Ocular Therapeutix – Piper Sandler Fireside Chat - OCULAR THERAPEUTIX INC

All right, maybe we could get started. My name is Biran Amin, I'm one of the biotech analysts here at Piper Sandler. We've got a fireside webinar with Ocular Therapeutics this afternoon. I'd like to welcome Dr. Praveen Dougal, their CEO and chairperson. So, PraveEN, welcome. You know, a lot going on in the retina field, but maybe, you know, we could just step back and kind of calibrate where you are with Xpaxily. Can you just give us an update in terms of the regulatory filing that's expected Q4 this year, what we should anticipate as we head into next year? Barron, first of all, thank you for having me here. It's always a pleasure to speak with you, and thank you för the opportunity. And I totally understand that there's a lot going on outside. But what I would say is that as far as this company is concerned, really nothing has changed at all. You know, we said that we're going to have a pre-NDA meeting in the third quarter of this year. We did. It was a very successful meeting. We received the minutes from the FDA. We're very happy with the minutes. We said that wir're going be filing the NDA in the fourth quarter of the year. And we're right on track. Every day we're more and more confident and more and excited about our filing. And again, I totally understand and respect that there's a lot of stuff that has happened on the outside. for us internally not a thing has changed we just keep on executing and executing and executing and i keep on asking people just just tell me one thing that we said we would do that we haven't done and i don't don't think there's anything at all at least that i know of or as anybody has told me and my job is to is to continue to have uh the the team uh perform as they are by executing uh everything that we promised we would and we continue to do that so the answer to your question is internally, absolutely nothing has changed. So everything's on track in terms of NDA filing? That is correct. Okay. And then, you know, recently at AEO, I think news came out that Bill Boyd, the director of FDA's ophthalmology division, he's retiring in January. One of his deputy directors, Rhea Loy, is taking over. Can you just maybe talk about that? You know, Investors sometimes ask, change in leadership, does that mean change in views, your interactions with Dr. Lloyd to date, and how you kind of see her views of Xpaxly? Yeah, you're right. It did come out of that time. And what I would say is we are absolutely thrilled that Dr. Rhea Lloyd is going to be taking over. We know her very well. She's been there since the late 90s. We've interacted with her numerous times, all of us, particularly when I was on the other side as a practicing physician. Dr. Lloyd has been in every one of our meetings. She signed off on everything that the FDA has signed off upon. She is absolutely lockstep with Wiley Chambers, Dr. Wiley Chambers and Dr. Bill Boyd. And what I would say is when this was announced in iAccelerator in the academy, Dr Chambers said, reiterated in a panel that he was with me, there will be no changes. This is absolutely seamless. Very importantly, he also said this is exactly why companies get a spot. And he turned to me and he said, to build confidence in the community that if there's any change, that this will be continued, exactly why companies get a spa. And for the record, as far as I know, the ophthalmology division has never broken a spa, and by the way, that whole spa process, Dr. Lloyd was involved in the entire thing. And on Sunday, when Dr. Bill Boyd gave his talk, he reiterated that Dr. Lloyd is absolutely lockstep with everything he expects to be completely seamless. And clearly, our relationship with her, as well as the fact that we have a spa, as well as that she's attended absolutely every meeting and signed off on everything, is going to assure us with great confidence that this will continue seamlessly. And we haven't seen any change and expect any change in the direction of what we're doing, which is a single trial submission. Got it. I've received an investor question. Would you expect a priority review when this application goes in? Well, so I think it's important to understand that what we'RE trying to do here is with the support and collaboration of the FDA, and this is not a sudden thing. This has been going on for at least two years. We are going to be submitting a package that is as efficient as possible and as safe as possible. We're doing everything possible at this point to make sure that that package will be the best package that we can possibly have. We already are on an accelerated path. That's important to understand. We have a 505B2, and we already are in, we believe, the most efficient and most accelerated path for this single trial submission. There's really no reason to veer from that at all. Sorry, go ahead. No, I'm sorry. And then another investor basically emailed me earlier today saying his main concern is that now FDA has seen iPoint's two negative failed studies and, you know, Kodiak's positive phase three daybreak trial. and, you know, would it change their mind and would they want to see SOLAR data before considering approval of X-PAX link? Yeah, I mean, look, the bottom line is the FDA has seen none of those things, right? Because none of Those things have been submitted. I mean so that's actually a false premise. They haven't seen any of that. I mean they haven't Seen any of the trials that you talked about unless there's a package that's submitted and the FDA always asks for raw data. Right. Not the press release, not what's out there, but raw data. The FDA hasn't seen any of that. So that's simply not true. And the FDA is not going to go by the noise in the community. They simply are not. And they're not going make a judgment based on a press release for anybody. They want to see the raw data, that's what they demand, and that's appropriate. So it doesn't change the FDA's view whatsoever, you know, unless they're biostatisticians, they're clinicians, they'RE scientists, and their decision is based on raw data. That's it. It's not based on PR. It is not based on publicity. It's not based on incomplete data. And there's, as far as I know, none of those studies have been submitted. And why wouldn't one submit failed studies or incomplete studies? So there is absolutely no influence of that in regards to our submission whatsoever. The other question that has been raised is, could there be a class effect? That simply doesn't happen with the FDA. I mean, you can think of anti-VEGFs that have failed, right? Even anti-VEGF that have been approved by the FDA that have failing in the community. That doesn't influence the FDA, if it did, we would have no other anti-vegfs thereafter, but yet we do. And I'm sure you can of that with other classes of medicine. Just like that, not all TKIs are the same. The irony of the whole iPoint experience is what happened, and we can discuss this in detail, and we should, is everything that we predicted would happen. And again, it's not that I'm trying to say that we're clairvoyant, but this was absolutely predictable. And we've been saying this for two years. And this exactly happened. We said that there was going to be a signal. We said that they're going to miss the primary endpoint. And for reasons that were very obvious to us, based on the only time we saw their drug by itself, which is in the diabetic retinopathy study. We said, and we should discuss this in detail as well, we said that the study was poorly designed because there was no attention paid to patient selection whatsoever. And this is the first study that I know of where previously treated patients were mixed with treatment naive patients. Patients were randomized and then loaded. There was zero attention paid to patient collection. All of these things are exactly the opposite of what we've done. And we've got the strongest TKI to suppress VEGF. And that's all we claim to do. We don't claim to doing anything else except to suppress VEJF with the strongest PKI possible. But getting back to your question, none of this is going to influence the FDA. We're moving forward with them as briskly and as safely as possible. We're going per their guidelines. We're completely collaborative, and we're completely lockstep with them. What would you say to investors that say, you know, we've seen this story with TKIs over the last, it's not just, you know, I point with Lugano, but with others as well. It's been a tough road for this class. What would you tell an investor that, hey, you knows what, there's actually a promise here, this is differentiate it? I guess, how would you address that concern, that investor concern? Look, it's a great question. And I can answer that by experience because I'm old. And it's an appropriate question to ask, actually. And in many ways, they're right. But let's just go back in history. Again, I lived through this, right, as to what happened with TKIs. What happened, and I was there from the very beginning, is when we first started using anti-VEGFs, there were two things we were sure about. We were sure that in this very complicated mechanism, biologic mechanism called angiogenesis, there had to be many, many other receptors, and it couldn't just be one receptor. And we were all absolutely certain that within a matter of a few years, we would be identifying other receptors that would also be effective in combination or separately. We were absolutely certain about that. That was one certainty we had. The other certainty that we had is we were absolutely certain that what we were doing, which is putting a needle in the eye every month and every six weeks at that time, was simply not tolerable. That something bad was going to happen to the eye. If you remember, and you're too young to remember, we'd actually take the patients to the OR to give injections because we were so concerned. And we knew that that was not something that what the eye was going to be able to sustain. Well, we were completely wrong on both those things. So where do TKIs come in? Well, based on that, we said, what can we find that will suppress VEGF because we know that works, but that we can give with other routes of administration because we knowthat giving intravitreal injections is simply not sustainable in the long run. So yes, you're right. We did a whole bunch of TKI experiments of which I was part of almost all of them, as well as my other colleagues, Jeff Heyer and Peter Kaiser and Nadia Wahid. But none of them involved intravitreal injections for the reasons that I mentioned. They were given orally, they were given by IV, they were driven by drops. And guess what? They all failed. It's not because of the TKIs, because of the route of administration, because what we're trying to do was to avert the intravitral injections. So TKI has got a bad name based on that. And if you go back and look at those studies, none of them were intravitreal. They're all a different route. And now what we know is, look, after 40 years, we haven't found another receptor that is additive to this. It's still the VEGF receptor. And what we've also learned is that it's fine to go ahead and give these injections on a regular basis intravitrally. The eye can sustain that, as miraculous as that may be. So when we give intravitral injections with TKIs that suppress VEGF, it works. And how do we know this? All you've got to do is to look at our data. There's no doubt based on, and we can discuss our data as much as you want when we should, especially with SOL1 data, that it's safe. Our safety data is very impressive, I believe. We've shown patient-level data. We couldn't give more information because we're very proud of our safety profile. We have durability. We've showed that with a single X-Paxley injection that the majority of patients, almost two-thirds of patients last for 12 months. And we've shown disease control with a single X-paxil injection. We've shown that there's OCT control, which is a barometer of the disease control, within 30 microns at month nine. And remember, this is in the most difficult patient population. These are patients that were specifically selected to lose vision. And if we can show that kind of data in this most difficult patient population, that data will only be better in the community. The fact of it is that TKIs absolutely work. We've shown that. This is the first study that has ever, ever in the history of this planet succeeded to show a superiority endpoint. And remember that it's done with a robust p-value of less than 0.0006. So the investor who questioned you is right, but it's not regarding TKIs. It's a reflection on the route of administration historically, and it's important to look at that. And there's no doubt whatsoever that TKAs work. And I'd go so far as to say that when you look at the two failed studies that iPoint had, there's also no doubt that the TKI there had a signal. And we said all along that it wasn't the proper TKI because it was a weak suppressor of VEGF. But there's no doubt that it had a signal. And what happened here, because of the TKI selection that they had, but very importantly, because they had absolutely no thought whatsoever to patient selection, that this was going to fail. And that's exactly what happened. But there was a signal, you mentioned better patient selection with solar and solar compared to Lugano-Lucia, that, you know, you've got a more potent TKI. From a release standpoint, do you feel that you've Got, you know, something that's more durable, that can deliver sustainably for six months compared to Dervium? Well, we clearly have shown that in the most difficult patient population you can recruit, right? These are patients who are absolutely selected to lose vision. Remember what we didn't sell one. We gave two loading doses of ILEA and we required patients to improve by 10 letters, we'll get to 2020, to prove that these were absolutely VEGF dependent patients, anti-VEGF dependent patients. They were VEJF responsive. And then we took the medicine away and allowed them to lose vision once. That is the most difficult patient to control. And despite that patient population, which actually, by the way, is the right patient population for this study because that's what we needed to see. To show a delta, we needed to have patients lose vision. If patients didn't lose vision, even for an effective drug, we wouldn't have been able to show a Delta. So that was the right way to pick this patient population for this particular study where patients were selected to lose vision and despite that, I think the results of Xpaxly in this patient population that we're quoting is absolutely remarkable. Now, it's important to understand that that's the opposite in SOLAR. And people sort of were befuddled in the beginning as to why we paid so much attention to patient selection and why we played so much tension to the actual loading process and why the ramp was so large in SOLAR. It's the largest ramp that I've seen in our field. It is a six-month ramp. And here we wanted to super select patients for absolute stability because that's what you want in a non-inferiority study, which is the opposite of what you would want in a superiority study, where you want unstable patients that are anti-VEGF dependent to lose vision. So here in SOLAR, what we've done is given three loading doses, which in and of itself should establish the plateau of stability, but that wasn't satisfactory for us. We have two months of simply observing the patients. And if there's a 30 micron fluctuation in the OCT, which is incredibly sensitive, those patients are weeded out. So we absolutely guarantee stability. And then two more loading doses, and only then do we randomize. Nobody has put that much thought into patient selection in a bespoke manner for each study. And this is completely different than what I pointed. Again, I'm not trying to pour salt on the wound, but we said this for two years that by mixing previously treated patients with treatment naive patients, you introduce variability by simply randomizing and then loading. There's no thought to patient selection whatsoever. And we know for a fact, in fact, on the paper that was written by Peter Kaiser and Jeff Heyer and Namrata Saroj regarding the V1 and V2 studies, that approximately a third of patients have are anti-VEGF addicts, and they fluctuate tremendously. And guess what? When you look at Lugano and Lucia, that's exactly what you see. About 30% of patients required numerous rescues because they weren't selected out. All those patients will be selected out and are being selected out, and so are. Those patients are the ones that would be fluctuating during that two-month observation period. And all of those patients would be selected out. So who we're randomizing are absolutely stable patients. So for SOLAR, you know, you're enrolling patients with minimal fluid variability. So you're, you Know, selecting out patients with higher variance. And clearly, you Now, that's likely going to help, You know, expaxily. What do you think, you know, how do you think the ILEA two milligram arm and every eight weeks and the ILea HD, the eight milligram every six months, how Do you think they're going to behave in this patient population? Well, look, I think I, I lay is a fantastic drug. I mean, you've seen that over and over again, right? I mean it's a fantastic drug. The bar for beating Ilea is extremely high level. You know, what we've done, I want to reiterate is we've not only achieved non-inferiority, we've actually achieved the holy grail, which is superiority versus what I think is a fantastic drug. So how do I think Ilea 2mg is going to behave? Well, remember, Ileia 2mgs is given on label. I think these patients are going to be very, very stable. And I think that Ileya 2mgr is going to behave as well as Xpaxilid, not only because the Xpxilid is that good, but also because the patient selection is that stringent for stability. I think they're both going to behave great. As far as high-dose ilea is concerned, you know, that's given per the expaxly arm, as you know. As a masking agent, right? And I think the way that that's going to behave is going to be not as good as the other two. That's our expectation. but but again it's it's really important to to realize that through this patient selection what we've tried to do is to guarantee stability and minimize any fluctuations and weed out those patients that are anti-veg f addicts that kind of attention has never been paid before and by the way it never had to be paid before in these massive studies and one might say you know look why wasn't this done before? It's because before, when you look at Anchor and Marina, when you Look at Hawk and Harrier, when You look at V1 and V2, these were massive studies that had, you know, 3,000 patients or 2,000, 3.000 patients. And one would argue that when the N is that large, you Know, this kind of imbalance can be mitigated. But we don't have those studies anymore. When the N is smaller, as in our studies, you know, unless you pay great attention to patient selection, you can be upended. An investor asks, you're waiting for readout with the two-year data, so two- year analysis, which is expected Q1 2028. Why, you know, push it out to Q1 2028. If approved in 2027, don't you want to have that data available to the market, to physicians? Yeah, the answer is yes. I mean, look, we'd like to put out as much data as possible. We're very confident in our drug. We've hit a superiority endpoint. And our goal here is to launch this product. We'RE set to do that. But the number one goal by far is to go ahead and have the best submission we can with the FDA. So anything that we put out is going to be in collaboration with the FDA and will not violate our work with the USDA. And that's really important. And people have also asked, and maybe you're going here, Barron, why don't you, now that your only competition is gone, and we considered iPoint competition because they're in the maintenance group as we are. You know, we're not a bolus drug. All the other ones, you know, including Kodiak are in the bolus group. And they'll compete with each other with non-inferiority and pricing and everything else if they get that far. We're in the maintenance group. We don't care what one bolus is with. You Know, we are a maintenance drug. And so was iPoint. And the question has been asked of me, and maybe you're going there with this as well. Why wouldn't you now because your only competition is gone and you've got a clear path forward, you have no other competition, why wouldn't you just go ahead and open up Solar? And it's not that that hasn't been thought through, but look, there's no reason for us to do that because what we don't want to do is we don'T want to pull the rug from under the FDA, right? I mean, we've worked with them for two years for single trial submission, and they've been extraordinarily supportive and cooperative, And now we're in the final stages. And the last thing we want to do is to change tracks and blindside the FDA. We're going to go through this process. Every day, we're more confident regarding a single trial submission. And that's the path we're goingto take. having said that, we also are responsible. We also realize that solar, while not necessary for FDA approval in the U.S., is going to be very important outside the U。S., and we're doing absolutely everything possible, everything that we possibly can to preserve the integrity of solar, and we'll continue to do that. It's mainly for the O.U.S. regulatory agencies. And I want to add that at some point, and we don't expect this at all, at some point, in the very, very little likelihood, and I don't want this to be taken as lack of confidence, it is not. And I just want to reiterate this, because every time I say this, somebody will say, well, you've never mentioned this before. But it would be irresponsible of me to put this company in a position where all my eggs are in one basket, right? So I have to make sure that there's a safety net no matter what. So people have asked this as well, in The Extraordinary unlikely that at some point the FDA says, you know, we also want to see SOLAR. The fact of it is it's there. And we've always said that from the very beginning. It's there with great integrity. We're preserving the integrity of SOLAR now. We're absolutely confident day by day that it'll be a single trial submission. Every indication, including the minutes from the FDA, including the formal type C meeting, the pre-NDA meeting, all of that have indicated that there's no reason to doubt that, but SOLAR is being preserved. The integrity of SOLAR is being conserved. Has FDA ever asked for data to see data from SOLAR in any of your discussions? No, that hasn't even been mentioned. Again, as far as the FDA is concerned, I don't want to speak for them, but I'll tell you about our interactions. They simply wanted to know if we could fulfill the obligation of 300 safety patients. I don't think they would have cared where those patients came from as long as they were the same age profile and as long as the dose of X-Paxilin was the same or higher. The target doesn't matter. And we said, yes, we can. And that was it. Solar has never been part of the conversation other than what I just mentioned for safety. Can you fulfill the safety requirements? We said, yes, this is how we're going to do it. We've discussed the mechanism with them, you know, at length to make sure that that solar remains completely unviolated. But as far as the approval process goes, that's never come up. Got it. An investor asked, and maybe you could elaborate on this a little bit, why would reading out Solar jeopardize submission? Maybe you could just walk us through that in terms of Solar, when it would potentially read out at year one, and what that would look like if you had done that versus taking the year two look. Yeah, it's a great question. And look, we have great, great confidence in the success of SOLAR more than ever. But realize that when you have, in the middle of a review process, when you have a major phase three card turn, there's no way any reviewer will not want to see that data. It's just not logical. Anybody would. And again, I've worked with the FDA and the other side for 30 years, they will make scientific decisions. If there's data out there, especially phase three study data, there's no way that somebody would want to see that. As soon as you have a card turn like that and they want to See the data, that triggers a major amendment. That means that all the advantage that you had in terms of the timing is all gone. The clock begins all over again. And we didn't want that to happen. And that's the reason we made the decision that we did now we have taken the risk of a major amendment off the table completely got it and then i guess you know some uh some i guess investors feel that um you need solar from a standpoint of you know it's every six months do you feel like you know doctors will know how to use expaxly if it's approved based on you know the sole one data that's available to them. So that's first question. And second question, an investor is actually asking this, you know, they want to ask, they Want me to ask you about the Kodiak data. And do you feel docs could potentially, you know? Would that be a competitor, Tarkozyma, would that be competitive to XPaxulate? So a couple of questions there for you, Praveen. Yeah. So let me take one at a time. You know, very appropriate, great questions. Let me take the first one, first and the second one, second. The first question, you know, is this so we want to provide enough data for doctors to use X-paxilin? It's a very appropriate question. And, you know. My flippant response, and this is not my response, but my flippante response is, you know, name me one drug in my field that's used per the phase three study trial design. You know, name one drug that's use per label. And it just simply doesn't exist. There's not a single drug that's used per phase three or per the label. Every drug is used, treat, and extend as far as the anti-VEGFs are concerned. And there's no such study. There's no Such Label, all right? And then the other thing that I also flippantly ask is to say, you know, what's the best-selling drug in our field? Not by revenue, but by volume. And it's Avastin. And there is no data for that, really. I mean, there is not a study There is no phase three study. I mean I guess the CAT study would be close, but there is study for that really. There's not approval for that. But yet that's the Best-Selling Drug. So doctors look at data. Doctors will figure out how to use drugs in general. And it's not going to be per study. It's not gonna be per label, but it's gonna be logical. And having practiced for 30 years, the questions, I know what questions they ask is the same questions that I would ask. what they will ask is to say, is this drug safe? And the answer is, of course it is. And this is why we gave patient level data and so on. I mean, nobody does that. Nobody goes and gives patient level data. And we did because we're very proud of the safety profile. The second question they'll ask is how long does this drug last? Andthe answer that we have is about as pure as you can possibly get a single injection. You just follow this most difficult patient population that's designed to lose vision. And what you saw was that in two-thirds of patients, these patients did not require rescue for a year. So you have a clear answer there. And the third question they'll ask is what kind of disease control does this drug provide? And that's based on the OCT. And what we're able to show there is that with a single injection, again, in this most difficult patient population that the majority were within a 30 micron stability by OCT. And that's unheard of. So everything that they need is right there in SOL1. All those three questions have been answered. And in this last academy, we've gone a step further. And I would encourage you to go to our website to download that talk. And what we're able to show is that if you give, after the loading doses, if you are dry, if the eye is dry, a single X-paxilla injection can be given, there's a 75% chance that that eye will remain dry for nine months. That's remarkable. A 75% chance with a single injection that that I will remain drive for nine months. Now, what's important to ask is what do we mean by dry? Right? What do we mean by drive? Well, what we mean, by drawing in this algorithm that we presented in the retrospective analysis in the AAO is less than 10 nanoliters of volume of fluid. Nobody has used that criteria for dryness. It is so strict. Nobody has used that. It's the strictest one by far. Now, segueing to Kodiak, they have not disclosed what their definition of dryness is. I think they should. I don't know what the AI algorithm is, But, you know, I would be very interested to know, and you should ask, if it is that stringent. I don't know of anybody else that has been that stringent in the definition of dryness. Pivoting to your second question regarding Kodiak, look, KodiAK is not our competition. It's a bolus injection. There are lots of questions that I have about the study, but it's a molus injection, their competition is going to be the Avastins, the Ileas, the Vibismos of this world. As I said earlier on, we're a maintenance drug. We had one competition, which is iPoint. That's gone now. And we have a clear path to approval and we have no competition. You know, we don't care, you know, when this drug is in market, what the physician bolus is with. It could be Avastin, it could be Vibismo, it could Beylea, Lucentis. And if the Kodiak drug makes it, it Could be the Kodiak drug. And some patients occasionally, and I think very few, may also require supplementation. And we don't care what bolus injection one supplements with. These are all non-inferiority drugs. They're all going to have their own pricing pressures, etc., etc. They are all bolus drugs. We're in a different orbit. We're going to, we believe, have a superiority label with premium pricing, and we're the only ones in that field. As far as the Kodiaks data is concerned, Look, there's a lot that we have to see. You know, we need to know who these 24-week patients are. Are they in the beginning? Are they at the end? It could be after four loading doses. It couldbe after six loading doses where they retreated. Is it 24 weeks? And then they go back to four weeks after that. What is the total number of injection? I believe the median number has been given, but the total number hasn't. And that would be good to know because it'd be good to know if the treatment burden was reduced. It would also be good to know what the AI algorithm is. You know, what's the definition of dryness? What ticked off the retreatment? And I believe they've said that the AI part has a separate regulatory approval process. It'd be good zu know if that exists. I mean, I don't know of any AI algorithm that has gotten approved. It'd also be to understand what the disease control is. I mean, what I saw there was that there was no delta between ILEA and the Kodiak drug, whereas if you look at Vibismo, there is, and that delta is early. And it was surprising to me that if you're going with a PRN drug versus a drug that's designed to treat to dry versus ILEIA, which is on label, that you wouldn't see a delta, whereas with Vibissimo, you did, you know, even with the on-label dosing. And then finally, well, not finally, but the safety part. Again, I don't know what to make of the safety part. I think we've just seen a minority of patients with selected safety that has been given. It'd be good to understand the entire table with all the patients. Again we've given patient level safety. I Think everybody should provide that. Finally the regulatory path. I mean don't know what a PRN drugs regulatory path is. I do know that in the AAO meeting, Bill Boyd said there is no regulatory path for a PRRM because we have no idea what we would put on the label. And he's right. I mean, what would you write on the level? Treat it well? I mean what would you write? So I don't what the regulatory path. Again, I mentioned the AAI part. So look, maybe there are great answers to all these. I don't know. There may be, but there are a lot of questions. But having said that, look, I've got no beef with Kodiak at all. I just, as a clinician, as someone who's practiced for 30 years doing clinical trials, those are questions that I'd like to know myself. But again, there may be fantastic answers to All Those. There probably are very good answers. I Just Don't Know Them. But, having said, that it's not competition for us. It's a bolus injection. The only competition that we've had as a maintenance drug doesn't exist anymore now. Praveen, with the SOLAR trial, would you potentially consider disclosing the baseline characteristics of the trial at some point? I think that would give us a fair, I think, good insight in terms of how to compare solar to the patient population in not just Lugano, Lucia, but also Daybreak. Is that something that, you know, you would potentially consider, you know in the next few months? You know, and it's a very fair question and the other thing that you'd also want to see is, look, did you actually screen out these patients that you said, you know would be fluctuating, I mean in a masked fashion? And that's a very, very fair question. And was it consistent with this, a third of patients are fluctuating that are anti-VEGF addicts kind of thing that we've said over and over again? Was that what you saw as well in a masked fashion? And again, these are very, very appropriate questions. We certainly discussed that. My answer to you is it's not out of the question at all. It's a very appropriate question. But please realize that we're in a period now where we're engaging with the FDA. The decisions that we make have to take that into account, right? I have to go overboard to think about making sure that that interaction stays as good as possible, that the preservation of data per their eyes stays as as good als possible. And I understand how important this is in terms of the valuation of the stock and everything else. And it's not that that doesn't matter. it does matter. I mean, I keep saying this. I'm not one of these people that says I couldn't care less. I's just going to do my job. We've got enough money kind of thing. It does matter, I mean I'm disappointed at where we are. I care about our shareholders. I am a shareholder. That's how I'm compensated for performance. So I absolutely do care. So when people ask these things, I'm absolutely sympathetic to it. This is an absolutely appropriate question to ask, but my decision or our decision as a company will be based on our interaction with the fda got it um how do you how should we think about commercial launch you know typically when you have new entrants in in the sector you know physicians you know you you were once in that seat you would prescribe in your worst patients so is that the patient population that you feel is is um you know, where docs are going to prescribe Expaxly? I guess, so that's the first question. The second question, you know how should we think about the label? Like, you know, based on Sol1, is it going to be every six months redosing? Is it going to be more flexible? What's the language going to be around that? And then do you anticipate any monitoring, safety monitoring of patients in the label? Yeah, so all great questions. So let me just throw the safety right away. Absolutely not. I mean, why would you? I mean our safety profile is as good as I can hope for. We've shown patient level data, so I'll knock that off right away and say absolutely not as far as the safety monitoring is concerned. But let me just talk about the launch a little bit. I firmly believe that there's no group better to launch in retina than we are. We've been on the other side. By we, I've talked about me and my colleagues, Peter, Jeff, Nadia. We have been on on the side. We know how to launch in retina. We don't know anything else. We're a one-trick pony, but we know retina inside out. And when you launch, there's an arc to launching. There's a logistic part in terms of the J code, in terms of samples, in terms of protecting your ASP, and so on and so forth, there's also a process. It's sort of like a pyramid process. You have to pick the people that are going to use it first, and then the next group, and then next group. And that message has to come out in a proper manner. And then you have to go ahead and launch ISTs, or investigator-sponsored trials, to support your message and to perhaps probe into things that you haven't answered. And one of the obvious thing, so I'll tell you right now, is, is this a first-line drug or is this a maintenance drug? Now, we haven't proven that it's a first line drug. There are a few patients in our Australian study where it was used as a first line drug in patients who are treatment naive, but that's not proof. That's a sign. And at this point, look, what we're saying is that it is a maintenance drug because that's what the data shows. We're not, you know, overextending our data. But I'm sure there'll be people that are going to be studying this as a first-line drug down the road. But right now, we've shown data that it's a maintenance drug. So there's an art to launching, and we know that in retina really, really well. And that's the launch part. As far as the logistics are concerned, we started preparing for launch a long time ago. As you remember in the last raise that we did, we said that we're going to do this to scale up. We've done that. We've got more than enough inventory. we've got the right personnel. I named the people. David Robinson is leading this. I can't think of a better person. What you haven't asked me about, and I hope you do at some point, is diabetic retinopathy because that's three and a half times as big. So the scale up is really pertains at this point to the launch of diabetic retinapathy and diabetic macular edema. It's both that we're anticipating. As far as the label is concerned, obviously we're not in any labeling discussions, But our expectation is that we will have the first and only superiority label for obvious reasons. We will have flexibility of dosing of six months to 12 months. The 12 months because we deliberately kept patients masked, as you remember, for the sole one card turn till 12 months to be able to get 12 months on the label. So a superiority label with flexibility of dosing, 6 to 12 months with repeat dosing. And I just want to be clear about repeat dosING because there's a lot of questions about that. The FDA will have more than enough patient data to look at repeat dosIng. Remember, in every company, not just us, in every company as part of this process in the mid-cycle review, the FDA wants to see safety data for the second year. Every one of those patients will have been redosed. Everybody at week 52 in Sol 1 is redosed. And remember that when we give them the 130 patients to satisfy their safety requirements for the initial submission, every one of those Sol R patients will have been redosed, so the FDA will have more than enough information regarding redosing, so we expect redosing to be on the label as well. On the Sol 1 year 2 data, will you disclose that data next year? Yeah, so, we haven't made any commitments at this point. it would be inappropriate to do so. And look, we're going to go through this process with the FDA at this point. That's what we're focused on. What we don't want to do is to in any way subvert that process. And during the review period, it's very important that whatever we disclose or don't disclose, that we keep the integrity of our relationship with the FDA. you talked about expaxly being a maintenance drug you know we hear this you know actually on the investor side the last two days or this week with regenics bio and with the 4d molecular therapeutics they had investor days where they talked about you know the durability of gene therapy out to two years potentially what are your thoughts on gene therapy as potential of competition to expect. Yeah, look, I see that as an entirely different thing altogether. I think the bar for gene therapy is incredibly high. And again, this is not per company. It's just gene therapy in general. I Think everybody knows that. I I think the experience has been that if you're going to have a product that you put in irreversibly, it's got to be perfect for the rest of the patient's life. And perfection is really hard to achieve, especially when there you have such great alternatives. And again, look, I practiced for 30 years. My criterion for making a decision in the 30 years that I practiced, and even now as I make corporate decisions, is would I do this on my mother? Would I dothis on my father? And it's not done in isolation. It's done when there are other therapies that are available. So the question becomes to save a single injection. That's really what it comes down to, because as I said earlier on, you know, they're drugs like ours. Actually, the only drug really is ours that reliably goes to one year. To save an injection, would I go ahead and irreversibly change the eye for the rest of the patient's life? I don't know. I mean, but what I will say is, look, you Know, in these things, I'm not trying to be, you Now, critical or anything else. I'm just stating a fact. And The fact of it is, is that if you're going to do that in this context of having these great drugs, the data has to be perfect. And for a long time, not just for one year, but these patients live for, you know, 10, 15, you knows, sometimes 20 years thereafter. And the eye just has to perfect for that whole time. And I think that's just a fact. If that can be achieved, then yes. If that cannot be achieved then I think it will be difficult. I do want to talk about diabetic retinopathy. I know we have 15 minutes left. You mentioned three to three and a half times as large as what AMD. Your stock, your valuation currently does not reflect any value for diabetic retinoopathy Can you just talk about I guess investor perceptions on diabetic retinaopathy they like, why are you, why is the company not receiving credit or valuation on this? What's, what's the biggest drawback? Yeah, it's, it'S, it' s a great question. And, and that's really my fault. The fact of it is one of the things that, that I intend to do after our submission is to focus as much as I can on diabetic retinopathy and, and, And provide, you know, whatever I can to, to get people excited about diabetic retina. You know, I just remind people of the results of the Helios study, the original Helios. It's absolutely spectacular in my opinion and the opinion of my colleagues. We're all clinicians. You know, the fact that you've got a disease that affects young, productive people who are completely asymptomatic and who really have a ticking time bomb in their eye, and there's a 30 to 40 percent chance of a blinding complication a year upon year by fact, and There's not a single patient really that gets treated for that is simply not acceptable. It shouldn't be acceptable to humanity, especially when you know what the treatment is. And the reason that a lot of investors and analysts come back to me and say, look, I don't think there's any kind of a market in diabetic retinopathy. And I say, why? And they say, well, I talked to a KOL and they say they never treat patients with diabetic retina. And I ask them, well, did you ask them why? And they say, well they won't come in. It's not sustainable. And they're right. That's the whole point. We know what it takes. We know that suppressing VEGF is nearly miraculous. And when I was in practice if there was going to be a miracle, it's injecting a patient with pre-proliferative diabetic retinopathy or advanced non-proliterative diabetic retinaopathy and seeing them 72 hours later where you see a completely different eye with Lucentis or Avastin. It absolutely works. It's the easiest anti-VEGF driven disease to treat because the disease occurs right at the vitreous base. The results are absolutely miraculous. Nobody doubts it. But they're also right that these patients simply won't come in every month or every other month. Why should they? They're completely asymptomatic. You know, if you're a lawyer, if You're a postman, if Your a truck driver who would take one day a month off or one day every other month off to get a needle in the eye for something that they can't see the effect of and they're completely asymptomatic but there's another side of the coin that doctors don't talk about which is a rebound effect when you suppress VEGF like that with a huge bolus injection you're gonna get a rebound effects so if this patient doesn't show up and likelihood is they won't at some point, there's a risk of really bad things happening. And you can imagine an accountant coming to a doctor saying, you know, I had no problems whatsoever and you convinced me to come in every month or every other month and get a needle in my eye. And I did. And then I missed a month because it was tax season. It was April 15th and now my eye is full of blood. Well, that patient is not going to be very happy with the doctor because of the rebound effect. So that's the reason patients aren't treated. What we have is in the Helio study, in the control arm, 30 to 40% of patients, as I said, have a visual threatening complication. In the control army, it was 37.7% or so. So right along the lines of what you would expect. After one year in the X-Paxley arm with a single injection, after one year, that that rate was zero, zero. And that's remarkable. And every patient with diabetic macular edema improved. So if that is shown, and we believe we will because we've got a very favorable endpoint, the ordinal endpoint, which now has been validated with a spa, the discussion with the patient would be, you know, you've got about a 30 to 40% risk of a blinding complication year upon year. But if you come to see me, but once a year, as you would to go to your dentist for teeth cleaning, I can reduce that risk to zero. That is very appealing. That's absolutely doable. And guess who would drive those patients? It's not just the doctors. It's the optometrists or the general physicians. It's The Payers. The PayERS would absolutely drive these patients. You know, when I was on the board of a PayERS system called Banner Health in Arizona, we had these non-mydriatic cameras in PCPs' offices where diabetics would simply come and plop their head and a picture was taken and the picture would go to our office. And our office would look at that and say, you know, you can come back in a year, you should come in six months or say come in right away. And it's not just the human impact of saving loss of vision, but the cost of saving lost vision is massive. And again, in this entire thing, the market is enormous. There's absolutely no competition. We have a superiority study. We have an endpoint that's validated by a spa that's an ordinal endpoint that will give every patient three shots on goal. And we believe that we will have a label that encompasses all of diabetic retinal disease. So not just diabetic retinopathy, but also diabetic macular edema, because we're enrolling patients with non-central involving diabetic macula edema. when could we expect the trial uh to complete enrollment and and for data so it's a really good question look uh again it's all about patient selection right so we haven't given your guidance to that as yet and as you can imagine there's an enormous amount of interest here it's global trial there's there's nothing for these patients it's it's tremendously easy to enroll patients having said that we have a window of the kind of patients that we want right what you don't want to have is patients that don't have enough disease. Then you won't see a delta. You also don't wanna have patients that have too much disease. Then you may not be able to stop the natural history and they may get complications anyway. So it's very, very important for us to screen those patients that are right at the window that we want. So again, it's all about patient selection in all of these trials. And we're being very, Very careful with patient selection. We're very happy with the enrollment. It's a global study. And when appropriate, we'll certainly guide you. That's going to be my job after the NDA filing and acceptance. This is what I hope to talk about on a regular basis. And I'm hoping to show you evidence that this is a major thing, a major opportunity for this company. So I guess more to come in 2027. Can you talk about, you mentioned, you know, this is a once-yearly treatment in diabetic retinopathy. Do you believe that that's the right interval for patients? And do you feel that that would appeal to patients? Well, again, I don't mean to nitpick here, but it's not just diabetic retinochlea. It's diabetic retina and diabetic macular edema and effectively any diabetic retinal disease. this is absolutely doable, I believe. Look, I'm not sitting here telling you every patient will do it. But, you know, there's nothing out there and the market size is ginormous. So even if a percentage do it, and they will, it's a huge market far bigger than wet AMD. You know, once a year injection, I mean, you think about that yourself is absolutely doable, you Know, for someone who's, you're working in the field, and simply has to come in and people do that for teeth cleaning. You know, people go to dentists for that. And as I say earlier on, if we do this right and we've had, you know, pair interactions and so forth already, this will be driven by everybody, but it will be specially driven and perhaps required by payers. Again, the amount of money that they will save by not having diabetic macular edema, by not have vitreous hemorrhage, by having proliferative vitreo-retinopathy is enormous. Is there any risk on the susceptibility of Helios 3 given the change in FDA leadership? I don't think so. Again, as I said before, it's no different than with wet AMD. We have a spa for that program as well. We have spa for the wet AMD program, and I dare say that we have more spas in this company per trial than any other company, at least in my field, that's for sure. And there's a reason we have that. And remember, all of this is signed off by the same team that includes Dr. Lloyd. You know, she's very well aware of all of our submissions. She's been in every single meeting. I see no reason whatsoever for this not to be completely seamless. And, you know, this is where the spa becomes, to give people confidence, this is where this spa becomes invaluable. And this is the reason that we got the spa. We got the spa not just because of leadership changes, but because, you know, for all intents and purposes, we realized that SOLE-1 is an unusual study. It follows the FDA guidelines exactly, but in order to give people confidence that it does so, we got a spa. We wouldn't have gotten a spa if that wasn't true. There's no reason the FDA would have given us a spa, the same thing for diabetic retinopathy. We have a very favorable endpoint, an ordinal endpoint that nobody else has been able to achieve where patients literally have three shots on goal instead of one shot on goal at random. And in order to validate that, we sought a spa and we got a spa. So there should be no question as to our track for both of these programs. Can you just talk about cash runway? You've got commercial prep that's underway, an NDA that's about to be filed. you know 4q a potential launch in the second half of next year um where does the runway take you um in relation to some of the these activities yeah so our guidance has not changed baron at all i think in the last earnings we said that we had nearly 600 million in cash and cash equivalents not quite but nearly and we said we had enough capital to take us to 2028 on a very conservative basis and that's still the case. That hasn't changed at all. Got it. And then what data can we expect in upcoming meetings over the course of either this year or next year? Is there anything that we should be looking out for? Well, I mean, look, I think what you can expect, you already saw something which I think should be talked about more, which is the data that we presented at AAO. I think it's important to talk about disease control. We'll dive into that even further. The fact that we're able to provide that amount of disease control within 10 nanoliters of volume, I think is absolutely remarkable. We're going to dig into that even more. You'll see more data coming out regarding that, I believe. And then, you know, there are other catalysts that we'll have in this regard that will be coming out as well. But again, I just want to emphasize that we'RE engaging with the FDA at this point, and we've got to be very, very careful. As much as I'd like to go ahead and show you a whole bunch more data, we've gotta be very careful to make sure that the integrity of this study is protected and that our FDA interactions are as clear and as collaborative as possible. I'm thrilled with our interactions, but that's really my primary goal, is to make sure that our submission is as efficient, as safe as possible? I do have a last investor question. It's around, you know, I guess this OSN meeting. They're asking, why is Ocular not having a presence at the OSN meeting in New York City in early November? I believe there's a good chance that we will be there. I mean, look, you know, it's a public thing. You know, there have been many other legal complications, as you well know, with iPoint. Now all of that has passed. and that gives us a lot more leeway to go ahead and discuss things a lot more freely and you know at this point it's an important meeting and and i believe that there's a good chance that we will be there great i think we're up on time uh praveen you know appreciate this as always um and look forward to more interactions uh in the near future baron thank you thanks for the opportunity it's always a pleasure to talk with you and hope to see you again soon. Great. Thanks everyone on the call.