Overcoming Pitfalls During the Development of mRNA Therapies From Bench to Bedside

The promise of mRNA therapies came into the spotlight during the COVID-19 pandemic with the rapid development and approval of two mRNA vaccines (Moderna’s Spikevax and Pfizer/BioNTech’s BNT162b2), which proved themselves to be at the forefront of the vaccine race to stop COVID-19. At the same time, mRNA vaccines for other infectious diseases took off in development, as mRNA therapeutics across a range of modalities also prospered in areas such as autoimmune, rare diseases and oncology, and each came with their own set of unique and inherent challenges during preclinical to clinical development. One of the most common and obvious pitfalls during the development of mRNA therapies is projecting not only how the downstream expressed products will work in a disease setting, but also how the mRNA constructs will express in different preclinical species and in humans. Understanding mRNA expression and downstream product activity is needed to set safe and efficacious doses; and designing proper preclinical and clinical studies is a requirement to understand the mRNA and expressed product kinetics, as well as the pharmacology. This talk will focus on the challenges of developing mRNA therapies from bench to bedside with examples of how quantitative modeling has allowed for the accelerated development of such therapies to move successfully through the pipeline, overcoming development challenges and setting a framework to the data and study designs along the way.