AGTC Pursues Gene Therapy on Multiple Tracks

AGTC is pursuing six different genetic treatments for four different retinal diseases, and expects to have clinical data from its Phase I trial of its lead candidate for treatment of X-linked retinoschisis later in the year, company chief business officer Stephen Potter reported at the “Paying for Breakthrough Eye Therapies” session at OIS@ASRS.

“From our standpoint, all the diseases that we’re going after have no current therapies today, and there are over 200 monogenic diseases of the eye that can cause vision impairment,” he said.

AGTC is developing its lead agent, RS1, in a partnership with Biogen. It has also partnered with Biogen in developing RPGR, an agent for X-linked retinitis pigmentosa, for which it expects to file an IND in 2017, Potter stated. AGTC is also working on two agents for achromatopsia, one of which is entering Phase I and the other is in the IND-enabling phase; and two for age-related macular degeneration (AMD), both of which are in the proof-of-concept stage.

Potter explained the mechanism for AGTC’s biological agents. “We can use the virus to carry the payload into the cell, and then once it’s there it uncoats the cell, releases the DNA, the gene of interest, forms an episomal structure, and then uses the cellular machinery to create the protein that we’re interested in,” he said.

The goal is to achieve “long-term protein-replacement therapy with a single injection,” Potter added.
AGTC is also branching out from ophthalmology and into otology to target genetic defects in hearing, he said.

Participant:

Transcript:

Stephen Potter: It’s a pleasure to be here, and I know that I’m standing between you and learning how to pay for all these things. So I will be pretty brief, and if anybody has questions later they can certain ask. We are a public company, so read our forward looking statement if you want to invest. I’m going to start with just a quick overview of the company. It’s a University of Florida spinout that is focused on genetic therapies for inherited retinal diseases. Our lead indications are focused on gene therapy programs to treat those patients with blinding diseases. We’ve also recently announced that we’re also going to go into otology to look at genetic defects in hearing. We are a company that we believe has very strong capabilities within the gene therapy space. One of the things that we argue is you have to custom design each genetic therapy for the indication that you’re going after. So the capsid, the promoter, the gene, the manufacturing, the delivery and the like all have to be custom designed in order to make an effective therapy. We have an extensive IP portfolio across all these elements. We have a broad pipeline, which I’ll show you later. And we have a very significant and successful relationship with Biogen to help us develop a couple programs. So I’m not going to go into the science, but I think this cartoon is intended to show that we are taking advantage of what nature has figured out. We can use the virus to carry the payload into the cell, and then once it’s there, it uncoats, it releases the DNA, the gene of interest, forms an episomal structure, and then uses the cellular machinery to create the protein that we’re interested in. So essentially what we’re trying to accomplish here is long term protein replacement therapy with a single injection. And there are certainly animal models now that are going at least a dozen years. So the promise for long term therapy is very real. So I don’t need to tell this group why ophthalmology is an interesting place to be. But from our standpoint, in all the diseases that we’re going after have no current therapies today, and there are over 200 monogenic diseases of the eye that can cause vision impairment. And we all know that people fear loss of vision almost as much as death, so there’s an enormous opportunity to make a real difference to patients. One of the nice things about the eye as well is that as we go into these orphan eye diseases, there are an awful lot of animal models that capitulate the genetic disease. The clinical endpoints are well understood, it’s easy to put together a clinical trial program. And importantly, gene therapy has reached the point in time where the safety of the vector itself is pretty well understood. So it’s really now down to can we deliver the right proteins to the right place at the right time and show a therapeutic benefit. So by way of example, one of our lead programs is something called X-Linked Retinoschisis. And if you look at the left hand side about halfway up, those green slides, you see on the left hand side is the normal retina. And next to it is what happens with XLRS. You see this sort of delamination of the retina and the RS1 gene is essentially a structural protein that holds things together. So if we’re able to put the protein back in there, we ought to be able to get the retina to reassemble, come back to a normal structure, and hopefully help these patients. Now these patients have terrible vision. They have difficulty reading. They even have difficulty recognizing people’s faces. So it’s a really debilitating disease. As I said, we’ve got good animal models. There’s a favorable regulatory environment, and the clinical program is pretty straightforward. Endpoints: the nice thing about ophthalmology is the endpoints are pretty clear. Obviously for the patient, they want to be able to see better, so visual acuity and visual field are the things that we’re focused on the most. But we also are looking at additional endpoints for support. So an ERG can show whether the electrical connections are improving. Essentially gets to mechanism of action. If we are able to get the retina to come back together again, and then obviously if we can look at the schisis cavities and see if they’re getting smaller, that would support the idea that the protein is working. So this is our pipeline. XLRS is in the clinic. Achromatopsia B3 is in the clinic. We expect A3 to be in the clinic shortly, and XLRP hopefully by the end of the year or early next year. So we have a number of programs to push forward. Each one is a different disease, a different indication. And then a number of different research programs, including AMD. See if we can figure out places where gene therapy could provide a unique solution to solving some of these problems. And we obviously have ongoing research for additional indications. I think that’s it. Thank you.