HBM-9033

Cambridge, MA, Rotterdam, NL, Shanghai, CN — March 31, 2025 Harbour BioMed ("HBM" or the "Company"; HKEX: 02142), a global biopharmaceutical company committed to the discovery and development of novel antibody therapeutics in immunology and oncology, today announced its financial results for the year ended December 31, 2024. Dr. Jingsong Wang, Founder, Chairman, and CEO of Harbour BioMed, commented: “The year 2024 was a pivotal period for Harbour BioMed, marked by significant progress in research and development, strategic business expansion, and operational excellence. Despite a challenging macroeconomic environment, the Company demonstrated remarkable resilience, navigating inflationary pressures, global supply chain disruptions, and geopolitical uncertainties while remaining focused on its long-term growth objectives. Throughout the year, Harbour BioMed advanced its strategic transition toward becoming a sustainably profitable global biotech engine. The Company expanded its research and development pipeline with a strong focus on immunology, autoimmune diseases, and inflammation therapeutics. Several key clinical-stage programs progressed significantly, reinforcing our vision of delivering life-changing medicines to patients worldwide. The Company also made substantial investments in its technology platforms to ensure its core antibody discovery capabilities remain at the forefront of biopharmaceutical innovation. The strategic growth of Nona Biosciences, a subsidiary of Harbour BioMed, further solidified our position as a leading partner in the global biotech ecosystem. Additionally, we strengthened our business collaborations, securing multiple licensing and co-development agreements with top-tier pharmaceutical companies to drive sustainable revenue growth. As we look ahead to 2025, we remain committed to expanding our global presence and delivering breakthrough therapies to patients.” Full Year 2024 Financial Highlights Harbour BioMed reported total revenue of US$38.1 million for the year ended December 31, 2024, with an overall profit of approximately US$2.7 million. The Company has been profitable for two consecutive years, demonstrating the uniqueness and resilience of its business model. Compared to 2023, the Company's revenue sustainability has continued to improve. Annual recurring revenue increased from US$5.7 million to US$16.9 million, reflecting a growth rate of 196.5%. Cash profit[1] reached a record high of US$30.68 million. Meanwhile, Harbour BioMed has maintained a strong financial position. As of December 31, 2024, the company's cash and cash equivalents totaled approximately US$166.8 million, providing a solid financial foundation for future growth. [1] cash profit: operating net cash inflow. Advancing a Robust and Differentiated Pipeline Harbour Therapeutics, a sub-brand parallel to Nona Biosciences, is now individually responsible for the development of the Company’s products pipeline. With a growing focus on immunology, inflammation and oncology, Harbour Therapeutics manages a highly differentiated portfolio that includes multiple innovative drug candidates in both clinical and Investigational New Drug (IND)/IND-enabling stages. In inflammation and immunology, the Company has built a robust preclinical pipeline encompassing bispecific and multi-specific antibodies generated using the HCAb-based Bispecific Immune Cell Antagonist (HBICATM) technology, as well as ultra long-acting biotherapeutics for immune-related diseases. In oncology, the Company is leveraging its HBICE® platform to develop bispecific and multi-specific antibodies with novel designs and differentiated mechanisms, such as HBM9027 (PD-L1xCD40) and HBM7004 (B7H4xCD3). In addition, the Company is utilizing its Harbour Mice® and XDC platforms to explore multiple therapeutic modalities, including HBM9033, a mesothelin-targeted ADC, and other ADC/RDC programs in early-stage development. Main products in the clinical stage include: Batoclimab (HBM9161) is the first anti-FcRn monoclonal antibody completed Phase I to pivotal trials in China. As a novel, fully human anti-FcRn monoclonal antibody, batoclimab has the potential to be a breakthrough treatment option for a wide range of autoimmune diseases. In December 2023, the Company voluntarily planned to include additional long-term safety data and re-submitted the Biologic License Application (BLA) for batoclimab to the National Medical Products Administration of China (NMPA) in June 2024. In July 2024, NMPA accepted the BLA for batoclimab for the treatment of gMG. The Phase III pivotal clinical trial results of batoclimab were published in JAMA Neurology in March 2024, demonstrating sustained efficacy and safety with long-term use of batoclimab in the treatment of gMG. HBM9378 is a fully human monoclonal antibody against thymic stromal lymphopoietin (TSLP) generated from the H2L2 Harbour Mice® platform. It is a co-development project conducted by the Company and Kelun-Biotech, with both parties equally sharing the rights. HBM9378 has fully human sequences with a lower immunogenicity risk and better bioavailability compared to other TSLP-targeting competitors. Its long half-life optimization and outstanding biophysical properties support favourable dosing and formulation advantages. The Company received IND approval of HBM9378 for moderate-to-severe asthma from the NMPA in February 2022 and completed a Phase I clinical trial in healthy subjects in China. In November 2024, the Company submitted an IND application for HBM9378 for chronic obstructive pulmonary disease (COPD) to the NMPA, which was approved in February 2025. In January 2025, the Company and Kelun-Biotech entered into an exclusive license agreement with Windward Bio, under which Windward Bio was granted an exclusive license for the research, development, manufacturing and commercialization of HBM9378 globally (excluding Greater China and several Southeast and West Asian countries). Currently, Windward Bio is preparing a global Phase II clinical trial for HBM9378. Porustobart (HBM4003) is a next-generation, fully human heavy-chain-only anti-CTLA-4 antibody discovered and developed using the HCAb Harbour Mice® platform. It is also the first fully human heavy-chain-only antibody which entered clinical development globally. Compared with conventional CTLA-4 antibodies, porustobart has unique, favourable properties, including significant Treg cell depletion and optimized pharmacokinetics for improved safety. Additionally, by enhancing antibody-dependent cellular cytotoxicity (ADCC), porustobart increases the potential to selectively deplete intratumoral Treg cells, helping to overcome the efficacy and toxicity bottleneck of current CTLA-4 therapies. The Company has implemented a global development plan for multiple types of solid tumors with an adaptive treatment design for porustobart. Positive efficacy and safety data have been observed in the monotherapy trial targeting advanced solid tumors, as well as in combination trials with PD-1 inhibitors for melanoma, CRC, NEN and HCC. HBM1020 is a first-in-class fully human monoclonal antibody generated from the H2L2 Harbour Mice® platform targeting B7H7. As a newly discovered member of the B7 family, B7H7 expression is found to be non-overlapping with PD-L1 expression in multiple tumor types, potentially playing a more significant role in tumor immune evasion. With its excellent product design and target features, HBM1020 presents great potential to address significant unmet medical needs for solid tumors. In September 2024, the Company presented the latest clinical data for patients with advanced solid tumors at the ESMO Congress 2024. The data demonstrated excellent safety and tolerability profiles for HBM1020. Of the 15 patients who received post-treatment tumor assessments, 7 patients (46.7%) achieved stable disease (SD), with two patients showing tumor shrinkage of 11% and 25%. Main products in IND and IND-enabling stages include: HBM7020 is a BCMAxCD3 bispecific antibody generated using the fully human HBICE® bispecific technology and Harbour Mice® platform. HBM7020 can crosslink targeted cells and T cells by binding to BCMA and CD3 on the cell surface, leading to potent T cell activation and cell elimination. By incorporating dual anti-BCMA binding sites for optimal cell targeting and monovalent-optimized CD3 activity to minimize CRS, HBM7020 demonstrated potent cytotoxicity with broad applications in both immunological and oncology diseases. In August 2023, HBM7020 obtained IND clearance from the NMPA to commence a Phase I trial for cancer in China. In 2024, the Company restructured its development strategy to target immunological diseases and is currently preparing an IND application. HBM9027 is a novel PD-L1xCD40 bispecific antibody developed using the HBICE® bispecific antibody technology and Harbour Mice® platform. The development of PD-L1xCD40 bispecific antibody further expands the Company’s bispecific immune cell engager into the cutting-edge DC/myeloid cell engager field, showcasing the HBICE® platform’s versatile geometry formats and plug-and-play advantages. In January 2024, HBM9027 obtained IND approval from the Food and Drug Administration (FDA) to initiate a Phase I clinical trial in the U.S. HBM7004 is a novel B7H4xCD3 bispecific antibody. Using HBICE® bispecific technology and Harbour Mice® platform, this bispecific antibody was designed to provide innovative solutions for cancer immunotherapy from both efficacy and safety perspectives. The development of B7H4xCD3 bispecific HBICE® further consolidates the Company’s bispecific immune cell engager platform, demonstrating the HBICE® platform’s versatility and plug-and-play advantages. In preclinical studies, HBM7004 demonstrated an intratumor B7H4-dependent T cell activation manner. In multiple animal models, HBM7004 showed strong anti-tumor efficacy, remarkable in vivo stability, and reduced systemic toxicity. Additionally, in preclinical models, HBM7004 exhibited a strong synergistic effect when combined with a B7H4x4-1BB bispecific antibody at a low effector-to-target cell ratio, indicating an encouraging therapeutic window. The Company is currently conducting IND-enabling studies for HBM7004. HBM9014 is a first-in-class, fully human antibody targeting leukemia inhibitory factor receptor (LIFR) for cancer treatment. It was discovered using the Harbour Mice® platform. HBM9014 blocks multiple IL-6 family cytokine pathways via LIFR to inhibit their function in promoting tumor progression, metastasis and chemoresistance. In preclinical studies, HBM9014 showed significant in vivo antitumor efficacy and enhanced efficacy in combination with cisplatin in multiple tumor models. In addition, HBM9014 exhibited strong tolerability in toxicology studies conducted on primates. In 2025, the Company will continue to actively explore drug development strategies and seek collaboration opportunities. Strategic Business Collaborations Maximizing Platform Value Harbour BioMed’s ongoing commitment to global partnerships is critical to driving both scientific and commercial success. In 2024, the Company continued expanding its business collaborations with leading academic institutions and select industrial partners, focused on driving innovation and efficiency worldwide. Leveraging its technological advantages, Harbour BioMed established Nona Biosciences to better empower industry innovators and support collaborators from Idea to IND (I to ITM). Nona Biosciences is a global biotechnology company committed to providing integrated solutions for partners worldwide, across academia, biotechnology startups, and biopharmaceutical giants. Since its launch in late 2022, Nona Biosciences has achieved remarkable success, securing numerous international collaborations across various innovative formats. The subsidiary has established four leading technology units based on HCAb, including protein engineering, conjugation technology, delivery technology, and cell therapy, to accelerate the development of next-generation therapies. Nona Biosciences signed a global out-license and option agreement with AstraZeneca in May 2024 for preclinical monoclonal antibodies to be used in developing targeted oncology therapies. In December 2024, Nona Biosciences entered a research collaboration and license agreement with Candid Therapeutics to discover next-generation T-cell engagers. Over the past year, Nona Biosciences has also formed research collaborations with multiple partners across various therapeutics areas, including Boostimmune, Alaya.bio, Umoja Biopharma, Alkyon Therapeutics, OverT Bio, and Kodiak Sciences. In January 2025, the Company announced a license agreement with Windward Bio for HBM9378, an anti-TSLP fully human antibody for immunological diseases. In February 2025, HBM Alpha Therapeutics, an innovative biotechnology company incubated by the Company, announced a strategic collaboration and license agreement with a business partner to advance novel therapies targeting corticotropin-releasing hormone (CRH) for various disorders. These collaborations further highlight the Company’s unique strengths in pushing technological boundaries and exploring new innovation pathways. With its industry-leading technology platforms and a flexible business model, the Company will continue seeking new opportunities to expand its collaboration network and maximize the value of its platforms. Incubating Breakthrough Collaborations for the Future To fully harness the potential of its unique platform technologies, Harbour BioMed continues to explore the scalability of its platform applications. The Company is incubating several joint ventures focused on next-generation therapeutics, ranging from multivalence antibodies to cell therapies. These ventures aim to broaden the application of platform technologies and create additional value for the Company. This innovative incubation model facilitates the integration of incremental resources for the diversified development of next-generation innovations, requiring minimal marginal investment while offering a high return on value growth. Representative projects include HBM Alpha Therapeutics and Shanghai NK Cell Technology Limited. 2025 Outlook: Expanding Global Presence and Driving Innovation Looking ahead to 2025, Harbour BioMed will continue driving business growth and accomplishing its mission through two key pillars, Harbour Therapeutics and Nona Biosciences. Harbour Therapeutic will advance multiple clinical trials of its internal pipeline to fully advance the global clinical development project, while Nona Biosciences will continue providing integrated discovery solutions to biotech and pharmaceutical companies, ultimately fostering an innovation ecosystem that promotes biological advancement. A range of products derived from the Company’s Harbour Mice® technology platform and T-cell engager technology will be advanced in immunology, and the ADC platform will be upgraded to the next generation. Through a combination of in-house development and business collaborations, Harbour BioMed will build a portfolio of products with differentiated competitive advantages both in immunology and immuno-oncology. Maximizing the value of its platform through strategic collaborations will continue to drive the Company’s global expansion. In 2025, as the preclinical product pipeline matures, the company expects to expand its collaboration network even further and enter into broader global partnerships, solidifying its leading position in the global market. About Harbour BioMed Harbour BioMed (HKEX: 02142) is a global biopharmaceutical company committed to the discovery and development of novel antibody therapeutics in immunology and oncology. The company is building a robust and differentiated pipeline through internal R&D capabilities, strategic global collaborations in co-discovery and co-development, and selective acquisitions. Harbour BioMed's proprietary antibody technology platform, Harbour Mice®, generates fully human monoclonal antibodies in both the conventional two heavy and two light chain (H2L2) format and the heavy chain-only (HCAb) format. Building upon HCAb antibodies, the HCAb-based immune cell engagers (HBICE®) bispecific antibody technology enables tumor-killing effects that traditional combination therapies cannot achieve. Additionally, the HCAb-based bispecific immune cell antagonist (HBICATM) technology empowers the development of innovative biologics for immunological and inflammatory diseases. By integrating Harbour Mice®, HBICE®, and HBICATM with a single B-cell cloning platform, Harbour BioMed has built a highly efficient and distinctive antibody discovery engine for developing next-generation therapeutic antibodies. For more information, please visit www.harbourbiomed.com.

一年一度的AACR盛会马上就要到来，包括本土大pharma代表恒瑞，齐鲁，百济，石药，先声药业，以及公司以宜联生物，信达，君实，再鼎，乐普生物，礼新为代表的biotech都有poster或者报告摘要等展示。下面小编收集了十多家小编感兴趣的，也基本上代表了国内最前沿研究的几家公司以供大家一起学习。 （声明：排名不分先后，就是小编个人收集顺序） 乐普生物 - MRG007是一种靶向钙粘蛋白17、聚糖连接、基于艾考替康的抗体药物偶联物，在临床前研究中显示出强大的抗肿瘤活性和良好的安全性 MRG007是一种潜在的同类最佳CDH17抗体偶联药物（ADC），由乐普生物研发，主要用于治疗消化道癌。2025年1月22日，乐普生物宣布与ArriVent BioPharma达成全球独家许可协议，授权ArriVent在大中华区（包括中国大陆、中国香港、中国澳门和中国台湾）以外地区开发、制造和商业化MRG007。 礼新医药 - LM-350的临床前评价：一种用于胃肠道癌症治疗的创新性抗CDH17抗体药物偶联物 - LM-168的临床前评价：一种具有良好疗效和降低毒性的下一代抗CTLA4抗体 诺纳生物/辉瑞 - PF-08052666（SGN-MesoC2; HBM9033）是一种基于拓扑异构酶1抑制剂的ADC，靶向MSLN，在卵巢癌、肺癌和结直肠癌的临床前模型中显示出强大的抗肿瘤活性 PF-08052666（也称为SGN-MesoC2）是一种在研的抗体药物偶联物（ADC），由辉瑞（Pfizer）和Seagen公司联合开发， 由国内诺纳生物引进，其linker/payload平台采用了宜联生物的ADC平台。 齐鲁制药 - QL615，一种四特异性T细胞接合剂，对MET和EGFR阳性肿瘤的活性高度受限，同时通过CD2提供共刺激 - QLS1209，一种高效选择性PKMYT1抑制剂，在具有CCNE1-Amp和/或FBXW7-LoF突变的肿瘤中显示出活性 - QL535，一种新型的CD2-刺激T细胞接合器，靶向PSMA阳性前列腺癌症，与CD28三特异性抗体匹配，具有细胞毒性，最大限度地减少细胞因子释放和T细胞耗竭 - QLS5132，一种具有更宽治疗窗口的高选择性抗CLDN6 ADC - QLS4131，一种针对BCMA和GPRC5D的专有T细胞接合剂，用于治疗多发性骨髓瘤 - QLS5133——一种针对实体瘤的新型CDH6靶向抗体-药物偶联物（ADC） - QLS1103，一种治疗晚期实体瘤的高效选择性PARP7抑制剂 - QLS1304，一种治疗ER+HER2-乳腺癌症的高效选择性KAT6A/B抑制剂 石药集团 - SYS6051，下一代组织因子靶向抗体药物偶联物，用于治疗表达TF的恶性肿瘤 - SYS6042，一种新型的抗TROP2 pH敏感抗体-药物偶联物（ADC），具有改进的治疗窗口 - SWY2321是一种新型拓扑异构酶I抑制剂连接的双特异性ADC，靶向EGFR/cMet，具有强大的抗肿瘤功效 - SYS6041，下一代叶酸受体α靶向抗体药物偶联物，用于治疗表达FRα的恶性肿瘤 - 针对CD47和CD20的双特异性融合蛋白 泰诚思 - AT65474，一种具有专有有效载荷的高选择性抗CLDN6u202f ADC AT86474在临床前CDX卵巢癌小鼠模型中进行了评估，其中每周两次低至1mg /kg的剂量观察到实质性的肿瘤生长抑制。由于ROR1过表达也存在于许多实体肿瘤中，如胰腺癌、胃癌、乳腺癌和肺癌，因此AT86474的使用可以扩大，使更多的患者受益 - AT2604是一种高效的ADC，靶向碱性磷酸酶ALPP和ALPPL2 AT2604在胃癌（NCI-N87）和胰腺癌（HPAC）小鼠异种移植模型中均表现出1 mg/kg （QW3x2剂量）的强肿瘤生长抑制作用（>90%）。此外，在非人类灵长类动物中进行的一项毒素前研究表明，AT2604在NHP中耐受性良好，高达10 mg/kg （QW3x3剂量），并且没有表现出任何不可逆转的不良反应；这意味着AT2604比其他基于vedotin的adc具有更高的安全性。综上所述，这些数据支持AT2604在人体试验评估方面的持续发展。 先声药业 - 新型异基因抗cMet CAR-NK细胞产物与治疗性抗体联合治疗实体瘤 - 新型异基因抗DLL3 CAR-NK细胞疗法治疗小细胞肺癌 - 现成的BCMA/GPRC5D双靶向CAR-NK细胞疗法联合Daratumumab治疗多发性骨髓瘤 - SCR-A008的临床前发展：一种用于胃肠道癌症的CDH17靶向ADC - SIM0680，一种治疗表达ENPP3的实体瘤的强效抗体药物偶联物 - SCR-A002，一种针对实体瘤的新型FGFR2b靶向ADC - SCR-A006，一种创新且潜在的同类最佳EGFR/cMet双特异性抗体药物偶联物 - SCR-A0011是一种针对cMET和B7H3的新型双特异性ADC，具有强大的抗肿瘤功效 - SCR-A003的临床前开发，这是一种新的基于拓扑异构酶I抑制剂的抗体驱动偶联物（ADC），靶向LIV-1治疗实体癌症 - 在接受化疗的中国广泛期肺癌小细胞癌（ES-SCLC）患者中预防性使用曲拉西利：一项多中心、单臂、观察性现实世界研究 信达生物 信达宣布，将在 2025 年美国癌症研究协会（AACR）年会上公布多项最新临床前数据，包括公司旗下一系列双抗、多抗及抗体偶联药物（ADC）肿瘤管线。 - IAR037的临床前数据，这是一种新型CD40/PD-L1双特异性抗体，用于治疗对免疫检查点抑制剂耐药的晚期实体瘤 - IBI3010的临床前特征，一种靶向FRα的双对位抗体药物偶联物（ADC），用于治疗表达FRα的肿瘤 标题：IBI3019，一种全球首创（First-in-Class）的EGFR/CDH17/CD16A三特异性抗体，在临床前研究中对结直肠癌（CRC）展现出强效疗效和优异的安全性特征 标题：IBI3026，一种全球首创（First-in-Class）的抗PD-1/IL-12融合蛋白，通过解除免疫反应的抑制并强效激活肿瘤微环境中的T细胞和NK细胞，展现出成为新型肿瘤免疫疗法的潜力 标题：IBI3014，一种在单一分子中整合ADC杀伤作用与检查点阻断功能的TROP2×PD-L1双抗ADC，在临床前模型中展现出良好的疗效与安全性 标题：Trop2×B7H4双抗ADC在妇科肿瘤治疗中展现出更好的疗效和安全性 标题：一种2+1形式的MUC16靶向T细胞衔接器诱导MUC16依赖性T细胞活性并表现出卓越的抗肿瘤活性 标题：一种PD1-IFNα融合蛋白，由减毒IFNα与临床验证的PD1单抗融合而成，可诱导PD1依赖性IFNα信号通路激活并展现出卓越的抗肿瘤活性 创胜集团 创胜集团宣布将于当地时间2025年4月25-30日在美国芝加哥举行的2025年美国癌症研究协会 (AACR) 年会上，以壁报形式首次公布靶向FGFR2b的新型抗体偶联药物（ADC）的临床前数据。 题目：Characterization of novel humanized FGFR2b antibody-based ADCs site-specifically conjugated with topoisomerase I inhibitor payload in preclinical tumor models 该ADC采用糖基转移酶介导的定点偶联技术，结合新型拓扑异构酶I抑制剂载荷，在临床前胃癌和结直肠癌模型中，相比非定点偶联以及以MMAE为载荷的ADC具有更强的抗肿瘤活性。 亚盛医药 本次将要展示的数据涉及公司五个品种，包括：原创1类新药奥雷巴替尼（商品名：耐立克®；研发代号：HQP1351）、Bcl-2抑制剂APG-2575、FAK/ALK/ROS1三联酪氨酸激酶抑制剂APG-2449、胚胎外胚层发育蛋白（EED）抑制剂APG-5918以及IAP拮抗剂AS03157。 1. Olverembatinib (HQP1351) in combination with lisaftoclax (APG-2575) overcomes venetoclax resistance in preclinical models of acute myeloid leukemia (AML) 2. Effects of olverembatinib (HQP1351) in combination with BCL-2 inhibitor lisaftoclax (APG-2575) in T-cell acute lymphoblastic leukemia (T‑ALL) 3. Embryonic ectoderm development protein (EED) inhibitor APG-5918 exhibits potent antitumor activity and synergizes with androgen receptor (AR) inhibitor enzalutamide in preclinical prostate cancer (PCa) models 4. APG-2449, a novel focal adhesion kinase (FAK) inhibitor, enhances the antitumor activity of chemotherapy in preclinical models of small-cell lung cancer (SCLC) with activated FAK 5. Discovery of AS03157 as a highly potent and orally active antagonist of inhibitor of apoptosis proteins (IAPs) 君实生物 1. #CT010 Phase I dose-escalation and expansion study of JS107, a claudin 18.2 (CLDN18.2)-targeting antibody-drug conjugate (ADC), as monotherapy or in combination for patients (pts) with advanced solid tumors JS107是君实生物自主研发的注射用重组人源化抗CLDN18.2单克隆抗体MMAE（Monomethyl auristatin E）偶联剂，拟用于治疗胃癌和胰腺癌等晚期恶性肿瘤。JS107可以与肿瘤细胞表面的CLDN18.2结合，通过内吞作用进入肿瘤细胞内，释放小分子毒素MMAE，对肿瘤细胞产生强大的杀伤力。此外，由于MMA可透过细胞膜，JS107还具有良好的旁观者效应，对CLDN18.2阴性肿瘤细胞发挥杀伤作用。临床前体内药效试验显示，JS107具有显著的抑瘤效果。此外，动物对JS107的耐受性良好，JS107表现出较好的安全性。 2. #CT025 JJS203, a CD20×CD3 bispecific antibody with a 2:1 structure, demonstrated promising responses in patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) in a Phase I study JS203为君实生物自主研发的重组人源化抗CD20和CD3双特异性抗体，主要用于复发/难治性B细胞非霍奇金淋巴瘤的治疗。JS203由抗CD20段和抗CD3段组成，通过联结并活化T细胞（结合CD3）和淋巴瘤细胞（结合CD20），可有效促进T细胞杀伤淋巴瘤细胞。临床前体内药效试验显示，JS203具有显著的抑瘤效果。此外，动物对JS203的耐受性良好。 3. #LB212 Efficacy and safety of JS015 (an anti-dickkopf-1 antibody) in combination with standard of care in patients with gastrointestinal cancers JS015是君实生物独立自主研发的重组人源化抗DKK1单克隆抗体，主要用于晚期恶性实体瘤的治疗。JS015能以高亲和力结合肿瘤微环境中分泌的DKK1，阻断DKK1与其配体LRP5/6的相互作用，激活Wnt信号通路。同时，JS015还能够通过结合DKK1，促进NK细胞活化、抑制髓源性抑制细胞（MDSC）活性，抑制免疫抑制信号的传导，发挥抗肿瘤作用。 翰森制药 翰森制药原研创新药阿美乐®（甲磺酸阿美替尼片）AENEAS2（联合化疗用于晚期非小细胞肺癌一线治疗，HS-10296-306）及ARTS（非小细胞肺癌术后辅助治疗，HS-10296-302）两项Ⅲ期关键临床研究均以口头报告形式入选。 1. Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2)  全体大会口头报告（Plenary Oral Presentation） 2. Aumolertinib as adjuvant therapy in patients with stage II-IIIB EGFR-mutated NSCLC after complete tumor resection: A randomized, double-blind, placebo-controlled, phase 3 trial (ARTS) 全体大会口头报告（Plenary Oral Presentation） 作为中国首个原研三代EGFR-TKI，阿美乐®（甲磺酸阿美替尼片）创新性地引入环丙基结构，具有良好的脂溶性和稳定性，能更好地透过血脑屏障，且不良反应发生率低。目前，阿美乐®已有三项适应症获批上市，分别是：二线治疗既往经EGFR-TKI治疗进展，且T790M突变阳性的局部晚期或转移性NSCLC患者，一线治疗具有EGFR外显子19缺失或外显子21（L858R）置换突变阳性的局部晚期或转移性NSCLC成人患者，以及含铂根治性放化疗后未出现疾病进展的不可切除的局部晚期EGFR外显子19缺失或外显子21（L858R）置换突变的NSCLC患者治疗 宜联生物 苏州宜联生物医药有限公司（“宜联生物医药”），一家临床阶段的生物科技公司，将在此次AACR年会上公布3项创新研究数据，包括两款ADC项目YL217（靶向CDH17）和YL242（靶向VEGF），以及下一代双毒素ADC技术平台。 1. Preclinical development of a next generation antibody drug conjugate (ADC) targeting CDH17 for treatment of solid tumors YL217是一款靶向CDH17的抗体偶联药物，主要针对消化道肿瘤而开发。CDH17集中表达于胃癌、结直肠癌、胰腺癌、肝细胞癌等肿瘤组织中，其表达与胃肠道起源的多种癌症的转移进展相关，并在晚期、高分化型肿瘤中上调。YL217采用宜联生物的新一代肿瘤微环境可激活的新型毒素连接子平台技术（TMALIN®）所开发，已启动 I期临床试验。 2. Preclinical development of YL242, a non-internalized antibody-drug conjugate (ADC) targeting soluble VEGF for treatment of solid tumors YL242是一款靶向VEGF的抗体偶联药物，VEGF是已经充分验证的肿瘤治疗靶点，但无法通过传统ADC技术而开发。VEGF富集于肿瘤组织附近，并在血管生成中发挥重要作用,其表达与多种癌症的进展相关。YL242采用宜联生物的新一代肿瘤微环境可激活的新型毒素连接子平台技术（TMALIN®）所开发，即将启动 I期临床试验。 3. An innovative dual-payload ADC combining topoisomerase 1 inhibitor and a tubulin inhibitor efficiently overcomes drug resistance 迈威生物 迈威生物宣布将于当地时间 2025 年 4 月 25-30 日在美国芝加哥举行的 2025 年美国癌症研究协会 (AACR) 年会，以壁报形式公布 6 项研究成果。 1. A B7-H3-targeting antibody-drug conjugate, 7MW3711, and PARP inhibitors synergistically potentiate the antitumor activity in B7-H3-positive cancers 7MW3711 是一种新型 B7-H3 靶向 ADC，已获得 FDA 授予的 ODD 资格，用于治疗 SCLC 患者。7MW3711由创新抗体分子、新型连接子和新型负载Mtoxin™（TOP1i）组成，针对实体肿瘤表达靶点，结构稳定、成分均一、纯度高，适合工业化放大。7MW3711 是一种新型 B7-H3 靶向 ADC，已获得 FDA 授予的 ODD 资格，用于治疗 SCLC 患者。7MW3711由创新抗体分子、新型连接子和新型负载Mtoxin™（TOP1i）组成，针对实体肿瘤表达靶点，结构稳定、成分均一、纯度高，适合工业化放大。 2. Design and synthesis of the novel camptothecin analog MF6 for application into site-specific antibody-drug conjugate 3. MW-C01/C02, novel CLDN1-targeting antibody-drug conjugates, demonstrate compelling anti-tumor efficacy and favorable safety profiles in preclinical studies 4. 2MW7061, a novel LILRB4xCD3 bispecific T-cell engager targeting monocytic acute myeloid leukemia 5. An innovative T cell engager platform with optimized CD3 affinity and formats for targeting hematologic and solid tumors 6. 7MW4911, a novel cadherin 17-targeting ADC, demonstrates potent efficacy in preclinical models of gastrointestinal cancers 7MW4911，有效载荷是MF-6，DAR值为4。迈威预计在2025年下半年在国内和美国提交IND申请，用于治疗晚期实体瘤，特别是结直肠癌、胃癌、胰腺癌等消化道肿瘤。 基石药业 基石药业5款自主研发创新药物的最新临床前研究成果将同时亮相2025 AACR，包括三抗CS2009、双抗CS2011及出自公司自有抗体偶联药物（ADC）平台的三款创新ADC分子CS5006、CS5007与CS5005。 1. CS2009: A first-in-class trispecific antibody targeting PD-1, CTLA-4, and VEGFA with potential to be a next-generation backbone therapy with combined checkpoint inhibition and anti-angiogenesis CS2009是一款靶向PD-1、VEGFA及CTLA-4的三特异性抗体，其创新的分子设计预期能通过优先结合肿瘤微环境（TME）中的PD-1/CTLA-4双阳性T细胞提升疗效，同时避免作用于CTLA-4单阳性细胞以降低系统性毒性，是潜在的同类首创/同类最优的下一代肿瘤免疫骨架产品。临床前研究显示，相较于潜在竞品（如PD-1/CTLA-4双抗、PD-1/VEGF双抗及抗PD-1/抗CTLA-4联合疗法），CS2009具有更强的抑瘤效力，且安全性突出。CS2009的全球多中心I期临床试验正在澳大利亚开展，涵盖多种晚期癌症，例如非小细胞肺癌、卵巢癌、肾细胞癌、宫颈癌、肝细胞癌、胃癌等。 2. CS5006: A novel integrin β4-targeted antibody-drug conjugate (ADC) with robust antitumor activity in preclinical studies CS5006是一款同类首创、靶向全新靶点ITGB4的ADC，在非小细胞肺癌、头颈鳞状细胞癌、食管鳞状细胞癌等实体瘤领域有广阔的应用前景。临床前研究显示，ITGB4 ADC在多种动物模型中均表现出强效抑瘤作用，且耐受性良好，这也为推动该同类首创分子的后续临床前开发、以及进入临床评估提供了有力的数据支持。 3. CS2011: A novel bispecific antibody targeting EGFR and HER3 that demonstrates promising anti-tumor activity in preclinical evaluation CS2011（EGFR/HER3双特异性抗体）为CS5007（EGFR/HER3双特异性ADC）的双抗骨架，EGFR/HER3双抗可协同阻断EGFR与HER3信号传导，显著增强抗肿瘤疗效，同时最大程度减少对正常组织的毒性。CS5007的构建依托于基石药业自主知识产权的ADC平台，具备同类最佳的潜力。CS2011与CS5007的目标适应症涵盖非小细胞肺癌、头颈鳞状细胞癌及结直肠癌等实体瘤。 4. CS5007: A novel EGFR and HER3 dual-targeted antibody-drug conjugate (ADC) with potent antitumor activity 5. CS5005: A novel SSTR2-targeted antibody-drug conjugate (ADC) with robust anti-tumor activity in preclinical studies 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，其在体外及体内研究中均展现出令人鼓舞的抗肿瘤活性。 和誉医药 和誉医药将在2025年美国癌症研究协会（AACR）年会上以壁报的形式发布其自主研发的EGFR Exon20ins抑制剂ABSK112和PRMT5*MTA抑制剂ABSK131以及KRAS抑制剂的最新临床前研究成果 1. Preclinical evaluation of ABSK112, a selective and CNS-penetrant compound with strong HER2 inhibitory activity for treating HER2-driven solid tumors Abstract Presentation Number：LB240 ABSK112是一款具有较好活性、选择性和入脑特性的二代EGFR Exon20ins口服抑制剂。在临床前研究中，ABSK112展现出较好的入脑特性，针对野生型EGFR的更优选择性，以及广泛的Exon20ins突变覆盖谱，并在多种EGFR Exon20ins突变的小鼠肿瘤模型中表现出较好的体内药效，有望在临床上获得更好安全窗和药效。（信息有些打架，待确认） 2. KEAP1 loss-of-function modulates ROS and AKT-mTOR pathway leading to resistance to KRAS inhibitor Abstract Presentation Number：LB278 3. The MTA-cooperative PRMT5 inhibitor ABSK131 exhibits potent activity and broad synergistic potential in MTAP-deleted cancer models Abstract Presentation Number：LB427 在大约10%-15%的人类肿瘤中MTAP基因呈纯合缺失状态。已经证明PRMT5*MTA抑制剂与MTAP基因缺失呈合成致死关系。一代PRMT5抑制剂因为无法区分PRMT5*MTA和PRMT5，导致在临床应用中受限于其狭窄的治疗窗口。一些选择性的PRMT5*MTA抑制剂已经进入到了临床阶段，但它们的活性和选择性还有待进一步提高。ABSK131是一种高选择性的可入脑的MTA协同PRMT5抑制剂，其卓越的特性支持其快速的临床前开发。该抑制剂具有更好的活性，选择性以及透过血脑屏障的能力。 4. Discovery and characterization of a highly potent and orally available small-molecule inhibitor for diverse KRAS mutations Abstract Presentation Number：LB431 真实生物 真实生物自主研发的新一代“小分子药物”+“新型毒素”的双平台项目，被列为“Late-Breaking Research（最新突破性研究）”亮相展示于此次AACR年会。 报告题目： Overcoming resistance to camptothecin-based topoisomerase I inhibitors through a novel core scaffold design strategy” 公司在研的新一代毒素可以解决耐药问题，对比常用的ADC毒素（例如SN-38、DXd等喜树碱类化合物）抗肿瘤活性相当，但是成药性更高（比如透膜性、非外排等）。在已发现的多个候选毒素中，在耐DXd癌细胞株中的效力比DXd高出50倍以上。 再鼎医药 1. 标题：一款可应用于实体瘤治疗的新型靶向LRRC15的抗体药物偶联物（ADC）的发现与特性研究 2. 标题：通过抗PD-1单链抗体顺式递送活性降低的IL-12而展现出强效抗肿瘤活性 识别微信二维码，可添加药时空小编 请注明：姓名+研究方向！