Pipeline

Indication:
Phenylketonuria (PKU) is a rare, inherited disorder that leads to a toxic accumulation of the amino acid phenylalanine in patients. PKU is caused by an autosomal recessive error in the phenylalanine hydroxylase (PAH) gene, which results in a deficiency of the enzyme needed to break down phenylalanine. Untreated PKU leads to irreversible intellectual disability, microcephaly, motor deficits, eczematous rash, seizures, developmental delay and psychiatric symptoms.

Unmet need:
The worldwide prevalence is 6:100,000 (Europe 8:100,000 & Americas 5:100,000). Dietary interventions are insufficient and current approved therapeutics do not reconstitute the normal biochemical pathway​. Only 10% of PKU patients are treated with a therapeutic, therefore physicians and patients are seeking new treatment options.

Programme:
Evox is developing an exosome-delivered AAV encoding the phenylalanine hydroxylase (PAH) enzyme, which may have several significant advantages over other gene therapy approaches. Exosome-delivered AAV significantly improves cellular delivery and increases transgene expression in animals, thereby lowering the AAV dose needed. Exosome-delivered AAV demonstrates resistance to neutralising antibodies in animal models suggesting that repeat dosing may be possible.