Project
COVend objectives
COVend aimed to deliver a new effective therapy against endothelial damage in Acute Respiratory Distress Syndrome (ARDS) for the clinical management of COVID-19 and other conditions involving endothelial dysfunction. The project tested a host-directed therapy targeting the endothelium with the FX06 peptide in a multinational phase II clinical trial. Its goal was to evaluate FX06’s potential to prevent disease progression from mild or moderate to severe illness, improving outcomes and preparedness for future pandemics.
Clinical research and regulatory progress
COVend completed Good Manufacturing Practice (GMP) production of FX06 and received regulatory approvals for its Investigational Medicinal Product Dossier (IMPD). Following consultations with the German Federal Institute for Drugs and Medical Devices (BfArM) and the European Medicines Agency (EMA), the clinical protocol evolved into a mechanism-based ARDS trial (IXION2.0), conducted across six sites in five countries. Despite a limited cohort (18 of 263 planned patients), all were successfully treated and followed, generating valuable safety and mechanistic data.
Molecular and mechanistic insights
Using proteomics, metabolomics, and lipidomics, researchers analysed 69 samples from 18 patients, identifying molecular signatures across 460 proteins, 101 metabolites, and 466 lipid parameters. Experimental studies confirmed that FX06 protects pulmonary endothelial cells from cytokine-induced dysfunction by modulating the RhoA–ROCK-1 pathway, preserving vascular barrier integrity and reducing inflammation. These findings position FX06 as a promising therapy for endothelial complications in COVID-19 and other systemic inflammatory diseases.
Other outputs
AI and data-driven modelling
Innovative AI-based Bayesian models and open-access tools to predict ARDS outcomes and support research even with limited clinical data
Health economics and policy impact
SHEPARDS health-economic framework and budget impact tools to assess the socio-economic value and implementation potential of ARDS therapies
Open Science and collaboration
Publishing open-access results and collaborating across major EU research networks to promote knowledge exchange and transparency, embracing Open Science principles
Communication and dissemination
Through active digital outreach, events and publications, COVend shared its findings widely, enhancing visibility and supporting broader awareness of its research impact.
COVend Policy guidelines
COVend policy guidelines present specific recommendations aligned with existing European regulatory frameworks, addressing six critical areas.
Insights into FX06’s Mechanism of Action
Using advanced systems biology and lab assays, UCD–SBI revealed how FX06 stabilises the lung endothelium by inhibiting the RhoA–ROCK-1 pathway.