CDH17

SEATTLE, Oct. 9, 2024 /PRNewswire/ -- Arbele, a leading innovator in biopharmaceutical & biotechnology focused on targeting cadherin-17 (CDH17), is pleased to announce strategic collaborations in precision oncology using artificial intelligence (AI) to advance targeted immunotherapeutics of bispecific T-cell engagers (TCEs) and antibody-drug conjugates (ADCs). These partnerships, aimed at advancing the quantification and prognostic prediction of CDH17 expression in tumor tissue and the surrounding tumor immune microenvironment, are expected to accelerate the development of precise companion diagnostics and effective clinical trials for the treatment of advanced cancer patients. Collaboration with BioAI: Development of IHC-Based Quantification Algorithm Arbele enters a strategic alliance with BioAI Health to develop a prototype of an immunohistochemistry (IHC)-based quantification algorithm. Leveraging the PredictX platform to develop AI-based models using Arbele's clinical trial data on colorectal cancer (CRC) biomarker screening, we join force to establish a gold standard companion diagnostic test for anti-CDH17 therapies for patient selection and prediction of clinical outcomes. "By partnering with Arbele, we are excited to apply our novel AI platform and expertise to accelerate the development of innovative treatment options for gastrointestinal cancers," said Thomas Colarusso, CEO of BioAI. "This partnership underscores our commitment to revolutionizing personalized medicine through cutting-edge machine learning." "BioAI's machine learning capabilities offer a transformative approach to biomarker identification and patient stratification through predicting CDH17 expression and its spatial interaction with immune cells in tumor microenvironment," said Dr John Luk, CEO of Arbele. "This collaboration is a critical step in guiding us the uses of the right treatment modalities and/or therapeutic regimens, thereby improving outcomes for patients with high mortality cancers." Collaboration with Chime Biologics: Accelerated CMC Process Development of novel ADC and TCE Arbele has entered a strategic alliance with Chime Biologics to accelerate chemistry, manufacturing and control (CMC) process development of the novel designs of ADCs and TCEs. The partnership supports multiple pipelines of about 10 first-in-class and best-in-class immunotherapeutics, including monoclonal, bispecific/biparatopic and TriAx antibodies within the coming 3 years. The collaboration will ensure Arbele continues to have at least 1-2 new molecular entities (NMEs) successfully filing for investigational new drug (IND) application and entering clinical studies in the next 5 years without any technical and supply-chain interruptions. The first deliverable will be anti-CDH17 ADC (ARB102A), for IND submission in early 2025. "Chime Biologics has partnered Arbele for several years, with our advanced biologics development supporting key milestones such as previous IND filings for multinational clinical trials," said Dr. Jimmy Wei, President of Chime Biologics. "We adopt the Quality-by-Design (QbD) strategy for process development to yield optimal outcomes cost-effectively, delivering innovative immunotherapeutics to enhance the global accessibility of these treatments." About Arbele Arbele founded by accomplished scientists and pharmaceutical executives in 2016 researching on cadherin-17 (CDH17) to develop innovative diagnostic platforms and breakthrough immunotherapeutic solutions; to provide early intervention and treatment for patients with advanced CRC, cholangiocarcinoma, pancreatic adenocarcinoma and subtype of ovarian cancers, for which effective treatment options are scanty with high mortality rates. For more information on ARBELE, please visit About BioAI BioAI is a leading provider of multimodal AI in precision medicine, offering world-leading machine learning technology to develop H&E-based predictive models and digital biomarkers. BioAI works with leading pharmaceutical, biotechnology, clinical laboratories, and academic cancer centers around the world. The company's proprietary PredictX platform enables the generation of advanced AI models using multimodal data. BioAI aims to revolutionize personalized medicine by developing novel AI-based biomarkers to more effectively guide patients to targeted therapies. For more information about BioAI and its innovative machine learning technologies, please visit bioaihealth.com. About the Chime Biologics & Chime Innovation Center Chime Biologics is a global leading CDMO that has introduced the first modular biopharmaceutical plant KUBio in the world to empower its partners' success in biologics in the whole process from cell line development to commercial manufacturing. Built in state-of-the-art technology at Shanghai Innovation Center and Wuhan manufacturing plant, Chime Biologics provides a one-stop CMC solution for biopharmaceutical customers around the world, making biomedicines affordable and accessible to all patients and fulfilling its commitment to human health. For more information, please visit: . For Press Contact: Dr Diana Hay, [email protected] For Corporate Inquires: Ms. Khim Poon, [email protected] SOURCE Arbele WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

MANCHESTER, N.H., Sept. 30, 2024 /PRNewswire/ -- BioAI, an emerging biotech company applying multimodal artificial intelligence (AI) to novel biomarker discovery, development, and diagnostics, has announced a strategic partnership with Arbele, a biopharmaceutical company dedicated to developing novel immunotherapeutic platforms for gastrointestinal cancers. The collaboration aims to leverage BioAI's PredictX platform to develop AI-based models using Arbele's clinical trial data, with a focus on colorectal cancer (CRC) biomarker screening. The goal is to create a companion diagnostic test for Arbele's drug assets, enhancing patient selection through advanced AI technology. "By joining forces with Arbele, we are excited to apply our novel AI platform and expertise to accelerate the development of innovative treatment options for gastrointestinal cancers," said Thomas Colarusso, CEO of BioAI. "This partnership underscores our commitment to revolutionizing personalized medicine through cutting-edge machine learning." Arbele's CEO & Founder, Dr. John Luk, commented, "BioAI's machine learning capabilities offer a transformative approach to biomarker identification and patient stratification. This collaboration is a critical step in improving outcomes for patients with high mortality cancers." The initial phase of the partnership will focus on developing a prototype machine learning classifier model for quantifying CDH17 expression patterns in CRC samples, using a combination of H&E (hematoxylin and eosin) and IHC (immunohistochemistry) stained images. This initiative aims to standardize and improve the pathologic assessment of treatment response biomarkers to facilitate more effective patient selection for Arbele's specific therapeutic programs. Both companies expect that this collaboration will pave the way for future advances in precision medicine, ultimately benefiting patients with gastrointestinal cancers. About BioAI BioAI is a leading provider of multimodal AI for digital health in precision medicine, offering world-leading machine learning technology to develop digital biomarkers and H&E based predictive models. They partner with leading pharmaceutical, biotechnology, clinical laboratories, and academic cancer centers around the world. With the PredictX Platform, BioAI aims to revolutionize personalized medicine by improving drug efficacy and patient outcomes. For more information about BioAI and its innovative machine learning technologies, visit bioaihealth.com. About Arbele Arbele is a biotech and biopharmaceutical company focused on developing proprietary immunotherapeutic platforms targeting cadherin-17 and other specific tumor targets for gastrointestinal cancers. By inventing "first in class" antibody-based biologics, Arbele aims to address critical unmet needs in cancer treatment. For more information about Arbele, please visit arbelebio.com. SOURCE BioAI Health WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

肿瘤免疫学作为近年来备受瞩目的研究领域，正以其迅猛的发展态势引领着细胞疗法的繁荣。自2017年诺华的Kymriah获美国FDA批准上市以来，全球共有11款CAR-T细胞疗法产品获批上市，其中5款为国内上市。 据沙利文分析，2021~2025年全球CAR-T市场预计将以47%的CAGR增长到80.3亿美元，并将以21%的CAGR增长到2030年的211.4亿美元，而中国2030年的CAR-T市场规模则有望达到289亿元。这得益于上市CAR-T疗法在血液瘤治疗中取得的显著成效，CD19、BCMA两大热门靶点实现了精准打击。然而，当我们将视线转向实体瘤时，情况就变得复杂起来。 ◀︎来源：沙利文 实体瘤往往是个坚实的团状物，丰富的肿瘤相关成纤维细胞（CAF）和血管还会包裹它，形成了天然厚实的物理屏障，CAR-T细胞往往难以浸润。同时，实体瘤会抑制某些趋化因子的分泌，影响T细胞向肿瘤微环境的迁移。面对肿瘤微环境（TME）的低pH、低氧、高渗透特性，CAR-T细胞的存活能力与杀伤力被极大的削弱。 并且，实体瘤中的肿瘤特异性抗原（TSA）很少，目前发现的肿瘤高表达靶点多为肿瘤相关抗原（TAA），在正常组织中也有少量表达，且具有高度异质性，导致安全有效的实体瘤靶点十分稀缺。 面对占比90%以上的实体瘤，CAR-T疗法存在巨大的临床需求。随着CAR-T研发的持续深入，针对实体瘤的解决方案也逐渐丰富，比如多样化的靶点选择、武装化的CAR-T改造、新颖的逻辑门控设计，既是细胞治疗行业竞争的重要突破口，也是克服实体瘤挑战的关键“密钥”。 扫描二维码下载《Incucyte®长时程活细胞成像应用文集》 滑动查看 探寻实体瘤靶点，谁将兼具有效性与安全性 合适的实体瘤靶点能够有效提高CAR-T细胞特异性，避免杀伤机体的健康组织。近年来，Claudin18.2的靶向药物在胃癌等恶性实体瘤的治疗中展现出了卓越疗效，不仅安全可靠，且患者耐受性良好，已被视为胃癌、胰腺癌等实体肿瘤免疫治疗领域的新星。 ◀︎来源：实体瘤免疫细胞疗法的全球竞争格局分析报告，数据统计截止2024.3.1 2024年2月，国际知名期刊《Front Immunol》刊登了一则关于靶向Claudin18.2的CAR-T细胞疗法治疗晚期胰腺癌患者，并达到完全缓解的病例报告，引起行业的广泛关注。 在Claudin18.2这样的经典实体瘤靶点之外，对新靶点的探索也从未停止。2023年10月末，Chimeric Therapeutics宣布，美国FDA已经批准其全球首款CDH17靶向的CAR-T细胞疗法CHM 2101的IND申请，预计将在2024年开展一项针对晚期结肠直肠癌、胃癌和神经内分泌肿瘤患者的多中心1期临床试验。 这些进展将激发研发人员对CAR-T的进一步研究，以开发靶向一些类似的先前未被重视的TAA。 CAR-T“武装化”，应对肿瘤微环境 工程化修饰CAR-T细胞促使其分泌刺激因子或PD-1是一个具有前景的研究方向。 去年年初，强生旗下Janssen Biotech与Simcha达成一项合作，强生将把Simcha的抗诱饵白细胞介素-18（DL-18）技术融入选定的CAR-T细胞疗法候选产品中。IL-18在CAR-T细胞中表达能够增强CAR-T细胞增殖和抗肿瘤活性，同时还可减少CAR-T细胞的使用量及全身给药的副作用。IL-18还可能对各种类型的肿瘤具有广泛的活性，包括免疫原性强的“热”肿瘤和对免疫治疗有抵抗性的“冷”肿瘤。 今年《NEJM》上发表的一篇研究论文也展现了一种创新的联用武装策略，研究者将CAR-T细胞疗法和双特异性抗体这两种独立的癌症治疗策略结合起来，让靶向EGFRvIII的CAR-T细胞表达并分泌靶向野生型EGFR的T细胞接合抗体分子（TEAM）。在该产品的1期临床试验中，3名患有复发性胶质母细胞瘤的患者在接受CARv3-TEAM-E T细胞疗法治疗后，肿瘤在几天内就出现了显著消退，其中1名患者的肿瘤近乎完全消失。 ◀︎来源：《NEJM》 逻辑门控：双保险提升安全性 面对大多数实体肿瘤靶抗原与正常细胞共享所产生的毒副作用，研究人员试图应用布尔逻辑门控（Boolean Logic Gate, 包含AND,OR,NOT）方法对CAR-T细胞进行脱靶毒性预防。 ◀︎逻辑门CAR-T细胞的原理 （图片来源：参考资料[4] ） 在来自于斯坦福大学在《NATURE》上发表的“CAR-T cell design: approaching the elusive AND-gate”一文中，作者设计了一种基于AND的逻辑门控细胞内网络（LINK CAR），使之可以保护只表达一种目标抗原的正常组织，扩大CAR-T细胞靶向的分子范围，在实体瘤的治疗中能够提高特异性和安全性。 多重精准检测 助力实体瘤CAR-T行稳致远 这些新的技术探索极有可能为肿瘤治疗领域带来了革命性的变革，为患者提供新的希望与可能性。然而，这些创新性的治疗策略发展也对临床前研发阶段中的多个关键指标，尤其是细胞表型检测、杀伤功能的即时性与持久性，以及脱靶毒性等方面，提出了新的挑战和迫切的需求。 一 细胞表型的精准检测提高治疗效果 在针对实体瘤CAR-T细胞疗法的研究中，对新兴细胞表型地不断探索，不仅可以揭示细胞的生物学特性，还有助于开发新型的细胞治疗策略。通过掌握细胞表型的规律，甚至可能干预细胞与宿主环境的相互作用，从而提高细胞治疗的效果。 T细胞的体外扩增是CAR-T等过继细胞疗法生产工艺的关键步骤。在赛多利斯发布的“An Optimized, Multiplexed Assay for Screening Ex Vivo Conditions which Increase Memory T Cell Frequency” 一文中，研究表明：在体外T细胞扩增过程中，让T细胞产物中产生更高比例的Tscm和Tcm对于细胞治疗的显著临床改善至关重要。而传统的检测方法需要在不同平台上运行多个分析过程才能确认不同种类细胞的各项关键参数，不仅效率低下，还会大量消耗宝贵的样品。 因此研究人员在T细胞表型和功能分析监测中应用了赛多利斯的iQue®高通量流式细胞仪，该设备具有较宽的固定动态范围，可在不同阶段对记忆型T细胞表型和功能进行空间和时间的分析，避免不同时间点的差异，从而增强数据完整性。 此外，iQue® 可以实现高通量、多功能的细胞因子分析。在文章中，研究人员同时进行IFN和IL-10分泌情况的定量分析和表型分析来评估细胞功能，并且使用了来自三个供体的人外周血单核细胞(PBMC)，在14 种不同的培养条件下进行筛选研究。这种一站式的分析方法不仅提高了筛选研究效率，还能提供更为全面和深入的生物学洞察。 ▲iQue® 分析结果显示记忆型T细胞频比例变化（图片来源：参考资料[5]） 二 高效、精准的杀伤力， 是各类创新策略的殊途同归 肿瘤微环境严重削弱了CAR-T的杀伤力，而杀伤力直接决定了其治疗癌症的效果。可以说，CAR-T细胞高效、精准地杀伤肿瘤细胞是各类创新策略的殊途同归。为此，研究者在探寻更安全的实体瘤靶点与逻辑门开关等策略。然而创新策略能否真正奏效，还需检测来验证。 美国费城儿童医院的研究人员以神经母细胞瘤作为研究对象，筛选出了特异存在于肿瘤细胞表面的多肽，以这些多肽为靶点的CAR-T称为PC-CAR，并选择一种源自PHOX2B的未突变的神经母细胞瘤肽为靶点，使用Octet® 分子互作分析系统测得其与PHOX2B亲和力为13nM。 随后，研究人员运用Incucyte® 实时活细胞分析系统来检测免疫细胞的杀伤活力。在杀伤实验中，加入Caspase 3/7 红色荧光染料后，Incucyte® 可对细胞进行实时、动态、连续地监测分析，并通过高分辨率红色荧光面积和绿色荧光面积直观得出信息。红色荧光面积升高快，绿色荧光（靶点细胞即肿瘤细胞）下降快，则代表杀伤效果越大，非常直观。 同时，集成式软件可以简化数据分析，快速获得结果，并生成可供发表的图表和绘图。从下图可以看出，Incucyte® 的分析数据显示，PC-CAR对SKNAS胶质瘤细胞（呈递PHOX2B）的杀伤作用明显，有望成为攻克实体瘤的有效靶点。 ▲ Incucyte® 实时活细胞成像（图片来源：参考资料[6]） a左图为PC-CAR对SKNAS胶质瘤细胞（呈递PHOX2B）的杀伤作用明显，a右图为PC-CAR对其他肿瘤细胞（不呈递PHOX2B）的杀伤则不明显；b图从靶细胞动态增殖水平来观察，发现PC-CAR对SKNAS等胶质瘤细胞的杀伤作用明显。 三 控制脱靶毒性：安全性的重要防线 控制脱靶毒性是细胞疗法研发中对安全性的重要考验，尤其是面对靶点多为肿瘤相关抗原（TAA）的实体瘤。CAR-T在攻击实体瘤时，存在攻击到正常细胞的风险，导致脱靶毒性，不仅降低治疗效果，还会带来严重的副作用。因此，在临床前研发阶段，研究人员需要深入探索脱靶毒性的发生机制，并开发有效的预防和减轻脱靶毒性的策略。在验证逻辑门CAR-T的杀伤力与脱靶效应时，也有研究者运用了Incucyte® 实时活细胞分析系统作为“检测神器”。 2022年4月27号，斯坦福大学医学院的Crystal L. Mackall教授课题组在《Cell》杂志上报道了一种名为SNIP的高性能药物可调节系统，可利用FDA批准的一款小分子来调节CAR-T活性。研究人员使用Incucyte® 快速准确地评估了不同版本的SNIP CAR-T针对靶细胞的杀伤活性，以及药物对SNIP CAR-T细胞的调控活性。 ▲ SNIP工作机理（图片来源：参考资料[7]） 如下图所示，Incucyte® 的分析结果显示，SNIP CAR-T细胞平台提供了可靠的安全开关，降低了CAR-T细胞的脱靶毒性，SNIP系统在Off状态下没有明显的“泄露”活性，一旦被激活则具有更强和更快的肿瘤杀伤动力学。在ON状态下具有肿瘤杀伤活性且强于组成型的CAR-T细胞，同时其在多种原位实体瘤模型中的疗效均优于组成型CAR-T细胞平台。 ▲Incucyte® 分析数据（图片来源：参考资料[7]） 四 万事具备，只待快速放行 除了脱靶效应外，CAR-T细胞治疗的安全性与快速准确的微生物质量控制检测也密不可分。微生物污染可能会导致接受者危及生命的感染，因此无菌检查是任何细胞治疗产品的放行检测中的关键组成部分。快速、准确、高效的检测方法能为细胞药物的安全性提供有力保障。 目前的药典推荐的无菌检查方案需要14天才能确定排除污染，这对于有效期短的细胞疗法药品太久，更何谈那些用于治疗晚期病人的自体细胞疗法药品。因此，市场对不依赖于微生物生长的快速检测方法的需求与日俱增。 有研究者使用人外周血单核细胞（HPBMC）、Jurkat 细胞和中国仓鼠卵巢（CHO）细胞作为代表性背景模型，评估了Microsart® ATMP 提取试剂盒和Microsart®  ATMP 细菌/真菌/支原体测定快速检测试剂盒在高密度细胞培养物中的检测能力。 结果表明，即使在高细胞背景下，赛多利斯Microsart® ATMP无菌放行试剂盒也可以快速检测微生物污染，在3小时内提供QC结果，这相比基于培养法的QC放行节约了90%以上的时间，不仅有助于降低细胞治疗产品的风险，保证患者的安全，还能加快治疗药物的临床可及速度。 细胞疗法的卓越应用，其核心在于对细胞生产制备与检测环节的精细控制和高质量保障。面对挑战重重的实体瘤治疗，目前急需采用高效、可靠的检测手段来优化升级CAR-T设计，以提供精确无误的细胞质量和数量信息。这不仅有助于细胞治疗产品在临床前的全面评估，还能确保生产后的标准化检测得以准确进行。 赛多利斯凭借一系列先进的技术和产品，为CAR-T疗法的研发提供了坚实的后盾，显著提升了研发效率，并极大地增强了患者治疗的有效性与安全性。展望未来，随着科技的持续进步，我们期待更多借助先进技术支持的CAR-T疗法能够成功上市，为实体瘤等疾病的治疗带来划时代的突破，造福广大患者。 扫描二维码下载《Incucyte®长时程活细胞成像应用文集》 细胞治疗解决方案 “点击阅读原文，查看细胞治疗解决方案” -参考文献- [1] Guocheng Zhong , Xiaomin Zhang , Zheng Guo ,  et.al. Complete remission of advanced pancreatic cancer induced by claudin18.2-targeted CAR-T cell therapy: a case report. Front Immunol. 2024 Feb 29:15:1325860. doi: 10.3389/fimmu.2024.1325860. eCollection 2024. PMID: 38487523. [2] Feng Z, He X, Zhang X, Wu Y, Xing B, Knowles A, Shan Q, Miller S, Hojnacki T, Ma J, Katona BW, Gade TPF, Schrader J, Metz DC, June CH, Hua X. Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues. Nat Cancer. 2022 May;3(5):581-594. [3] Choi BD, Gerstner ER, Frigault MJ, Leick MB, Mount CW, Balaj L, Nikiforow S, Carter BS, Curry WT, Gallagher K, Maus MV. Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma. N Engl J Med. 2024 Mar 13. doi: 10.1056/NEJMoa2314390. Epub ahead of print. PMID: 38477966. [4] Zhao Z, Sadelain M. CAR T cell design: approaching the elusive AND-gate. Cell Res. 2023;33(10):739-740. doi:10.1038/s41422-023-00828-w [5] Liu, Z., et al. An Optimized, Multiplexed Assay for Screening Ex Vivo Conditions which Increase Memory T Cell Frequency. Sartorius Application Note, 2019. [6] Yarmarkovich, M., Marshall, Q.F., Warrington, J.M. et al. Targeting of intracellular oncoproteins with peptide-centric CARs. Nature 623, 820–827 (2023). [7]Labanieh L, Majzner RG, Klysz D, Sotillo E, Fisher CJ, Vilches-Moure JG, Pacheco KZB, Malipatlolla M, Xu P, Hui JH, Murty T, Theruvath J, Mehta N, Yamada-Hunter SA, Weber EW, Heitzeneder S, Parker KR, Satpathy AT, Chang HY, Lin MZ, Cochran JR, Mackall CL. Enhanced safety and efficacy of protease-regulated CAR-T cell receptors. Cell. 2022 Apr 20:S0092-8674(22)00391-9. [8]Jan-Niclas Luebbers, Dr. Alexandra Mueller-Scholz, Dr. Diana Patzelt, Kai Nesemann,利用Microsart® ATMP 试剂盒和快速实时PCR 技术 检测高细胞密度Jurkat、HPBMC 和CHO 培养物中的微生物污染. Sartorius Application Note, 2020. -END- 赛多利斯服务热线 400 920 9889800 820 9889