Periodic Reporting for period 2 - COVend (Biomarker and AI-supported FX06 therapy to prevent progression from mild and moderate to severe stages of COVID-19)
Reporting period: 2023-02-01 to 2024-07-31
ARDS is a significant medical issue with no currently available drug-based treatments. It can occur due to various factors, such as viral or bacterial infections, severe trauma, major surgery, or blood transfusions. In ARDS patients, the exchange of gases in the lungs is hindered by damaged alveoli, dysfunctional capillaries, and fluid build-up. The surface of our blood vessels is lined by endothelial cells that function as important regulators of vascular homeostasis controlling immune competence, inflammatory equilibrium, blood coagulation and other essential vital functions of the cardiovascular system. Viral infection induces damage of the endothelium and results in an auspicious spiral that may lead to capillary leakage, thrombosis, ARDS, and multiorgan failure ultimately manifesting in high morbidity and mortality. Thus, understanding and counteracting the disease in this context is crucial to improve patient outcomes. FX06 operates as an endothelium-protective drug and may prevent detrimental host inflammatory responses including endotheliitis, hyperinflammation, and hypercytokinemia (better known as cytokine storm). Strikingly, it does not rely on host-virus interactions and thus acts independently of any viral mutations. FX06 does not manipulate the host metabolism or immune system and is in general well tolerated. The COVend Project aims to develop an FX06 precision therapy for the clinical management ARDS of different etiology, focusing on the prevention of disease progression to severe illness. The main objective is to test the therapeutic candidate FX06 in a placebo-controlled, double-blind, randomised, multi-national phase II clinical trial. COVend brings together clinicians, biochemists, data scientists, and economists to gain a comprehensive understanding of ARDS and identify effective treatment strategies for real-world scenarios. IXION2.0 is being conducted in 5 European countries (France, Germany, Lithuania, Romania and Spain) and is open to patients of all genders and all ethnicities, ensuring a diverse study population representative for all European citizens. The main project goals include preparing and distributing the investigational medicinal product (IMP), conducting the clinical trial, investigating the molecular profile of COVID-19 and its change upon FX06 treatment, creating additional solid evidence based on sophisticated in vitro studies with endothelial cell lines, developing biomarkers and open source decision support applications for an FX06 precision therapy, and evaluating the health-economic benefits and cost-effectiveness of this therapy. Based on the scientific knowledge gained in COVend and IXION2.0 we aim to aid patients with ARDS related to COVID-19 or other aetiologies and contribute to a society that is prepared for future disease outbreaks.
The consortium has made significant progress in developing and implementing an organizational framework for managing the research and innovations. The therapeutic candidate FX06 has been prepared for clinical trial and comprehensive toxicological studies have been completed, confirming the safety of FX06 in model animals. The first multi-centre clinical trial IXION was approved and implemented in nine clinical sites across Europe. Unfortunately, due to the unexpected development of the COVID-19 pandemic, the recruitment of patients was not possible. The consortium made an immense effort in adapting the clinical study protocol, processing all the necessary approvals and putting up in place a new strategy of the clinical trial, widening the patient focus to ARDS related to COVID-19 or other etiologies. The multi-centre clinical trial IXION2.0 is fully implemented in six clinical centres across the EU to evaluate the potential of FX06 in treating ARDS related to COVID-19 or other aetiologies. Sample management workflows to analyse the proteomic, metabolomic and lipidomic profiles of ARDS and FX06 treatment have been developed. Additionally, the consortium is investigating the effect of FX06 against cytokine-mediated effects on pulmonary endothelial cells, unravelling the molecular mechanism and providing additional in-depth evidence for the clinical efficiency of FX06. Data analysis and AI-supported modeling to identify novel biomarkers for personalised decision support has been initiated by investigating the data structure with dummy data. Finally, the consortium is evaluating FX06 from a health economic perspective to assess its socio-economic benefits and cost-effectiveness. Here, relevant policies, barriers, and facilitators for market access and reimbursement have been sucessfully identified.
COVend has made substantial contributions to multiple facets of ARDS and COVID-19 research and its broader implications, particularly in the fields of biomarker discovery and health technology advancements. Within (WP2), comprehensive toxicological studies for the compound FX06 have been successfully completed, laying the essential groundwork for upcoming clinical trials aimed at evaluating its efficacy in treating capillary leak-associated clinical conditions. Additionally, the scientific findings achieved in WP5 and WP7 have significantly enhanced our understanding of capillary leak phenomena in COVID-19-associated ARDS, as well as in similar conditions stemming from other causes. These insights are not only critical for advancing medical knowledge but also for assessing the broader economic implications of such conditions. The progress made thus far holds promise for reducing the economic burden and recovery time for affected families, employers, and the working population. Furthermore, healthcare professionals, hospitals, and the pharmaceutical industry stand to benefit from this project, as it has the potential to lower healthcare costs and introduce a novel therapeutic option to the market.