental validation, CStone identified elevated ITGB4 expression across multiple tumor types—including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), and head and neck squamous cell carcinoma (HNSCC)—with minimal expression observed in normal tissues. Preclinical in vivo and in vitro studies have demonstrated CS5006's promising therapeutic potential, highlighting its ability to effectively killing tumor cells. 1. Bioinformatics analysis identified high ITGB4 expression in colorectal tumor tissues, supporting ITGB4 as a promising tumor-associated antigen for CRC. In the tumor microenvironment, ITGB4 was selectively overexpressed on tumor cells while remaining low expression in normal tissues. 2. Immunohistochemistry (IHC) staining confirmed limited ITGB4 expression in normal tissue but high expression in tumor tissues from patients with CRC, sq-NSCLC, HNSCC and ESCC. 3. ITGB4 antibody demonstrated high affinity and internalization rate. 4. CS5006 preclinical proof-of-concept models using ITGB4-vedotin and ITGB4-DXd showed potent antitumor activity in both in vitro and in vivo studies, along with favorable pharmacokinetic (PK) profiles. （1） ITGB4-vedotin exhibited strong antigen-dependent cytotoxicity in ITGB4-positive tumor cell lines in vitro and demonstrated potent antigen-dependent tumor inhibition in CDX models in vivo. （2） ITGB4-DXd also exhibited potent antigen-dependent cytotoxicity in vitro and strong tumor-inhibitory effects in vivo CDX tumor models. （3） Both ITGB4-vedotin and ITGB4-DXd exhibited favorable PK characteristics. In summary, CS5006 is a first-in-class ADC targeting the novel tumor antigen ITGB4 and is currently undergoing comprehensive preclinical evaluation. Preclinical data have demonstrated strong antitumor activity across multiple animal models, particularly in solid tumors such as non-small cell lung cancer, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma. The compound also exhibited good tolerability, providing strong support for its further clinical development. The patent of CS5006 has been filed in April 2023. Poster Information: About CStone CStone (HKEX: 2616), established in late 2015, is an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies. Dedicated to addressing patients' unmet medical needs in China and globally, the Company has made significant strides since its inception. To date, the Company has successfully launched 4 innovative drugs and secured approvals for 16 new drug applications (NDAs) covering 9 indications. The company's pipeline is balanced by 16 promising candidates, featuring potentially first-in-class or best-in-class antibody-drug conjugates (ADCs), multispecific antibodies, immunotherapies and precision medicines. CStone also prides itself on a management team with comprehensive experiences and capabilities that span the entire drug development spectrum, from preclinical and translational research to clinical development, drug manufacturing, business development, and commercialization. For more information about CStone, please visit . Forward-looking statements The forward-looking statements made in this article only relate to events or information as of the date when the statements are made in this article. Except as required by law, we undertake no obligation to update or publicly revise 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. All statements in this article are made on the date of publication of this article and may change due to future developments. Disclaimer: only for communication and scientific use by medical and health professionals, it is not intended for promotional purposes. SOURCE CStone Pharmaceuticals WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED