Public Funding for EVOX Therapeutics Limited

Argininosuccinate lyase (ASL) deficiency is the second most common urea cycle defect. In the most severe form of the disease, symptoms present early in the new-born period progressing to coma and consequent death if untreated. Later presentation can present with aspecific neuro-disability. Patients are managed by pharmacological and dietary intervention, but ultimately patients require a liver transplantation for long-term survival. However, liver transplantation is associated with its own risks, i.e., mortality, morbidity and life-long need for immunosuppression. Delivering a functional copy of the mutated genetic material or protein offers an attractive alternative to liver transplantation. Exosomes are emerging as a highly effective drug delivery system. Evox Therapeutics Ltd (EVOX) has developed a 'unique' exosome delivery system that can carry biopharmaceuticals across the blood brain barrier to treat neurological diseases. Thus, EVOX uses its proprietary technology to genetically engineer cells that produce bespoke exosomes, ~100nm extracellular vesicles, that can carry proteins, small molecules or various forms of RNA. Moreover, these engineered exosomes have protein decorated surfaces that enables entry into the brain across the blood brain barrier. EVOX has several programs in its pipeline for developing exosome-based therapeutic interventions to treat lysosomal storage disorder and importantly the neuro-pathology of these diseases, and the ability to alter the exosome membrane allows targeting precisely some organs or cell types and to cross the blood-brain barrier when administered in the bloodstream. EVOX's in-house R&D programs and commercialisation efforts are led by a team of over 2 dedicated scientists and field experts with a passion for developing novel therapies that will transform the treatment and management of numerous CNS diseases with significant unmet medical need. Innovate UK Strand 1 award will enable EVOX to test its ASL protein-enriched or mRNA-enriched engineered exosomes in vitro and in vivo in collaboration with UCL. Tests will be carried out on human hepatocyte cell lines _in vitro_, ASLD-derived cells differentiated in hepatocytes and neurons to assess the efficacy _in vitro_, and in mice with/without ASL deficiency to test the optimal dose range, the duration of effect and frequency of re-injection and distribution across the body. This will provide pivotal data to enable further development for first-in-man clinical use.