Oxford University spin-out Evox Therapeutics has won a £656,000 ($858,000) grant from a UK medical charity to test its large-molecule delivery technology in Duchenne muscular dystrophy (DMD).
Duchenne UK wants Evox to see if it can deliver full or partial lengths of dystrophin, the protein lacking in patients with the muscle-wasting disease, using its exosome technology. Exosomes are extracellular vesicles that are used by cells to transport molecular ‘cargo’ between them, typically substances that are simply too big to cross cell membranes by other means.
The funding round will help Evox carry out preclinical studies on dystrophin-bearing exosomes, to see if the approach can be an alternative to other emerging DMD therapies that try to restore the function of the protein in muscle.
At the moment that includes already-market drugs that skip over or ignore the mutation in the dystrophin gene – such as PTC Therapeutics’ Translarna (ataluren) and Sarepta’s Exondys 51 (eteplirsen) – as well as experimental gene therapies that try to deliver a working dystrophin gene that are in clinical trials and gene-editing approaches such as CRISP/Cas9 that attempt to correct the gene in situ.
One of the big problems facing gene therapies that the dystrophin gene is long – in fact the longest gene sequence in the human genome – so truncated versions coding for ‘microdystrophins’ have to be used in gene therapies that are based on viral vectors.
Duchenne UK’s co-CEOs Emily Crossley & Alex Johnson said that Evox’s technology may also help overcome one of the problems with gene therapy, namely that patients can have pre-existing antibodies primed to respond to the viruses used to deliver the gene sequences to cells.
“They are ‘resistant’ to the virus…so the replacement gene carried by the virus will never reach its target,” they said, adding that exosomes could provide a new method for “effectively, safely, and repeatedly” delivering genetic material coding for dystrophin to muscles without this problem.
“We will conduct research to assess the potential of our exosome drug platform to deliver functional dystrophin which is missing or defective in these patients,” said Evox’s chief executive Tony de Fougerolles, who joined the company last year from Ablynx.
“This work will also allow us to explore targeted delivery of exosomes to muscle which may be beneficial not only for Duchenne patients, but also ultimately for patients with other musculoskeletal diseases,” he added.
Evox spun out of Oxford University in 2016 with £10m in seed funding, and raised another £35.5m in a second-round financing a few weeks ago.