For the successful translation of RNA technology into a drug, it must meet key requirements, including cell-type-selective delivery and pharmacological activity before moving into clinical development.
Our significant pre-clinical development capability enables multiple shots at goal for identifying successful future programmes. From this engine we identify therapeutic candidates that we believe have potential in the clinic.
All indications that we identify as potential targets for our technology go through our process of proof and selection, often working with collaborators from world leading academic institutions. This includes pre-clinical proof-of-concept, chemistry, manufacturing and controls development, non-clinical safety assessment and clinical trial design.
Current pre-clinical programmes
Messenger RNA (mRNA) delivery
Rather than decreasing gene function, mRNA delivery is an exciting new method of introducing messenger RNA activity into the cell, in conditions where this is of therapeutic interest. This way improved gene expression is achieved without having to make permanent changes to the genome, thus avoiding safety concerns.
We have already demonstrated our ability to deliver functional mRNA in vivo and are actively exploring new opportunities in this space.
MicroRNAs (miRNAs) mediate natural cellular mechanisms which exist to regulate gene expression. Endogenous and exogenous miRNAs are incorporated into the RISC-complex within a cell and prevent target protein production by mRNA cleavage or translation inhibition.
We have established that our delivery platforms are suitable for miRNA delivery and continue to investigate the potential applications of this exciting new class of RNA therapeutics.
Atu111 is our RNAi therapeutic candidate focused on vascular stabilisation to reduce vascular leakage within the lung. It uses our DACC delivery system and the siRNA payload targets Angiopoietin 2, a widely researched mediator of vascular permeability in inflammatory conditions. Atu111 is currently being tested in lung indications.
So far, pre-clinical data has been generated in mouse and non-human primate studies (Lung-Targeted RNA Interference Against Angiopoietin-2 Ameliorates Multiple Organ Dysfunction and Death in Sepsis, Stiehl et al, Crit Care Med, 2014).