Novel macrodiolide Immunosuppressants

ongoing

Several major unmet medical needs, such as autoimmune disorders and neuroinflammatory conditions, are characterized by aberrant Type-1 interferon production, suggesting that new drugs that specifically target this central inflammatory signalling axis could provide significant value for patients and for society. In this project, we will develop the foundation for future commercial exploitation of a class of novel macrocyclic immunosuppressants which has been shown to possess unprecedented broad inhibitory activities against several innate immunological pathways that converge on the transcription factor IRF3 linked to interferon production. Based on diverse preliminary data that span both cellular biology and chemical synthesis strategies, the planned work is aimed at securing a strong IP-position by providing novel structure-activity relation data on relevant cellular activities linked to IRF3-activity. The project will proceed to identify potential compound leads with favourable pharmacokinetic properties to be pushed forward for future in vivo experiments. The primary focus will be on ability to permeate the blood-brain-barrier (to address major neuroinflammatory conditions) and on achieving good plasma stability. Alongside the concrete experimental tasks and strengthening of the IP-position, a broader business plan and associated funding strategy will be prepared. This involves engagement of key future stakeholders and establishment of an advisory board. Overall, the planned activities serve to make the project ready for a pre-seed investment or acceptance into an biotech-accelerator program following completion of the ERC-PoC project.