行业动态：新型肝脏环试验将彻底改变药物安全性评估
德国柏林，2024 年 5 月 28 日
 

摘要

衰新型肝脏环试验将彻底改变药物安全性评估

德国柏林，2024 年 5 月 28 日

在一项开创性的举措中，器官芯片技术的领军企业 TissUse 宣布启动“肝环试验”。该试验由 ESQLabs（计算模型专家）、全球生物制药公司 UCB（该试验的发起者）以及另外五家制药公司（奥里昂公司、赛诺菲安万特研发公司、施维雅技术/施维雅生物公司、阿斯利康和勃林格殷格翰）共同参与，旨在验证肝微生理系统（MPS）在预测药物引起的肝损伤（DILI）和内在清除率方面的可重复性和准确性，这标志着非临床药物评估范式的重大转变。

利用微流控器官芯片进行创新

肝脏环试验借助了 TissUse 公司前沿的 HUMIMIC 器官芯片技术，该技术在肝脏微生理系统（MPS）的发展中发挥了核心作用。“我们的微流控平台不仅在于模拟肝脏功能，更在于构建器官与器官之间更全面的相互作用，从而更准确地呈现人体生理状况，”TissUse 公司首席执行官雷克·霍兰德博士说道。

此次试验的核心在于 ESQLabs 提供的计算建模专业知识。器官芯片数字孪生平台负责人克里斯蒂安·马斯博士表示：“通过将我们的先进计算模型与肝脏微生理系统相结合，我们不仅提高了系统的预测准确性，还为临床转化设立了新的标准。”

基于监管里程碑

该倡议是在成功将 MPS 数据纳入监管申报文件（例如 Inipharm 的用于治疗非酒精性脂肪性肝炎（NASH）的肝脏 MPS 模型）之后推出的。通过肝脏环形试验，该联盟旨在为将 MPS 数据用于监管提交提供更大的信心，并最终支持决策制定。

开创性研究指南

在欧洲药品管理局（EMA）和欧盟委员会联合研究中心（JRC）的欧盟替代动物实验参考实验室（EURL ECVAM）的见解和建议指导下，肝环试验旨在改进其方法并扩大应用范围。“在非临床药物评估的关键时刻，ECVAM 和 EMA 的支持对我们工作的指引至关重要，”UCB 体外 ADME 团队的副主管兼负责人、肝环试验的发起人雷纳·克拉思（Reiner Class）表示。

关于合作伙伴
TissUse 是一家总部位于德国柏林的生物技术公司，在器官芯片技术领域处于领先地位，致力于开发能够模拟人体生物学的复杂体外系统。esqLABS 专注于计算建模，提供创新解决方案以弥合体外和体内研究之间的差距。

TissUse 公司开发了一种独特的“多器官芯片”平台，该平台利用人体组织在系统层面上提供了前所未有的临床前洞察。这一赋能技术平台由一个微型结构组成，能够真实地模拟多种人体器官在生理环境中的活动。TissUse 的多器官芯片为例如毒性、吸收、分布、代谢和排泄（ADME）特征以及体外疗效的预测提供了新方法，减少了实验室动物试验，并简化了人体临床试验。

自 2012 年以来，TissUse 公司的多器官芯片已在药物开发、化妆品、食品与营养以及消费品等众多领域得到应用。

由首席执行官斯蒂芬·沙勒博士领导的 ESQlabs 公司，在药代动力学/药效学和基于生理的药代动力学建模以及基于生理的定量系统药理学领域提供建模和模拟解决方案。该公司依靠开源的 OSP 套件，并积极参与其用户社区，为该套件的发展做出贡献。借助 OSP 套件，ESQlabs 目前为生命科学和药理学领域的客户提供多种服务，包括模型构建开发与优化、数据整合以及咨询服务。ESQlabs 拥有一支由约 30 多名科学家组成的团队，他们在建模、统计学、药理学和软件开发等领域拥有丰富的专业知识。用于创建人体生物学数字表示的 OSP 套件的应用范围和用户群在不断扩大。首席科学家克里斯蒂安·马斯博士领导着用于器官芯片和微生理系统的数字孪生平台开发工作，其专业知识对于该项目至关重要。

Novel Liver Ring Trial Set to Revolutionize Drug Safety Assessment

Berlin, Germany, May 28, 2024

In a first-of-its-kind initiative, TissUse (a leader in organ-on-chip technology) announced the commencement of the Liver Ring Trial. This collaborative effort involving ESQLabs (a computational model expert), UCB, a global biopharmaceutical company and initiator of the ring trial, and five other pharmaceutical companies (Orion Corporation, Sanofi-Aventis Recherche & Développement, Technologie Servier/Biologie Servier , AstraZeneca, and Boehringer Ingelheim) aims to validate the reproducibility and accuracy of a Liver Micro-Physiological System (MPS) in predicting drug-induced liver injury (DILI) and intrinsic clearance, marking a paradigm shift in non-clinical drug assessment.

Innovating with Microfluidic Organ-on-Chips

The Liver Ring Trial leverages TissUse's cutting-edge HUMIMIC organ-on-chip technology, which has been central to the development of the Liver MPS. "Our microfluidic platform is not just about simulating liver functions; it's about creating a more holistic organ-to-organ interaction, thereby offering a more accurate representation of human physiology," stated Dr. Reyk Horland, CEO at TissUse.

Central to this trial is the computational modeling expertise provided by ESQLabs. Dr. Christian Maass, platform lead digital twins for organ-on-chips, remarked, "by integrating our advanced computational models with the Liver MPS, we are not only enhancing the system’s predictive accuracy but also setting new standards for clinical translation."

Building on Regulatory Milestones

This initiative follows the successful inclusion of MPS data in regulatory filings e. g. Inipharm's liver MPS model for NASH (non-alcoholic Steatohepatitis). With the Liver Ring Trial, the consortium aims to provide more confidence to use MPS data for regulatory submission and, ultimately, support decision making.

Guidance for Groundbreaking Research

Guided by the insights and advice from the European Medicines Agency (EMA) and the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) of the European Commission’s Joint Research Centre (JRC), the Liver Ring Trial aims to refine its methodology and expand its application. "We are at a pivotal moment in non-clinical drug assessment, and the support from ECVAM and EMA are invaluable in directing our efforts," expressed Reiner Class, Associate Director, and team leader in the in vitro ADME team at UCB and initiator of the Liver Ring Trial.

About the Collaborators

TissUse is a Berlin, Germany-based, biotechnology company pioneer in the field of organ-on-chip technology, committed to developing sophisticated in vitro systems that mimic human biology. esqLABS specializes in computational modeling, offering innovative solutions to bridge the gap between in vitro and in vivo studies.

TissUse has developed a unique “Multi-Organ-Chip” platform that provides unparalleled preclinical insight on a systemic level using human tissues. This enabling technology platform consists of a miniaturized construct that closely simulates the activity of multiple human organs in their true physiological context. TissUse’s Multi-Organ-Chips provide a new approach to predict, for example, toxicity, ADME profiles and efficacy in vitro, reducing and replacing laboratory animal testing and streamlining human clinical trials.

TissUse’s Multi-Organ-Chips have been utilized in a large variety of applications including drug development, cosmetics, food and nutrition and consumer products since 2012.

ESQlabs, led by CEO Dr. Stephan Schaller, offers provides modelling and simulation solutions in the field of pharmacokinetic/pharmacodynamic and PBPK modeling, as well as physiology-based quantitative systems pharmacology. It relies on the open source OSP Suite, to which it actively participates to the user-community and contributes to development. Using the OSP Suite, ESQlabs currently offers various services, including model building development and refinement, data integration, and consulting for clients in life sciences and pharmacology. ESQlabs has a team of about over 30 employees scientists with extensive expertise in areas such as modeling, statistics, pharmacology, and software development. The application scope and user base of the OSP Suite for creating digital representations of human biology is constantly growing. Principial Scientist Christian Maass, PhD, is leading the platform development for digital twins for organ-on-chip and micro-physiological systems, whose expertise will be essential in the project.

UCB is a Brussels, Belgium-based global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system.

Press contact TissUse GmbH:

Dr. Reyk Horland
CEO
TissUse GmbH
Oudenarder Str. 16
13347 Berlin
Germany

Tel.: +49 (0)30 51 30 264-00
Fax: +49 (0)30 51 30 264-01
E-mail: info@tissuse.com
Web: www.tissuse.com

北京佰司特科技有限责任公司 (https://www.best-sciences.com)

类器官串联芯片培养仪—HUMIMIC；灌流式细胞组织类器官代谢分析仪—IMOLA；光片显微镜—LSM-200；

蛋白稳定性分析仪—PSA-16；单分子分析仪（磁镊力谱测量仪）—HiMT；单分子质量光度系统—TwoMP；超高速视频级原子力显微镜—HS-AFM；微流控扩散测量仪—Fluidity One-M；

微纳加工点印仪—NLP2000DPN5000；台式原子力显微镜—ACST-AFM；全自动半导体式细胞计数仪—SOL COUNT；农药残留定量检测仪—BST-100；