Most people with an inherited metabolic disease have a mutation in genes that code for enzymes involved in metabolism. Enzyme deficiency or inactivity leads to accumulation of substrate precursors or metabolites or to deficiencies of the products of the enzyme in question. Hundreds of IEMs exist, and their symptoms, treatments, and prognoses vary widely. Although individually rare, collectively IEMs may affect about 1 in 1,000 to 2,500 new-borns. In certain ethnic populations, the rate of inherited metabolic disorders is higher.
The IEMs are conventionally classified as disorders of carbohydrate metabolism, amino acid metabolism, organic acid metabolism, or lysosomal storage diseases (LSDs), an area in which Evox is actively developing exosome-mediated replacement therapies. Most IEMs have no to very few treatment options available, with the main interventions being symptomatic disease management, organ transplantation, severe dietary restrictions or palliative care. One particular class of IEMs which lack effective treatments is the urea cycle disorders (UCD). UCDs are caused by a deficiency in one of the six enzymes or two mitochondrial transport proteins involved in the production of urea, resulting in accumulation of toxic levels of ammonia in the blood (hyperammonemia), with an estimated US incidence of approximately 1 in 35,000 live births. Among the most common UCDs are ornithine transcarbamoylase deficiency, argininosuccinic aciduria, and citrullinemia. Due to the high unmet medical need across various UCDs, Evox is actively pursuing the development of potentially transformative treatment options for these patients.