SMRT-FIT - characterisation of SupraMolecular RNA Therapeutic formulations to accelerate regulatory path to First-In-human clinical Trials

This A4I project will support Innovate-UK funding for development of a novel "**S**upra**M**olecular" **R**NA **T**herapeutic (**SMRT**) delivery system and flexible, scalable RNA-manufacturing process for the sustainable manufacture of biologic drugs. Combined, the material and process will reduce considerably the material-use and energy-costs compared to the current state-of-the-art. Specifically, the **SMRT-FIT** project will address opportunities and complexities which have arisen recently (as a result of exciting new findings) that mean an increase in the range of information will be required in support of a **F**irst-**I**n-human clinical **T**rial of **SMRT** formulations. The project will involve collaboration with the UK National Measurement Laboratory (NML) that brings world-class analytical methods and experience to provide deep characterisation of the formulations with findings presented in a format that meets the needs of regulators (such as MHRA). RNA is the medicine platform of the future with many application-types in clinical trial. RNA therapeutics are suitable for manufacture without using cell-based processes, so it is possible to take an RNA sequence to a candidate vaccine or therapeutic in weeks. A particular advantage is that same manufacturing plant can be used to produce an extraordinary array of drugs from personalised medicines to vaccines. In the Innovate-UK Sustainable-Medicines-Manufacturing Project "SUMMIT", the SMRT delivery technology is being developed alongside Centillion Technology's Biofoundry-in-a-Box (BiaB), a small-footprint, continuous-flow-based manufacturing technology that will synthesize target RNA and formulate it into SMRTs in-line. Both BiaB and SMRTs are UK innovations. The supramolecular delivery system requires no ethanol in formulation, has potential to avoid cold-chain storage and to be tuned to different applications. Combined, these technologies are suitable for global manufacture of RNA therapies. Whilst we anticipate that RNA can be used for a wide range of indications, SUMMIT's immediate use case is as a vaccine. Vaccines are used for healthy people, consequently regulatory requirements are extremely demanding, so very full characterisation will be required. Humanity has never been at greater risk of zoonotic-pathogen outbreaks, recent high-profile examples include zoonotic viral pathogens (SARS/MERS/Ebola/Influenza/monkeypox). The COVID-19 pandemic demonstrated the capacity for rapid development, high efficacy and positive safety profile of mRNA vaccines as needs arise. The focus of this A4I-CEP application is to generate methods and data towards meeting the regulatory requirements that would facilitate commissioning of first-in-human clinical trial of SMRTs. If approved, this UKRI-funded work will have facilitated a significantly more sustainable RNA delivery technology that has been developed in and commercialised from the UK.