Eyevensys Non-Viral Gene Therapy for Ocular Diseases: Interview with Patricia Zilliox, CEO of Eyevensys

Eyevensys, a clinical-stage biotechnology company based in France, has developed a method to perform non-viral […]

Eyevensys, a clinical-stage biotechnology company based in France, has developed a method to perform non-viral gene therapy in the eye, with the aim of treating ocular diseases. The system uses ocular electrotransfection to deliver therapeutic genes into the eye. Consisting of an ocular device and an electrical pulse generator, the system can deliver DNA plasmids into the ciliary muscle. The idea is that the transfected cells in the eye allow for sustained local production of therapeutic proteins, which can then produce effects in a variety of structures in the eye, including the retina and choroid.
To date, the company has tested its system in treating non-infectious uveitis, an inflammatory condition in the eye that can lead to vision impairment. One of the major cytokines involved in the ocular inflammatory process is tumor necrosis factor alpha (TNFα). The treatment involves delivering genetic material (a plasmid) that encodes for an anti-TNFα protein.
On October 10th, Eyevensys presented results from its phase I/II clinical study of its gene therapy in non-infectious uveitis patients at the Annual Ophthalmology Innovation Summit in San Francisco. The trial included patients with late-stage non-infectious uveitis, and those treated using the gene therapy showed improvements in vision and macular edema up to 6 months after just one treatment.
The treatment did not elicit any serious adverse effects in the patients, and overall it was well tolerated. Eyevensys is also investigating the potential to deliver genes that encode for other proteins with utility in a variety of ophthalmic diseases, such as glaucoma and retinitis pigmentosa.
Medgadget had the opportunity to talk to Patricia Zilliox, CEO of Eyevensys, to discuss the technology.
Conn Hastings, Medgadget: Please give us an overview of the limitations of current treatments for ocular diseases.

Patricia Zilliox, Eyevensys: We see four key treatment approaches being used now for retinal diseases, and each of these have a variety of limitations, but some of the main issues are that treatments have a limited duration of any positive effect, they require frequent readministration or ongoing medical or lab monitoring, and in some cases there is a lack of full retinal exposure or poor ocular bioavailability of the treatment.

Our Electrotransfection System technology offers a long duration of protein expression, which keeps administration to a minimum. It’s also minimally invasive, so there’s less potential for an eye injury or any ocular side effects. We do this with non-viral vector plasmids, which can encode a variety of therapeutic proteins with a low risk of immunogenicity, so it’s less likely to generate an immune response.
Medgadget: Please give us some background on the Eyevensys non-viral gene therapy system. How does the system work?
Patricia Zilliox: Our technology is based on a two-part system, an Ocular Device and a Pulse Generator. We use these in tandem to deliver the DNA plasmids encoding for therapeutic proteins to the ciliary muscles. Once inside the ciliary muscle, the muscle becomes a production site, like a biofactory, and can start to produce the protein, and then these proteins travel to the retina at the back of the eye. We’ve validated this model in animals and observed efficacy in these pre-clinical studies for the treatment of uveitis, wet AMD and retinal degeneration.
Medgadget: What is it like for patients to undergo gene therapy using the system?
Zilliox: For patients, knowing that they can treat these conditions in a minimally invasive way can be a relief, especially when considering alternatives, such as ocular implants, or a treatment requiring multiple administrations. Additionally, we are really trying to improve therapeutic outcomes for these conditions, so the fact that patients are seeing continued visual improvement means that quality of life continues to improve for these patients, too, which is an important goal for us. This system, however, is not able to correct or edit gene mutations.
Medgadget: How long are the delivered genes expressed in the treated tissues?
Zilliox: In our phase I/II trial studied patients with advanced stages of disease, and based on the data from part 1 of the study, we saw therapeutic protein expression up to 8 months after treatment.
Medgadget: Please give us an overview of the recent phase I/II trial of the treatment in non-infectious uveitis.
Zilliox: The data we just presented are from part 1 of our phase I/II clinical safety study for EYS606, which is a non-viral vector that encodes an anti-TNFα protein. We had nine patients in the U.K. and in France that presented with late-stage non-invasive uveitis. We had three patient cohorts with three patients each with different dose levels for the three cohorts.
At the lowest dose, we observed more than 10 ETDRS letters of improvement in one patient, which is significant in uveitis, which can ultimately cause blindness. The highest dose resulted in two participants seeing +12 or more ETDRS letters of improvement. Based on these results, we are eager to move forward to the next part of this trial.
Medgadget: How do you see this type of technology developing? Are you planning any other trials for different ocular diseases in the future?
Zilliox: We expect to continue to develop this technology beyond just uveitis and potentially to apply it to other therapeutic targets. We have a robust preclinical pipeline that is looking at retinitis pigmentosa, dry AMD, and other conditions, and we are confident that the technology can handle so much more. We have an extensive patent portfolio on the electrotransfection technology as it applies to the eye, so there is much more to come on the R&D side from Eyevensys.
In terms of upcoming trials, we expect to stay focused for the moment on uveitis, so we’ll be continuing our clinical trial work with EYS606—we have part 2 of the phase I/II trial in the EU that we are set to launch, that will confirm the safety of the maximum tolerated dose and give us an initial sense of efficacy. We are also preparing to launch a phase 2 trial in the U.S. for the same therapy in development. We did receive IND clearance from FDA late August 2019. In this case, we will be testing our therapy in development against active chronic non-infectious uveitis, and we will look at administration closely, and the efficacy of one administration compared with two.

Original Article: (https://www.medgadget.com/2019/11/eyevensys-non-viral-gene-therapy-for-ocular-diseases-interview-with-patricia-zilliox-ceo-of-eyevensys.html)