Capital Markets, and it is our great privilege to have Ocular Therapeutix joining us for a fireside chat. Representing the company, we have Pravin Dugel, Executive Chair, President, and CEO. Pravin, thanks so much for joining us. How are you doing today?
Great, Lisa, and thank you. Thank you for having us in this great conference. Honored to be here, and thank you for the invitation.
Excellent. Pravin, just to kick things off, would you like to give us a brief overview of the company and talk about where things currently stand with the pivotal trials for Wet AMD?
Absolutely. We are in great shape at this point. I couldn't be happier and prouder of the company. Really, the motto has been to execute, execute, and execute. We are delighted that we have enrolled SOL-1, which is our superiority study, well ahead of schedule. We are actually even more delighted with the quality of patients that we have. The entire company at this point is focused on a single priority, which is the conduct of SOL-1 and SOL-R. The way we look at the conduct of SOL-1, we're masked, obviously, is by looking at three important parameters. Remember that we have specifically chosen patients to be perfectly suited for each study in a bespoke manner. In this study, there are patients that are specifically chosen to fail for a superiority study.
What we're looking at is we're looking at the number of rescues, we're looking at the profile of the rescues, and we're looking at whether those rescues. We're absolutely thrilled with what we're seeing based on all three of those parameters.
Got it. You know, Pravin, I just want to touch on the fact that you've been in the CEO seat of Ocular for just over a year now, and this follows your prior tenure at Iveric Bio, which was acquired for $5.9 billion by AbbVie in 2023. So can you remind us, you know, what was it about the phase I AXPAXLI data that made you want to take the reins again at Ocular?
Yeah, so it's a great question. You know, I knew about Ocular Therapeutix when I was in Iveric Bio because we had an internal team, and I also employed an external team to look at what would be out there the best format for sustained delivery. And both of them independently came back with this. So I knew the technology was the best that was out there. To the credit of the team before us, they had secured a SPA and a very clear regulatory pathway, which we can discuss in detail. As a physician who had practiced for 30 years, I also knew the enormous need out there. At the end of the day, we're trying to solve two problems, right? The first problem is that of sustainability, and the second problem is that of a better visual outcome.
It is important for people to understand that despite how good Lucentis and Eylea are, and they are fantastic, there is literally a 40% dropout rate in this country in the first year. Those patients are all going blind, and that should be totally tragic. It is absolutely unacceptable. That is a problem that needs to be addressed with a target that is known. The second problem, which has not really received as much attention as it should, is even those patients who actually hold on to the treatment and go through the treatment, after about two to five years, almost all of them end up getting worse than baseline. That is because of fibrosis. Because of the way we treat, which is a constant oscillation up and down, the back of the eye gets thicker and thinner and thicker and thicker and thinner on a constant basis.
It's kind of like it's kind of akin to having multiple concussions, and these patients fibrose and atrophy. We really do believe that with sustained delivery, where there's a constant suppression as opposed to these periodic oscillations, there will be less of a chance of atrophy and fibrosis, and the long-term visual outcomes will be better. Again, we're trying to solve two problems here. One is that of sustainability, and the second is that of long-term visual outcomes.
Got it. Before we dive into more details, you know, just since it's topical, can you tell us about how your communications have been with the FDA in light of the recent changes? Has it been business as usual, or have you noticed any differences with the new commissioner in town, Marty Makary?
Yeah, so the answer is very easy. Absolutely nothing has changed. The FDA has been absolutely consistent. The only thing that happened before the new administration is that Dr. Wiley Chambers, who was running the FDA, has retired. Everybody else that's there has been there and has worked with them for 20, 30 years. Their guidelines based on how to conduct trials, their guidelines based on the fact that sham is not proper masking, has not changed one bit. We know this in many interactions that we've had with them, and the public knows this as well. I mean, I'll give you some examples. You know, one of the examples, for instance, is just last week, Dr. Boyd, who took over Dr. Wiley's position, was the keynote speaker at a major meeting in Fort Lauderdale, and he reiterated everything that he had said and Dr.
Chambers had said before, which is that sham is not proper masking, that there's a way to run these trials with reduced, with no regulatory risk, which is exactly what we've done and been rewarded with a SPA. The second thing that I would mention is, look, there was a CRL that was received, as you know, for HD EYLEA for six months, and that was based on improper masking, which really confirms how serious the FDA is in regards to what they've set forth as their guidelines, which is that, look, this is the way you conduct trials with minimum regulatory or no regulatory risk, and sham, in fact, is not proper masking because patients can see the medicines coming in. That's been very, very clear, and now they've been more consistent with this than ever.
Got it. That's really helpful. Maybe just one more macro question for you. Since there's been a lot of discussion about the potential risk of pharmaceutical tariffs, you know, to the industry, and this concept of most favored nation pricing has come up recently, how is Ocular kind of navigating all of these almost lightning-fast changes coming from the government?
The good news, Lisa, is that it really doesn't affect us at all. Everything that we have is really done in-house. We manufacture internally in Bedford, Massachusetts, where our headquarters is. There's nothing that's brought in from outside, so the tariffs don't apply at all. The IP is all in the US, so it really doesn't affect us at all. It's business as usual, and we're very fortunate that, as I say, we've got a closed loop where everything is within the U.S..
Got it. Got it. That's helpful. Pravin, let's talk about Wet AMD more broadly and the current landscape. You know, this field, it's about a $10 billion market today. It's really been dominated by one therapeutic modality, the Anti-VEGFs. We've just seen, you know, approval not too long ago of a novel third-generation treatment, but we've also seen a push towards having patients use biosimilars as well to keep costs down. Is there room for more innovation at a time when the government is trying to find a way to reduce costs? How should we think about this?
This is absolutely exactly the time, and what we have potentially reduces costs a great deal. Let me just describe this. First of all, the market is huge, as you said, but that's just the tip of the iceberg. The market is that big despite the fact that there's a 40% dropout rate in the first year in this country alone, right? What does that mean? That really means that 40% of these patients in the first year are going blind. They're not dropping out of the healthcare system. They're dropping out of coming in to get injections on a monthly or bimonthly basis. Blind patients, unfortunately, are the most costly patients. Their mortality doesn't change, their lifespan doesn't change, but their resource use goes sky high.
They cost a lot of money, and it's tragic when there's a known target and a known treatment that 40% of patients in the first year are going blind. With our treatment, if we reduce that dropout rate by even 10%, that's a quarter million more patients, a quarter million that will not go blind. That's not only something that, from a humane point of view, we should be doing, the cost savings of that is absolutely tremendous. This is a win-win situation with this drug that doesn't even take into account the second problem we're solving, which is better long-term outcomes of the patients that do get treated. This drug is exactly the right drug to have in this environment at this time, and it's de-risked. It's de-risked because, as you said correctly, this is a known target.
The risk for this is really quite minimal.
Got it. And how might you use, like, how do you vision AXPAXLI might be fit into real-world use in a retina clinic? You know, the biggest pushback often heard from investors on these longer-acting Wet AMD treatments is that doctors are not going to be motivated to use them because they get paid per injection, and more injections is, you know, good for business. Since you are a retina specialist and you've treated many patients with Anti-VEGFs, you know, through your career as a physician, what are your thoughts on this debate about more doctors wAnting to have more injections and not being as motivated to use a longer-acting treatment?
Being a physician who's practiced for 30 years before changing my career, I can tell you this very easily. The one thing that I would tell you is never ask a physician about economics because doctors know nothing about economics whatsoever. That's the first thing. It's an absolute win-win-win situation from a cost-saving economic point of view. Let me just describe that. If you ask your KOLs, I'm sure what they'll tell you is, "Look, I make my money by injecting," and they do. This is a better drug, but, you know, I guess I'm going to have to take a bit of a hit for the patient. I'll make less money because I'll inject less. Nothing could be further from the truth. Let's just start with the payers. I just started that already. 40% of patients drop out. They all go blind.
These patients are the costliest patients there are. The amount that we will save the payers in the dropout rate, the payers will be really happy. We will potentially be able to charge a premium based on that and other things. I think society for the payers, which would pass on as a high premium for the drug for us. From a physician's point of view, if we reduce, as I say, the dropout rate by 10%, a quarter million more patients, there's a huge increase in the attachment of patients these physicians will be able to treat. Now, granted, they're not injecting the same patient over and over again, but the number of patients that are now eligible will be much, much greater. That's in Wet AMD alone.
That doesn't even include, for instance, the other diseases that we're going after, such as non-proliferative diabetic retinopathy, for which there is no treatment. Not only will they be able to inject as much as they want, but potentially they'll be paid higher for each injection. All of this without having to buy anything new, not a single piece of new equipment, not change the workflow, nothing changes. This drug is going to be adopted the very next day, and it's a win-win-win situation economically for the payers, for the doctors, and for patient satisfaction.
Got it. That's very helpful. You already touched on this on fibrosis, and I do want to dive into it a bit more. Obviously, the Anti-VEGFs have been very successful at keeping eyes dry, and, you know, we understand AXPAXLI could really help solve this patient compliance issue. You know, one thing that is not discussed as much is fibrosis and the fact that Wet AMD patients, despite being on Anti-VEGF, still might have fibrosis of the retina, which will impact their vision. How could AXPAXLI actually treat this problem in Wet AMD patients?
It's a great question. When the Anti-VEGFs came, the first thing we thought of was the way patients will lose vision if they stay on the Anti-VEGFs is by rebleeding, which makes common sense, right? As it turns out, rebleeding is extremely rare, but they do lose vision, and they do lose vision fairly early, two to five years, and on a steady basis. The way they lose vision is by fibrosis and atrophy. Now we know why and how that happens. Because of the periodic way we treat these patients, the back of the eye gets thicker and thinner and thicker and thinner, and it's a bunch of neural tissue. It's like having multiple concussions. We know that if we can decrease those oscillations, the formation of fibrosis will also decrease, and the visual outcomes will be better.
We know that studies have been done. The way AXPAXLI will help is because it's going to last for 9-12 months, and there's going to be constant suppression. You're not going to have these oscillations. There is a very, very good chance that the amount of fibrosis that's going to occur is going to be less, and the chronic visual outcomes is going to be far better.
Got it. Got it. Very helpful. Let's talk about the pivotal trials that are ongoing right now, SOL-1 and SOL-R. On the recent trial modification, why did you decide to include redosing at 12 months in SOL-1 and shorten SOL-R by a third of patients? The redosing, I understand, allows you to explore an annual dose regimen in addition to a biannual dose regimen, but doesn't reducing SOL-R by a third of patients reduce the powering? How should we think about this?
No, not at all. Let me just kind of give you a recap of what happened, and there are three things to really understand. Let me just come to the conclusion first. There are two take-home points of this. The first take-home point is that this is an absolute win-win for us. We gave up absolutely nothing. Nothing changes. Our primary endpoint does not change. We gave up nothing. What we won from this, what we got from this is that we can get to the finish line faster and cheaper, period. We will get this approved much faster and much cheaper. The second take-home point is we are extraordinarily grateful to the FDA for their collaboration. They have gone out of their way to collaborate with us, and we have gone out of the way to make sure that we fulfill every one of their requirements.
Let me start from the very beginning. The first thing deserves the credit for getting the SPA for SOL-1, right? If you remember this trial design, the trial design had a primary endpoint at month nine. The study also ended at month nine. Now, the FDA has a requirement for safety purposes, and only for safety purposes, not for efficacy, that they want to see a certain number of patients marked, I'm sorry, the two-year mark only for safety. Because the trial ended at month nine, we couldn't use any of those patients. For that reason, SOL-R, the second study had to be way overloaded. It was nothing to do with power whatsoever. It had everything to do with the fact that now we needed a certain number of patients to be followed for two years where they're safe for the FDA safety requirement.
That was one of the consequences. The other was that our PIs came to us and said, "Look, you've put us in a really difficult position because once the trial is successful and ends at month nine, the patients have nowhere to go. They just got to wait until a drug is approved." That is a really difficult conversation to have with these patients, and they're right. The second thing that we saw was the label for Vabysmo. They got a four-month label, but in fact, there are very few patients that actually crossed the four-month threshold. We were very confident, we are very confident that with AXPAXLI, there will be a far greater number of patients that will cross the one-year threshold. We really felt confident that we could get the 12-month mark on the label.
The third thing that happened, and this was the gating item because people have said, "Oh, why didn't you do it as soon as you come in?" This is really important, and it speaks to the quality of patients that we're recruiting. There's a bunch of us that have been doing clinical trials in our practice for 20, 30 years. We sat around on the table and we said, "We have never in our entire career ever seen patient retention this good." Just think about that. Patient retention this good in a trial that they said could never be recruited. Putting all that together, we went to the FDA and said, "Hey, can we not jeopardize the SPA?" The one thing we never want to jeopardize is the SPA. Can we go ahead and have a second year in SOL-1 where we dose every six months?
Can we then go ahead and use that together with every six months in SOL-R to be the cumulative number that you need for your safety requirements? They said, "Yes." We said, "If we can do that, is it okay if we reduce the number for SOL-R? Because now we do not need 825 patients, we can reduce it by a third. We just need 555 patients. Can we do that?" They said, "Yeah, while preserving the SPA." In addition, what we decided to do was to say, "Look, we will keep this masked until month 12 because we will have masked data for month 12 with the potential of having 12-month data in our label." We are very, very grateful to the FDA for their collaboration. We gave up nothing. The powering does not change. The primary endpoint does not change.
The bottom line is we simply get to the finish line faster and cheaper.
Got it. Can we just touch on the control arm for SOL-1? You're dosing a single dose of 2 mg Eylea at baseline, and you're having to observe patients for nine months for the primary endpoint, and then up to 12 months where redosing will occur. Given we already have some AXPAXLI data, investors kind of have a good idea in terms of how AXPAXLI is going to perform over that time, but we do not really have a lot of data available to us on regular 2mg Eylea. What are your expectations in terms of how the control arm should perform in SOL-1?
Yeah. So it's a fair question, but let me just backtrack a little bit and talk about the study design. The study design is actually what the FDA recommended, right? This is not something we kind of came up with, you know, out of nowhere. The FDA has very, very firm and strict guidelines in their website that they put forth in February 2023 and said, "Look, if you want to do trials at no regulatory risk, this is the way you design a superiority trial. This is the way you design a non-inferiority trial." We followed their recommendations to a T, and that's why we have a SPA for SOL-1. Now, in response to your question, look, we have internal modeling regarding what we expect from Eylea at month nine.
What I can tell you that's publicly available that probably would be most appropriate is the TALON study, which is done by Novartis. There, that was not a super selected patient population. That was a treatment extend study. Drugs were already on board and the patients were extended. Even then, less than 20% of patients actually made it to month nine. In a super selected patient population, as we have, the patient population that's VEGF dependent, we believe that that delta, which only needs to be 15% between AXPAXLI and Eylea, will actually be even greater. Remember, the point here is that we have a super enriched, super selected patient population that is bespoke and designed specifically for each study. For SOL-1, this is a VEGF dependent patient population that's designed to fail once.
The reason for that is we want the maximal delta that we can get, right? What we need to get, what we're aiming for, and really what we need for success for SOL-1 is a delta that's 15% or greater.
Got it. Pravin, are you looking at the blinded event rate in SOL-1? If so, is that tracking with your expectations?
Yeah. We always say masked. We never say blinded for obvious reasons, but yes, you know, we have to, right? I said earlier on, the main goal of this company is to make sure the trial conduct of SOL-1 is as good as possible. We aim to deliver the FDA the cleanest, cleanest study they've ever seen in terms of SOL-1 and SOL-R. That's our goal. What we look at under masking is we look at the number of rescues. As I said, we chose a patient population that's designed to fail because they're VEGF dependent. We want to see a high number of rescues. The second thing that we look at is we look at the cadence, the profile of the rescues. We have an idea of when we want to see the rescues.
We don't want to see anything anomalous, and we watch to see when the rescues occur. The third thing we look at, very importantly, is we look to see if the rescues are on protocol or not. What I can tell you is based on those three parameters, I couldn't be happier. We're absolutely thrilled with the number of rescues, the profile of the rescues, and I can also tell you that the vast, vast, vast majority of rescues are on protocol.
Got it. Got it. That's super helpful. Maybe let's just touch on SOL-R. On the enrollment progress, you know, you gave an update in January where you shared 311 patients had enrolled or at least 50% by my math under the new trial size. I know you haven't updated enrollment since, but can you give us an idea if enrollment is maybe accelerating now that you're kind of over the halfway point? We've seen this happen in other studies. Just curious what you're seeing with SOL-R.
Yeah. Great question, Lisa. In January, we gave an update of 311 patients because we wanted to show that what we had designed in these complementary trial designs actually worked very, very well. We did not lose any patients. All the patients in SOL-1 were bolused into SOL-R. That is why we had 311 patients. We specifically said these patients were enrolled in various stages of loading and randomization. We have not given an update since. We will when appropriate. We are absolutely thrilled not only with the pace of recruitment, but the quality of patients we are recruiting. We are absolutely thrilled with that. Remember, by design, it is a fairly long ramp because we want to make sure these patients are as stable as possible before they are randomized. That is exactly what we see.
We made it also very clear in our earnings report, not last one, but the one before, that we have a primary endpoint at week 56 that is not blended. It is a singular primary endpoint at week 56. We also made it very clear that our non-inferiority margin is the largest the FDA allows, which is 4.5 letters of vision.
Got it. Maybe just one last one in the couple of minutes we have left. How are you thinking about commercializing AXPAXLI? Are you planning to launch this solo? Are you planning to seek a partner? Are you envisioning a global launch? How should we think about this?
Look, we're not seeing any collaboration at this point at all. The only reason for collaboration is if we were in need of capital or expertise. We don't require either. We're financially very well disciplined and very well capitalized, and we've got more expertise in retina than anyone else. The advantage that I have in this company that I didn't in Iveric Bio is, look, it's a known and mature field. With geographic atrophy, I had to convince people that there was a market here. There's no convincing to do. In Iveric Bio, I really didn't have a full commercial team. Here, we've got a fantastic commercial team that is very successful in selling DEXTENZA. The answer to your question is we intend to go all the way globally, not just in the U.S., but outside the U.S. as well.
Having said that, we, as well as every other public company in this country, are in the market and on sale every day, but we intend to go all the way. Whatever happens along the way happens.
Got it. Pravin, I think that's all the time we have for today. Thank you so much for joining us, and we'll see you next time.
Lisa, thank you for having us here. It's been a pleasure. Thank you.