Syncona has the finishing line in sight with $20m gene therapy investment

After years of disappointment, gene therapy has finally found its niche. Or so believes Syncona, the Wellcome Trust’s evergreen fund, which has invested £12m ($20m) in an Oxford University spin out that is working on a treatment for an inherited form of progressive blindness.

The cash should be enough to take the therapy all the way to the market, in the most severely affected patients at least, says Chris Hollowood, a partner at Syncona. Considering the track of record of companies that have attempted to bring a gene therapy to market this is a bold investment move by the fund, only its second since it was set up in 2012.

NightstaRx is the company that has been set up around the technology, developed by Professor Robert MacLaren at Oxford’s Nuffield Laboratory of Ophthalmology. His lead programme is in choroideraemia; the gene therapy uses a small modified virus to deliver the correct version of the mutated gene that causes the condition to cells in the retina of the eye.

They can then start encoding for the Rab-escort protein 1; the absence of this protein causes the slow degeneration of the choroid and retina and resulting vision loss. Many sufferers – the condition is X linked so they are mostly males – are registered blind by their 50s. It is thought to affect 1 in 50,000 people.

Proof of concept

Earlier this year Prof MacLaren published data in The Lancet from the first six patients enrolled in a single arm phase I study. After six months all showed improvements in vision; the most marked improvements saw one patient gain two lines of vision, another four lines. The patients recruited were at an advanced stage of the disease, when spontaneous improvements in vision are highly unlikely to happen.

Gene therapy has also shown an impact in another inherited retinal dystrophy, Leber congenital amaurosis 2 (LCA2), and this has provided “proof of concept” for this technique, Mr Hollowood says. Encouraging work in this area done by The Children’s Hospital of Philadelphia was last year spun out into a company called Spark Therapeutics, with $50m of venture capital. It is running a 24-patient phase III study with a similar gene therapy that seeks to correct the RPE65 mutation that causes LCA2; data are due next year.

Mr Hollowood maintains that after years of figuring out the best applications for gene therapy the eye has emerged as a “sweet spot”.

“It’s a compartment within the body, so the virus won’t escape. You have to treat a relatively small number of cells to get an effect, so that makes it very amenable to gene therapy, and in term of dosing, the amount of vector you need to produce is very small,” he tells EP Vantage.

As such, Syncona believes that its money should be enough to establish market-ready manufacturing, run a phase III study and get the product to market in the US and Europe.

“It’s an orphan indication, a severe disease, and the phase I data showed outstanding efficacy. Those ingredients allow us to believe it can get registered.”

Pushing on

Grant applications have already been submitted to the Medical Research Council to fund a phase II study in earlier stage patients, but NightstarX wants to push on with a phase III study in late-stage patients at the same time.

“Late stage patients are about to go blind. Given their severity, we should be able to put pivotal trial around that, and get a fairly expedited route to market,” Mr Hollowood says. What that phase III might look like, or how long it might take, has yet to be determined.

From Syncona’s point of view, NightstaRx is exactly the sort of proposition that the fund is looking for, he says.

“Our strategy is defined by looking for opportunities where Syncona can be a significant investor in the business to the point of profitability. NightstaRx has a therapy that we believe can get registered with money we can provide, without necessarily needing a partner downstream,” he says.

Of course, this technology still needs to be proven in larger studies and success would be a notable achievement for the tainted and still high risk gene therapy space. If Syncona can also show that early stage investors can make money from their high risk bets, this will be another milestone of note.

Study Indication NCT ID
Phase I study of vector AAV.REP1 Choroideremia NCT01461213
Phase III study of vector AAV2-hRPE65v2 Leber Congenital Amaurosis 2 NCT00999609

To contact the writer of this story email Amy Brown in London at or follow @AmyEPVantage on Twitter

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