Joe
00:06
Hello and welcome to Pathfinders, a podcast series from RBC Capital Markets where we uncover the key trends and catalysts shaping the fast moving world of biopharma and healthcare. I'm your host, Joe Coletti. Today we're at RBC’s Global Healthcare conference here in New York, and today, we're going to be exploring innovative therapeutics intended to improve the lives of patients with serious retinal disease.
00:28
Joining us is Pravin Dougal, MD, executive chairman, president and CEO of ocular therapeutics, which is seeking to redefine the treatment of retinal diseases. The company has two ongoing registration trials for its lead program, AXPAXLI and wet AMD, with the first of those trials, SOL-1, slated to read out in q1 of next year. Pravin has over 30 years’ experience as a retina specialist. He is an internationally recognized clinical researcher with a Lifetime Achievement Award from the American Academy of Ophthalmology, and has extensive leadership experience with the Keck School of Medicine and is a founding member of the spectra Eye Institute.
So today, we'll explore how Ocular’s innovative therapeutics pipeline is helping drive better long term outcomes and treatment of retinal disease, including wet AMD, which is the leading cause of blindness in the United States. We'll also explore the trends shaping investor strategies in this exciting space.
Pravin, it's great to have you here.
Pravin
01:25
Joe, thank you. It's an honor, and thank you for having me here today.
Joe
01:28
So Ocular is aiming to transform the experience of retinal disease treatment. Can you talk about what drives that mission and what your latest clinical program is helping to reduce the burden, and how it's helping to reduce the burden on patients and providers alike?
Pravin
01:44
I, frankly, have a long family history of macular degeneration, so this affects, you know, me personally. And also having practiced for 30 years, you know, I see what's happening. I'm old enough to remember when we had absolutely no treatment for wet macular degeneration. And all we would do is to watch patients go blind, and our job was to sort of like time when they would go blind and say, Ms. Jones, you know, you ought to get your affairs in order, because it may be two months, it may be six months, or whatever it is.
02:10
There was even a point, Joe, believe it or not, when the standard of care was to actually laser the center of vision. So if somebody would come in with vision of, I don't know, 2080 say, you know, the standard of care was to go ahead and laser the center of vision and make them 2200 which is legally blind, and we would say, Ms. Jones, you're going to thank me two years from now, because the blind spot that I just created with the laser is actually smaller than it would have been had I not done anything and left it alone. It was really that barbaric. And then came along this medicine called Lucentis, and then Eylea after that. And it was truly miraculous. It's not just that we could preserve vision, but we could actually improve vision. And amazingly, that's still the drug that we have. You know, 30, 40, years later, maybe it may be a version two of it with VABYSMO and high dose Eylea, but it's still the same target, and that target is tried and true, and those drugs are fantastic.
03:06
So what's the problem? There are two problems that we're trying to solve. The first problem is obvious that bed of sustainability, these injections, as good as they are, require that patients come in and spend an entire day in the office once a month or once every other month, in general. It's simply not sustainable. And despite these almost miraculous treatment in this country, 40% of patients drop out of treatment in the first year. Just think about that, 40% - almost half the patients. And what do these patients do? These patients end up going blind, and that's simply not acceptable, and it's absolutely tragic. So that's one problem we're trying to solve, that of sustainability.
03:49
The second problem, which receives less recognition but is equally important, is that even those patients who remain on treatment after about two to five years, they end up losing vision anyway, and now we understand how they lose vision. It's not by re-bleeding, but by fibrosis and atrophy. So think of what happens in the back of the eye when you inject every month or every other month, the back of the eye gets thick and thin and thick and thin, and it's a bunch of nerve cells. So it's kind of like having multiple concussions on a regular basis. It fibrosis and scars, and that's how patients lose vision. And there's good evidence that if you can suppress on a constant basis, that you will reduce the amount of fibrosis and you will improve long-term outcomes. So very importantly, we're trying to solve two problems, that of sustainability and that of better long term vision outcomes.
Joe
04:43
I bet there's a lot of people listening that don't know much about what you just said. And it's, kind of, it's truly shocking at so many levels. I want to talk about what MD as the leading cause of blindness the United States, which we mentioned earlier. And you mentioned, sort of, that there's this high unmet need for treatments that last longer and work better. How is AXPAXLI positioned to reshape this space in your view, and what gives you confidence in its potential to expand the market?
Pravin
05:10
So one thing that we were, at least I was completely wrong about those decades ago and me and my colleagues, is that we thought that there was no way that you could actually put a needle on the eye on a monthly or bi-monthly basis. As it turns out, injecting the eye is absolutely safe and easy to do and well tolerated. That's the part that's actually easy to do, and now that's the norm. That's what doctors feel comfortable with. And not only that, but you get the medicine exactly where it belongs.
05:46
The challenge is, how long does the medicine last, and how safe is it? And what AXPAXLI is, is a drug that's FDA-approved drug. It's a tyrosine kinase inhibitor in a platform that's an FDA-approved platform that has been used in outside the eye and extensor for instance, as well as in about 5 million patients with other targets in neurosurgery, urology, etc. And those two things are married to release in the back of the eye. It's a tuneable hydrogel, so you can actually tune this to last for a few months, to last for nine months, to last for 12 months, etc. It's an absolutely tuneable hydrogel. The beauty of this is that there's nothing left behind. There are no carcasses floating around. There's no shells. When the drug is gone, the hydrogel is gone. It simply dissolves away. It's a perfect format for a tyrosine kinase inhibitor, which will go ahead and target, a target that we've known for four decades is going to be effective.
Joe
06:53
Sort of incredible, especially when you talk about sort of the high patient drop rates and the burdens of treatment that currently exist. And just to clarify, so, what I'm hearing when you talk about trying to support more consistent long term outcomes with patients, it's not only making the treatments last longer without showing up at the doctor's office every month, but also have less impact on the eye. Is there any other part of what you guys are doing on top of that that I'm missing?
Pravin
07:18
There's a lot to talk about, obviously, Joe, but right now we're talking about wet macular degeneration alone. I want to be very clear that every single drug in the history of this planet that inhibits VEGF, that has worked in wet macular degeneration, has also worked in a whole bunch of other retinal vascular diseases, such as diabetic retinopathy, diabetic macular edema, retinal vein occlusion, etc, etc, etc. So although we're targeting wet macular degeneration first, with success in wet macular degeneration against VEGF as a target, there's absolutely no reason this drug shouldn't and won't be used in all those other diseases as well. So the potential exists for this drug really to be the most impactful drug that we've ever had in this field, by far, and that really is what I'm most excited about, is the potential impact that this is going to have. And honestly, this is a well-known target, and I just keep repeating that, because the risk of this is really low at the end of the day. It's a known target. We know it works.
08:23
The other thing also that's really important is the potential societal impact, not just in terms of numbers, but in terms of the cost to humanity, as in terms of just economics as well as the human cost. And let me just explain – so those 40% of patients that drop out in the first year in this country alone, and by the way, it's a heck of a lot more outside the U.S., they all end up going blind and having been in boards of pairs. What I do know is that the most costly patients, tragically, are also the blind patients, because mortality doesn't change, right? Lifespan doesn't change, but the consumption that's required, the use of resources, escalates massively.
09:10
And if we're able to reduce the dropout rate by even 10%, which we clearly will do, that means a quarter million more patients in this country alone will not go blind. It's not just the human factor, which is the most important, of course, but the economic impact of that, the cost savings, is tremendous.
Joe
09:32
Is there anything else when it comes to when you think about those populations sort of underserved by today's care, it's clear that like this can have a major impact on some of those populations. Is there anything else you want to add about how you guys think about kind of market access or even expanding reach with something like this to patients?
Pravin
09:52
So everything we've talked about, Joe, has been in the U.S, and we're here, and that's the reason. But, you know, I'm an immigrant in this to this country. So, you know, from my point of view, outside the US is near and dear to me. You know, whatever we talk about in the U.S., in terms of the 40% dropout rate, the access to these drugs is very, very limited in areas that I visit, in areas that I used to do, you know, charitable services and so forth in Asia and parts of Europe, the impact that this will have there, really, as much as it is in the U.S., is even greater out there. And again, it's tragic that patients have to suffer from blindness, when we know that there is a proven target that is effective that we've known about for four decades.
Joe
10:34
So I want to ask you some questions about just developing these treatments for a second, and because, as we know from interviewing many folks, developing a breakthrough therapy is sort of one challenge, and scaling it is another. How are you ensuring that Ocular has the right infrastructure, partnerships, funding in place to support both successful trials, but also sort of future commercialization.
Pravin
10:56
Yeah, so the one thing about retina that really is important is that it's a very small field. There are not very many retina specialists, and everybody knows everybody. It's a very, very networked field. There are about 3,000 retina specialists in the U.S., and between us in this company, we pretty much know all of them, and pretty much know everybody outside the U.S. as well.
11:18
One of the reasons I'm here is because I had the chance to get the best of the best of the best retina specialists in this planet, together, and we did, and I know this sounds very arrogant, but there's never been a collection of better retina specialists in a company ever. Some of us have practiced for 2030, years. We know what patients need. We know what doctors look for. We know what buy and build looks like. We know what commercialization looks like, and all of that is being built at the highest standards possible in our company right now. The great thing that I have here, which I didn't have in my previous company, is that I don't have to tell people that there's a market out there. In my previous company, in Iveric Bio, we developed a successful product for geographic atrophy. We didn't know what kind of a market there was in geographic atrophy. We knew was going to be big, but we had to convince people of that. But there was no evidence. Here there's ample evidence of how large the wet AMD market is. That's despite the 40% dropout rate. So despite the just seeing a tip of the iceberg, it's still a huge market. The other thing that I have here that I didn't have to the full extent in Iveric Bio is a complete commercial team. We have a product in Dextenza that we're selling very successfully. So having a commercial team and being able to bolt on a retina product is a huge advantage. Our goal is to go all the way. We don't need any collaboration at this time. We certainly don't need collaboration for capital. We don't need collaboration for any expertise. We will go all the way and commercialize this product in the U.S. and outside the US.
Joe
12:58
Excellent. I want you to talk a little bit about your proprietary technology platform, ELUTYX, and can you maybe just tell us kind of what it is, what it does, but also, how does the platform differentiate Ocular from other players, and how might it open doors to new indications in the future.
Pravin
13:16
So it's a platform, Joe, that I knew about my previous company, and I had two independent groups find the best sustained delivery platform out there, and they both came back with the same conclusion, which was this. So I knew about this from ways back, and as I say, it's an FDA approved platform with an FDA approved drug. We're just putting the two together. The platform is a tunable, completely dissolvable hydrogel. The hydrogel is composed of peg bonds together with amine hydrogels. And that will release based on the proprietary formation of the peg. Now it's important to state that the API is not pegylated. Okay, the peg is around the ELUTYX implant, and that's really what's tuneable. But the API itself is not pegylated. Does not need to be pegylated. So, the beauty of this is that you can tune this to release in a month. That's what Dextenza is. It's exactly the same hydrogel. Or you can tune it to be released in 10 months, which is what AXPAXLI is, or anything in between, or more. So that's the beauty of this. One of the very first things that I look at with any technology that's looking to overcome the current treatment of the anti VEGF is safety. These anti VEGFs that we have right now, Eylea, Lucentis, high-dose Eylea and VABYSMO they are phenomenally safe. They're magnificent drugs. So if you're looking to outdo them, you better be darn safe. And what I looked at with this is not just that, over 5 million patients have been using this throughout the body with the same ELUTYX technology, not only that, everything that I saw within the eye with AXPAXLI had absolutely no safety issues, and still does not. But what really convinced me was our glaucoma product called PAXTRAVA. And PAXTRAVA is deliberately put in the most sensitive part of the eye, which is at the angle, right behind what we call the corneal endothelium. And the corneal endothelium is a mono layer of neuro ectodermal cells that's extraordinarily sensitive to any inflammation, any toxicity, and once those cells die, they don't regenerate, and they cause corneal thickness, corneal edema. It's sort of a test place and a test case for everything. And we deliberately put PAXTRAVA there, and there was absolutely no change, no change in the corneal endothelium, no change in the corneal thickness. And what the translation that to me is that it's absolutely, perfectly safe.
Joe
15:55
That's an incredible result, even if I do say so myself, and I'm glad you talked a little bit about safety. I actually want to pivot back to accelerating the path to NDA submission while staying aligned with FDA guidance. Where do your lead programs stand today, and how are you building momentum across sort of clinical and regulatory milestones this year.
Pravin
16:14
We have been absolutely careful and obsessive about doing everything the FDA wants us to do. The FDA, in February of 2023, issued very clear draft guidelines and said, This is the way we want you to conduct clinical trials, if you want to do it at no regulatory risk. This is the way we want you to conduct a superiority study. This is the way we want you to conduct a non-inferiority study. It's in their website. It's about as clear as day, and that was issued in February 2023. We have followed their guidelines absolutely obsessively, because we don't want to take any regulatory risk whatsoever. We were rewarded with a spa agreement for the SOL-1 study. That study has recruited extraordinarily well. We're not only looking at the speed of recruitment, which is important, but to me, even more important is the quality of patients. And right now, that study is masked, the SOL-1 study. So what we look for to see the kind of trial conduct we have and the quality of patients we have, is we look at the number of rescues. We want the rescues to be high because we specifically chose the patient population that was VEGF dependent. So we want the rescues to be high because we want that delta between our drug and ILEA to be as great as possible.
17:34
And indeed, we're seeing a high rescue rate, exactly what we want to see. The second parameter that we look for is we want the cadence, the profile of rescues to be what we expect it to be. We don't want it to be anomalous. In other words, we want the rescues to occur when we think they should occur. And that's exactly what is happening. The third thing that we look for is we want to make sure we deliver the FDA an absolutely clean study. So we want those rescues to be on protocol. And what I've said is that the vast, vast, vast majority of rescues are absolutely on protocol. So we couldn't be happier with the trial conduct of SOL-1 that is said to read out in the first quarter of 2026 we're absolutely on schedule. The second study is called SOLAR. That's the non-inferiority study, and what we said publicly is that our recruitment for that study is going phenomenally well. We have not given guidance as to when that readout is expected, we will and when appropriate.
Joe
18:34
So it's no secret with aging populations and rising rates of diabetes globally, retinal disease is going to continue to be a growing public health challenge. So when you're talking to investors at our conference and other locations, how are you kind of talking about, the tail winds that are going to be affecting this market, the demand, and then sort of the need and the opportunity, kind of going forward, both the public health need, but then you know the opportunity from a business standpoint.
Pravin
19:00
One of my favorite questions that anybody can ask, because I think we're in great shape in that regard. So let me just talk about the market in general, and then the market specifically, now, with all the changes and the instability that has occurred. So in general, the opportunity for this drug, as I mentioned earlier, is enormous, right? Every drug that that targets VEGF, that has worked in wet macular generation, has worked in diabetic retinopathy, diabetic macular edema, retinal vein occlusion. So all those, those fields are absolutely humongous. Now we do have a small study that we're extremely excited about in non-proliferative diabetic retinopathy, where we gave this drug one injection, and after 48 weeks, the results were remarkable. And let me explain, so patients that have non proliferative diabetic retinopathy left alone. These are young people that are in the workforce, that have diabetes. They may be doctors, lawyers, truck drivers, what have you.
19:58
They can't come in on a monthly basis to get an injection in the eye, or a by monthly basis, they're asymptomatic and they're not coming in. So those patients aren't treated at all, the percentage of patients being treated in this country is far less than 1%. However, left alone, their risk of vision-threatening complications, year by year, is 30 to 40% vision threatening complications. So in our study called Helios, when you look at the control arm, indeed, the risk of vision threatening complications was 37.5%, which is in line with what's expected. With a single injection of AXPAXLI after 48 weeks, that risk was zero, literally zero. The impact that this drug can potentially have with that and other things is huge. So that conversation with investors is really quite easy. Now for the company itself, in this macro environment, the instability that we see, look, we've been extremely conservative and disciplined from a regulatory point of view, from a financial point of view, from a regulatory point of view, we already discussed the fact that we've done everything exactly as the FDA wants, and that SPA that we have right now looks really valuable in this time of instability and the interactions that we have with the FDA looks great. As far as financial responsibility is concerned, we've been very, very disciplined with our capital. We're well capitalized. We're capitalized into 2028, so we're capitalized to see the positive results of SOL-1 and SOLAR as well. Obviously we didn't anticipate this kind of a macro environment, but the fact that we did everything conservatively and exactly the way that one should do it, in a disciplined manner, both from a regulatory point of view and a financial point of view, has been very beneficial for us in this unstable environment.
Joe
22:00
So this leads us to our final question, and look, it's a pivotal time for Ocular and you've outlined so much about the company, I think our listeners certainly maybe didn't fully appreciate before listening to this, but I wanted to get a sense from you. You know, when you think about the next 12, 18, 24, months, where else do you see exciting growth opportunities for the company, but also, how else might you be scaling the company to sort of meet this future demand that we mentioned?
Pravin
22:27
So that's a great question, and that's our focus right now. The first thing I want to tell you is, look, the company is laser focused on the sole trials. We don't have a whole bunch of shots on goal. I don't want a whole bunch of shots on goal. A company of our size, when they say they got lots of shots on goal, that means that they really don't have any shot on goal. We got one shot on goal. It's an empty net, and that's the shot we're going to take. And the entire company is focused on that. And because everything is done in house. We have total quality control, we have total IP control, and we can scale up. We've already demonstrated we can commercialize something with Dextenza. We're scaling up to commercialize this on a global basis, and that's happening right now. We've got the team to do it. We certainly have the funds to do it at this point, at least, to begin doing it. We have the expertise to do it, and we have the path to do it. So this is the primary focus, which is to make sure that we're ready to commercialize this on a global scale.
Joe
23:29
We want to really thank you for your time today. I think we've learned a lot. I think that the innovation that's going on at your company is pretty incredible. And we wish you all the best, and we hope you'll come back and join us again soon.
Pravin
23:40
Thank you for having me. It's an honor and a delight to be here, and thank you for the invitation. It's really been fun and informative. I really appreciate it.
Joe
23:50
Thanks for listening to Pathfinders in Biopharma, brought to you by RBC Capital Markets. Please remember to subscribe to get more great content and be alerted about future episodes. This episode was recorded on May 21, 2025. If you’d like to learn more or continue the conversation, please visit rbccm.com/biopharma. See you all next time.