Periodic Reporting for period 2 - EXPERT (EXpanding Platforms for Efficacious mRNA Therapeutics)
Periodo di rendicontazione: 2021-03-01 al 2022-08-31
Our frontrunner application is based on activating the immune system to eradicate cancer. The field has up to now witnessed exciting clinical data in some selected applications underlining proof-of-concept. For example, ex vivo mRNA transfection of dendritic cells provided remarkable therapeutic benefit in advanced melanoma patients. These results were accomplished by one of our industrial consortium partners. Still, it does not take advantage of the promise of mRNA to be an off-the-shelf platform product, which would strongly boost the therapeutic impact.
This example motivates EXPERT partners to build innovative nanomedicine-platforms that tackle the bottlenecks for widespread therapeutic mRNA application.
EXPERT will address three major research goals that have limited mRNA therapy from displaying its full potential:
1. The ability to achieve functional target tissue delivery of mRNA by nanomedicine design
2. The capacity to efficiently reach target cell cytoplasm, the site of mRNA activity
3. The capability to circumvent adverse immune responses towards mRNA nanomedicines
In this second period, we have identified a new class of lipids that forms an integral part of the new lipid nanoparticles that show attractive biological properties. These will be our frontrunner modalities. We are assembling flanking technologies for their scalable and reproducible manufacture and provide technologies to measure their quality. Also, emerging and exploratory carriers show different biological behavior that we are trying to exploit in specific settings.
The guidance provided by EXPERT on the critical factors for successful development of formulations with this lipid is applicable in many therapeutic areas. This knowledge will benefit the new ionizable lipids and will strengthen the competitive position of European advanced therapy research and development.
For the emerging and exploratory carrier materials we have seen interesting biological performance. These could be exploited in specific disease indications. A surprising finding was that exploratory carriers could outperform the current state-of-the-art materials 1000-fold. This means that there is a clear opportunity to learn form these systems and transfer attractive properties to the established materials.
Together we are building a portfolio, where we expect the frontrunner established lipid nanoparticles to be ready for clinical trials whereas other materials have contributed to new design ideas that fill the pipeline for selected applications.