Axovant Sciences have announced an agreement giving them the exclusive global rights to ACO-AAV-OPMD, part of the investigational ‘Silence-and-Replace’ gene therapy program for the treatment of oculopharyngeal muscular dystrophy (OPMD) from Benitec Biopharma.
Silence-and-Replace gene therapy technology suppresses mutant protein production while restoring expression of functional protein through the delivery of a combination of DNA-directed RNA interference (silence) along with a functional copy of the gene (replace) in a single vector construct. This method can be applied to various genetic diseases including autosomal dominant disorders caused by nucleotide repeat expansion.
AXO-AAV-OPMD is an investigational gene therapy that has been granted Orphan Drug Designation by the FDA and European Commission, and is currently in preclinical development, with a planned placebo-controlled clinical study due to begin in 2019. There are currently no approved products for the treatment of OPMD, which is caused by mutations in the gene coding for polyA-binding protein nuclear 1 (PABPN1), which can lead to formation of intranuclear inclusion bodies causing muscle cell pathology.. This investigational therapy is given as a single administration directly into target muscle tissue, utilizing an AAV vector to silence the mutant PABPN1 gene which causes OPMD and replacing it with a functional copy. Data from mouse models of OPMD showed AXO-AAV-OPMD provided up to 86% inhibition of PABPN1 expression, while restoring functional PABPN1 up to 63% of normal levels.
Axovant will pay Benitec an upfront payment of $10 million for rights to the AXO-AAV-OPMD program and five additional investigational gene therapy products, as well as payments tied to development, regulatory and commercial sales milestones. Benitec will also receive 30% of the net profits on worldwide sales of AXO-AAV-OPMD and tiered royalties on the other gene therapy products that result from this collaboration. “The Silence-and-Replace technology is a unique approach in gene therapy, using a single vector to suppress mutant protein production while also restoring expression of the functional protein, and could be an elegant solution to tackling autosomal dominant genetic disorders,” commented Fraser Wright, PhD, Chief Technology Officer of Axovant.