
Pioneering molecule for the treatment of inflammatory bowel disease
Inflammatory bowel diseases are a group of chronic inflammatory conditions that can severely affect a patient’s quality of life and have no effective treatment. Researchers at the University of Barcelona (UB) are participating in a public-private consortium to develop a promising drug designed to effectively address the inflammation caused by these disorders, significantly reducing the side effects of current treatments.
The innovative drug has a unique mechanism of action based on Orikine’s Foldikine© technology platform, based on bispecific cytokine engineering. The aim of the three-year project is to bring this promising molecule to the threshold of human clinical trials.
‘Inflammatory bowel disease remains a major unmet medical need and this approach could improve the quality of life of patients, especially for those who do not yet respond, or who over time lose the ability to respond, to current therapies,’ explains Giuliana Magri, researcher at the Faculty of Medicine and Health Sciences and coordinator of the Mucosal Immunity laboratory at the Immunology Unit of the University of Barcelona-Campus Clínic, who is leading the UB’s participation in the project. It is a consortium led by Orikine, a spin-off of the Centre for Genomic Regulation (CRG), with the participation of researchers from the CRG and the Spanish National Research Council (CSIC).
A dual molecule to control inflammation
Although the causes that lead to the development of inflammatory bowel diseases are not fully understood, these disorders are largely dependent on the interaction of the environment with the immune system. In this context, cytokines are biomolecules of great potential interest as therapeutic agents, due to their key role in modulating the immune system and maintaining tissue homeostasis.
Despite this potential, only a handful of cytokines are approved for therapeutic purposes. ‘The reason is that many of them can have adverse side effects, as they are not specific enough and often target different cell types, which adds to their high production costs,’ explains Giuliana Magri.
Foldikines are molecules designed to precisely control the immune response, offering unprecedented therapeutic potential to address autoimmune and inflammatory diseases. ‘This innovative and unique approach is opening up new possibilities for treatments where traditional therapies based on classical cytokines have not been successful at the clinical stage,’ adds the UB researcher.
In this context, the new consortium has developed, thanks to state-of-the-art protein design technologies, a dual bispecific molecule called Folkidin-1 (FLDK-1), which allows the different functions of this cytokine to be uncoupled. ‘In other words, it is able to activate the anti-inflammatory functions of the cytokine and deactivate the pro-inflammatory ones to minimise the side effects on patients,’ says Giuliana Magri.
Experiments with patient samples
Based on this dual concept devised by Orikine, the consortium’s goal is to optimise a candidate molecule for preclinical drug development. In this process, the CRG is responsible for the improvement of the molecule, through in silico computational techniques, of FLDK-1, using the ModelX and FoldX software platform, which allows the design of improved cytokines and folkidins.
Orikine will be in charge of designing, producing, purifying and testing the function of the selected variants, while the CSIC team will test the molecule in different animal models of inflammatory bowel disease.
Finally, the UB team will play a key role in demonstrating the therapeutic potential and efficacy of the new molecule in patient samples, a critical step in the development of the future drug.
Thus, the result of this ambitious project will be a molecule ready to begin the CTA (Clinical Trial Application) or IND (Investigational New Drug) phase of regulatory preclinical studies to advance the molecule in subsequent clinical phases, with the support of significant in vitro and in vivo evidence of its efficacy, confirming the previous results obtained by Orikine.
The three-year project, reference SCPP2300C010468XV0, aims to develop FLDK-1, a potent and selective first-in-class drug for the treatment of inflammatory bowel disease. For this, the University of Barcelona has obtained funding of 258,149 euros in the framework of the public-private collaboration project line, call 2023, financed by the Ministry of Science, Innovation and Universities, the State Research Agency and ERDF.