[creativ_pullleft colour=”light-gray” colour_custom=”” text=”Episode 116″]
EyeGate CEO Stephen From reports positive results of Phase Ia/IIb trials of EGP-437, regulatory progress for its Ocular bandage gel, and potential fundraising plans.
Tom Salemi: Welcome back, OIS listeners. This is Tom Salemi. Hope you had a great holiday break. I did. I had a great time with the family. Spent a lot of time in the car, but got to visit Washington, DC and take in the sights down there. So it was a wonderful time and a wonderful holiday. I hope you enjoyed yours as well. But we are back at work. And we are going to lead off this OIS Podcast season with an interview that I did back in December with Stephen From. He is the CEO and President of EyeGate Pharma. And they’ve had some great news on the clinical side. We, unfortunately, since the interview was done, have seen some negative news on later stage clinical trials, both from Ophthotech, which we covered in the last Podcast we did of 2016, and just this week, Innotech. We’ll get to the Innotech story and also the Encore Vision story in the future. We’re going to try to cover those on the Podcast, but we wanted to get this interview that I did with Stephen back in December out to you in the new year. Again, EyeGate had some real positive news released on December fifth. It has a third stage of its phase 1B2A trial assessing its lead product candidate. It’s EGP437. It’s for the treatment of ocular inflammation and pain post-surgical in cataract patient. So they had some positive news; also had some other news in its pipeline that Stephen From will cover, and talked a bit about financing that it received in 2016, both in a deal from Valeant and also from the DOD. But also Stephen discusses the company’s capital needs going forward. So I hope you enjoy this visit with Stephen From of EyeGate Pharmaceuticals. And again, thanks for returning back to the OIS Podcast. We certainly missed you and look forward to bringing you more tales of innovation going forward. But let’s get into this interview with Stephen From.
TS: All right, well, Stephen From, welcome back to the Podcast.
Stephen From: Hi, Tom, thanks for inviting me.
TS: Oh, very happy to have you back. This is likely our last Podcast of the year, so it’s nice to end on some positive news. You and I connected for the first time earlier this year, I think back in February on the Podcast. And at the time, you had gone public and you had a deal with Valeant that you’d inked, and you had some clinical trials to look forward to. Now we’ve got some early results, at least, to talk about today, specifically the phase 1B2A trial assessing your lead product candidate, EGP437 for the treatment of ocular inflammation. Take us back to the beginning for a moment and tell our listeners a little bit about EGP437.
SF: OK, definitely, Tom. So EGP437. It’s our formulation of a corticosteroid, dexamethasone phosphate, and it was formulated specifically so it could be delivered through our platform, which is based on iontophoresis. So a really nice way to noninvasively deliver a large bolus or a lot of drug into the eye very quickly.
TS: And in this trial that you’ve got news on from this week – well, let’s get into the trial. It’s a phase 1B2A trial, again, assessing it as a treatment for ocular inflammation. Tell us a bit about the trial. How large was it? And what were the parameters of the trial?
SF: Yeah. So the total size was 80 subjects that were enrolled. And really what we’re trying to understand here is what was the correct dose and dosing regimen using the platform. You know, one of the things when you have a drug delivery system, even if it’s the same drug you’re delivering, if it’s to a different patient population, you have to really play around with all the different variables to understand what’s the best or correct method to deliver. And so although we’re in phase 3 for anterior uveitis, going into a new indication, even with the same drug/device combination, requires doing some initial work to understand what’s the correct dose and regimen to be using. And that’s what this study was all about. So what we did was we did a lot of little cohorts. So there were 80 subjects enrolled, but there were 8 different cohorts, so ten subjects per cohort. And that allowed us to try different – so with iontophoresis, the two main variables that we applied are time and current. And so the combination of those two allows a lot of different variables or different – call it milli minute, dosages for iontophoresis. So that’s why we had eight different arms with the study.
TS: And who were the patients? They had – had they just undergone cataract surgery? What was the population like?
SF: Yeah. So it was just patients that had just undergone cataract surgery, and as it’s dexamethasone, we’re looking to mitigate their inflammation and pain post-surgery. So if you can remember back from our first Podcast, the iontophoretic device is a cup that sits on the surface of your eye, and it’s donut shaped, so it sits on the sclera, the white portion of the eye. And that gets attached to a lead which gets attached to a small-hand-held generator. OK. So the way this study was set up is right in the actual surgical suite – although it doesn’t have to be in the surgical suite – but post the surgery, you get your first treatment with the applicator. OK. And then there would be subsequent treatments and follow up visits if required.
TS: So how long did this trial go on for?
SF: So we’ve been – I think we’ve been working on this trial now for I think ten months. About ten months. We did it in tranches. Although there were eight cohorts, we started with a tranche – we actually started with one cohort just to see how it would work, to set a baseline. And then we went and established an amendment to that protocol with three different cohorts, and then we did it again with another additional four cohorts. And so that’s how we evaluated after each sort of stage. We did three stages that added up to the eight cohorts. And we finally got to the end here, and we’ve got two arms that look really great, and we want to move those forward into a phase 2b study.
TS: And how did you measure the results? What were the positive findings that have you encouraged?
SF: I mean the main thing, it’s very similar to anterior uveitis. You’re looking at cell counts, right? So anterior cell chamber count, and you do this through a slit lamp. And so what we’re looking for is a zero cell count at day 14. So two weeks post the surgery, which happens to be the same endpoint for anterior uveitis. And we’re also looking for pain or elimination of pain or mitigation of it starting right at 24 hours after surgery.
TS: So where do we go from here? Where does EyeGate go next with this particular indication?
SF: So we’ve tried a lot of different combinations of, as I mentioned before, the current times time. And we have two of the arms that really did well with the results. And again, we’re looking at day 14, two weeks. And we also look at day 28, which is a month end. And we’re trying to understand what percentage of the population treated have zero cells, zero inflammatory cells in the anterior chamber. And out of all of those cohorts, we chose two that we want to move forward into a full phase 2 study. And the interesting thing about these two cohorts and why we chose these two: we had a lot of cohorts do well, but these two did extremely well. And funny enough, they’re at the end of – they’re at the opposite ends of the spectrum as far as time and current goes. One’s a really high dose, actually gets applied – the current gets applied over a four-minute period. And the other one’s actually a really low dose where the treatment’s done over 90 seconds or a minute and a half. Yeah, so it’s really interesting. Where you think there’d be a nice little bell curve or something, we didn’t see that. We actually had good results with a low dose and good results with a high dose.
TS: Any speculation as to why?
SF: Well, you know, yeah. I think it’s because even though low dose puts in so much drug that it doesn’t matter that you’re going to a much higher dose. I think you only need so much drug, and going to that much higher current actually is putting in more than is actually needed.
TS: Interesting. So what is the timeline for the next trials you’d like to perform on this indication?
SF: So we’re looking to get this started, I’d say, late Q1 of 2017. You know, putting the protocol together, we’re going to get all the KOLs together, finalize a phase 2 protocol, and submit that to the FDA, and do all the other things to initiate the study. So it’s going to take us about three, three and a half months to do that. So I’m looking towards the end of Q1 to get the first patient enrolled.
TS: Wow, that’s exciting.
SF: We’re excited about it too, because you know, uveitis has been really exciting for us. It was a great proof of concept. But to be able to extend that same product into another indication is, I think, really beneficial for us.
TS: Yeah, we were about to say the same thing. I was going to say it was nice to have two products in the pipeline; let’s look a little further ahead. Give us an update on your uveitis program. And I read earlier this year that you secured at least some of the milestone payments that you were due in your deal with Valeant. Can you give us a little detail on that?
SF: Yeah. So we have it structured so that as we do the development, we’re able to get some milestone payments. So based on where we are with either enrollment or on some of the other work that has to get done in order to get ready for an NDA filing, we’re able to collect some milestone payments. So it’s a great structure for a small company like us because it’s always nice to be able to increase your cash flow. So we’re happy that that happened. And I hope to be able to have another one in the near future.
TS: So the release reads that you’re eligible to receive milestone payments totaling up to 32.5 million. So we haven’t reached that point yet?
SF: No, we haven’t. We’re nowhere near that yet. So but the point is the beauty of it is it’s a lot of these times, the deals end up being more back ended. And that typically is the case. But we wanted to be able to structure this so that we could manage our cash flow a little better, and they were willing to accommodate us on that, which was nice of them.
TS: And what is the status of the uveitis trial?
SF: So we’re still enrolling. We have not publicly disclosed where we’re at with enrollment.
SF: And I would say for – you know, there’s 250 subjects we’re looking to enroll, which for anterior uveitis is a large study. And the enrollment’s going well. I see us finishing the enrollment sometime in the first half of next year.
TS: Hey, everybody, Tom here. I just want to take a quick break to let you know that we have a write-up in our Eye on Innovation Newsletter this week. If you’re subscribing to the Podcast, but don’t get the Eye on Innovation Newsletter, I suggest you go to OIS.net, just provide us your email. That’s all we need, and we’ll send you the Eye on Innovation Newsletter to your inbox. This week, Michael Lachman of IQ research, whom we partner with to run our OIS Index, gives a rundown of the first order of the OIS Index. And obviously it was a tough one for ophthalmology. We won’t soften the words. We’ve had some difficulty with clinical trial results. I mentioned Ophthotech earlier on. But some other companies have had some difficulties, and some companies have had some successful quarters as well, Ocular Therapeutics being one of them. So I suggest if you do get the Eye on Innovation Newsletter, take a look at that article by Michael. He did a great job. And if you don’t, just go to OIS.net, provide us with your email, and you’ll get that email newsletter sent directly to your inbox, and you’ll be able to see all the information about the OIS Index. Now back to this interview with Stephen From of EyeGate.
TS: I was going to ask in both populations, is one easier to secure patients than the other? Or are they both difficult to sort of find the right people who fit correctly?
SF: It’s really easy compared to – so uveitis and cataract surgery the opposite.
SF: So having gone through uveitis for so long now, going to cataract surgery is kind of like a breath of fresh air, there’s so many of those patients. So it’s very quick to enroll.
TS: Is 250 a large trial for uveitis? I mean as you indicated, it’s a lot of people. But is the number of patients required for the trial, is that in line with other trials in the space?
SF: That’s a good question. And I think for phase 3 it is in line, but it’s not a large patient population. So depending on what your inclusion-exclusion criteria, you know, your visit schedule looks like, it can be a little bit burdensome to try and enroll. Having said that, though, I think our enrollment, you know, it’s a little bit behind what I wanted it to be, but it’s not that far off.
TS: And how many sites are you using for that trial?
SF: Well, again, because it’s a small patient population, you know, there’s less than 200,000 incidences of this a year in the States, we have 50 sites up and running right now, all in the US.
SF: And again, we’re a small company, so that’s a huge endeavor for us to take on.
TS: I would understand that, sure. And finally, for EGP437, you also had noted macular edema as an area of interest. Any progress in that space?
SF: So we have stopped – well, we finished the enrollment. We completed the enrollment in that 1B2A study. And we got great results from that, and we’re really right now assessing along with the KOLs where we do go with that. Unfortunately for us is we don’t have a lot of resources yet, so we kind of have to pick and choose our battles and where we think we can get the most value in the quickest timeframe. And we wouldn’t be able to do both cataract surgery and macular edema right now at the same time. Cataract surgery is a lot quicker and easier to enroll.
TS: That makes sense. Is it likely – I know you’re a public company, so you have to be careful of what you say. But it’s an interesting problem to have, to have one drug that can be applied to many different areas, and one of them just sort of probably is a path of least resistance. How do you sort of weight where you’re committing your resources? It’s a question a lot of early stage and smaller companies face. But is it sort of a daily question as to we’re going to divert resources here or there? Or is there a longer range plan that you drew up a time ago, and you’re sort of sticking to it, and the results are fitting what your expectations were?
SF: Yeah, well, that’s a loaded question. Data is coming at us almost daily, and you have to be ready to be very flexible on changing whatever it is you’re doing based on the data that comes in. It’s interesting because I’m getting ready for a board meeting next week, and I just had lunch with a fellow colleague that’s at a competing company in ophthalmology in this area. And I told him I’m getting ready for a board meeting next week, and he tells me he gets his board book out three weeks before. And I said, If I did that, I’d be out of dates by the time I got to my board meeting. That wouldn’t make sense. But we’re always looking for creating the most value we can for the investors. And that’s one of the reasons why cataract surgery makes the most sense right now, as well. Even with the eye drop that we just had a meeting with the FDA with. I mean that’s another one that we’re trying to focus on because we very quickly, I think, can create some value for the company.
TS: Is this the Ocular Bandage or is this something else?
SF: Yeah. So it’s called the Ocular Bandage Gel, which is based on cross-linked hyaluronic acid. And we just had a formal meeting with the CDRH arm of the FDA, and we’re trying to understand if we’d be eligible to go down the 510K de novo path, and they gave us the thumbs up on that. Which is huge –
TS: Right, that was last month, correct?
SF: Yeah, yeah, that was just recently, yeah. So we’re very excited about that because this is going to be a prescription eye drop and it’s going to have a label on it that’s acceleration of re-epithelialization of the cornea. So it’s like acceleration of wound healing. So that’s really a big, huge win for us to be able to do that.
TS: So how dose that change your other plans with your other trials? Or does it?
SF: Well, luckily it doesn’t because you know, going down the device route is – I don’t want to say it’s simpler, but it doesn’t cost as much to do that. So I think that’s one of the reasons why I acquired – so that came from a company we acquired called Jade Therapeutics. And having the ability to have one of the – so this is one of the first prescription eye drops that will exist in the United States, and it’ll be the first eye drop that’s going to have a label that says acceleration of re-epithelialization of the coronary, OK. So there’s nothing out there right now. You know, if you get a wound on your cornea, you can have an antibiotic and a bandage contact lens put on it, but to actually have something that can accelerate the closure of the wound? You know, that doesn’t exist. We have amniotic membranes and so forth for more severe abrasions, but for just normal epithelial defects, to have something that can close the wound faster, you know, that I think should be ideal for a lot of optometrists and ophthalmologists.
TS: And what is the – it’s a 510K. Is it a 510K de novo or is there a predicate that you can point to that is going to clear the lane for you, so to speak?
SF: Yeah, so there’s no predicate, so it’s a de novo. So that’s one of the reasons why we wanted to have a formal – we had a pre-submission meeting with the FDA to discuss with them if we could be eligible to go down the 510K de novo path. And they’ve agreed with what we submitted, and so they’ve given us a clear green light path to go down through a 510K de novo. And also to be able to – they gave us the path on how we can have this label that allows us to say that we accelerate re-epithelialization.
TS: So what would a likely timeframe for that trial, and you would hope, approval someday? What would that be? Do you see that being measured in a year or two, or more?
SF: No, I think a year actually. We’ll be done all our clinical work by the end of next year. In fact, we’ve just finished enrolling in our first in man study, and it was an open label for us to just learn about the product in the clinic. And we’re going to get started on our next study late Q1. And then we’ll do our pivotal study second half of next year.
TS: And are you operating – do you have your staff within EyeGate? Are you using sort of a virtual model? How are you managing these multiple programs?
SF: So we’re 12 FTEs right now. And I think, based on all the good data that we’ve just had in the last quarter, we actually are going to need to ramp up a little bit for next year because we have a lot of clinical work ongoing next year. So we’re actually looking to hire a little bit more depth for our clinical operations team. But you know, we use CROs and we outsource a lot of work.
TS: Interesting. How many people do you think you might bring on board?
SF: Well, definitely bringing on three more people for clinical operations.
TS: That’s great.
SF: So right now we have a CMO and two clinical operations, people that handle the studies for us, along with CROs.
TS: And would they be dedicated to only one of the projects, or do you see them working on all three?
SF: Those people coming in are going to be – they’re going to have to be able to work on all three.
TS: That would make sense.
SF: So I mean there’s even more than that. So we’ve got uveitis phase 3, we’re going to have cataract surgery phase 2 with the lead in to the phase 3 by the end of next year. We’re going to have the Ocular Bandage Gel next study and then the pivotal study. And then with the Ocular Bandage Gel, we’re actually doing a study in another type of epithelial defect, the one we’re working on right now. So we’re going to have multiple studies ongoing for both the iontophoretic platform and the hyaluronic acid platform. Which is a good place to be, so Tom, think about it this way. By the end of next year, we’re looking at filing an NDA for uveitis, phase 3 for cataract surgery, filing a 510K de novo for the cross-linked hyaluronic acid, and finishing the clinical studies for the extended indications for the hyaluronic acid Ocular Bandage Gel. So we’re hoping to be in a lot different position at the end of next year than we are today at the end of this year.
TS: That’s outstanding. And how do you stand for financing? I know you got I think the second part of a phase 2 SBIR grant from the Department of Defense, close to half a million dollars.
SF: Yeah, we did. Yeah. So half a million dollars is great, but it’s never enough, nowhere near enough to do what we’re trying to do next year. So our balance sheet is not as strong as I’d like it to be, so I do see us having to go out in the first half of next year to do a fund raise. I’m hoping to do, you know, I’m hoping to do a good size. The next fund raise I do I would like it to be able to cover up all that work we’re doing. So I have enough money to do all of the filings that I need to for what’s in the clinic today.
TS: Well, that’s a lot of programs to put in the Power Point. So I think it should be a compelling sell.
SF: Yeah. You know, the one thing that I need to start doing now is actually talking a lot more about the Ocular Bandage Gel. You know, up until a month ago, I wasn’t quite sure about the clinical pathway, wasn’t quite sure what indication, what the label would look like. Now we’ve got all that behind us and we’re actually going to have top line data for the first in man study probably within the next three of four weeks.
TS: Wow. You going to take any time off for the holidays at all over there?
SF: Yeah, I plan on taking a few days off. But then I gotta get ready for next year, right?
TS: That’s great. Well, there’s so much going on, I suspect we’ll have you on the Podcast again next year when you’ve got some more progress to report. I appreciate you taking some time today.
SF: Yeah, perfect. I appreciate it too, Tom. Thank you very much.
TS: Well, that’s a wrap. Stephen From, thanks for joining us on the OIS Podcast and for bringing us up to date on EGP437, and your other news as well, the Ocular Bandage sounds particularly hopeful. So we know some of this is in the early stages, but still, it’s great to hear positive results in the ophthalmology sector. And we look forward to following EyeGate’s success going forward. Thank you also to our OIS Podcast listeners. Again, it’s great to be back and to bring you these stories. These are your stories; this is your sector; OIS is your forum for telling them. So if you think there’s a subject I should be covering that I’m not, feel free to reach out. If you think there’s someone I should have on this show that I have not, again, feel free to reach out. You can email me directly. My email is Tom@Healthegy.com . Healthegy is spelled HEALTH followed by the letters EGY.com. Healthegy is a multimedia provider of events and content centered around healthcare, and in particular ophthalmology. We’re eager to tell the stories of successful innovators in healthcare. So do reach out and let me know who I should be talking to and what we should be talking about. And that’s a wrap again for this OIS Podcast. Thanks for rejoining us in 2017, and tune in next week for another great tale of innovation. Take care, everybody. Happy new year.