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Awesome. Thank you all for taking the time to join us today. For those unfamiliar, my name is Jack Allen. And for this session at the Baird Health Care Conference, we have the Ocular Therapeutics team and we have Praveen Dougal, the CEO. Thank you so much for taking The Time to join Us, Praveem. Jack, thank you for having us here. I like to kick it off with a brief overview of the company, but the CEO tends to do a better job than the analyst. So I'll send it over to you for a couple of minutes on Ocular and then we'll jump into some news. You had some updates this morning. So, Oculotherapeutics is a company based in Bedford, Massachusetts, and what we have is a TKI, or tyrosine kinase inhibitor, on a proprietary hydrogel platform. The idea is to go ahead and block a receptor, VEGF, which we know works very well in diseases such as wet macular degeneration and diabetic retinopathy. There's more than 40 years of data showing that, and tries to solve two problems. The first problem is that of sustainability. We know that despite having a very effective treatment in this country alone, more than 40 percent of patients drop out in the first year. So that's the more obvious problem that we're trying to solve. The second problem that were trying to saw was that even in those patients who continue to get treated and happen to be able to come back, after about two to five years they inevitably lose vision. is probably because of the pulsatile nature of treatment where we give injections every month or every other month, and that causes a thickening and thinning in the back of the eye, much like a concussion in your brain, which causes scarring and fibrosis. So we're trying to achieve a greater degree of sustainability as well as a better long-term outcome by suppressing a known and validated target. Got it. That's a great overview. And we'll get into the data and all of the background surrounding Axe-Paxley, but it would be remiss if I didn't jump in with the press release this morning. You're looking to bring Axe Paxley to market in 2027 and file the BLA, sorry, BLA or NDA by the end of this year. And you had a positive meeting with FDA that you put out some news before market opened today. Maybe could you just overview the updates and your confidence in the ability to file by the beginning of the year? And, you know, what we've done from the time that this team came in about a year or two, two and a half years ago, is we've been in constant touch with the FDA and everything we've done is exactly according to the FDA guidelines. And that's why for SOLE 1, our successful Phase 3 study, we have a SPA, a special protocol agreement. From the very beginning, we have discussed with them the possibility of a single trial approval. And what they've said has been very clear and very consistent, which is that you need two evidentiary standards before the card turn and two evidentary standards after the card turn to allow for a single trial submission. And those evidentiary standards have never changed in the last few decades. First, you need to have a study, this is before the car turn, that is properly masked. That means no sham. It doesn't mean that sham can't get approved, but just not with one trial. So properly masked, the second one is that it has to be properly powered. Now both Both of those boxes have been checked officially because we have a spa, obviously. And after the card turn, the two boxes are one, the p-value has to be less than 0.001, and ours is less than the 0.0006. And the second is that you have to be able to supply the FDA at the time of the submission with at least 300 patients who have been exposed to the drug for safety reasons only, and we're able to do that. So we checked all the boxes. We are in line with all the evidentiary standards, and in a Type C meeting, we have official confirmation by the FDA that we're able to submit with a single trial. And part of that process was a pre-NDA meeting, which is really an operational meeting that we said that we would get completed by the third quarter of this year, and the press release this morning shows not only that we are doing it in time, but that we were completely aligned with the FDA in order to have our complete submission in the fourth quarter of this year. That's great. That's a great context. And you touched on the submission. So it seems like it's going to be supported by the efficacy data from SOL-1 and then some safety data from Sol-R. Can you just talk a little bit more about the mechanistic aspects of, I mean, Sol runs a closed, maybe there's a long-term follow-up, but the primary evidence from SOL 1 has been unmasked and unblinded, and that's your evidence of efficacy. But then there is a dynamic where you're taking data from an ongoing study with SOLAR. That's correct. How are you protecting the integrity of that study as you accrue that safety data? Yeah, that's a fantastic question. And look, SOLAR, the second study, the non-inferiority study, is very important for us, for OUS regulatory agencies. And as you mentioned, it's vital for us to protect the integrity OFSOLAR. The FDA simply wants 300 patients that have been exposed to the drug. And that's true of any study. It doesn't have to be the same target. It could be any other target, any other disease target. It doesn'T even have to bE the same dose. It can't be a lower dose, but it can be a higher dose. And what we needed to do was to get the safety data from approximately 130 patients from SOLAR. Now, we wanted to do that but protect the integrity of the study. So what we're going to be doing is having only the safety data go to a third party who is then going to go ahead and transfer that to the FDA. So we'll not be in that chain whatsoever. We'll also take an alpha hit. Now, arguably, we don't have to take an alpha hit because it's only safety data and it'll be a third party. But we'll take a very small alpha hit anyway to, again, protect the integrity of solar. So we're doing absolutely everything possible to protect the integrity of solar, not because solar is necessary for FDA approval in the U.S., but we believe that protecting the integrity of solar will be very important for regulatory agencies outside the U.S. Yeah. Is that process and the mechanisms there something that the FDA is familiar with and that you've already discussed with them and all agreed to? They're certainly very familiar with that. This is, again, we typically don't get into discussions and the details of our discussions with the FDA, but suffice it to say that there's really nothing that we do that the FDA is not aware of. We do it with complete alignment and collaboration with the FDA. Great. Anything else to dive into as it relates to the more recent update? Or should we step back and talk about Axipax, the sole one data, and familiarize some people with the effect that you've seen with the drug? Yeah, I think the important point here, Jack, is that there's obviously been other news, not from our company, but from others, which have maybe muddied the water a little bit in general. And there was some question, I think, as to whether that has changed anything in terms of our determination to go forward with this trial and anything with the FDA. And I think today's press release answers that. Nothing has changed whatsoever. You know, certainly our alignment with the FTA remains, you know, absolutely intact. And what the FDA has told us has not changed one bit. And our pace has not change. and really nothing has changed. I think the takeaway from the press release today is that we're hitting every single target that we said we would hit. Yeah. I guess maybe we can compare and contrast versus the competitor. You have single-agent efficacy data in SOL1 that is pretty undisputable versus the competitors designed a non-inferiority study, and unfortunately their results did not bear out as they had hoped. I mean, the strength of the data package that you have with SOL1 is differentiated from that. Can you just dive in a little bit more as it relates to the SOL1 data, what we saw, and how you designed that trial to show the indisputed effect of Oxypaxil relative to the standard of care idea? You know, Jack, I don't know what there is to compare. I mean, we have a successful study, and they've got a failed study. I mean that's the end of the story. I mean I don' t know what else there is there to say. You know again, I do' n't take any kind of joy whatsoever in seeing failure. And as I said many times, I'm grateful for the fact that when a study fails, somebody stands up and says, yes, the study fails or the study failed. After whatever was done after that is is something that to me is quite confusing. I think we need to protect the integrity of science. I think. We need to be honest. I. I think we need to be truthful, and I think there's a certain sanctity in making sure that what we're talking about is scientifically valid. I think it's a service that we do to our patients to make sure that we tell the truth and not spin things, and look, I've been part of many failures in my life and in biotech. For 30 years, as you know, I was on the other side doing clinical trials, and most of them frankly failed, and some of them do fail. Nine out of ten of them fail. And when that happens, no matter how hard you compete, you stand up and say, you know, we missed the primary endpoint, we failed, and that's it. I mean, the story ends at that point. And then you move on to other things. And that's what keeps the science going, andthat's what keepsthat's us educated. And at the end of the day, that'swhat's best for patients. Yeah, and so let's make it more about Ocular and the data there. Can you just level set what you saw with SOL1, the positive study that you showed an undisputed effect as compared to ILEA and the rescue rates in that trial? So the first thing to say is what we have done is in very close collaboration with the FDA. And what the FDA has stated in 2023, in February of 2023, is to say we will not allow sponsors to do a study against a label that nobody uses. And I think everybody knows that as good as the anti-VEGFs are, there's not a single human being in this planet who is treated per label, whether it be ilea or lucentis or vibesma or high-dose ilea, it's simply not possible and nobody does that. Everybody does treat and extend. The FDA knows that, we know that, and they made it very clear that if you want to do a study that is risk-free in terms of the regulatory purposes, here are the guidelines. And they clearly laid out the guidelines for a superiority study and a non-inferiority study. And it started with making sure that it's properly masked. In other words, not having a sham arm. We followed those guidelines exactly. And we were rewarded with a SPA. And the SPA validates that. And what we did, as I said, is we met the two evidentiary standards prior to the car turn. Immediately after the car term, we hit a superiority endpoint that nobody else has before. There's not a single study in my field that has hit a superiority endpoint versus an anti-VEGF. And we did with a p-value of less than 0.0006. And now being able to supply the 300 patients for safety purposes allows us to check all the boxes to provide a complete submission to the FDA. Yeah. And for those less familiar, though, with SOL1, can you just talk about the design of that study and what you showed as it relates to superiority versus ILEA? Yep. Well, What we showed there is, again, designed as per the FDA's requirements, which is as pure as it can possibly get, a single injection of ILEA versus a single injection of Vax-Pax-Li after the loading phase. And the primary endpoint was the percentage of patients who lost vision. And that vision that was the threshold, the FDA has always said, is going to be 15 letters. Why 15 letters? Because that represents a doubling of the visual angle. And we showed that to a statistically significant degree. There were far fewer patients that lost that amount of vision with X-Paxley than with ILEA. Now, that was the primary endpoint. And one may look at the primary viewpoint and say, wait a minute, is this really clinically relevant? And that's not an unfair statement. What I can tell you is that from an FDA's point of view, and again, I don't mean to talk for the FDA, But from what I understand from the FDA's point of view, this is about as pure a comparison, as transparent a comparison as you can possibly get. And from their point of vue, it's akin to a single cycle of treat and extend. We do that all the time. We give an injection and we allow the injection to wear off, and then we adjust the frequency based on that. That's what treat and extent is. Now, the retort may be, but we don't wait for 15 letters of failure, and that's absolutely true. But from an FDA's point of view, the OCT, which is what we use clinically, is not something that's approvable for this disease. And from their point of vue, the 15-letter threshold is a line in the sand. They're not going to change that. They didn't change that because that represents a doubling of the visual angle. We abided by all of their guidelines. However, the clinical part of this is that it was important for us to be able to show clinicians, look, the primary endpoint may be something that you're not familiar with. The study design may be Something that you are not familiar with. But look at the endpoints that we have achieved, the secondary endpoints, after achieving the primary endpoints. You have to achieve the primary endpoint first to talk about the secondary endpoint. But look those endpoints those are all absolutely clinically relevant. What do I mean by that? There are three things clinicians want to know. The first thing is they want to know if your drug is safe, because the anti-VEGFs are remarkably safe. We showed safety data to the patient level right off the bat. Nobody does that. There's nothing more to show. We showed patient-level safety data because we're so proud of the safety profile. The second thing that we did, the question is really going to be, how well does this drug control disease? and what we're able to show is that with a single injection at nine months there was OCT control within 30 microns. That's unheard of with a single injection. The third question is how long does this drug last and we're able to that after one year with a single injection two-thirds of the patients were rescue free. So all of those questions that clinicians want to know have been absolutely answered within the sole one study alone. Yeah so it's both a regulatory pertinent data set and also a clinically correct data set for both aspects of that. And then the other data set that you're driving now towards is SOL-R. I think you've thoughtfully designed, this is a non-inferiority study, and you've thoughtfully designed the trial to have a run-in period where you're identifying patients that aren't going to see substantial differentiation post the run-on period. Can you just talk a little bit about that run-and-period and how you've designed the trail to select for patients that are well, I guess, predisposed to be in a non-inferiority study in that way? Yeah, I think that's a really good question. And patient selection is extraordinarily important in our field. And let me kind of step back a little bit. All of you are used to, you know, oncology and immunology, et cetera. You know, those fields are at least 75 years more advanced than our field, and we have no disease stratification whatsoever. If I were to go to you, Jack, and say, look, I've got a drug for colon cancer, I mean, you just kind of look at me or laugh at me, you'd say, like, what kind of colon cancer? What stage? What grade? But yet, I can go to many of you and say, look, I've got a drug for wet macular degeneration, and you're okay with it, right? I mean, but the fact of it is, look. We have patients with wet maculogeneration that require Lucenta sometimes every two weeks, you know, sometimes every six months. They all look exactly the same. And that's why we have Treat and Extend, because we have absolutely no disease stratification. And when you're doing massive studies like Anchor and Marina or Hawk and Harrier, those factors may balance out. But when you are doing smaller studies like we're doing, patient selection and de-risking the patient population is terribly important. And we've done that in a custom way, in a bespoke way for each study. For SOLE1, we specifically needed patients who are going to lose vision, who are anti-VEGF dependent. And so we tested them. We gave two injections of ilea. We wanted to make sure that they improved by 10 letters or got to 20-20. And then we allowed them to fail, meaning lose vision once, just once, before they were rescued. That was the purpose, right? On the other hand, with SOLAR, because it's a non-inferiority study, that's not what we want. We want actually the opposite kind of patients, so we want rock-solid stable patients. So what we're doing there is we're going ahead and loading with three doses, and one could say that after three doses you've sort of reached a plateau in every anti-VEGF study where patients are stable, but we're not satisfied with that. Now we've got two additional periods of simply observing the patient, and what we'RE observing for is any kind of fluctuation whatsoever. If they have any fluctuations, they're weeded out. if they're rock solid stable, then they get two more loading doses, and only then are they randomized. It's a very long ramp. It is a very, very thoughtful ramp. And what we're ensuring is that the patients that are randomized are patients that as stable as we can make them before they're randomized. And that increases the risk of success of this non-inferiority study by de-risking the patient population. Yeah. And this noninferority study, as you say, is primarily for XUS approval, but it is one of the studies that is going to drive the multi-dose kind of treatment effect as well. I think in the release this morning, as it relates to the U.S. approval you alluded to, including some repeat dose data there, how do you think about the read-across from the SOLAR data to the US NDA from the multi‑dose perspective? Yeah, so let me just make it very clear. Our expectation, again, we haven't had labeling discussions with the FDA. I want to make that very clear, it's obviously premature to do that. But our expectation and our hope is that our label will be the best label in this field ever, which is the first and only superiority label that allows for flexibility of dosing from six months to 12 months with repeatability. And you asked about repeatability, well, realize that every patient in SOLE1 has had repeat dosing. At week 52, every patient INSOLE1 was redosed. So what we'll be giving the FDA is a lot of redosing data from SOL1 as well as every patient from SOL-R. So I think it's legitimate to have the expectation and the hope that we will have redosing in our label. And as I say, realize that every patient that we Will be submitting is going to have been redosed. Do you have any expectation for solar data ever making it to the FDA as it relates to a label amendment as well? I'm just curious. I know it's crucial for the ex-U.S. approvals, but could it also help expand the label as well in the U.S.? It certainly can, and we haven't publicly discussed the details of that. But what's important to realize is that the solar card turn is now at week 96. As you know, that study is going to be amassed all the way to that point. And the reason for that is not just de-risking SOLAR, but also because we want to have a possibility at a superiority result versus high-dose ilea. And that superiority result can take a number of parameters, right? It could be visual acuity and or something like number of injections, OCT thickness, atrophy, fibrosis, et cetera. Depending on those results, we'll have further discussions, I'm sure. But at this point, it'll be a little premature to predict that. Got it. Very thoughtfully designed program in wet AMD. Can we step back now and talk about the commercial opportunity? We've talked about ILEA, ILEAI-DOS, Vibismo, SysVismo. What do you see as the best commercial comp here? And where do you think Axipaxi plays in the long term in the commercial landscape in wet AMD? Yeah, so let's just talk about the commercial thirst, first of all, in terms of a drug like this that has increased durability, right? You know, what I will tell you is I'm old enough that, you know, I was part of the entire anti-VEGF process. We first had Anchor and Marina. We had no other treatment. Phenomenal studies that a phenomenally good company, Genentech, did, just pristine studies. They had a seven-year head start with Lucentis. You know, then came a company that we'd never heard of called Regeneron, and then came ILEA. Now, ILEAs not safer, it's not stronger, but ILEa may arguably last a week or so longer. And after seven years, which is really infinity in our field, ILea absolutely dominated. And you can see that happening now as well, right, with Vibismo. It's not safer. It's Not necessarily stronger, But it may last a couple of weeks longer, and it's dominating the market. So there's a great thirst to have something there that will allow more sustainability because it's tragic to see that 40% of patients in this country are going blind and dropping out or dropping out and going blind. So we're in a different orbit altogether, right? We're not expanding by a week or two. Two-thirds of our patients are rescue-free at month 12, and that's remarkable. We've never seen a drug that's able to control disease and give us the durability that this drug has. As far as adoptability goes, it'll be adopted, in my opinion, immediately. There's no overhead to this. There's not a single piece of new equipment to buy. The workflow doesn't change. We expect to have very favorable pricing, although we're not in any pricing discussions at this point. But this will be, in our opinion, very easily and very, very quickly adopted. As far as the launch process is concerned, as you know, we have a commercial team already that's selling Dextenza. We have enhanced that team. We're ready to launch. We have a fantastic leader in David Robinson who launched ILEA, which is the most successful launch in our field. And that team is already set. As far As the scaling up of manufacturing is concerned. As you know in September we did a raise. We use that largely to scale up our production. We've done that. It is all done internally. There are really no tariff issues or anything like that, internally meaning in Bedford, Massachusetts. And we're ready for the launch. We have more than enough inventory. Our scale-up at this point really is not so much just for wet AMD. We're already set for that. Our scale-up at this point is in anticipation of diabetic retinopathy, which is three and a half times as big as the wet macular generation. I want to touch on that, but briefly on the commercial opportunity in wet AMD. There are a lot of large companies with massive marketing teams in wet AMD. How do you think about competing against that as a smaller, earlier stage, earlier biotech? Well, I mean, again, it's important to sort of shift a little bit from what the audience and you may be used to, which is oncology and immunology and so forth. Realize that in the height of Lucentis sales, Genentech had, I think, 55 sales reps. That's not a lot. So it's not like we need hundreds and hundreds of sales reps, but those sales reps have to be really, really good and really well networked, and this is why we kept the Dextensa team, right? This is why we have a commercial team, this is why we've worked so hard to make sure that we we enhance the commercial team from the very, very beginning. And by the way, it's a, you know, Retina is a very networked field. We know everybody. This company has more Retina talent per capita than any other company in the planet, and we say that we're for Retina, by Retina. We know everybody, we've trained a lot of people, and the PIs are also our customers, and look how we recruited. So I am very, very much looking forward to the launch. I think it'll be seamless. We're ready to do it. We couldn't have a better team, and I couldn't be more excited. And it's becoming an increasingly concentrated space, too, as the retina clinics kind of consolidate and drive their purchasing power towards single contract deals, right? So as you say, Lucentis launching with 55 reps. I'm sure there are more reps now with these companies, but it could be a situation where you have a concentrated set of buyers that you have to approach and you have existing relationships with already. Yeah, and again, it's not just me. Obviously, we have a great team of extremely well-established retina physicians. And that kind of inside baseball knowledge, if you will, is extraordinarily valuable in retina more than anything else. And we are well-designed for the launch. Great. You alluded to diabetic retinopathy. This is a space that maybe people are a little less familiar with, given the pharmaceutical landscape there. But could you just level set as it relates to bringing axopaxil into diabetic retinoopathy when we could get the data from those ongoing phase three studies? Yeah. First, what I would say is, look, if you as a physician have ever injected an anti-VEGF in a patient with diabetic retinaopathy, what you see is nearly miraculous. It works extraordinarily well, and it works fairly quickly, but it works phenomenally well. On the other hand, if you look at patients with diabetic retinopathy, that's also a tragedy. They're young people. They're people that are in the workforce. They may be accountants. They may Be lawyers. They may BE car drivers, but they're working, and their risk of having a blinding or vision-threatening complication is about 30% to 40% year upon year. I mean, just think about that. It's like having a ticking time bomb in your eye. And one naturally would wonder, well, if you've got a drug that works so well, how come nobody's getting treated in a disease where, you know, apparently there's a ticking-time bomb in their eye, right? And nobody's being treated. And the reason for that is because these patients who are asymptomatic simply cannot come in on a monthly or bimonthly basis to get these injections. What we saw in the Helios study is that with a single injection, when we looked at patients at month 12 in the control arm, Approximately 27% of patients had a vision-threatening complication, which is well in line with what you would expect. So it's actually a representative patient population. That's the control arm. In the study arm with X-Paxil, with a single injection after a year, the rate of vision-Threatening Complications was literally zero. And when we as clinicians looked at that, we said, wow, that is phenomenal. That's absolutely doable. I mean, the conversation would be, you know, Ms. Jones, you have a 30% to 40% chance of having a vision-threatening complication year upon year. Right now you're seeing 20-20, but there's a ticking time bomb in your eye. And if you come to see me but once a year, much like you go to your dentist for your teeth cleaning, I can reduce that risk literally to zero once a years. That's doable. And the patient population for that is three and a half times bigger than wet macular generation. And by the way, it's not just diabetic retinopathy. It's also diabetic macular edema because in this Helios study, the registrational study, we're also including patients with non-central involving diabetic macula edema. And the results of our original study for diabetic maculardema was also absolutely remarkable. They all improved. So our expectation, again, we haven't had labeling discussions, obviously, with the FDA, but our expectation is that we will never have to do another diabetic retinopathy study again, and the label will allow physicians to treat all of diabetic retinoopathy, including diabetic macular edema. And when should we expect the data from the pivotal program then? Yeah, so that's recruiting extremely well right now. It's a global study. We haven't guided you as to the milestones as yet, but we will when it's appropriate. Great. Now, it seems like a great pitch, not only for the patient, but also from a health care system perspective. I would imagine there's quite a bit of cost saving getting rid of those catastrophic events. Absolutely. And I guarantee you it will be the payers that will actually drive this process. Years and years ago, I was on the board of a company, of a big payer company called Banner. And what we had was we had these non-midriatic cameras in all the PCP's office. and the pictures would come to my office and we'd say you know come back in six months or come back right away but you know the cost savings is not just the human say it's not just a human that factor but the cost savings of someone being treated prior to getting diabetic macular edema or prior to giving a vitreous hemorrhage or prior to gaining attraction detachment is enormous so absolutely the payers will want this and they'll actually drive the patients to get this these injections that's great well hopefully Hopefully then the study enrolls in good pace and we can get to that data set and bring that to market as well. Praveen, I think we're coming up on time here, but maybe the last question I had was what catalyst should we look for in the next six to 12 months? And I think part of that's going to be the NDA submission and regulatory discussions. And then how is the company positioned from a cash balance perspective in funding the business? In our last earnings report, we said that our cash balance was approximately $666 million. were funded into 2028, and very conservatively, and that has not changed. As far as catalysts are concerned, look, you saw one today. Obviously, we look forward, and we all look forward to the full NDA submission. We've said that that's going to be in the fourth quarter of this year. We're on target for that. We will also have numerous other catalysts that will be announced. One of the things that I'll tell you is, at this point, I very much look forward to talking about diabetic retinopathy and showing you more data on diabetic retina. We're not really getting any credit for diabetic right now, but it's a huge field and you should look forward to getting more catalysts in that regard as well. That sounds good. We'll have to keep an eye out for that. Thank you so much for joining us. Thank you, Jack. Thanks for having me. Thank you.