Treatment of critical COVID-19 patients through removal of IL-6 by magnetic blood filtration

MediSieve是一家屡获殊荣的医疗器械公司，开发了磁血液过滤（MBF），这是一种类似于透析的体外技术，其中靶向磁性颗粒（TB-MP）被注入体外回路，特异性结合患者血液中的疾病相关靶点。然后，血液流过磁性过滤器（MF），该过滤器捕获颗粒和结合的目标，而剩余的血液不受影响地返回患者。目前正在开发6种TB-MP，靶向IL-6、内毒素、IL-10、IL-18、CD 19和CD 20。在该项目中，MediSieve建议加快其抗IL-6 TB-MP的开发，并将MBF作为治疗英国和全球严重COVID-19患者的治疗方法。该项目将支持动物试验和临床试验中的验证、监管批准，并为项目后的广泛分布奠定基础。COVID-19研究已将IL-6驱动的超免疫反应鉴定为死亡率的重要贡献者，其中升高的IL-6（p<0.0001）是死亡率的预测因子（Conti，J. Bio.霍先生AG. 2020; Mehta，Lancet 2020）。此外，一项对191名COVID-19住院患者的回顾性研究发现，超过50%的患者发生败血症（Zhou，Lancet 2020）。通过专注于IL-6，MediSieve可以迅速将产品推向市场，以减轻细胞因子风暴和超免疫反应以及继发性脓毒症，这是COVID-19患者死亡率高的原因。体外数据表明，成人IL-6水平可在4小时内降低90%。MF已完成GLP临床前动物研究和生产验证;已准备好进行首次人体试验。IL-6 TB-MP已通过体外血液测试验证，并准备进行动物试验。该项目将通过临床前验证、生产验证和监管批准加速IL-6 TB-MP和整个系统的开发，以使人体临床试验为全面发布做好准备。

MediSieve is a multi-award-winning medical device company developing Magnetic Blood Filtration (MBF), an extracorporeal technology similar to dialysis, in which Targeted Magnetic Particles (TB-MPs) are infused into the extracorporeal loop, binding specifically to disease-relevant targets in the patient's blood. The blood then flows through a Magnetic Filter (MF) which captures the particles and bound targets, while the remainder of the blood returns to the patient unaffected. There are 6 TB-MPs currently under development, targeting IL-6, endotoxins, IL-1ß, IL-18, CD19 and CD20\. In this project, MediSieve proposes to accelerate the development of its anti-IL-6 TB-MPs and to apply MBF as a treatment to severe COVID-19 patients in the UK and worldwide. The project will support validation in animal trials and clinical trials, regulatory approvals, and lay the foundations for widespread distribution post-project.COVID-19 studies have identified IL-6 driven hyperimmune reactions as a significant contributor to mortality with elevated IL-6 (p<0.0001) a predictor of fatality (Conti, J. Bio. Reg. Hom. Ag. 2020; Mehta, Lancet 2020). Additionally, a retrospective study of 191 hospitalised patients with COVID-19 found that over 50% developed sepsis (Zhou, Lancet 2020). By focusing specifically on IL-6 MediSieve can rapidly bring a product to market to alleviate the cytokine storm and hyperimmune reaction as well as the secondary sepsis that is the cause of significant mortality in COVID-19 patients. In vitro data suggest that adult IL-6 levels could be reduced by 90% in 4 hours. The MF has completed GLP pre-clinical animal studies and manufacturing validation; it is ready for first-in-man trials. The IL-6 TB-MPs have been validated with in vitro blood testing and are ready for animal trials. This project will accelerate development of the IL-6 TB-MPs and whole system through pre-clinical validation, manufacturing validation and regulatory approval to enable human clinical trials in preparation for full scale release.