Ocular Therapeutix at Stifel 2025 Forum: Eyeing a Disruptive Future

On Tuesday, 27 May 2025, Ocular Therapeutix (NASDAQ:OCUL) took center stage at the Stifel 2025 Virtual Ophthalmology Forum. Executive Chairman, President, and CEO Praveen Dugal outlined the company’s strategic focus on its promising product, Xpaxli, aimed at transforming the anti-VEGF treatment landscape for retinal diseases. While the company expressed confidence in its clinical and regulatory strategies, challenges in patient retention and market conditions were acknowledged.

Key Takeaways

• Ocular Therapeutix is positioning Xpaxli as a superior alternative in the anti-VEGF market, addressing current treatment limitations.
• The company is conducting two major trials, SOL-one and SOLAR, with strategic patient selection to enhance success rates.
• Confidence in regulatory alignment with the FDA was emphasized, with ongoing discussions reported as positive.
• Plans to enter the diabetic retinopathy market are in place, contingent on macroeconomic stability.
• High retention rates in clinical trials were highlighted as a positive indicator of Xpaxli’s potential.

Operational Updates

• Ocular Therapeutix is advancing its SOL-one and SOLAR trials, with modifications in patient inclusion criteria and dosing strategies.
• Dugal reported "fantastic discussions with the FDA," underscoring a clear regulatory path for Xpaxli.

Future Outlook

• The company aims to secure a superiority label for Xpaxli, allowing flexible dosing intervals of six to twelve months, with potential for redosing.
• Entry into the diabetic retinopathy market is planned, though timing will depend on broader economic conditions.
• Ocular Therapeutix remains confident in its regulatory strategy, minimizing risks associated with approval processes.

Q&A Highlights

• The decision to proceed directly to a phase 3 superiority study was defended by confidence in existing data.
• The importance of precise patient selection for each study was emphasized to ensure tailored treatment approaches.
• High retention rates in trials were noted, reflecting patient satisfaction and treatment sustainability.

For further details, readers are encouraged to consult the full transcript of the conference call.

Full transcript - Stifel 2025 Virtual Ophthalmology Forum:

Annabel, Interviewer: Good afternoon, everyone, and thanks for sticking around with us at our ophthalmology conference. It’s our pleasure to have Ocular Therapeutix as the next fireside chat. We have Praveen Dugal who joined Ocular Therapeutix as the executive chairman, president, CEO, covered all the bases there. That was just over a year ago. So, you know, why don’t you just tell us how things have gone?

Tell us a little bit about the background of what drove you into Ocular Therapeutix after a spectacular, sale. Right? And And and how has that company evolved over over the course of the year?

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: So, Annabel, first of all, thanks for having us here. It’s really a pleasure to talk with you again, and we’re always very grateful for any opportunity to tell a story tell our story. So, my story about how I joined here is really very simple. I was very happily retired for all three months. I had absolutely no intention of coming back, although I loved every single second that I spent in, IVERIC bio.

Absolutely loved it. But the reasons are very simple. It’s because it was a confluence of factors led by the fact that having practiced for thirty years in the real world, I know what the need is. I know what the bar is for success in this need. There’s a known target and we’re simply not able to reach the amount of patients that we need to reach given the medications that we have.

And we can talk about that later on. So that was one, the need that was there. The second is the technology that Ocular Therapeutix has. And I was very familiar with this technology because I looked into this in my previous company and I was very I am and was then very convinced that this is this is the way to go as a tunable, completely dissolvable hydrogel. The third is the data that I saw, and the data was absolutely consistent with everything I’m saying, which is that this is a extremely safe product that is efficacious.

And the data to me was very convincing. And again, we can talk about that in detail. And finally, it was the regulatory path forward and that’s credit to the team before us who obtained the SAW for the first study, which is the SOLO-one study. And so it was clear that there was a very clear and obvious regulatory path forward that was consistent with the FDA’s most recent guidelines. So those are the reasons that I joined.

And since then, the company has evolved quite a bit as as you know, and I couldn’t be happier. I couldn’t be more confident, and I’m delighted that I came back. I’m loving every second of this even more.

Annabel, Interviewer: Okay. So maybe we can go into each of these factors. So, you know, obviously, we all know the anti VEGF market’s been around for for twenty years. The market is starting to evolve with longer duration assets. There’s obviously still unmet needs.

And, you know, I guess I’m looking for you to tell me how you see ex Paxley disrupting this market. Some people say the sweet spot of treatment is around six months. People want flexibility. How do you see ex Paxley sort of disrupting this market and what your, you know, your TTP is, your, like, target profile or TPP, sorry, target product product profile. Like, what is the ideal profile for you?

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: It’s it’s a it’s a great question. So so let me just give you sort of a bit of a context historically, and I can do this because I’m old enough to to do so. And, you know, this I remember that when I was in training and when I had hair almost as much as long as yours, we had absolutely nothing. You know, we would watch these patients go blind and then came came really essentially a miracle, which is the anti VEGF. And they are really a miracle.

You know, when you think about watching people go blind day after day after day and suddenly something called Lucentis comes in and and the vision actually improves, not just maintains, but improves. And then Eylea come in and then the second generations come in. It is it it is absolutely remarkable to have lived through that evolution. But I think what a lot of people don’t realize is this the following as miraculous and good as these drugs are in a known target in this country alone, forty percent of patients think about that almost half the patients in the first year drop out of treatment. I mean, is tragic and that should be absolutely unacceptable after more than three decades.

And the reason they drop out of treatment is because it’s simply not sustainable. Patients simply cannot come in for a needle in their eye every month or every other month. It simply is not happening and these patients are going blind. And that’s tragic. The second thing, people also may not realize is that even those patients that able to come in, of those patients after about two to five years, almost inevitably, they all end up getting worse than baseline.

Now we used to think when we saw that data, it was because of rebleeding. But as it turns out, rebleeding is actually quite uncommon. It’s because of fibrosis and atrophy. And when you think about what’s happening, the way we’re giving these medications in a pulsatile manner in the back of the eye, which is nerve cells, there’s oscillation. So the nerve cells in the back of the eye, the retina get thick and thin and thick and thin.

It’s akin to having multiple concussions, and it’s not surprising that there is atrophy and fibrosis after that. So, what we’re trying to do here, Annabelle, is to solve two problems. The first problem is the obvious one, which everybody talks about, which is that of sustainability. It’s a known target. We we know how important this is.

If you just look at how if you look at Lucentis, for instance, that had a seven year head start on Eylea and Eylea is not stronger, it’s not safer. It may last a week longer and it totally overtook the market. And now you see that evidence with Vibismo. Again, Vibismo is not stronger, it’s not safer, but it’s dominated the market because it may last two weeks or so longer. So there’s a real thirst for that.

So we’re trying to solve that problem. The second problem that we’re trying to solve by not having these oscillations is that a better long term outcome. So those are the two problems that we’re trying to solve.

Annabel, Interviewer: Okay. Great. So obviously, we’ve heard now from a number of companies today and there’s a lot of different approaches to this, whether it is, you know, with t k other TKIs, whether it’s other forms of VEGF, whether it’s gene therapy. So, you know, maybe you can sort of tell us where expaxly fits in that and how you might be different from, you know, say a gene therapy or another TKI. Or are physicians comfortable with a TKI versus going to a new and improved anti VEGF?

We’ve heard it all today. So we’re coming from that context.

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: Well, it’s really quite simple. And this is something that I’ve said when I was on the other side and, I was a physician, that was, working with, you know, 40 some odd companies. And there are companies that would say, look, what is it that is necessary? And that’s really what you’re asking to supplant the standard of care that we have right now, which is anti VEGFs? Because rarely, I I I would say, and and maybe you you know some exceptions, but I’ve yet to find one in in the systemic market where a single target, a single version of a drug has dominated for this amount of time.

And the reason for that is because these drugs are darn good. They’re really, really good. So what do you need to do? Here’s what you need to do. It’s really quite straightforward.

There are three boxes that need to be checked, and those boxes need to be checked sequentially. So if you don’t check one, you can go to the other. The first box is that of safety. These anti VEGFs are extraordinarily safe. Lucentis and Eylea and the second versions are extraordinarily safe.

So if you don’t have a safety profile that’s at least as good as theirs, that box is never checked, you’re done. Simple as that. The second box, if you get past the first box is that of efficacy. These drugs, these commercially available anti VEGFs work in a hundred percent of patients unless you’ve got the diagnosis wrong, right? They may not as work as well as you want them to work or last as long as you want them to last, but they work in a known target.

So if you’ve got an efficacy rate that’s sixty percent to seventy percent, that second box is not checked, you’re done. And the third box is that of adaptability. We have changed our practice entirely with these anti VEGFs. We have these large practices where we see 50 to 80 patients a day. There’s an economic advantage to injecting.

There’s an overhead that we have. If this drug, if a drug cannot fit in that workflow and cannot be easily adaptable and easily adaptable, then you’re done. So those three boxes need to be checked. They need to be checked sequentially. And I believe that ex practically checks all of those boxes very easily.

Annabel, Interviewer: Okay. Got it. So in the real world, do you see this as a completely shifting the treatment paradigm, or do you still see a place for anti VEGF? Is it a replacement, or is it a treat and extend tool?

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: Yeah. So, you know, I guess and it’s it’s a great question. It’s an appropriate question, which is, look, do you see this as a first line drug, an initiation drug, or do you see this as a maintenance drug? And I think my flippant answer, and I’m not gonna give you a flippant answer, but my flippant answer would be, you know, why do I care at the end of the day, even if it’s a maintenance drug, this is gonna be the most impactful biggest drug that our industry has ever seen. And that’s true.

However, I believe that this will be a first line agent. And why do I say that? Because of two reasons. We’ve got great evidence that’s now been been published, and you can see it in some of our presentations with nonhuman primates. That steady state is established within twenty four hours.

And we have human evidence. We have patients that we saw in our study in Australia where this drug was used as monotherapy in a treatment naive patient population, and the results are akin to what you would expect to see with a commercial grade anti VEGF. So I firmly believe that this drug is all that you will need, that we will need as an initiation drug as well as the maintenance drug. But even if I’m wrong, at the worst case scenario, if it’s a maintenance drug with two injections of islet assay and then Xpaxli for the next twenty years, this will still be the most impactful drug in our field without a doubt. I do want to tell you that we are using loading doses in both studies.

And the reason we’re using loading doses is not because I think that we biologically need them, although that’s not what we’re out to prove or disprove. The reason that we’re using loading doses is toward to your other questions that I’m sure you will have is for patient selection. And patient selection is absolutely key and is the most underrated element in my mind in terms of clinical trial design and the chances of success of clinical trials in our field. So the loading that we’re using in a bespoke manner that I think is extremely thoughtful is entirely because we want to select the proper patients for the proper studies. And I hope we go into detail regarding that.

Annabel, Interviewer: Well, let’s go into detail regarding that right now. So what is that proper patient? What is that patient selection you’re looking for? And how is it different from other potential programs that are they finding the right patient? What what do you think is the right patient?

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: So so I’m so glad that you asked this because this is one thing that I think is is most poorly understood and is absolutely crucial. So let me let me back up a little bit. You know, I’m a one trick pony. All I know is retina, nothing else, but you deal with things in oncology and immunology and rheumatology all the time. If I were to come to you and say, hey.

You know, I’ve got a drug for colon cancer. You wouldn’t let me get away with that, right? You would say, do mean colon cancer? What kind of colon cancer? What stage?

What grade? All those things. Well, wet macular degeneration, for that matter, all of our retinal vascular diseases, are no less variable than colon cancer. And you know this because if you talk to our KOLs, they will tell you even now, look. There are some patients, and these are exceptional, obviously, that I have to absolutely treat every two weeks.

There are other patients that I can get away with treating every six months. We have no way of knowing who those patients are. We’re fifty years behind oncology because we have no genetic marker. We have no anatomic biomarker. They all look the same.

And by the way, that’s why we do treat and extend. The reason we do treat and extend is because we have no idea how a patient is going to behave. Now in the real world, you can get away with doing treat and extend. And in clinical trials, we have gotten away with this and not addressing this because the studies that have been done by companies like Novartis and Genentech and others have been massive studies with 2,000 or 3,000 patients. And you can say that with numbers that are that large, these things get mitigated and equalized.

But when you’re doing studies that are less than a thousand patients, you better be darn sure that you’ve got the right patients in order to not screw up your studies. And this has been done. Studies have been upended without naming names by improper patient selection or lack of patient selection. So what we have done is to put a huge amount of thought to proper patient selection to go ahead and super enhance and de risk our patients. In the first trial, which is a superiority study, what we have done is specifically selected patients without fibrosis, with the most amount of VEGF receptors and we’ve tested them to make sure that those VEGF receptors respond.

So these are patients with good vision, not previously treated treatment naive. We’ve tested the VEGF receptors by requiring that they improve by 10 letters. We’ll get to the twenty twenty, a perfect superiority patient selection to allow them to go ahead and be loaded up and allow them to fail once. This is in contrast to our second study, which is a non inferiority study. Here, that’s not what we want.

We want stability because stability is king in a non inferiority study. Here, we’ve got three loading doses, and then we’ve got something that nobody else has ever instituted, which is two opportunities to observe the patient. And what are we observing for? We’re observing for fluctuations. Those anti VEGF addicts that are unstable, we weed them out, and then we have two more loading doses, and only then do we go ahead and randomize.

So perfectly selected for a non inferiority study for absolute stability. Again, there’s a huge amount of thought that has been put into this. This makes the recruitment a lot more challenging. But on the other hand, it also thoroughly derisks our studies in a very bespoke manner and an appropriate manner for each study.

Annabel, Interviewer: Okay. That was a lot, but I’m gonna ask you one more straightforward question. So many would argue that your first study being a superiority study is, you know, not necessarily de risking. It’s unconventional, and you’re it’s unconventional having gone from just phase one studies into the superiority studies. So what was it in the phase one that allowed your former your predecessors to be able to leap to that phase three registrational study?

You know, that’s that’s highly unusual. You would think that you’d have a phase two dose finding, dose exploration, find what the right dose is, optimize it, and move forward. Are you working with something? I guess one could argue that you could have scrapped that and started a phase two, or you can work with what you have. So, you know, what got you comfortable working with what you have and then optimizing that?

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: So, Annabel, do you remember when we spoke in my previous company? We spoke in iveric bio. Remember the first was not phase three study and the same questions were asked of me, wait a minute, this is a phase two study, isn’t it? And guess what? The drug is approved.

My point is that the FDA doesn’t care what you call the study. You can call it a phase 1,000 or a phase zero. It simply has to be properly masked, and it has to be statistically significant. So in many ways, let’s go back to the SOLAR and SOLAR studies. One would argue that those studies were really not designed by us.

They were really designed by the FDA. As you know, what happened was that in February of twenty twenty three, everything changed because the FDA came out with guidelines that they very specifically wanted people to follow if they were going to do trials without regulatory risk. They said, this is how you design a superiority study. This is how you design a non inferiority study. The most important aspect of that where they were they’ve made it very clear that sham is not proper masking.

And why is that not proper masking is because when we numb the eye and give an injection, we numb the skin of the eye, what we call the conjunctiva. We do not numb the optic nerves. So the patients can see just fine. The vision doesn’t change. And if you can see tiny little floaters with old people like me, you can sure as heck see a whole bunch of fluid coming in.

So patients would know, they said, you just injected me or you didn’t inject me because the sham was touching the outside of the eye with the hub of the syringe. So the FDA said, look, sham is not proper masking. It doesn’t mean that they’re going to prevent you from doing a study with sham, but they’re going to say, look, you’re not properly masked. So even if you go ahead and get your primary endpoint, we may not approve you because you’re not properly masked or your barrier for success may be far higher. We were not willing to take such risks.

And sure enough, we were rewarded with a stop. So clearly the FDA approves of what we’re doing from a regulatory point of view in both studies. So we’re very, very comfortable that we have a clear regulatory pathway where we’ve taken no regulatory risks. So although the study design may look unconventional to you, the fact of it is that it’s validated by a SPA and it’s exactly what the FDA wants. The second part of your question is what gave me this amount of confidence?

It’s very simple. It’s the data, the quality of the data and the consistency of the data. So let me explain. The quality of the data is such that these patients in this disease do not get better by themselves. It’s not one of those things where the disease fluctuates.

If you don’t have proper treatment, these patients go blind. And in these studies, this drug was used as monotherapy. It wasn’t used as combination therapy in addition to an already known anti VEGF that works. So it’s very difficult to to decipher which drug is actually having an effect. In fact, as I told you earlier, there were patients in the Australian study where this drug was used as monotherapy treatment naive patients.

So what we’re seeing as far as the data is concerned is the drug by itself unaided by anything else. And these patients do not get better by themselves. So that’s the quality of the data. The consistency of the data is the following. In the history of this planet, every single drug that inhibits VEGF and works in wet macular degeneration has also worked in diabetic retinopathy as well as diabetic macular edema.

If this drug had not worked in diabetic retinopathy in our HELIOS study, I’d be sitting here trying to tell you why that disease is somehow weirdly different when every other drug has worked. Luckily, I don’t have to do such a thing. This drug has been absolutely consistent in all the targets that where it’s been investigated, including wet macular degeneration, including diabetic retinopathy, including diabetic macular edema. So the quality of the data and the consistency of the data gives me an enormous amount of confidence in the success of this drug.

Annabel, Interviewer: Okay, that was helpful. So maybe you can talk about some of the changes that you made to both of these trials. Can you just detail them and explain why you implemented them this far into the study?

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: Yeah. So this is the beauty of having two studies that are complementary that are actually not the same study twice. I know that’s what’s traditionally done, which is a knee jerk repeat the study. Now what that does is make it a very simple design of study, obviously, but the second study really is is a missed opportunity in my mind because it really doesn’t provide any new information. In our case, when you take these two studies together, it provides all the information that a physician would need, in order to go ahead and have confidence in this drug and for us potentially to get the best label in the market, which is a superiority label with the flexibility of dosing at six to twelve months and repeatability.

But to answer your question, here’s what happened. The team before us deserves the credit for getting the stop. However, the study stopped at month nine when the primary endpoint was reached. What that meant was that the FDA’s requirement of having a certain number of patients hit the two year mark, for efficacy, only for safety, not efficacy would have to be the burden would have to be borne by the second study. So it absolutely overload the SOLAR study with eight twenty five patients, not for powering, but just to meet this requirement.

It also meant that our PIs came to us and said, hey, know, once the study is positive at month nine, I have nothing for the patients. And that’s a difficult argument to have. And they were right because we’ve had those discussions before in our previous lives. The second reason is because we saw the label approval for Biodismo and realized that they got a four month label with very few patients having crossed the four month barrier. So threshold was very low and we were certain and are certain that more than those patients would actually cross the barrier at twelve months with Xtaxlo.

And the third thing, and this was the gating factor, and this is why we didn’t do it immediately, is because all of us who collectively have had hundreds of years of experience in clinical trials sat together and said, we have never seen patient retention this good in the twenty or thirty years we’ve been doing clinical trials. Think about that. Think about what that speaks to in terms of the quality of patients we’re recruiting. So based on all those things, we went to the FDA and said, Hey, we do not jeopardize the stop. But what we’d like to ask you is whether we can go ahead and have a second year where we dose every six months.

And if that can be counted along with SOLAR for your safety. And they said, yes. And we said, well, if we can do that, we can reduce the number of patients in SOLAR by a third. And they said, fine. And we also said that, look, we can keep it masked for twelve months.

We have the potential of getting twelve months on the label. So look, there are two take home messages from this. The bottom line is that’s a total win for us. We gave up nothing. The primary endpoint remains the same at month nine, the powering remains the same.

What we got in return was the ability to get to the finish line faster and cheaper. The second thing that it tells you is the kind of relationship and collaboration we have with the FDA. This is a total win for us. Thanks to the corporation of the FDA. And I believe the reason for that is we’ve done everything exactly according to what they wanted us to do and taken no risk from a regulatory point of view whatsoever.

Annabel, Interviewer: Okay. Just on the retention question. I know we’re running out of time, but, I mean, this is a longer duration drug. So the idea is that you’re injecting one a drug once. So is it by default, you’re gonna retain them because they haven’t needed to take a second shot yet.

So when you talk about retention, can you tell us at what point you’re counting that retention?

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: Yeah. Up to the current up to the point of the study to right now.

Annabel, Interviewer: So have you had patients taken multiple injections So

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: so what we haven’t done is we haven’t disclosed, you know, what patients are at what stage in that level of granularity. But let me give you the context of this. Remember, this was a study that everybody said could never be recruited. Now they also said, well, you can’t recruit it. It’s a no brainer to succeed.

But they said that this study could never be recruited, and we recruited well ahead of schedule. Then they said, even if you could recruit it, doctors aren’t going to follow protocol. They’re going to go ahead and rescue you whenever they want. And we’ve said over and over and over again, the vast, vast, vast majority of patients that we’re seeing under masking are being rescued And the third thing they said was even if those two things happen, patients are just gonna drop out whenever the heck they want.

And we’re saying right now we’ve never seen retention this good. What does this all mean? For us, it gives us even more confidence in the success of SOLA-one, gives us great confidence. The second thing that it does is that it validates the quality of the sites that we’ve picked and validates the quality of the patients that those sites have picked.

Annabel, Interviewer: Great. So I mean, are out of time, but I do want to make sure I hear that correctly. When you read out on SOL R, what will that tell us for SOL-one? Is it a drug? Do we know how the drug will behave from SOL R that we can read into SOLR one and be confident that the SOLR one is gonna get us to where we want?

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: So I think it’s the other way around you’re asking. Right? Because remember, SOLR one is gonna read read out. So I think

Annabel, Interviewer: Oh, yes. I’m sorry. I got it backwards.

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: Think what you’re saying is with a positive SOLR can you give us confidence in SOLA1 being And the answer is yes, we’ll supply that. But here’s the easy answer. The easy answer is really very, very simple, which is to say, look, once SOL-one is positive, the superiority study at month nine, right? That means that this drug can last for nine to twelve months, right? Month nine being the primary endpoint.

So the simple extrapolation of that is look, if the drug lasts for nine months, Why would it not last for six months in SOLAR, particularly when we have a non inferior margin of 0.5 letters? Again, if the drug lasts for nine months, why would it not last for six months? Yeah. Remember, this is in a very, very selective patient population that I’ve described. This is not your regular patients coming off the street, right?

That’s what most trials do. This is a patient population that has been super selected with a total of five loading doses and two opportunities to observe for absolute stability. So in that patient population, in that super selected, super enriched de risk patient population, if you know a drug already lasts six already lasts nine months, why would it not last six months?

Annabel, Interviewer: Yeah, good point. We unfortunately are out of time and I didn’t even get a chance to touch on Doctor, but is that trial starting? When did that start? Is it starting and where are we? What’s the timeline on that?

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: So we’ve had fantastic discussions with the FDA. We’re thrilled with the results. We will update you when appropriate. We believe that our regulatory pathway is absolutely clear. The only thing that’s giving us a little bit of pause is the general macro environment that we can’t control.

We wanna be absolutely, physically, completely disciplined and responsible. So that’s what’s giving us a little bit of pause, nothing else. Once there’s a little bit more stability in the world, we will go forth. And we really are not under any competition whatsoever. There is no competition.

Others have thrown in the towel already. And as I say, we have a clear regulatory path forward. This is a humongous market. We are thrilled with our Helios results. We will absolutely do the study and we will absolutely own that market.

Annabel, Interviewer: Great. Well, thank you for your time. I appreciate it and look forward to seeing the outcomes.

Praveen Dugal, Executive Chairman, President, CEO, Ocular Therapeutix: Fantastic. Annabel, thank you again. We’re so grateful that you’ve had us here and any chance that we have to tell our story, we’re extremely grateful for you. So thank you.

Annabel, Interviewer: Fantastic. Thanks.

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