Welcome, Pravin. It's great to have you here.
Jessica, thank you. It's an honor to be here. Thanks for inviting us.
I hear it's just over a year that you've been at the company. Perhaps you could give us a little bit of background and what attracted you to Ocular Therapeutix?
It's been a year, but it seems like it's been a dozen years. You're right, it's been a year. I was very happily retired after my last company, and I had no intention at all of getting another job, although I loved my time at Iveric Bio. I think it was several things. First of all, I knew about the technology. In the previous company, we had a drug for geographic atrophy, so it's natural to look for a platform that would be a long-acting type platform. We had two independent groups look at that time for the best platform available, and both came up with what we have here, which is the ELUTYX™ technology. Technology was certainly one reason. The other was the regulatory pathway.
The fact that this company had a SPA and a clear regulatory path that followed the guidelines of the FDA as per their latest guidelines in February 2023 was a big attraction. Finally, it was the opportunity. I, as a clinician who's practiced for 30 years, know the need and the importance of having something that is more durable and has a better outcome. It was a combination of those three things that brought me here.
Great. Perhaps we can dive into your lead program, AXPAXLI™, and give the audience a little bit of background here in the market that it's addressing.
Sure. AXPAXLI™ is a TKI that is in a hydrogel, a tunable hydrogel. We're trying to solve two problems here. One that's fairly obvious and one that may not be quite as obvious. The one that's fairly obvious is that of sustainability. We know that in this country alone, despite having a treatment for wet age-related macular degeneration, 40% of patients discontinue treatment within the first year. That's an enormous number. Imagine that, 40%. These patients end up going blind. If we're able to decrease that dropout rate by even 10%, that means a quarter million patients more in this country alone would not go blind. The need is enormous. We have a known proven target.
We're certainly trying to cure that problem, that of sustainability, by having something that stays longer so patients don't have to come in every month or every other month for a needle in the eye. The second one is that we also know that even in those patients who do stay with the program, with the treatment, after five years, almost inevitably, these patients end up losing vision over time, getting worse than baseline. It's not because of rebleeding. It's because of fibrosis and atrophy. What we know now is that the way we give these medicines in a pulsatile fashion causes the back of the eye to get thicker and thinner and thicker and thinner. That's what causes fibrosis and atrophy.
There's good evidence that if you can minimize the pulsations, as we would by having these near zero order kinetics and suppress on a constant basis, we will have better outcomes. The two problems we're going to be solving are that of better sustainability as well as better long-term outcomes.
Great. Thanks very much for that. Now, you have a very comprehensive clinical program at Ocular Therapeutix. Perhaps you can dive into the three trials that you have, including the.
CLLE. Yep.
Absolutely. What we've announced is in wet age-related macular degeneration, we have two Phase 3 trials, both of which are now completely recruited. The first trial is a superiority study called SOL1. We believe that this will allow us to get a superiority label. That trial will read out in the first quarter of 2026. We also have a non-inferiority trial. These aren't the same trials duplicated, but these are complementary trials. This is a non-inferiority trial called SOLAR, and that goes up against EYLEA® at 2 milligrams. We have said that is expected to read out in the first half of 2027. We've also announced an open-label extension. The most important part about that open-label extension is that this drug will be dosed every six months. There are numerous things we'll look at.
For reasons that are very strategic, the one that we're most interested in are the crossover patients. We believe that we're on track to get a superiority label, which is extremely important to us for various reasons that I hope we'll discuss. Not only do we believe that we'll get that, but we believe that those crossover patients, because they've been on the pulsatile therapy that I've described now for two years before crossing over, will really never catch up to those patients that started on AXPAXLI™ from the beginning. We believe that we'll have data to show that to get the best results, one has to start on AXPAXLI™ from the very beginning. Having a superiority label, we believe that we have the potential to be immune from pricing pressures as well as from step therapy.
With this additional data, we believe it'll put the drug in a very good position.
Perhaps you can just give a little bit more granularity on step therapy and kind of how your drug would be introduced with the superiority label.
Sure. So again, as I said, with the SOL1 study, we have a SPA with SOL1. It's a superiority study where we're following exactly the guidelines of the FDA, their latest guidelines as of February 2023, and again, validated by a SPA. We believe that with positive results, that will put us in a very good position to have a superiority label. It will be the first and only of its kind in our field. In fact, I don't know of another study that's a superiority study that's either active or even being contemplated. That puts us in a special position for quite a long time. What does that mean? What does the superiority label mean? Frankly, if you ask a doctor and ask them, "Look, does a superiority label matter?" You know, 10 out of 10, I assure you, will say, "Look, I never look at the label.
It doesn't mean anything to me." It's the wrong question to ask. The right question to ask a doctor is to say, "Look, does it matter to you that you get to decide what drug you want to give to your patient? Does it matter to you that you don't have, you're not forced to use an inferior drug and wait until it fails to step up to the drug that you want?" Every one of them, 10 out of 10, will say, "Yes, that absolutely matters to me." That's what a superiority label does. It makes you potentially immune from step therapy where you're forced to use an inferior drug, allow the patient to fail, and then apply to hopefully get to use the drug that you wanted to use in the first place. That's really what step therapy is.
We believe that with a superiority label, we'll be immune to that. In addition to that, as I said earlier on, we'll have data from our open-label extension that will show, we believe, that if you don't start on AXPAXLI™ from the very beginning, you won't get the best outcomes with the crossover patients. Not only will we be in a different level, shall we say, with the superiority label, not only will we not be subject to pressures of pricing and step therapy, but we'll have data to support that as well.
Great. Just maybe to remind the audience in terms of the primary endpoint, the actual clinical trial design for SOL1 would be great.
Yep. For the superiority study, the primary endpoint is at month nine. The primary endpoint is the proportion of patients who maintain vision. Those who are counted as failure are patients who lose 15 letters of vision or more. The primary endpoint is at month nine. However, we will have alpha protected data up to month 12. The reason for that is that we believe that we have a very good chance of getting flexibility in our label as well. We will have a superiority label with the flexibility of dosing every 6 to 12 months with repeatability based on these two studies.
Okay. From a timeline standpoint, you'd be releasing the first data set from SOLAR1 at the nine-month time period?
We will have access to all the data at that point. In the first quarter of 2026, we'll have access to the primary endpoint, the nine-month data as well as the alpha protected 12-month data.
Okay. Great. In terms of the SOLAR equivalency study, a non-inferiority study, perhaps again, go through the details.
SOLAR is, again, completely enrolled, as we've announced. The primary endpoint for SOLAR, the non-inferiority study, is at week 56. Now, it's a singular endpoint. It is not blended, and that's very important. We believe that it's an optimal endpoint for us. It is two months after the last dose for both AXPAXLI™ as well as for EYLEA®. We also have a masking arm. We followed the guidelines of the FDA to a T, and the FDA has specifically said verbally, as well as in written documents, as well as in their guidelines, that sham injections, which is what we used to use, is not proper masking. It's not proper masking because patients can see it. Remember when you're numbing the eye for an injection, you're numbing the front part of the eye, the conjunctiva. You're not doing anything to the optic nerves.
The patients can still see very well, so patients can absolutely see when the drug comes in and doesn't. For that reason, the FDA has said sham is not proper masking, and if one uses sham, you're doing a study at risk. We're not willing to take any risks, so we have no sham in either of our studies. In order to avoid using sham, you have to have a masking arm, and that masking arm in the SOLAR study is required to have the same cadence as well as the same rescue criteria as your drug. You can choose anything you want. The FDA really doesn't care. It's for numeric analysis. It's not for any analysis that would be statistically significant or anything. We specifically chose to go up against high-dose EYLEA®, so we'll have numeric analysis against high-dose EYLEA®, which we will use to our commercial advantage.
Okay. I believe that you've used patient enrichment in terms of patient targeting, etc. Perhaps you can comment on that.
Yeah, I think that that's one of the most important things, Jessica, that we've done. Having done this for 30 years, I don't know that I've been in any program that has been as thoughtful as we have been. I don't take credit for this. This is my colleagues who are absolutely fantastic in designing trials that are so very carefully designed and patients that are selected to be completely de-risked in a bespoke manner. I think few people realize how variable macular degeneration is. If you talk to a retina specialist, they'll tell you there are some patients that they can get away with injecting even with regular ILA or Lucentis once every six months, but there are others that they have to inject every two weeks. They all look the same. You know, we're 75 years behind oncology, for instance. We don't have any genetic biomarkers.
We don't have any anatomic biomarkers. You can imagine that years ago, when we used to do very large studies with 2,000 patients or so, this would have balanced out. When you're doing smaller studies, as we are, the patient selection is absolutely key. There are companies that have been blindsided unintentionally because of patients that were super VEGF dependent, for instance, that were biased on one side or the other. We wanted to avoid that. What we did in the superiority study is specifically have patients that would be VEGF dependent. It's very important that they don't have any fibrosis. It's very important that they don't have any atrophy. It's very important that they be treatment naive. We took patients that had good vision, that were treatment naive. In other words, no fibrosis, no atrophy, 20/80 or better.
Presumably, they would have the most amount of VEGF receptors that would be active. That wasn't enough. We tested them. In other words, we required that they improved by 10 letters or more or got to 20/20. We loaded them up and allowed them to fail once. They were rescued after the first failure. That's the SOL1 study. Failure meaning a net of five letters of vision, which amounts to 15 letters in the absolute. That's the perfect patient population you would need for a superiority study, specifically choosing patients that are VEGF dependent. That is very different from SOLAR. In SOLAR, what we want in a non-inferiority study is absolutely rock-solid patients. Here, what we've done is to get treatment-naive patients, have three loading doses. If you look at any anti-VEGF study, after three loading doses, the vision stabilizes. We've gone further.
We've had three loading doses, and then we have two periods of observation. This is unique. Nobody has this. It's never been designed before like this. Two periods to observe the patient. Two periods, right? What we're looking for is any kind of fluctuations. We want absolutely stable patients. If there are any fluctuations, those patients are weeded out. Once we're sure that we have absolutely stable patients, two more loading doses, and then we randomize. We have super selected and de-risked patient population that is appropriate for each study in a very, very thoughtful manner. We're very proud of that. That is very different than what others have done. Obviously, it's much harder to recruit when you're this selective, but it also de-risked the trial entirely.
When you talk about the complementary nature of these two trials, I mean, ultimately, what label are you looking for? How broad is the coverage in terms of wet AMD patients?
Yeah. What we're hoping to get is the first and only superiority label against a drug. This will put us in a different orbit. There's no one else that has it. There's no trial going on or even contemplated with a superiority label. We're hoping to get a superiority label with the flexibility of dosing of every 6 months to 12 months with repeatability based on a combination of both those studies. We're also hoping that all the questions that doctors, patients, and payers would have will be answered by both those studies together. If a doctor wants to know, for instance, how long this drug actually lasts, SOL1 will tell him or her. If the doctor wants to know how this drug will do against the standard of care, SOLAR will tell him or her.
If the doctor wants to know, for instance, is this drug repeatable, SOLAR will tell him or her. In addition to that, because of the masking arm of SOLAR, we'll also have in our back pocket the comparison to high-dose ILAA. That's again for numeric analysis only, but we'll have that data, and we'll be using that for commercial advantage. That'll also provide a lot of data. We think that with a combination of these two studies, we will be able to provide all the answers that doctors, patients, and payers will need regarding our drug. I will also say that I really do believe that this is going to be a landmark of how thoughtful trials are designed. Up to this point, everybody repeats the trial again, right? It's the same study done again. I think everybody expected us to do SOL2.
When you think about it, the second trial is good for approval, is good to validate the first trial, but really provides no additional information. In my mind, that's a wasted opportunity. Here, with the second trial that's complementary, we've provided additional information that's going to be very valuable. I know that the FDA loves it. We collaborate with them very, very well. Having two different trials of two different designs come to the same conclusion adds much more validity to the data.
All right. Any questions for Pravin on trial design? Great. You mentioned that SOLAR data will be available first quarter 2026.
Yes.
Maybe we can just dig down a little bit in terms of what you're specifically looking for, and then how does that translate, if at all, to what you might expect to see in SOLAR?
Yeah, it's a great question. I've spent a lot of time here talking about how the patient population is different, right? On the other hand, here's what I know we have to do. First of all, when the SOL1 data is positive, when we hit statistical significance, we also realize that the primary endpoint, which is a loss of 15 letters of vision, or the % of patients who maintain vision, may not be entirely clinically applicable. We know that in real life, doctors really don't wait for a 15-letter loss. I totally understand that. The goal that we have is to take parts of that data of SOL1 and translate that into data that will provide confidence to people that, look, this can be translatable to SOLAR, and this gives me a great deal of confidence that SOLAR will succeed. I totally understand that.
That's what we aim to do. We aim to go ahead and get data from SOL1 and specifically be able to say, look, this translates into success for SOLAR. We will do that. We will provide that data. We're completely aware of that. That's the way we'll narrate that story and provide that data. However, having said that, there's a lot already available that should give a lot of confidence in the success of SOLAR. One we've talked about, which is the patient selection, it has a longer ramp than any study that I know. It assures, I think, as much as a study can, that the patients who will be randomized will be completely stable. Three loading doses, two observation periods, two more loading doses. The other thing also about the trial design is the primary endpoint. The primary endpoint is at week 56.
It's not a blended primary endpoint. It's a singular primary endpoint. It is optimal for us. It's two weeks, I'm sorry, it's two months after the last dose of each drug.
Okay. Great. You mentioned that there's a masking involved here. Obviously, the data for SOLAR is available first quarter of 2026, but I believe you've had some commentary in terms of what you've looked at on a blinded basis.
Yeah. You know, on a masked basis, what we have looked at are, and we've said this publicly, and this is a population basis, right? These certainly are not individual patients, which would be impossible to distinguish anyway because the target is the same and there's no telltale sign of anything because the mechanism is the same. We have looked at the general population under masking. What we've looked at is the following. We've looked at the number of rescues. We're very satisfied with the number of rescues. We've looked at the cadence or the pattern of rescues. We're very satisfied with that. There are no alarming signals. The alarming signals would be if it was, you know, a whole bunch of rescues very early or a whole bunch of rescues very late. That's not happening. We're very, very happy with the pattern of rescue.
Last but not least, we've looked to make sure that the rescues are on protocol. I've said this over and over again. The vast, vast, vast majority of rescues are on protocol, and we're very, very happy with that. Under masking, that's what we're looking at. That's all we're looking at. We're very happy that we're seeing what we're seeing with those three parameters that I just described.
Great. In terms of SOLAR, is there any, I mean, you obviously indicated that accrual has been completed, expected data first half of 2027. Any interim reviews that we'll see before that?
Yeah, we haven't guided you to any of the Jessicas yet, but you know it's really too early. As you know, that ramp is very long, as it's a six-month ramp, and it's just really too early to comment on any mass data for SOLAR.
Okay. Great. In terms of timing with respect to the actual filing, perhaps you could comment on that.
We expect to have two successful studies upon filing. That's the traditional requirement of the FDA, and we will file as soon as we hit the 56-week mark in SOLAR with successful results. We believe that our filing will be very efficient for two reasons. On the front end, because we'll be filing a 505(b)(2), because both axitinib and the hydrogel are approved products, that'll save us at least two months. On the back end, because we have a Special Protocol Assessment, much of the work has already been done, so we believe the filing will be very efficient.
Great. Excellent. You mentioned the long-term extension study. How does that incorporate into the filing? Does it have any impact at all, or what type of data timing would that be visible?
That has no impact on the filing whatsoever. It's for safety purposes primarily. It also gave us the information that I mentioned, but that will not hinder the filing in any way whatsoever.
Great. I'm sorry, I didn't ask the question. From a patient standpoint, are these only U.S.-based patients, or how is the trial, or how do we think about the global opportunities?
It certainly is a global drug, right? I mean, it's been very, very well. I just came back from a meeting in Europe. It's been very well received throughout the world. It is, you know, obviously, the market is enormous out there as well. As far as the clinical sites are concerned, most of the patients, the vast majority, are from the U.S., also from Argentina, some from India and Australia.
Great. In terms of pursuing ex-U.S. regulatory approvals, what would we envision from that?
Those discussions are ongoing. We haven't guided you as to the formal conversations as yet. What you can see, though, is that there are some things that we've done to completely align with OUS regulatory agencies. One of the things being the modification we had in our rescue criteria for SOLAR that we announced in our last earnings call. That, in part, was done to align entirely with OUS regulatory agencies, and we've done so. We believe that we have a very clear path to file outside the U.S. as well.
Okay. Great. One thing that I really enjoyed when I myself understood how the drug ultimately would be used is kind of what physicians are doing today in terms of the treat and extend versus how, again, AXPAXLI™ would be incorporated. I think this is fascinating and very helpful in terms of getting out there quickly.
Yeah. Right now, what we're doing is we're doing something called treat and extend for the reasons that I mentioned earlier on. We're about 75 years behind oncology and rheumatology and all the other fields. We just don't have any genetic markers. We don't have any anatomic markers. Patients come in, they all look the same. We have no idea really what cadence to treat them. We do what really is trial and error. That's a difficult thing because we wait until failure before we treat again, and we figure out a cadence which can change. As far as frequency is concerned, we have no idea how frequently we'll have to treat a patient. From a scheduling point of view, it's very difficult on the physician. It's very difficult on the patient as well.
What we believe we will provide here is a drug that is in our comfort zone, by the way, is to see a patient every six months or so for chronic disease. What we believe we'll provide here is an extremely reliable every six months drug. If a drug lasts for 9 to 12 months, that's exactly what you need for every six-month visit. If a patient gets sick, there's a safety net. If the doctor's not there, there's a safety net. I believe these patients will be seen every six months, and eventually, I believe that patients will be treated on a fixed basis every six months. I don't think that'll happen right away. We are very used to doing treat and extend, and in the beginning, we'll probably still continue to do treat and extend.
At a certain point, I think doctors will feel very comfortable with saying, "Look, come back every six months, and I'll go ahead and inject you every six months." It'll be much easier on the patients. It'll be much easier on the doctors. My prediction is that that's what will eventually happen.
Great. I think it's reasonable to talk about commercialization because it's rather near the term here. Obviously, there's been a lot of successes in the wet AMD from a standalone basis. Maybe just what would you need to do from an infrastructure standpoint for the United States first, and we can talk about Europe after that.
Yeah, that's a great question. We're doing it now. As you know, it's a closed loop. We manufacture this ourselves. We're investing. We have been and continue to be investing heavily in scaling up with the manufacturing in terms of automation, in terms of buildings. That's going on now. That's a big, big investment for us, and it's going very well. It's not something we haven't done before. As you know, we already have a marketed product in DEXTENZA®, which is the same hydrogel. We're used to scaling up our manufacturing, and that's just being done in a much grander scale at this point. The other advantage that I have in this company that I didn't have previously is that we have a commercial team. We have a tested and proven commercial team that sells DEXTENZA®.
You may or may not realize that the commercial team, the salespeople don't have to be huge for our field. At the height of the Lucentis sales, I think there were about 55 salespeople. It's not a lot. We already have that. The salespeople just have to be very experienced and networked and connected. We have that with the folks that we have with DEXTENZA®. We've got a great commercial team. We'll be ready and set to go. We already are.
Fantastic. Here also we're looking beyond wet AMD. We've got diabetic retinopathy and diabetic macular edema. Saw some recent congratulations SPA news on the diabetic retinopathy standpoint. Let's talk about those two programs.
What we had was a small study called Helios, and it was primarily a safety study. When we looked at the results, we as clinicians, and there are lots of clinicians in our company, were all unanimously astonished. We were astonished because every single parameter in that study, every single parameter favored the drug. Everybody who got better had the drug. Everybody. Everybody who didn't get better didn't have the drug. Every patient with diabetic macular edema that was non-center involving improved. I mean, every single patient. If you look at the control arm, the most clinically relevant factor to look at is something called vision-threatening complications. These are potentially blinding progression of the disease. Natural history shows that that occurs between 30% and 40% year upon year. In the control arm, it was 37.5%, so right in line with the expectation.
In the treatment arm, with a single AXPAXLI™ injection, a single injection after week 48, that was reduced literally to zero. Zero.
Wow.
That's astonishing. From my point of view, as a clinician, what that means is that I can sit down with a patient and say, "Ms. Smith, you've got diabetic retinopathy. Your chance of having a blinding complication is 30% to 40% year upon year. If you come to see me but once a year, as often as you go to your dentist for teeth cleaning, I can reduce that risk literally to zero." That's really doable. That is sustainable. The population for nonproliferative diabetic retinopathy is about 3.5 times bigger than wet macular degeneration, and they're pretty much untreated. Less than 1% are being treated because the treatment, which is very effective, the anti-VEGFs, is just not sustainable. Nobody's going to come in who's asymptomatic every month or every other month.
To have somebody come in and reduce their risk of going blind if this repeats to zero once a year is doable. Based on that, we said, "Look, there's an enormous opportunity. There's no competition whatsoever. The regulatory road is wide open for us. Why don't we go ahead and think about doing this and collaboratively work with the FDA?" We applied for a Special Protocol Assessment, and we're very, very happy and proud that we got a Special Protocol Assessment. We believe that we have a clear regulatory path forward. We're very happy with the feedback that we have. We believe that we have a novel and very exciting and doable primary endpoint. We'll announce that, and we'll announce the clinical trials.
You can do it.
Very, very shortly. We have an investor day coming up at the end of this month, and we will do so, but we are very, very, very excited to do the diabetic retinopathy DME program.
In terms of starting that trial, is that a 2026, or is that something that?
We'll be announcing that in our investor day very, very shortly. Otherwise, we wouldn't have anything to announce. There we go. This is a teaser.
Great. Okay. We've got also diabetic macular edema that you're.
Right. We will be studying both. Because in the Helios trial, every single patient with diabetic macular edema got better. I mean, every single patient. We absolutely will be studying that as well.
Will you look for a Special Protocol Assessment there also?
No, that is as you hear about it, but the SPA that we have will.
Allow us a study where we'll be able to capture everything.
Maybe why did you need a SPA?
It's a great question. I mean, look, what we have done from the very beginning is to say we will do everything according to the FDA's guidelines, and we will not take any regulatory risks whatsoever. We've been adamant about that, and we've been, again, rewarded with a SPA for SOL1. In every single conference, the FDA has reiterated what we've said about sham, which is that sham is not proper masking and sham is done at risk. That's why we got a SPA for the SOL program. For the diabetic retinopathy program, we have a novel primary endpoint. We wanted to make sure that it was exactly what the FDA would validate, and that's why we had a SPA. This really just shows the company's commitment to collaborating with the FDA and making sure that we're doing everything according to their requirements and not taking any regulatory risks whatsoever.
Now, will there be any additional indications beyond these three that you might pursue?
You know, Jessica, as you know, every single anti-VEGF that has been approved that has worked in wet age-related macular degeneration has also worked in diabetic macular edema, diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, etc., etc. It's the same receptor. It's the same target. There's no reason to believe that it wouldn't work in those other diseases as well.
Okay. Great. You mentioned your investor day. Any other teasers that we might be hearing?
There are a lot of catalysts to come. Again, we're working very hard to make sure that investor day, which is on the 30th of September, will be as robust and as exciting as possible. I hope everybody tunes into that, and I hope everybody comes to that.
Great. Thank you very much.
Thank you. Thank you for allowing me.
It's a lot on the horizon.
Thank you so much.
Thank you.