Ocular Therapeutix, Inc. (OCUL) Earnings Call Transcript & Summary

All right. Good afternoon, everyone. We're going to go ahead and get started here. Welcome to the Ocular Therapeutix 2026 Investor Day. So during today's presentation, certain statements we will be making constitute forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially as a result of a variety of factors, including risks and uncertainties identified in the Risk Factors section of our annual report on Form 10-K and our other SEC filings. With that in mind, it is my pleasure to introduce Dr. Pravin Dugel, Ocular's Executive Chairman, President and CEO.

Good afternoon, and thanks for being here. This is a terrific day for us, and I really appreciate you spending the afternoon with us. You'll hear a lot of data today. You'll hear a lot about our strategy today, and you'll hear also why we're so incredibly excited to have you here. The last time we were here in this very place was in September. And at that time, for those of you who are here, which I think is most of you, I said that I would like to have this company defined by 3 characteristics. And those are that this company is courageous, it is bold and it is opportunistic. And today, you'll hear the confirmation of that. That is absolutely true with everything we're going to say today, you'll hear that, that stands and even more so than ever. And when you are courageous and bold and opportunistic, you do things that people say you can't do. And when you say you're going to do it, there are going to be naysayers. And I realize that we have naysayers. So what do you do to combat naysayers? It's really easy. You establish credibility. And how do you establish credibility. The way you establish credibility is by executing and executing and executing absolutely flawlessly and consistently without failure, and that's what we've done. And let me just review some of the things that we've done. So when we first got this team together in 2024, we were told that SOL-1 would be an impossible trial to recruit. You remember that. In fact, the enrollment has not only been outstanding, but has been well ahead of schedule. We've executed that flawlessly. Later on that year, we were told that SOL-1 would have poor retention and many off-protocol rescues. And in fact, the retention and the on-protocol rescues have been exceptional, so good that they're better than any other retina study. Again, that has been executed flawlessly. And then we were told last year that the modifications that we made in SOL-1 would negate the SPA. Well, they haven't. The SPA has been retained because we had complete FDA alignment as you'll hear about today as well. And that has been executed flawlessly. And then earlier this year, we heard that SOL-1 was going to fail. In fact, we heard from some that SOL-1 had already failed. In fact, SOL-1 succeeded spectacularly and AXPAXLI did something that no other drug has done. It reached superiority against an anti-VEGF, which had never been done with a p-value that had never been gotten less than 0.0006. Again, we executed that flawlessly. Now today, you've been told that there is no way the FDA will accept a single trial for NDA submission. And in fact, what you'll hear today is that we have complete formal and documented. And yes, I know this has been going around, but we do have FDA minutes. We wouldn't be doing this without the minutes, obviously. documented alignment with the FDA that we will have a complete package for submission with SOL-1 alone and safety-only data from solar at the end of this year. you'll hear the details today. Again, we will execute that flawlessly as well. This is not a new thing. If you look at this, you'll see that there are other trials that have been approved. In 2025, there are 28 single trial approvals. This is 61% of evaluable approvals, and this is almost half of them are nonorphan diseases. Tomorrow, there will be another narrative. There will be another bear narrative and we will do what we have done over and over and over again to combat that we will execute flawlessly as we always have, whatever that narrative is. So here's what you'll hear today. You'll hear that the further we dig into SOL-1, the more confident we are, the more convinced we are about the impact that AXPAXLI is going to have. The durability and the disease control is absolutely unmatched with a single dose, and you'll hear about that more today. You'll also hear that there's a clear path to market. You'll hear that we have aligned with the FDA formally on a complete package submission that we will have in the fourth quarter of this year. Now many of you may wonder why we haven't already submitted and why we already haven't already submitted our NDA and filed. Well, what I said earlier was that we were courageous. We were bold and we're opportunistic, but we're not reckless. Speed without guidelines kills, right? And our guideposts are the U.S. FDA. We have waited until we have full and formal alignment with the FDA, and that is why we're talking to you today. and we will wait until we have the complete package, and that is why we will submit responsibly and completely in the fourth quarter of this year. The goal here is the same. It's the fastest path to FDA approval with the least amount of regulatory risk, we are doing this carefully, thoughtfully and responsibly. And because all the time lines have been pulled up, we have to be ready for launch. And you'll hear today that we're absolutely ready for launch, and you'll hear our commercial strategy as well. So what have we learned from SOL-1? Well, what we've learned from SOL-1 is we knew that EYLEA is a good drug. It's a great drug. We also have learned that EYLEA last a long time but we also learned that AXPAXLI is better, much better. It lasts longer and is a lot stronger. It's much better than we ever thought it would be, and we're thrilled with it. So when we learned that the FDA did not require the SOL-R efficacy data for our complete package, we have the opportunity to go ahead and not just hit the home run because we already hit the home run with SOL-1 but to go for the grand slam, which is a superiority versus high-dose EYLEA, having already secured the superiority versus regular EYLEA. And if we are able to do that, this will secure this drug for decades and decades to come. And that's what we're going after and why wouldn't we with newfound confidence. As you go through this today, what I'd like you to understand is not just the things that you're going to hear, but who you're going to hear from. You'll hear about regulatory from Art Ciociola. There's no one in this planet who has had more drug and device approvals than Art. He is simply the most experienced regulatory person there is. And I wager that the 3 people behind and put together are not nearly as experienced as he is other than Peter. You'll also hear from David Robinson. There's no better person to lead our launch than David Robinson, who's already led their launch and architected the most successful launch in retina in EYLEA. These are the people that you'll hear from. And on top of the team that we already have, there are no finer people to do this. What I would ask of you today is this, it's regulatory heavy, and I realize that, and that's appropriate, and that's the way it should be. But for a successful submission, there are really 2 things that are required, right? We always talk about the 1 but not the other. The second 1 is equally important. The 1 that's really -- that everybody talks about is speed. And that's important. I get it, but the 1 that people forget is risk. Speed kills without guidepost, as I said. So today, when you hear what we're going to do you'll get the details. But for everything we say, think how have they derisked this? How have they derisked the submission, how have they derisked the shareholders? And that's a really important thing because the goal remains the same. We're not just going to be best-in-class. Now we're going to absolutely be first-in-class. Gives me great pleasure to welcome the of the finest retina physicians in the planet who I'm absolutely honored to call my friends, people that have known for a very long time. Their words matter today. Their words will matter even more when AXPAXLI is approved. And I think you know them all. Arshad Khanani from Reno, Nevada, Lejla Vajzovic from Duke University and Darius Moshfeghi from Stanford University. And now I'm going to go ahead and hand it over to someone that I said last year was the greatest CMO on the planet, and that's truer today than it's ever been, Dr. Nadia Waheed.

Thank you so much, Pravin, and it's not -- thank you. And it is an absolute pleasure to be here today, and I'm excited to walk you all through our clinical program for AXPAXLI, starting with our SOL-1 study highlighting the unmatched durability in sustained disease control shown by AXPAXLI. I'm also going to talk a little bit about why clinicians will use this when it gets to market. SOL-1, as you all know, is the superiority study designed to compare head-to-head a single injection of AXPAXLI versus a single injection of aflibercept. The primary endpoint at week 36 was a proportion of subjects who maintain visual acuity, defined as less than 15 ETDRS letters of loss from baseline at week 36. Even though the primary endpoint was at week 36, patients were followed for rescue to week 52 to evaluate the 52-week durability and up to 12-month dosing of AXPAXLI. Patients received a second dose of AXPAXLI at 52 weeks. And the second year of the study was designed to evaluate safety of a q6 month dosing Accordingly, patients continued in their treatment arm and receive treatment every 6 months. SOL-1, as Pravin mentioned, is the first successful superiority trial of a novel agent versus an approved anti-VEGF. The SOL-1 study showed AXPAXLI had unmatched durability, sustained disease control and was well tolerated by patients. And so first, let's discuss in more detail the durability of AXPAXLI. So the SOLO-1 study met its severity primary endpoint with high statistical significance and a p-value of 0.0006. The study showed an observed difference of 18.3% and also had a highly clinically meaningful risk difference of 17.5% for patients treated with AXPAXLI compared to control in maintenance of visual acuity at week 36. And I will also show you some evidence downstream on how the Kaplan-Meier curve data is especially exciting for us as clinicians. At month 9, 3 out of the 4 AXPAXLI patients maintained vision with a single injection, demonstrating a strong potential for annual dosing. And at month 12, we saw 2 out of 3 patients maintained vision with a single injection. 90% of the patients maintaining vision at month 9 continued to maintain vision at month 12 clearly demonstrating both the durability of AXPAXLI as well as the predictability of response in these patients. And here is the Kaplan-Meier curve demonstrating extended durability, significantly delaying the first rescue injections in the AXPAXLI arm. As you can see, the time to approximately 30% of subjects requiring the first rescue is a whole 6 months later for AXPAXLI than it is for aflibercept. Now you're all used to seeing some time to 50% event rates in Kaplan-Meier curves. And of course, you're asking why we're using 30% here instead of 50%. That's because AXPAXLI patients never actually hit a 50% rescue rate even at the 1-year time point. So besides great durability, we also see sustained disease control with AXPAXLI. And so how do we evaluate disease control. So as retina specialists, we rarely just look at vision. We look at anatomy. And specifically, we look at fluid in wet AMD patients. As you may know, sustained fluid control leads to better maintenance of vision over the long term. And so let's discuss fluid control and what that means in clinical practice. This graph shows time to 75 microns increase in central [indiscernible] thickness from week 8. 75 microns is significant because this is often used as a threshold for retreatment in wet AMD clinical trials. Our SOL-1 study showed a 5-month delay in reaching 75-micron central subfield thickness gain from week 8 with the use of AXPAXLI, again, evidence of exceptional disease control in patients. But wait, there's even more. What's more interesting to look at for clinicians is to look at the threshold of more than -- greater than or equal to 30-micron increase in CSFD. And the reason I say that is 30 microns is a very small amount of increase in CSFD and because also fluctuations in retinal thickness of greater than 35 microns are associated with fibrosis and worst long-term visual outcomes. AXPAXLI showed about a 6-month difference in time to a 30-micron CSFD increase from we gate versus aflibercept, again demonstrating outstanding sustained disease control. So now that we've covered fluid control, let's move on to vision control. And I think all of you are familiar with this graph. We -- here, we see the mean change envisioned from screening. AXPAXLI demonstrated strong vision control up to 9 months with much fewer rescues indemnity. Aflibercept arm, as you know, this represents close to 3/4 of the patients in the AXPAXLI arm that remained rescue-free at week 36 versus only 56% of the subjects in the aflibercept arm. So now that we have dug into the unmatched durability and sustained disease control demonstrated by AXPAXLI, let's discuss how this is tolerated by patients. So AXPAXLI [indiscernible] well tolerated in the SOL-1 study, there were no treatment or procedure-related ocular serious adverse events and no subjects discontinue with the trial because of adverse events. Most importantly, there were no cases of endophthomitis, occlusive retinal vasculitis or nonocclusive retinal vasculitis observed with AXPAXLI. We are now in year 2 of SOL-1, where mass safety data is being monitored while we evaluate 6 monthly dosing, and the DSMC recommends trial continuation. To summarize, SOL-1 results highlight AXPAXLI's groundmaking profile. SOL-1 is the first Phase III trial to demonstrate durability out to more than 9 months showed up to 52-week visual and anatomic stability and demonstrated a well-tolerated safety profile. And so now that we've demonstrated that the SOL-1 results are highly positive, and we intend to submit our NDA based on these results, let's talk a little bit about what value each one of the SOL trials now brings going forward. So SOL-1 establishes efficacy and safety out to week 52, that will be the foundation of our NDA submission in wet AMD. This trial will support both our U.S. and ex U.S. regulatory filings while maintaining strong commercial relevance given the strong superiority results of the study and the possibility of bypassing step therapy. Now that SOL-R year 1 efficacy data is no longer a requirement for NDA submission. We are in the extraordinary position of using the SOL-R trial to best serve our long-term strategic objectives for AXPAXLI which are to be the best in disease agent for wet AMD, as Pravin mentioned. We're now adding a new key secondary endpoint of superiority compared to aflibercept 8 milligrams, HD EYLEA in SOL-R which will be evaluated at week 96. And we also hope to demonstrate prevention of fibrosis and atrophy with AXPAXLI relative to aflibercept 2 milligrams at this time point. Moving to SOL-X, our open-label extension study, subjects who have completed 2 years of safety follow-up in either SOL-1 or in the SOL-R study are eligible to enroll in the SOL-X trial for an additional 3 years of safety follow-up. We initiated SOL-X enrollment in April and believe this will be a tremendously valuable program, both from a commercial relevance as well as a long-term safety perspective. SOL-X outcomes may further expand AXPAXLI's potential by highlighting the need to start AXPAXLI treatment early or potentially risk worse long-term visual outcomes due to potential fibrosis and atrophy that may be seen with today's pulsatile treatments. And finally, let's talk about how SOL-1 success has impacted our diabetic retinopathy program, which we call the HELIOS program. So as you may recall, we first unveiled plans for our registrational program in diabetic retinopathy during our September 2025 Investor Day, we announced 2 complementary Phase III superiority trials, evaluating every 6 and every 12-month AXPAXLI regimens using a novel primary endpoint that we aligned on with which is an ordinal analysis of a 2-step change status on the diabetic retinopathy severity score or the DRSS as it's commonly known. Today, we're happy to announce that we will be streamlining this program to prioritize HELIOS III. This superiority trial will evaluate every 12-month AXPAXLI versus sham, and we will continue to target a broad diabetic renopathy label by including subjects, both without center-involved diabetic macular edema as well as patients with noncenter involved DME. And the primary endpoint will remain as the ordinal DRSS 2-step chain status. Here's an overview of the HELIOS III superiority trial design. We intend to randomize approximately 620 subjects with moderately severe to severe NPDR without center-involved DME. These subjects will receive either AXPAXLI or sham at randomization and week 48. The primary endpoint will be taken at week 56 from baseline, and subjects will be followed until week 96 for safety. As you will notice, we've removed the Q6 month dosing arm from this study. So why did we make these changes to the Helios program? Following our strong Solan results, combined with the tremendous evidence that we have already generated in the HELIOS-1 study, we can now confidently say that AXPAXLI will show durability up to 12 months in NPDR where we know that a once-a-year regimen is highly preferable and therefore, we streamlined the development to focus on this approach. Importantly, HELIOS III will also support our global regulatory objectives. And having said that, I'm now going to pass on to Peter to present to you the highlight of the day, which is our regulatory strategy.

Thanks, Nadia. It's now my privilege to share with you our U.S. regulatory strategy in wet macular degeneration. So here's what we're going to cover today. First, what are the FDA regulations and guidelines that clearly support a single trial submission. Second, why does our SOL-1 study meet all these FDA guidelines for a single adequate and well-controlled study. that we could file our NDA. And finally, what are some of the confirmatory evidence which are required to support the SOL-1 trial as part of a single trial submission. So let's first start with why we can do this. Section 115 of the 1997 FDA Modernization Act specifically amended and defined what the substantial evidence rules were and explicitly allows one adequate and well-controlled trial plus confirmatory evidence to receive FDA approval. The 1998 and 2023 guidance reiterated that a single trial plus confirmatory evidence meets that statutory requirement for substantial evidence for approval. As was mentioned by Pravin earlier, this is not new. The use of a single trial for FDA approval has been used in the past and in fact, has become increasingly frequent over the past few years in 2024, and 2025, the majority of Cedar approvals actually utilized a single trial approach. Moreover, over 40% of these approvals were non-orphan designations. So the 21 CFR Part III specifically defines what is an adequate and well-controlled trial. A study that uses sham, for example, which introduces bias is not adequate and well controlled and therefore, can only be corroborative and cannot be used as a single stand-alone trial. SOL-1, therefore, was prospectively designed to meet all the requirements as defined in 21 CFR Part 314. What about this thing, the SPA. While a special protocol assessment indicates the FDA has agreed specifically on the study design, clinical endpoints, study size and most importantly, the statistical analysis plan that they are adequate to address the scientific and regulatory requirements that support approval. SOL-1 is the only active wet macular degeneration study that's being conducted under a special protocol agreement. Is this important for a single trial submission of course, it is. And Dr. Boyd at the recent Retinal World Congress actually said that a special protocol assessment is an official agreement between a sponsor and the agency that we will accept a certain trial design and if successfully completing that protocol that this would be highly supportive of the approval of the product. The divisional ophthalmology has also stated that p-values less than 0.001 could be potentially supportive of a single trial approval. And at that same meeting, Dr. Boyd reiterated and stated specifically that a single adequate and well-controlled trial can support approval, often with very strong p-values, reiterating less than 0.001. The Division of Ophthalmology is also approved drugs like AXPAXLI, for instance, for noninfectious uveitic macular edema based on efficacy from a single trial. The PEACHTREE trial met its primary outcome with a p-value less than 0.001 and only 96 patients on study drug. The safety package include 296 patients with those additional patients coming from the open-label AZALEA study. As Nadia mentioned, the primary endpoint of SOL-1 was highly statistically significant, and the p-value was 0.0006 and this was supported further by 6 prespecified sensitivity analyses of the primary endpoint that were also statistically significant. So SOL-1 is the first study to show statistical superiority in preventing vision loss against an active anti-VEGF control. Moreover, almost 70% of the patients were rescue free at 1 year. And as Nadia mentioned, there was a 6 months difference in between that first rescue injection between aflibercept and AXPAXLI. Finally, three, hierarchically controlled secondary end points were statistically significant, showing that the clinical meaningfulness of SOL-1 is that we demonstrated the superiority on the primary outcome. We had a strengthening effect size over time, we had consistent visual and supportive anatomic outcomes. And together, that creates a fairly highly persuasive efficacy are given. Now the guidelines clearly define that 1 trial can establish effectiveness, but what they doesn't mention is the FDA still requires adequate safety exposure. The 2023 guidance tells us that a minimum of 300 patients with at least 9 months follow-up are required. So the AXPAXLI safety data set will include more than 300 patients on AXPAXLI for 12 months. How are we going to do this? Well, we're going to take the 170 patients from the SOL-1 study and who have 52-week safety results. We will perform an interim safety analysis of the SOL-R study looking specifically at patients who have passed the 52-week time point, and this will add more than 130 patients to the safety data set. And alpha penalty will be taken for this analysis but no mass efficacy analysis will be performed on that SOL-R data. We also maintained SOL-1 masking into year 2, specifically to be able to use this data for labeling purposes. And at the 120-day safety update, we intend to add the year 2 SOL-1 safety data to support repeat dosing. The 2023 guidance also defined what can be used as confirmatory evidence to support a single trial NDA submission. And we have broad confirmatory evidence to support our single highly statistically significant SOL-1 truck study. What are some of these? One, mechanistic evidence. We know that the role of vascular endothelial growth factor is one of the primary drivers of wet AMD. We also have agency reviews that acknowledge axitinib's potent and selective pan-VEGF receptor blockade. Class consistency is another evidence that they look for. In other words, do other members of the same pharmacologic class behave similar to the observed effect in SOL-1? Is it consistent in terms of mechanism action, disease, endpoints, direction of effect. There's extensive evidence, obviously, of the use of anti-VEGF and vision and anatomic gains in wet macular degeneration. AXPAXLI's effect in SOL-1 is in the expected direction, magnitude, time course, anatomic relationships and safety for this therapeutic class in the same disease. We also have strong pharmacodynamic evidence showing axitinib blocks all 3 VEGF receptors as well as both PDGF receptors with very high potency and specificity. And most importantly, this data aligns with the pharmacodynamic evidence from the INLYTA NDA. Animal models show that axitinib inhibits angiogenesis and parasite sprouting as well as in the gold standard rat CNV model, it inhibits angiogenesis and leakage. In a VEGF challenge model where you sustain VEGF suppression is crucial to prevent vascular leakage, traditional extracellular VEGF inhibitors work only in the short term whereas AXPAXLI shows sustained inhibition of vascular leakage for the entire 90-day duration of the study. Natural history edivants can be used to support which shows untreated wet AMD patients lose vision. While inhibition of VEGF maintains vision, real-world evidence support the use of anti-VEGF in wet AMD from the Iris registry as well as in our own analysis of a SOL-1-emulated population where the visual acuity and OCT results were identical or similar to SOL-1, but only required -- but didn't require 9 anti-VEGF injections. So this is what we plan to do. Per the FDA Type C written minutes, our planned NDA package will include the SOL-1 efficacy data at 52 weeks with no SOL-R efficacy data. The safety database will include both the week 52 safety from SOL-1 as well as the interim safety review from SOL-R to submit a complete NDA with more than 300 patients for safety review. And then at the 120-day safety update, we will provide the agency with year 2 of the SOL-1 safety data. No additional data will be provided that would trigger any major amendment while submitted during the NDA. And specifically, as mentioned before, no SOL-R efficacy data can be submitted because we will remain masked until our key secondary endpoint at 96 weeks. So this is what the time line looks like. after our release of our positive SOL-1 study in February '26, we moved very quickly to align with the FDA to derisk our NDA submission. In May, we had our in-person Type C meeting and that we have the written minutes that have reflected what was agreed to at that point and that was that the FDA agrees we could file our NDA with a single SOL-1 trial plus our confirmatory evidence. In the third quarter of 2026, we will have a pre-NDA meeting, which is planned to align with the FDA in terms of the formatting and logistics of those final exhibits. The NDA, what is submitted in the NDA has already been agreed to in the Type C meeting. In the fourth quarter 2026, we're going to perform that interim safety analysis of the SOL-R study, as I mentioned, and once we have that data in hand, we will file our complete NDA package in the fourth quarter 2026. 120 days later, we will provide the year 2 safety data, as mentioned, and no additional data that would trigger a major amendment is planned during the entire NDA review cycle. Another important aspect of our submission is not so obvious. The normal pathway is the 505(b)1 pathway. That's a standard full NDA submission pathway for a new chemical entity. In contrast, the 505(b)(2) pathway is a hybrid pathway. This NDA is used for drugs that are similar to but not identical to an approved drug. This hybrid application relies on the safety and efficacy of the previous submission and this accelerates approval time lines for new formulations, routes of administration or indication. Axitinib, as you know, was approved for renal cell carcinoma in 2012 and therefore, we plan to use the 505(b)(2) pathway. Why? Why should we do this? Well, if you submit a hybrid NDA using this pathway, it could speed up the review time by up to 60 days versus a traditional 505(b)1 pathway, speeding approval time lines. So Ocular Therapeutix is submitting a complete hybrid NDA package via the 505(b)(2) pathway that meets the FDA's substantial evidence of effectiveness and safety requirements. We have one positive adequate and well-controlled study that was performed under a special protocol agreement with the FDA. That has a highly statistically significant result of 0.0006. Our data has internal clinical coherence and is consistent with the data in that 3 out of key secondary endpoints were met with statistical significance as well as many of the other secondary endpoints, which all point in the same direction. We have a sufficient safety package that meets all FDA guidelines having more than 300 patients exposed for 9 months or longer, and we have broad confirmatory evidence to support the submission of SOL-1 as a single study. So now I'd like to invite Art to the panel area up here regulatory head, and we'll have a little kind of Q&A session. So Art.

So one of the things that many of you don't know is who this man standing next to us or sitting next to us is. And he won't talk about himself, so I'm going to do it for him. And he has extensive ophthalmic experience in numerous indications as a regulatory person. It's 35 years in both big and small pharma. He's been at Novartis, B&L, Pfizer, GSK. And most importantly, he has overseen the global approval of over 18 new chemical entities. So we were -- it was a cue for us to get here. But Art, before you joined us, you were having a very successful consulting career enjoying your "retirement". What made you decide to join Ocular full time?

Well, thank you, Peter, for your kind words. I decided I have a small story I want to tell about why I decided to join ocular. So when I was at Pfizer, there was a drug called Macugen. And it was the first drug approved for the treatment of AMD. It was first VEGF buyer. It was a co-development agreement with a company called Eyetech, which actually has offices -- was very nearby here. And I remember early on, I was introduced to the project team, and they told me about this drug, Optimer and they said, "Oh, it has to be injected". And I assumed this was some sort of infusion biologics or so. They said no. Patients are injected in their eye. It's an intravitreal injection. And I said, patients would accept this. They continue in the trial. They said, yes, they're not comfortable with it, but they do and so on. Peter, fast forward 20 years, lots of good drugs approved for AMD, lots of good drugs. Peter? There still remains patients who were injected every month, every other month, and I believe that puts a significant patient burden on them on the caregivers as well. And so Peter, I think this drug has that potential. Patients have been waiting, if you don't mind, 20 years for this drug. And I believe this will have a huge impact on patients' lives, patients' families. And I would not pass up the opportunity to join you, the other members, as I look at Nadia, she's waving at me, Jeff to get this drug approved for our patients in AMD. That's why I joined.

Well, we're glad you're here. Let's jump to the question, I think, is on everybody's mind sitting in this audience. And so we've talked about our regulatory discussions. We talked about how we can submit an NDA on SOL-1 alone. But I think everybody in the audience wants to know why haven't we submitted the NDA already?

Peter, it's a good point. As you kindly shared with the group, I have multiple NDAs that I have multiple sNDAs. And the key for me, Peter, is this balancing of speed and risk. Speed and risk. Yes. We all want to submit these applications as soon as we can. We want our patients to get these drugs as soon as possible. That being said, Peter, if you do not submit a complete comprehensive NDA will -- they can reject that application, of course. We don't want that. Of course, we don't want that. But Peter, here's what's really important for me as well is we've aligned with the contents of the submission, the agency understands what we're going to submit. As you nicely described here, we did it under a spa. We have safety database. We will have established already effectiveness as per the guidance. But what's really important, Peter, is we want to do it in a manner that the reviewers we'll take our application and review it in a timely manner and not ask extraordinary excessive number of questions, which always delays your application. So Peter, that is key for us as we go through that is that our development program fully aligned with the agency, their expectations through several meetings over the years, written correspondence. And of course, as you described, our recent Type C meeting results.

Well, let's talk about some of those interactions. The most recent one is probably the most important for what we're discussing here. Could you give the audience a peek behind the curtain, so to speak. They weren't in a room where it happens. So what happened?

Yes. It was good. I'm smiling. And many of you know the -- our previous commissioner, Dr. McCarrey, he wrote an op ed article in New England Journal of Medicine and said that FDA's policy would now go from 2 trials to 1 trial. And I got lots of questions. They said, what does that mean? Is FDA changing their standards? What is that? I said, no. I said, we've always had that option. Peter, as you described since the '90s, okay? There's a guidance 2023 guidance that was issued. It's actually very clear guidance and it says, yes, you can establish effectiveness based on a single adequate and well-controlled trial. And so Peter, as we discussed that. And we said, yes, it's a possibility. And I always said, it depends on the results of that study. FDA will require the ophthalmology division highly significant, clinically meaningful benefit has to be demonstrated. And Peter, in February, when our results were announced of a p value of 0.0006 with a clinically meaningful difference of 17% at week 36. And I still remember that hearing, oh no, here we go. This is the basis for our discussions and it meets the substantial evidence of effectiveness based on a single study. Hence, Peter, we had that -- we requested a Type A meeting -- I apologize, Type C meeting and asked literally a single question. Would the agency accept an application based on our -- I'm pointing at the screen SOL-1 study data plus confirmatory evidence, Peter. And that was the discussion that we had at FDA. And during that discussion, FDA said, you've presented a compelling argument. Your data package is significant and that they will accept that application for review. Peter, that's where we are today. And right now, my team is working really hard on assembling that NDA and progressing this as quickly as we can.

Well, today, we shared that in the fourth quarter 2026, we're going to submit the complete NDA. What are some of the gating items that we need to worry about? And specifically, what do you expect the role of SOL-R to play in that NDA.

Yes. Peter, you make a really good point here as you described there. We have to submit a complete comprehensive data package for FDA to review this in an expedited manner here. Peter, the gating item for us is the adequate safety database. As per the 2023 guidance, we need 300 patients exposed to exactly, and that's what we plan to do. by the fourth quarter of this year here, and that will be part of that submission. At the time of application, we will submit more than 300 patients who've been exposed to AXPAXLI for 12 months. That is the real key gating item for us here. As I shared, I've got a very experienced regulatory team experienced in numerous NDAs. Frankly, Peter, I will look at every page of this application when it goes in. So we're assembling that application now and pulling that together there. And frankly, we're going to give FDA exactly what they have asked for and what they require to expedite the review of this particular application. That's what's gating us.

Perfect.

Peter, I actually -- I have a question for you here. You just talked about SOL-R data and the impact on there, the change to week 96, top line data a bit later. I've gotten some questions. Give us some thoughts on that.

Well, when we talk about the SOL-R study, there's a few things that are very important. So first of all, what has not changed? And what has not changed specifically is, first of all, the primary outcome, which is week 56, noninferiority to EYLEA 2 milligrams and how and when we're going to evaluate that. There's no change to the non-inferiority margin. It's still 4.5 letters and because it's an adequate and well-controlled study with no sham injections per CFR 314. If we had to use the sham injection, that would have reduced our margins. So that's why we didn't use a sham injection. And there's no change to the study conduct. But I think the most important thing that has not changed is our absolute confidence in what we expect SOL-R to show. We expect to meet the primary outcome, and that confidence has only been increased since the results of SOL-1 and specifically analyzing the rescues and the visual and anatomic data from SOL-1 just gives us even more confidence that we are going to hit that primary outcome. But what has changed? When we receive the written guidance or written minutes from the Type C meeting, everything changed because now all of a sudden, SOL-1 is all we needed for our NDA. So that means we could use SOL-R specifically for commercial advantage. And that's really the important thing. SOL-1 will hopefully give a superiority label to 2-milligram EYLEA. But if we hit this superiority outcome in solar, then theoretically, we could have a superiority label to EYLEA 8 milligram, which would be an immense commercial advantage. So we have this potential to hit both these things. Now remember, in SOL-1, we -- the initial primary outcome or the VN primary outcomes at week 36. And initially, we were going to unmask at week 36, but we decided to hold off. We made an amendment and we decided to unmask at week 52. And it was really important that we did that because since we were masked, we had an outcome measure at week 52 that we could use, which was specifically talking about the fact that 2/3 of the subjects, at 52 weeks, were rescue free. This is an incredible feat in something now that we have a potential differentiator if we were to put that into the label. So have we not changed the masking regimen of SOL-1, we would not have been able to get that into the label. And we're doing an exact same thing in SOL-R. We want to maintain masking for that key secondary outcome of superiority to EYLEA 8 milligrams. And by doing that, that would allow us to be able to put it into the label. So that was our thinking behind doing that.

It's totally understandable, Peter. Let me just ask a follow-on question here. Why don't we just -- I've gotten this question, why don't we just look at a comparison of EYLEA HD at our week 56 time point?

Well, so if you look at anything when you do a study change like that, you put -- there's a lot of thought put into it. And first off, when you're doing a superiority evaluation, the first question you should ask yourself is, do you have enough patients to meet that superiority outcome. And so the answer to that question is, of course, yes, the SOL-R was sized specifically for this purpose. It's not something we talked about in the past, but we did do this on purpose. Second, the test should be performed when you have the highest likelihood of success. So our highest likelihood of success in solars meeting a noninferiority versus EYLEA 2-milligram Q8 at 56 weeks. Superiority to EYLEA 8 milligrams at 56 weeks would be a hard bar, right? Because if you remember, everybody was reinjected at 48 weeks. So that would be 2 months later, we would be doing the superiority test. In contrast, at the 96-week time point, the previous injection of EYLEA HD would have been 6 months prior. So in terms of hitting a superiority outcome, the highest chance of hitting that superior outcome will be at week 96, not at week 56. And so because of that, we decided we really want to -- we hit a home run as Pravin says, we want to hit a grand slam. The home run is superiority to 2 milligram. The grand slam is superiority to 8 milligram. And that's our goal by moving our key secondary to week 96.

That's good. Thank you for that, Peter.

Now Art, there are some confusion about the way we're going to be doing this. And specifically, this 120-day update. Perhaps you can comment what is expected at the 120-day update from the FDA?

Absolutely. Thank you for that. just for folks in the audience, as you many of you know, a 120-day safety update is a regulatory requirement. It's outlined in as Peter, as you said, 21 CFR 314 as well. And frankly, the intent of this really is to update the agency on any new safety risks that have been identified. I mean, think about it. It's now 4 months after the application has gone in. your database cutoff is prior to that. So the agency wants to know anything new that has been observed in clinical studies here. Now Peter, importantly, for us, as you outlined here, is that at the 4-month safety update, that was discussed with the agency at our Type C meeting is that we will be submitting the Solon 2-year data, which will provide us evidence to support repeat dosing in our labeling. And that is really important for us. The agency will want to see this long-term safety data, hence, that 2-year data that we will submit at the 4-month 120-day safety update as such. And the SOL-R day, as you pointed out, Peter, SOL-R efficacy data will not be submitted in that. I know there have been discussions about that as well. That being said, Peter, by doing it in this manner, this is the fastest regulatory pathway to our approval.

So anyone can summit at any day at any time. But the question is, will the FDA actually accept that submission for filing and basing everything we know so far, based on all our discussions with the FDA, sort of what is your confidence level that the FDA will accept the submission, number one. Number two, are you worried about RTF refusal to file? Or are you worried about having to do any major amendments?

Yes. So thank you for that, Peter. As you probably can understand my expectations and confidence in accepting this application, the agency, it's incredibly high, incredibly high. given what we've done outlining all of the criteria, the spa agreement here, the statistical analysis, the results our interactions with FDA, incredibly high, Peter. Peter, you're making me smile with a refusal to file, okay? There are many reasons for refusal to files, Peter? As you shared, I've done a number of submissions NCEs. I've done dozens and dozens of other SNDAs as well. SLAs as well, Peter, I've never gotten a refusal to file. So I'm smiling as you ask me that question here. So hence, I'm confident, as I shared with you, we will ensure that, that application is complete, comprehensive, all the hyperlinks work, everything. I not only have an experienced regulatory team. Peter I also supervised the quality team. who will also do QC on this application as we go through this. So I'm very confident we will not get a refusal to file.

Perfect. Glad to hear that. So we talked about this third quarter pre-NDA meeting. And some people will say, well, everything you just told us is complete BS. They haven't agreed to anything. They still have to do this NDA meeting -- pre-NDA meeting and the everything could change at this pre-NDA meeting. So for those of us in the audience who don't understand what a pre-NDA meeting is what do you expect the FDA to say or do at that meeting.

Yes. It's a good question, Peter. And pre-NDA meetings, I have every single application that I've submitted, we had a pre-NDA meeting. And these are operational meetings in that you align with the agency on the formatting, okay? It can be fun size. It can be any of those types of things. That's what the focus will be on, what are the agencies' expectations and how they want to see the data position. That will be the focus of these meetings here.

So it's not what we've already talked about.

No, No. No, that will not change. That will not change. We have this in our written meeting minutes, as you know, and that will be the content of our NDA. We want to make -- we want to ease the review of the reviewers. We want them -- we want to present them with the data, how they want to see it presented and that is the key. And Peter, as you know, if a reviewer has questions, doesn't understand what they'll do. They'll ask the question. They'll put your application aside. They'll move on to somebody else. And I want to minimize that. Our goal is to minimize those numbers of questions. So having that pre-NDA meeting, and I've asked for it to be in person, and I want to sit across from the reviewers and say, "Hey, how would you like this, "Hey, how would you like that? That's the focus. It's an operational perspective.

Perfect. So you've said multiple times today, and even Pravin has mentioned, that we actually have the meeting minutes in hand. I'm curious. Can you tell us anything about what's in the meeting minutes that may help us here?

Sure. Absolutely positively. I mean, the key for me, Peter, in the meeting minutes was that FDA stated, they concluded that Ocular has presented a compelling data package and that this application would be reviewable. I didn't say it would be approved or anything like that? Kidding. Kidding. They don't put that. No sir.

Another thing that people have said is why don't you do a rolling submission? Wouldn't that be easier? You just follow what you have with SOL-1 and when the data comes in from SOL-R later in this year, you just put it in and wouldn't that be faster?

So yes, Peter, I'll answer your question here. I mean rolling submissions are an option, of course. The key here, Peter, for me is for rolling submission and a lot of people don't realize. And with the rolling submission, you can submit various modules as you go through. Here's the but park. But the FDA will not start their review until the application is complete, not until it's complete. Peter, I think what we've outlined today is the fastest and derisked regulatory approach here. We've aligned with the agency. They know what they're going to get from us in that application here. We will support that with confirmatory evidence. We have an agreement on our safety database, 300-plus patients exposed AXPAXLI for 12 months. Peter, this, I believe, is a complete comprehensive submission package and it's the fastest way to get this new medication to our patients.

Well, I really thank you, Art. Before we wrap, any final comments, closing comments.

Peter, I think we've touched on a number of points here. I mean, to me, it's balancing this speed and risk aspects of it. We've talked about this. We've discussed this many times as we go through that. And Frankly, I think we've optimized our pathway as we go through that here. And I'm most excited about this application, the approval so that we can provide a longer durable treatment with better visual outcomes to our AMD patients, Peter.

Thanks,. Appreciate it. Get back to work. So now it's my pleasure to invite David Robinson, our Global Chief Commercial Officer, to the podium David is one of the most accomplished commercial leaders in retina with deep experience in launching therapies and building franchises. He was the key architect for the EYLEA launch during his time at Regeneron, arguably the most successful launch in retina history. He has end-to-end launch experience, including strategic strategy, planning, execution, and market access. Most recently, he was the Chief Marketing Officer for global ophthalmology at Merck, where he helped lead the global ophthalmology strategy and franchise. So it's my pleasure to pan the podium to David.

Thank you, Per. And there's nothing that makes a commercial guy happier than somebody with the enthusiasm of Art Ciociola. I have to say, nothing makes me any happier. So one of the things that I'd like to speak about today is not only preparing for a successful launch. But to give you a little bit of background, as Peter said, I started in the retina space in 2011. And one of the things that always is stuck with me is that patients love usually their retina specialists. I love the therapy, I love the fact that they had not only a therapy that would stabilize their disease but in many cases, improve their disease. So I was always taken a back by patients and physicians always ask us when we come in the office. Can you improve the number of times I have to come into the office a year. Can I come less? Can we -- how can we do that? So one of the things that EYLEA gave us was the opportunity to increase the opportunity not to have to come into the office so often. But again, it was only 8 weeks. So if you take a look at what we talked about today, Peter just discussed -- been discussed many times today, following a successful Type C meeting, we will be filing the NDA in fourth quarter of 2026 and preparing for our launch in 2027, assuming approval. If you take a look at AXPAXLI's potential, this is one of the things I'm the most excited about. This is a $15 billion market, but it's commanded right now by short-acting VEGFs. And we have an opportunity to drive this market with AXPAXLI with a change in how often patients have to be seen by their physician. And if you think about that marginally, if you look at VABYSMO, they have seen a small durability change, drive a big market. And after year 3, they had already generated $4.4 billion in revenue. We feel that the durability of exactly is unmatched by other current agents. You've heard a number of times today, 12 months with a rescue free rate at 69% rescue free rate after 1 year. and that gives us the opportunity to have up to a 12-month dosing parameter and gives us the opportunity to have a label that's 3x that of the current market today. The question I usually get is, well, what's your market? Where are your patients going to come from? If you look at how the market breaks down, it breaks down in 3 big buckets. That is, number one, patients are on therapy and within the PI patients that are on therapy and not within the PI either shorter or longer than and then a group of patients that discontinue. In fact, I always have felt it's interesting, the fact that there's a 44% discontinuation rate even after year 1. And we feel that AXPAXLI gives us the opportunity to bring patients back into the market, keep patients on therapy longer as well as have an opportunity to switch those patients that are currently on VEGF on label and ones that aren't on label. So if you look at where we feel like we can go with AXPAXLI in the beginning, we feel like it will be switches from current anti-TNF patients. And in the longer term, we feel like we not only have an opportunity to continue to get switches from VEGF, but an opportunity as well to take the naive patients starting on AXPAXLI and continuing on the drug longer. And since we have been -- since we released SOL-1 top line results, we've been talking to many, many retina specialists getting feedback from them. And one, physicians are telling us that this product will be rapidly adopted. Greater than 90% of retina specialists would adopt AXPAXLI within the first year of launch. Broad utilization and the fact that retina physicians say that improve disease control and predictable greater than 6-month duration will drive broad use. And it's easily incorporated into a retina physician's office and into the practice. By that, what I mean is the prefilled intravitreal injection is ordered, it is stored and is delivered in the same way as an anti-VEGF. So you put it into the practice and incorporate it quickly into the full account. And in fact, retina specialists post-SOL-1 have told us that 80% of them would use the product based on SOL- 1 results alone. So if you think about that, 80% of physicians 4 out of 5 say they will use exactly broadly when they have SOL-1 data alone. Our payer team has been out proactively calling on payers. In fact, so to date, they have seen 100% of the carriers that cover Medicare Advantage in Tier 1. They have also seen 100% of Tier 1 commercial lives payers as well. And payers are telling us that they acknowledge that a label with superior durability potentially transforms the market and could command premium pricing in the market. So a little bit about launch preparation. If you look at the current challenges in the market, we have no superiority label in the market today. That means approvals of up to date been based on noninferiority design, which means minimal differentiation in durability between agents or efficacy. And payers site that lack of differentiation is making it difficult to choose between treatments. Biosimilar entrants into the market, increased competition to discount or rebate means that the focus is a lot of times on financial and not safety, efficacy or durability parameters. We feel that, that gives us a clear market opportunity to differentiate based on a superiority label with predictive durable dosing and positive long-term vision maintenance outcomes. And we feel that the market is perfectly set for a product like AXPAXLI. There's 1.8 million wet AMD patients in the market today, but they are seen by a very concentrated call point. They're between 2,500 and 3,000 retina specialists. But more important than that, when you dig under that, about 600 physicians account for 80% of the utilization in the market, according to claims volumes. Not only that, but there's a very high initiation rate in AMD because of the fact that it can be a catastrophic disease as well as a high switch rate. And that's among physicians and patients requesting a switch to particularly a more durable, long-lasting agent. Our team is ready today. We have a team out in the field right now of 65 people salespeople as well as 15 reimbursement people. And that's our DEXTENZA team, been in the market, still in the market, very stable in the market. as well as a world-class retina leadership that's been responsible for decades of combined experience in the industry as well as in retina. Here are some of the key launch preparations that are ongoing. Nowhere close to an exhaustive list, obviously, but in 3 major buckets: commercial strategy and predominantly their launch scenario planning, we looked at a number of scenarios based upon all the work that's been done. And this change of looking at our new filing, et cetera, has really pushed us up, and it's really meant that our teams have had to do extra work, but I have to say this is one team that I've worked with, and I haven't worked with a team like this in a long time of preparation really being ready to go and really working on differentiatable plans and differentiate programs in this market, and I'm very proud of this team. Launch infrastructure, especially looking at patient support hubs. As you know, patient support hubs help patients get on drug, help physicians' offices get patients on drug. And then organizational enablement, particularly looking at talent planning and organization as well as training readiness. We are very committed to have our team ready to go day 1 when the product is ready. This gives you just a view into what we're looking at as far as our path to commercial readiness. Obviously, every line here, every arrow here has 100 arrows 100. But they're really in 3 big areas: preparing our team, preparing our market and preparing our product to be ready for launch. So we feel AXPAXLI has the potential to redefine the retina market. It's a large market size, and there's a global opportunity attached to exactly AXPAXLI redefines the retina treatment dosing in the market, superior label positions us to put AXPAXLI in a class of one. And all of that delivers to our payers, physicians and patients, economic predictability. Thank you very much. And with that, I want to introduce Dr. Jeff Heier, our Chief Scientific Officer at Ocular. Jeff?

Thank you, David. As I sit in the audience for events like this over and over, I'm repeatedly grateful to have the opportunity to be with the team of such exceptional and passionate experts, experts like Pravin, Nadia, Peter, Art and David and our teams back home. And on top of that, to be part of a team that can bring such an important and impactful drug to really the patients I've dedicated the last 3 decades of my life to caring for. Over the next several minutes, we will review key design elements of SOL-R that align with FDA guidance and increase the likelihood of study success, and we'll follow that with some concepts of outcome analysis. As we've really discussed in depth over the past 2 years regarding the SOL program alignment with the FDA, both in terms of the 2023 draft guidance and public and written communications is critically important to derisking the regulatory process. The FDA guidance for noninferiority trials allows for the investigational agent to be compared to label dosing of either aflibercept 2 mg or ranibizumab 0.5 mg with a noninferiority margin of minus 4.5 letters. Axpaxley dosed every 24 weeks is compared to aflibercept 2 mgs dosed every 8 weeks. However, the FDA guidance also states that a comparator arm should have the same dosing schedule as the investigational drug. And for that purpose, 1 arm has aflibercept 8 milligrams dosed identical to AXPAXLI with the same dosing regimen and intervention criteria satisfying the desired masking intention. As both Nadia and Peter have described earlier, exPaxly will be compared to 8 milligrams of flibercept dosed every 6 months for superiority. In addition, sham injections are not recommended due to an adequate masking, and this has been emphasized several times by the FDA and both in our communications and in public settings. And as such, there are no sham injections in SOL-R. While SOL-R was designed entirely in line with FDA guidance, given the strength of SOL-1 that you've heard repeatedly today and our recent FDA feedback year 1 efficacy is no longer a requirement for NDA submission. Because of this, we are amending the design of SOL-R and extending the masking period to week 96 to evaluate new important secondary endpoints. At week 96, we hope to show potential superiority in best corrected visual acuity over aflibercept 8 milligrams, and we hope to demonstrate prevention of fibrosis and atrophy with AXPAXLI relative to 2-milligram aflibercept. Why are we not taking these measures at week 56, Well, in addition to what Peter described, 8-milligram aflibercept's dosing interval in wet AMD was recently expanded for up to every 5 months after 1 year of treatment. This new key secondary endpoint will be evaluated at week 96 to align as closely with aflibercept 8 milligrams year 2 approved dosing interval as possible. Let's talk about the importance of patient selection. Many, if not most studies encounter hard-to-treat patients that can disrupt outcomes, and this has been apparent in numerous non-inferiority studies. Several of the leadership team at Ocular were intimately involved in this analysis of patients with early persistent fluid from the aflibercept VU Phase III program. When you look on the left, when this fluid is present, patients required monthly aflibercept for the best outcomes, and this was superior to every 8-week of libercept or monthly ranibizumab. When you look on the right, however, without early persistent fluid, all 3 arms practically overlap. In the Kodiak DASL trial, which was conducted with the old formulation of their drug, patients were placed in dosing regimens based on disease activity. However, the subjects with the most disease activity could not be treated more frequently than every 12 weeks. And not surprisingly, this wasn't adequate for some patients. And in fact, per Kodiak's own commentary, this was insufficient for some patients. Each of these last 2 programs that I've shown you had patients with high need that could readily disrupt noninferiority outcomes. The SOL-R criteria were carefully selected to exclude those high-need patients that typically require more frequent injections regardless of the intervention. Such patients have been seen in virtually every study and are most likely to disrupt noninferiority outcomes. In solar, following 3 monthly anti-VEGF injections, subjects were observed for 8 weeks without treatment and had to have a retinal thickness of less than 350 microns and could not increase by more than 35 microns from the lowest CSF or retinal thickness at any prior visit. Both of these criteria select for stable, well-controlled subjects. Another component of study design involves monotherapy following randomization. The trials for the first and second-generation anti-VEGFs: EYLEA, [indiscernible], Vabysmo, EYLEA HD, dosed only investigational product post-randomization in the active arm. Non-inferiority trials for agents aimed at extended duration on the order of 6 to 12 months and longer, are often preceded by anti-VEGF therapy in a loading phase, but then rely upon investigational product only post randomization in the active arm. This is the case for SOL-R as well as Susvimo, the port delivery system. Some studies do include mandated supplemental injections with controlled product post randomization, but run the risk of being considered combination therapy especially if additional supplemental injections are required. Keep in mind that once considered combination therapy a superiority study is typically required, and the bar for such studies is quite challenging to achieve as we have seen with some recent failures despite them having early phase promise. Given these considerations, how should the outcomes of noninferiority trials be interpreted. The Susvimo FDA review highlighted that efficacy outcomes may be impacted in patients who receive rescue or supplemental therapy. Key considerations include not only the number of rescues, but their cadence and timing relative to the primary end point. Subjects requiring rescue therapy, especially more than a single rescue may be considered either treatment failures or combination therapy. The implication of either of these designations can have a significant impact on regulatory review of efficacy outcomes. In addition to the number of rescues, the timing is equally, if not more important. Rescues close to the primary end point and certainly, within the 3 months leading up to the endpoint, garner more critical scrutiny. Such rescues are believed to have a visual acuity impact meaning they artificially increase the visual acuity measurements, making this a significant review issue for regulators. Needless to say, such factors are critically important to obtaining a clear interpretation of trial outcomes. So let's summarize this section and identify key components to understanding a noninferiority trial evaluating extended durability agents and we will highlight a few key points. First and foremost, did the trial meet its noninferiority endpoint. This is both obvious and intuitive Next, one should look at the rescues, how many subjects were rescued and if rescued, how many subjects required more than a single rescue. Of rescues, how many were in close proximity to the primary endpoint, especially within 3 months. And of course, was the trial protocol in alignment with the FDA. This includes attention to the comparator arm, study interventions and rescues and masking. And along these lines, does the use of other agents, both mandated and rescue or supplemental constitute combination therapy requiring a superiority design. All of these factors contribute to the interpretation of study outcomes and require careful analysis in order to fully understand and depreciate study success. So thank you. With this, I think it would be appropriate for us to step to the question-and-answer session. As Pravin already introduced, we have an exceptional panel of key opinion leaders, clinicians, clinical trialists in our Arshad, Lejla and Darius, and we're going to move right to them. So I'm going to ask all of you this, as you heard earlier, we met with the FDA and have alignment on submitting our MDA based on Sol 1 efficacy alone in the fourth quarter of this year. Were you surprised when we shared this news with you, Arshad, let's start with you.

Jeff, thanks for having me here. It's great to see everybody. I think this is fantastic news for the field. It's fantastic news for our patients, their caregivers, physicians and payers. But it's not surprising to me because Peter presented very nicely that you need a -- it's a very high bar of evidence that you need to submit one trial for approval and SOL-1 met that. And the reason for that is the first superiority study it's adequate and well controlled because of the SPA does not have sham injection because it follows the guidance. So as a clinical trialist and you do a lot of clinical trials, you've been doing much longer, Jeff, than I have.

Much longer than anybody in this room, except Pravin.

For -- I've been doing it for last almost 2 decades. And this is a very unique thing for the field. And I think this is what's going to drive the field forward. where many others will try to get there. But it's a very high bar. You've been -- you and I've been with many trials that have failed. Superiority is not easy. So we are very excited about it. And now Monday morning, I can go back to my clinic and tell my patients if something is coming sooner than I was telling them. I was telling them 2028. Now there's a potential to have this in 2027. And this provides great hope for our patients.

Thank you, Arshad. Lejla, I'd love your thoughts.

Thank you, Jeff. Too pleasured to be here with all of you. I will echo what Arsha just said. And for the first time, I heard this statistically you just mentioned in the survey, I would agree that -- and I'm going to join my colleagues retina specialists that 80% of us are comfortable using this product on day 1 after approval. And why am I so comfortable and why we're going to fit into this 80% positive report is because the data is confident, giving me confidence to do use on day on. I am excited by not only efficacy, but definitely safety. And when we talk about patch surveys, the American Society of Retina Specialists has a yearly survey for retina specialists. And they ask us what is the biggest unmet need. We always talk about safety being one. This child gives me confidence in safety. But second thing is going to be duration and treatment burden and to see the efficacy and durability of this product is very exciting. And I think coupled all of this gives me great confidence to use it on day 1, and I'm super excited now to know that we may have this option earlier than we thought.

Thanks, Lejla. Darius, anything you want to add?

I was completely unsurprised by that announcement. The data is very compelling, rigorous well-controlled study addressing a superiority outcome against the undisputed market leader, the actual gold standard, aflibercept for the last 15 years with a meaningful clinical outcome, which is maintenance of visual acuity, not just any kind of visual acuity, excellent visual acuity. You're losing 4.5 letters at 52 weeks at a baseline of 80 letters, there's no study that's ever exited at 75 letters at the end of 52 weeks. It's crazy vision. And then on top of that, you're exiting -- you're controlling for that 40% or 50% of patients that we lose in year 2 and 3, they're off the -- they're just disappearing from us. And we've got 6 months, 9 months, 12 months, we have 80%, 75% and 2/3 of the patients are making it to that time those time points with excellent fluid control, great vision control, and that's an extra safety measure, and that is not lost on the FDA. So for me, it's a no-brainer. You made an agreement with the FDA. You delivered on your end of the bargain, it's delivering for the unmet need. Why wouldn't they want to get this approved.

Thank you, Darius. Arshad, over the last few months, since the results have come out, there's been a lot of discussion about the SOL- 1 results. Can you comment on the significance of the trial hitting its superiority primary endpoint. Why is that different?

Yes. Jeff, as I said earlier, we have been involved with so many trials and it's a very high bar to its superiority. So I think there are 3 things I want people to keep in mind. Number one is this is a treatment that is superior to standard of care as Darius says, a fiber shop. This is the first time you're comparing head-to-head durability based on FDA guidance. And this is the only trial that has shown 9 to 12 months durability in clinic injection. So I think those 3 things are super crucial because that has not been shown before. Now what do physicians care about? Physicians care about OCT and anatomic control. And the data we have seen with patients with less than 30 microns of fluid, majority of them had that until 1 year. So if you have good anatomic control, you have durability head-to-head. So there's no marking the water with anti-VEGF rescues. This is clear durability head-to-head and safety, and we saw the safety that is well tote. So those 3 things on top of the efficacy, I think it's very, very compelling from this data set. And I think as Leila said and David said like 80% are excited to use it and physicians are going to use it the way they think it's best for their patients.

Great. Thank you, Arshad. Darius, as we've heard over and over, SOL-1 is the first of its kind study. And in some respects, the results have been different to interpret than others. When you've been at meetings what type of questions have you heard regarding the study? And what issues -- or what types of results seem most unclear?

Yes. It's really hard when you have something new, it changes your perspective on what's going on. So I really just try to focus on when I'm talking with my colleagues about the 3 things that really stand out to me about this study. just because it's a new study, it doesn't mean it's not going up against the high bar. So we focus on the superiority outcome right off the bat. You're beating the -- again, the gold standard in a meaningful clinical outcome, which is maintenance of excellent visual acuity. Then the next thing is safety. There is no safety signal here whatsoever. You have 94% and 97% of patients completing enrollment all the way through. There's no cases of endophthemitis, intraocular inflammation of any severe kind. You don't have any exclusive or nonexclusive vasculitis. And then, of course, you get the durability. And we felt very confident coming out of the Phase I trial monotherapy, bale you got patients making out to 52 weeks with good vision and fluid control. And why is that 52 weeks important? Because want to get to a 36-week outcome, you got to get a majority of your patients to 52 weeks in order to make that 36-week outcome. So we felt very confident, but working in conjunction with the FDA, you got to make sure that it's safe for the patient. So how do you make it safe? You choose a responder population. And in this case, the responder population is both on you get at minus 8 and minus 4 weeks, you get aflibercept and then you test to see if you get to 2020 vision or gain 10 letters, then you can qualify in the functional aspect. And then you also have to make it on the disease control aspect with respect to OCT fluid. You have to get below that 350 microns and show that you're a fluid responder. And interestingly, this results in this very nice group of patients with the best fluid control 220 microns, roughly at baseline and visual acuity of 80 letters. And what does that mean? It means you can only go downhill with respect to vision. And so they pushed back at me and say, "Hey, you got randomized AXPAXLI or aflibercept. But that's not how I treat my patients. I said, really, frankly, I don't care how you treat your patients because you're not going to get a better outcome even if you're treating monthly with aflibercept because when you look at the Marina data with ranibizumab or other data from aflibercept. If you do monthly treatments at 6 and out to 12 months, the best you can do if your vision is at over 75 letters is lose 5 letters at 6 and 12 months, okay? And so we're giving you that's with monthly injections. And so here you are, you're going out there and you're getting one injection and you're going out to 52 weeks and you've given up 4.5 letters. And then the light goes off because now they see, hey, this is actually paradomatic change that's meaningful and wait for it, I'm walking away at 75 letters of vision higher than any other trial has ever achieved. For me, once they see this and get it and they start thinking about it, now they get it.

Great. Thank you, Darius. Lejla, one -- probably among the data that's considered most impactful to clinicians has been the time to first rescue. In this room and on the webcast, we have many of the top investors in the country, if not the world, how should they look at this data and interpret it.

Yes. Well, Jeff, I completely agree. The time to first rescue to me is really the most clinically meaningful measure. Why because it really gives us the practical measure of durability in clinic. When a retina specialists look at this data, they really see evidence that rescue-free rates for AXPAXLI were significantly better than aflibercept rescue-free rates. As a matter of fact, if you look at the data itself, you see that AXPAXLI outperformed aflibercept by a measure of 6 months. So we're giving ourselves duration of 6 months flexibility for our patients. And when we talk about in general, recurrent treatments, patients missing appointments, missing treatments, we know that unfortunately, all of that leads to poor visual Q&E outcomes. And when we now have a 6-month advantage over currently approved and most commonly used therapy, I would say that is going to yield a really remarkable outcome in the real world. But injection-free rescue-free rates, I would say our measure that we talked about in clinical trial. But how about the real world. When I see a patient, I'm not thinking when was the last time I injected him. I'm looking at the OC team front of me. As a matter of fact, my patient is asking me, how is that OCT looking because we are all focused on anatomy. And from the current data what I see is that OCT that nonatomic measurements were very much solid all throughout the program. And in 9 months, really barely variated within a 30-micron difference. That data for me is even more significant because it really is going to mimic my real-world use of this therapy.

Yes. And Lejla, you mentioned the OCT and how we use that to gauge our treatments. When patients come in and look at the OCT, I tell them, fellows have spent 2 years learning how to read the OCTs and then they tell me, well, I've been with you for 8 years. So I feel I'm an expert as well. our shot, there's been discussion around how to interpret and understand the patient population of SOL-1 we've touched upon this patient had -- this patient population had the best starting visual acuity of any study we've seen. How do you interpret that from your clinical population.

Yes, being part of dozens of naive DMD trials, this patient behave like what they usually do. They got the 2 aflibercept injections, they gained vision as expected. So they were at peak vision. And after randomization, the goal was to maintain vision. They're not going to gain any more vision. So that's one thing. The second thing is that when I start recruiting for this study, and I know a lot of patients in almost all trials, but especially here, the recruitment was really fast because the patients coming in with naive at AMD are much earlier now than what they used to be back in the day. And in this study, we allow good vision patients. And what that did was led to very fast recruitment of the trial. So this kind of reflects the real-world patient population that we have in our clinic, which means that when we see this data where tooth of the patients are going 1 year in it, it translates into very quick adoption in clinic. So I think the only difference here, obviously, as I mentioned, is that patients started at randomization with very good vision, but I'm not surprised. I mean, this is what patients do. They gain vision and our goal was to maintain it and we were able to do that.

Yes, I agree with you. We see now more frequently than not these are the patients. This is how they present with wet AMD.

Yes, because optometrist OCT, we image them much earlier than what we used to, and catching the disease early actually is beneficial for patients.

Absolutely. So Darius, you've talked in the past about how durability itself is a safety feature. Can you describe what you mean by this?

Yes. Again, another excellent question. I may be unfamiliar to a lot of you guys for a couple of reasons. One is I'm a pediatric retina specialists by training and love. That's what I do. And the second thing is my niche has always been safety. I've served on over 20 data safety and monitoring committees. In fact, when I first started working with these guys, was the independent rescue monitor. And that's what attracted me to this company is its commitment driven from the top by Pravin to ensuring patient safety. And when you look at this drug and what it offers, is it gives us peace of mind. And what do I mean by that? Well, Nadia, you and everyone here on the panel, has alluded to that we monitor patients with OCT technology, okay? We either use fluid as a proxy to intervene or we use visual acuity. And if we see either of those things, then we can treat right then and there. And if we don't, we feel safe in extending their -- the next time they're going to come. and we extend in 2-week intervals. Keep in mind that the longest currently approved interval for a single bolus injection is 16 weeks in this disease, okay? So we feel comfortable extending you out to plus or minus 2 weeks in that window. Otherwise, you could lose vision, you could get too much fluid and get permanent loss of vision. You can get too much hemorrhage and get permanent loss of vision. Now think about this. we're talking a drug now that goes out in -- we're measuring outcomes in months and years, okay? Not weeks. We're sitting there at 9 months and 1 year. We have the -- 80% of patients are making 6 months. 3/4 of the patients are making 9 months. 2/3 of the patients are making it out to a year on a single injection, okay? And now I know that if my patient has an accident, has difficulty getting in either because they can't afford it or because family member isn't available because they want to go to a wedding, they're traveling or they just want to live their life, they can go out there, and I can very happily know that this patient is safe. They're going to -- and 75% of my patients are going to make it out to 9 months. If they miss their 6-month appointment, I'm not sending out Seal Team 6 to hunt down that patient, ensure that they can come back in and not be at risk for losing vision. That's what I'm talking about safety. It's complete peace of mind.

So do you have any safety concerns at all, not just about the durability?

Yes. So like I was involved in almost every single rescue call along with Barry and there's no safety signal here. I mean right off the bat, all you have to do is look at how many patients completed the trial. It was essentially 94% and 97%. There's no cases of endophthemitis exclusive or noninclusive vasculitis the floaters were related to the drug platform breakup. The timing was consistent with that. There were no visual acuity impacts from that. And that last follow-up, all of the drug particles that spontaneously resolved there is no safety signal here. The 9 cases of intraocular inflammation were mild or spontaneously resolved on their own accord. This is a complete -- completely safe drug that has been introduced in the last 15 years as a guy who sat on over 20 data safety monitoring committees.

Thank you, Darius. So I'm going to ask each of you this question. If you had to simplify the takeaway message from Sol on for practicing retina specialists, what's the single most important message from SOL-1. And a corollary to that is given what you've seen from SOL-1 and submission of a single study, is there enough here for you to initiate treatment. Arshad, yes.

Jeff, for me is durability 9 to 12 months. I mean I think we have never seen that in our field. for an in-clinic easy injection. And I think that correlated with anatomic control and the well-tolerated safety profile that Darius mentioned, I think it's enough for me as a retina specialist to start using space as soon as it's approved. Now SOL-R is important for redosing and more for commercial reasons. But I have a question for the audience. You came to me if you had wet AMD or your parents have wet AMD, and I offered you a 2-month drug versus a 9- or 12-month drug, how many in the audience will take a 2-month drug raise your hand? How many will take 9 to 12? So majority will be untreated looks like. We don't not treat wet AMD. Let's do it again.

They're filming in the back.

2-month drug. Okay. 9- to 12-month drug. Okay, a majority, right? Simple answer from a retina specialist as well as the patients.

Lejla?

I mean really well said, Arshad, I would completely agree, disease control, not only disease control, but maintenance of really good vision, visual acuity. And all of that come pulled with great safety, no questions. And Arshad Khanani is asking me, but really my patient is going to be asking me to use this because they very well will come to me saying, "Doctor, I want the 9- to 12-month drug".

Yes, 100%. Darius?

Yes, absolutely. I mean it's the durability plus it just raises the entire visual acuity floor, if you will. We're maintaining excellent vision out to 52 weeks. We have durability that's 125% to 200% more than any currently approved dosing regimen on the market today and who knows? It might even go longer, Jeff, we didn't hit that 50% rescue at 1 year. So we're going to learn a lot more about this drug, hopefully, pending its approval. But I think there's -- this is just -- my phone has been ringing off the hook from my patients. Like when can that drug be available for me?

Great. So Darius, we've just finished talking about SOL-1 superiority, how do you -- now as we look at SOL-R, which is a noninferiority, how do you look at the difference between non-inferiority and superiority trials.

Yes. This is an interesting one. I think we all get superiority. This drug is superior to that drug. Noninferiority is a little bit trickier. You weren't superior, but you weren't inferior. You were noninferior. What does that mean, okay? And so when I look back on 30 years of clinical medicine, I've never once had a patient, not once come into my clinic and say, "Hey, doc, can I have the non-inferior drug, okay? Just hasn't happened. And they asked me for the best drug and they asked me for the long-acting drug, okay? Just like you all said you wanted the durability, my patients want the durability. And so when we look at non-inferiority trials, they are aimed primarily at getting to the secondary key secondary outcomes, okay? And one of those is durability. So what they do is they give you this metric and they say, "Hey, the functional outcome, maintenance of visual acuity is your primary outcome, okay? And that's assessed at a certain time point, let's say, 52 weeks. And typically, they give you a noninferiority margin, anywhere between 1 to 5 letters, and it's usually on the minus side. So let's say you make it to minus 5 letters at 52 weeks, then, hey, you're noninferior to the gold standard and immediately, the discussion shifts to the key secondary outcome. My drug made 8 weeks, your drug made it 4 weeks I'm superior on durability, and that's what moves that product in the market, okay? However, you got to remember that little visual acuity tax you paid 5 letters because the FDA is keeping track of that. And so every 52 weeks, you're going to lose those 5 letters. And so the FDA says, "Hey, you got to protect the patient somehow. So they give you rescue criteria, which is where I come in. because then I deal with the sites to help them adjudicate these rescue criteria. And so if you get too much fluid or you lose too much vision, then we give you a rescue therapy, typically with the gold standard and that goes towards your evaluation of did you make the durability. And so the second tax that the patient pays is how many rescue therapies did you get. So you went to 52 weeks, you lost 5 letters and you got 3 rescue injections, but your durability was longer. Is that a win? I don't know. We have to leave that up for the patients to decide, but in superiority outcomes like AXPAXLI, we don't have to worry about any of that. we beat them, we're superior, and we give the greater durability.

Great. Thanks, Darius. So Arshad, how should we think about rescue treatments when we're looking at non-inferiority studies.

I think Darius made some good points. I think the key is that we need to make sure that we pretty much have no rescues or minimum rescues. As you said, and recently, many of you were at clinical trials at the Summit, and we had [indiscernible] Chambers and ask him the question in a panel, I was the moderator, how many rescues are allowed and the timing of the rescue and he said, any injection given after randomization is considered a rescue. So imagine if you are giving -- randomizing a patient and giving them your drug plus an anti-VEGF versus EYLEA, that's a rescue because this is post randomization. They don't care about the run-in phase but after randomization. So imagine if you have your own drug and you have aflibercept Q8 weeks, the delta, if you're giving a 6-month drug is only like 4 injections in the middle, right? The other one group for a year will get 6, your 6-month injection will get to. So the delta is very small. And if you're giving 2 injections or you're giving an injection a month before primary endpoint, as you said, Jeff, it's going to change your BCVA. So Wiley Chambers said anything after one, you get a penalty. And then the rescue has to be greater than 3 months from the primary endpoint. And also for us, right, as clinician, if you are giving 2 or 3 rescues and giving another treatment, it really doesn't address the unmet need of durability and treatment burden. So I think the noninferiority design, as Darius said, is an easy way to go, but it comes with a lot of criteria because we don't want a drug that will need a auto rescue because it's -- we already have good drugs. So I think that's why superior design is ideal, but it's a high bar for approval or to win in terms of primary endpoint. So yes, it was very lighting for me because I've been hearing from a lot of people, so I asked Wiley Chambers myself directly. And he was very, very strict and very to the point.

Yes. Lejla, can you comment on the non-design of noninferiority trials with regards to the selections of patients on and the use of multiple drugs after randomization. Arshad sort of touched on it there.

I'll echo what both of my colleagues here have said, first, it is very confusing for noninferiority trials. And certainly, we don't talk about that with our patients. They want the best truck, most certainly. But when we are digesting this information, you really have to look at 2 aspects, very important aspects. First is the loading phase that can happen pre-randomization in times post. But when you load pre-randomization you are selecting for the right patient to enter that a randomization and continue the trial. And that we have done in prior trials, [indiscernible], for example, in one of them and most certainly in SOL-R. Now that is the key aspect and really gives us a clean data to understand and for us a retina specialists to really digest. But I think what it gives us even cleaner data now that we randomize the patient is this coadministration. If you give monotherapy post randomization, you are really looking at efficacy of that drug alone. You will fully understand what is efficacy versus if you co-administering you're administering the study, the targeted drug versus what is approved currently on market. And one may wonder which drug is really truly giving the efficacy down the road? Is it what we're studying or is it really the therapy that's already improved in market. So I think that really works the waters and from perspective from scientific, from regulatory, it is harder to tease out information when you have co-administration of the drugs. And how does this apply to clinical care on just general real world? Well, I can tell you and assure you that conemidstre drugs on a same day in clinic is impossible. There's no way any of us will be able to accomplish that. And why do I say that? Because it's simply logistical 9 year. It's also approval 9 year. There's no way that insurance currently allows us to prove 2 drugs on the same day to give to the patient. I'm not sure how that's going to change in the future, but I doubt it would.

Yes, Jeff, I just had a follow-up on that. So in with our complement inhibitors, patients who have GA and neovascular AMD I'm not treating the same day because it is hard to get paid for it. And even though there are 2 different codes. Here, if you are doing 2 injections at the same time, you have to use the DMD code. And so injection, you're not going to get paid for forget that, but I don't think the drug will be covered either because you're injecting 2 drugs the same day for same indication. So I don't think that's very practical and also the busy clinic and patients don't like 2 needles.

And then [indiscernible] suggest come back for another day to do this, but let's be quite frank. We're talking about minimizing number of injections for our patient [indiscernible] treatment burden any time we're talking about additional procedures, we're just adding to complexity.

Yes. And then there's a 28-day thing that you cannot do wet AMD treatment less than 28 days based on the current anti-VEGF injections. So I think it's going to be very actually impossible to give 2 injections at the same day.

And I think the point about separate days in Boston, they'd rather go to Europe, then come from Cambridge to come back to Boston. So let's switch gears to some commercially oriented questions. Darius, how should investors think about the real-world the real-world questions of treatment burden. And we've talked a lot about the unmet need. So is this -- is there truly an unmet need from treatment burden.

Absolutely, there is, Jeff. As you pointed out earlier, we're doing OCT-guided treatment 97%, 98%, I think, from the most recent preference in trends survey from the ASRS. So we look at the OCT, we were making a determination, which means we're giving every single patient individualized care okay? But you may have 5,000 patients with this disease. So that's 5,000 different treatment plans. And then on top of that, every one of those patients has a varying degree of fluid control, predictability, responsiveness. And it is completely unpredictable from patient to patient. You just showed up there the data from the VISION trial. If you had fluid early on and view VISTA yes, sorry -- view VISTA trial, where you had fluid early on that adversely impacted how the patient would respond later on. And so here, what you have now is the potential, and it seems counterintuitive and maybe not what you would like to move away from individualized care and to standardize the practice. And what this leads to is predictability. If I can get 80% of my patients are going to make 6 months, I'm going to see that patient twice a year. It's easy. It's going to promote ease of scheduling. It's going to promote inventory control in my office. It's going to clear up my parking lot. It's going to be very predictable as to who's going to be there. You guys laugh at that, but parking right now, people spend 2 hours circling around the Byers Eye Institute at Stanford looking for free parking. And so it's a big deal when you're moving 550 patients a day. And you never really think of it, but if you can have predictability and normalization with maintenance of excellent visual acuity, no safety concern and no worry if the patient misses the appointment, by wait for it, 3 months, they're still under control. This is a game changer for how we are going to kind of transform the clinical practice and make it more predictable and less reliant on the OCT.

It's great. It's interesting. You said they'll drive around for 2 hours to look for free parking in Boston, they'll drive around for 2 hours to look for $50 a parking. Arshad, if AXPAXLI were to be approved on SOL-1 alone as our NDA submission, where do you see it fitting into the treatment paradigm for your wet AMD patients?

So Jeff, that's a great question. And I think the answer is majority of the patients, right? So when I think about my patients and a new drug, we have all these patients, hundreds and hundreds of patients in the clinic that are on injections, right? So we have 2 buckets. We have the one who are high need 4 to 6 weeks, and then we have the ones that are stable on the second-generation treatments anywhere from 2 to 4 months. So if I have a patient going 2 to 4 months, and I tell them, I gave you this new treatment that can go 9 to 12 months, they're all in, just like our audience. And then you have these patients run 4 to 6 weeks, very active treatment. You will give AXPAXLI to them. And because of sustained disease control, they may not need supplemental. And if they need supplemental, then we are going to give supplemental injection on top, but they're not going to be coming in every for to 6 weeks, but maybe every 3 to 4 months, right? So it's addressing a majority of the patients that are in our clinic. And then the third is the smaller number is naive patients, right? We do a lot of trials, so many of them go into clinical trials. But if they don't, They'll come in, they'll get an anti-VEGF and then 1 or 2. And then once the disease is controlled, you'll give them space. And I think Darius made a really good point. I treat patients differently than dairies. I don't do fixed dosing. I do treat and extend. So our experience with Board delivery system is the same. I have patients who only come and see me once a year for their refill. And then I have patients who come in every 6 months. And I have a few that need supplemental in between their refills. So I think I'm more of a treat and extender and I won't be surprised that with AXPAXLI, I have those 3- to 4-month patients now coming in once a year to see me.

Yes, it's a good point. And given the results of SOL-1, I've looked in my clinic in a similar manner, and I agree with you. I think the large, large majority of patients are going to benefit from AXPAXLI. Lejla given SOL-1 had a unique patient population, we've talked about it earlier diagnosis, better vision. How do you think about the potential impact of AXPAXLI if approved in the broader population?

Well, first of all, Jeff, while we call it a unique patient population that was enrolled. I would say that is really the patient population that's representative of the modern practice. What do I mean by that? While all of us are much more aware of disease itself, the awareness of wet eagerly macular degeneration in our community among optometric referral or general ophthalmologists. And our retina specialist is much further than it has ever been. That's leading to earlier diagnosis. But what's leading to even earlier diagnosis is actually amazing image technology that we have accessible, readily accessible everywhere. I mean one dates, I'm sure, going to be available in grocery stores to be image. So we're diagnosing patients earlier, identifying patients. And now we're actually talking about great visual QEs because we're diagnosing them earlier, and we are saving and maintain the visual [indiscernible] long term. So the bar is very high for [indiscernible]. So I do say -- I do feel comfortable that this patient population is very much the one we see in our practice. And on top of it, we do know that results were quite impressive, but also the enrollment was exceeding expectations. So clearly, the rest of the retina specialists agree that those patients are very much seen in our practices. But when you talk about broad label self for wet AMD. I will just kind of look at historic trials. When I look at, for example, for approval for geographic atrophy drugs, [indiscernible] one of the great examples patients enrolled in that trial were extrafoveal GEA patients. They showed efficacy and the drug approval is for general patient population, geographic atrophy. So it gives the retina specialist liberty to use it for geographic atrophy alone and for us to learn in a real world setting how that behaves. Now I know this is -- we're talking about superiority trials and it's very unique to now have a positive superiority trial? And why is that beneficial? Because I hope that it's going to translate to greater access for me to utilize this drug for any patient at Idem that would benefit from. And I think that's the biggest limitation now we have. It's really having to go through step part therapy and get there. And I hope the superior trial is going to allow us to now have this accessible to all our patients.

Great. think well, to wrap things up, I'm going to ask each of you this question. We've talked a lot about retina specialists and investors how they've interpreted the SOL-1 data set. What impact would a therapy like AXPAXLI have on long-term patient outcomes. If we're dealing with the improvement in adherence, follow-up and disease control. Arshad?

I think our hope as a field, right? And all of you are here doing this because we want to optimize the outcomes for our patients. So I know that patients who come less often are more compliant than patients who have to come every 4 to 6 weeks. And not because sometimes they don't want to come, it just life comes in the way. They don't have a driver. They got Sig, they got admitted and they miss 1 or 2 or 3 injections, they come in with the catastrophic hemorrhage, and now they're blind, and we can now recover that. So that's my hope, right? We are doing this because we want to have better vision for our patients. And based on the SOL-1 data, I just clean data set. That's the key is there's no contamination. It's a clean data set. We have a drug that can go up to a year in 2/3 of our patients with good anatomic control and safety. So I think that's the bottom line that the excitement is there from the retina community after they understand the trial. And I think patients are waiting for it.

Great. Lejla?

I'm going to tackle on adherence question, [indiscernible]. The real-world studies over and over, tell us that we lose about 50% to 60% of our patients in year 1 to 2. And that's primarily due to adherence missed appointments because real life happens, accidents happened, hospitations, other events were certainly too. So now to have a drug that's going to be a safeguard for my patients. So in case that life event happens, they will have therapy that's controlling their disease. And I think that really truly in the long term, I hope when it translates to even better real wall results than what we see in clinical trial.

Thank you, Lejla. Darius will give you the final word.

I always like that, Jeff. I look at it very strategically for the patient population overall. The problem with bolus therapy and increasing durability is that we know that the more injections you give, the better your visual acuity is and the converse is also true. The less -- the fewer injections you give, the worse your visual acuity is with current bolus anti-VEGF therapy. We've seen now with 2 studies, the surgical implant. And now with AXPAXLI, that if you have continuous drug release, you can maintain visual acuity for up to years going out, okay? And this addresses one of the central fallacies of the treat and extend OCT-guided regimen, which is that you should only treat for fluid and there's no functional benefit from continuous VEGF inhibition. The visual acuity decline is a late drop off, okay? Fluid comes first and then you lose it. And so if you only always wait until fluid, you're always behind in the functional outcome score. I think if you look 5, 7 years down the road, you're going to see what I see with my patients. I was just preparing a case report the other day of a patient that have done about 140 injections, now originally with ranibizumab then with aflibercept and now with VABYSMO over the last 10 or 12 years, that patient has fluid in both eyes, convexed contours and he's 2025 in both eyes. You continuously suppress the patient on monthly or every other month injections for a long term. And what I see happening is that guy was getting 30 injections, 10, 12 years in could get by with 20 injections. And that is a win for the entire patient population, okay? Not just here, everywhere that we have wet AMD. And I think that if you look at the IRIS database, which is run by the American Academy of Ophthalmology, and you go and say, "Hey, look at the visual acuity between 2015 and 2025, and we see that patients eventually lose vision because they get fewer injections, what you'll see is they're going to get fewer injections and the visual acuity is going to go up because we're having continuous suppression with long-term predictable durability.

P Great. Well, I want to thank the panel your insight and expertise is invaluable. And with that, I'll invite Pravin to come back up and give us a summary and takeaways.

Thanks, Jeff, and thank you. Great Job. Great job. As you guys move around for the Q&A part, please go ahead. What I would -- I'm not going to take along with this. You heard me say when I started out, look, there are 3 characteristics that define us. We're courageous. We're bold. We're opportunistic. But I also told you that I hope you take away from this that we're careful, we're thoughtful, and we're methodical in what we do. We look after this company like no other. We look after what we do step by step, even if you may not hear it every day. The fact of it is that we're not just going fast, we're going fast, but with very, very firm guardrails. I mean at the end of the day, I hope you realize how deeply infused that is in our culture. I mean how many times today did you hear the word derisked, how many times today, did you hear the word FDA Alliance? I mean how many times today did you hear the word Peter from Art. Okay. So thank you for being here. Look, I hope you realized with this, our hope here, our intention, our goal and we're right on track is not just to be best in class, is to be first in class, and we'll do that quickly but we'll also do that responsibly and thoughtfully. So let's just go to the Q&A. Please go ahead -- Biren, Go ahead.

Yes. Thanks, Pravin. And congrats to the Ocular team, a lot of updates. So a wonderful job. And I get you guys always keep us on our toes with all the updates. I've got like a list of like 10 questions, but maybe I'll just go with a multipart.

It was number 9.

All right. There you go. Maybe to start on the requirement for confirmatory evidence for the NDA submission. Will the pre-NDA meeting in Q3 discussed the confirmatory evidence that you shared with us? Or have you already shown that to the FDA? So that's first question. Second question, of the 6 components that made up the evidence for confirmatory evidence, were there any weightings assigned to the [indiscernible]. So is there a preference of order, for example, such as SOL-1 IRIS data? And then I guess in the context of SOL-1 study, what's the weighting of the confirmatory evidence of relative to the SOL-1 data set that the FDA is going to apply to that section?

All great questions. Let me have Art start off and then maybe Peter would like to jump in because Peter is kind of an Art want to be. So go ahead, Ark. Why don't you go ahead.

Let me answer your question. Thank you for your question. as I stated a little earlier, we've always agreed with the agency about what the content of that application will be. That is the SOL-1 data plus the confirmatory evidence plus our 300 patients worth of data. And the agency, as I shared with you, has confirmed that this is a compelling package and that will be reviewable. So the pre-NDA meeting is -- and I've done a lot of these pre-NDA meetings, really more about the formatting of those same data. In other words, I want to sit across the table from the reviewer and say, we're going to format it this way for this table. Is this acceptable. And that will be the discussion. So it's really an operational aspects of the formatting of that application. I hope that answers your question.

Okay. So this is like asking a man starving of thirst across the Sahara in desert to be water critic. Peter, anything to add?

Just a few things. So first off, yes, we have presented to the FDA confirmatory evidence. In terms of waiting, that would be asking crystal ball in terms of what they would want for the waiting Certainly, the most important is a positive well-controlled study with high statistical significance. That's what matters most. The confirmatory is that. It's confirmatory of that study. The fact of the matter is it's the breadth of our confirmatory evidence that probably made the agencies say the things they said in the minutes. Now does it -- again, it doesn't mean we get approved, but it just bolsters our position, I guess, is the best way to put it.

And do you want to repeat what Bill said regarding SPA?

Yes. I've been to many FDA meetings, certainly more than Pravin. And usually, when you get to the end of these meetings, they have a gajillion questions. And really, the fact of the matter is Bill probably said at least 3 or 4 times that our presentation or evidence, et cetera. is very compelling. And that word actually shocked me. And the next thing I shocked me was they only had really 1 question, which was, when can you file. And to me, that statement and the fact that there were no questions to us was an incredible meeting, quite frankly.

Go ahead, Nadia.

I will say the big differentiator for our program was that we went in with data. And we had obviously benchmarked against what been published before previously by the FDA as well as what Dr. [indiscernible] said. But we did go in when you went into that meeting with our data in hand and with the confirmatory evidence in hand. And so we were able to have a conversation that was not theoretical but more benchmarked in what is already available.

Very important point. We went in with data. Anything else to add, anybody? Okay. Next question.

You say your name.

I'm Tara Bancroft from TD Cowen. So that was all super helpful context, especially in underscoring your confidence in this particular pathway. But we also have to understand contingency plans and the however, unlikely event of a refuse to file or a CRL. What would that plan be? Like would you say that it's a CRL at the time. Like would you wait for 2028 SOL-R data? Would you unmask SOL-R at the time, something else? Anything to describe what would happen in these events would be super helpful.

Yes. I'll -- let me try and take a crack at it and then maybe Jeff and Nadia, Peter, or anybody else can answer as well. Look, it's very important to state that our confidence in SOL-R is greater than ever. I can't say that enough. I used to say that because of the ramp, which is extraordinarily well designed by this group. But now I can say that more factually because of what we've seen in SOL-1. And let me just repeat that because the bears repeating. Realize that using the SOL-R rescue criteria in SOL-1, 80% of patients at 6 months were rescue free. And that's remarkable. It's even more remarkable when you think about the patient population, this is exactly the opposite patient population that one would choose for SOL-R, right? For a non-inferiority study, you'd want a patient population that's absolutely stable. For SOL- 1, we had a patient population by design that was absolutely unstable. They were designed to lose vision. And despite that, we have a 80% rescue free rate at month 6. So clearly, when you go ahead and look at the ramp and you look at the way we've super enriched and super selected patients for stability, we fully expect that number to rise and that's with good reason. So our confidence in SOL-R has not changed, it's gotten greater, if anything, by far, right? That's the first thing that I would say. The second thing that I would say is we're not doing anything to SOL-R, right? As far as the primary endpoint is concerned, we're not changing anything. We're still masked and it's still running. That's available to us at any time. It's entirely flexible. But I will reiterate that it became very clear to us that a complete package for the FDA has nothing to do with the SOL-R efficacy data. That's it. So that gave us the green light to really use that data for the best leverage we can get in the community. Why would we repeat the same trial and do the -- and show the same results why not show with our newfound confidence in AXPAXLI that we can actually hit a grand slam when we've already hit a home run by going all the way and showing superiority to high-dose EYLEA that's logical and that's exactly what we're doing. Anybody else want to add? Peter, Jeff, Nadia art, anybody.

I think just to reiterate, the flexibility is tremendous here. We haven't changed anything. We're still running the study exactly the same, but the opportunity to demonstrate superiority to 8 mgs aflibercept at 96 weeks is just too great to not take.

And Tara, I also realized that we have the opportunity at that point also to look at atrophy and fibrosis, right, under masking. And if we're fortunate enough to show a delta there, which we think we will, there's potential of including that in the label as well. And imagine if we're fortunate enough to do that, what that gets you a label where you're shown to be superior to EYLEA and high-dose EYLEA potentially with a delta in fibrosis and atrophy. I mean that will corner the market for decades to come. Nobody is going to do a superiority study. I don't think based on what we've done. So it will absolutely solidify the market for decades and why would we pass up that opportunity. Bill? Who's next? Go ahead.

Daniel [indiscernible] from Bank of America. I had a question on your confidence that submitting the 104-week data from SOL-1 will not trigger a major amendment for the review? And then is that something you discussed with FDA during the Type C meeting. And also, how should we think about ex U.S. regulatory path? Do you think you will need SOL-R for that?

Yes, I can take a crack at that, and maybe I'll pass it on to Art and Peter or anybody else who wants to comment. Look, the words major amendment was never ever discussed in any of our meetings. It's a totally different path it's -- there's nothing to see, there's nothing to show we're masked, right? I don't see any way that there would be a major amendment whatsoever when we're not unmasking data at all. So I think that's completely off the table that's never come up, right? As far as the OUS part goes, David, that's a great question. Look, we are -- to be very honest with you, in a company such as ours, our job is -- I mean, we're not a large strategic that can fire everything at once. We -- our priority unabashedly has been the U.S. FDA. Now that that's there, we will continue and intensify our engagement, which has already started with OUS agencies. And having data that goes all the way to 96 weeks in this kind of a study will only add leverage to that. And they would love to see that kind of data with a fairly familiar study design but with twice as much information, right? So that actually is completely aligned with what we expect in our early conversations with OUS agencies. Art, any more about the major...

I can just add something quick. During our Type C meeting, we did not discuss the SOL-R. And our strategy was focused on single trial adequate well control, meeting the evidentiary standards for effectiveness and then our safety database that we would add to it. So that was our focus. I'll give you our OUS perspective here. I mean, we have -- we're working through that strategy now. And as you know, European and other health authorities have a very, very different perspective than FDA at times. So I really just think it's moving forward as we pull that strategy together and have those conversations with those regulators.

But they would love a study where you can provide to your information. Yes, Lisa go ahead.

Thanks for the event this afternoon. Ocular team, really appreciate all the detail here, especially on your thoughts on the regulatory path and the rationale. Just a couple of questions for me. So your competitor has a noninferiority trial ongoing right now that's going to read out soon. Should this fail either due to efficacy or a safety issue, would you consider unmasking SOL-R under this scenario? Or could the FDA ask you to unmask your ongoing SOL-R trial?

So Lisa, thanks for the question. Look, this has nothing to do with anybody else that's out there whatsoever. We're doing our thing because we have a study result that nobody has ever been able to achieve in the history of this planet. It has nothing to do with anybody else. I have no idea what they'll be doing good luck to them. But at the end of the day, no matter what happens, the way that I see it, what you've heard today, I think we'll all agree has completely immunized us from anything that happens to anybody else, which is exactly what we want to have. we want people focused on us, what we're doing because what we've achieved is something no one else has achieved. And whatever happens anywhere else, we're completely immunized from. Bill? Sorry, I can't -- I've got to go like this because I can't actually see anything from the spotlight.

Serge Belanger from Needham. Thanks for hosting us this afternoon. So first question for the company. based on the regulatory path you outlined today, what are your expectations for the label? And more specifically, how do you think it will reflect the products duration as well as the repeat dosing that you're looking for?

Yes, so it's a great question. Let me use this as -- I'll give you a quick response, but let me use this as a way to bring in and our 3 KOLs as well in terms of what a label means to them and what -- how they would use the product. But look, from our point of view, with this strategy, I don't see why we can't get the label that we are hoping for, which is a label that is the first and only superiority label with dosing from 6 to 12 months, they'll have all the information for that. And as Art outlined earlier on, there's a lot of redosing information that they will have as we continue with this strategy. So again, we haven't had labeling discussions with the FDA. It's premature to do that. But I think the other impact of this is how will the label impact the use of this drug, right? And what I'll also remind you is, look, the label is very important and not -- in my perspective, at least when I was practicing, not necessarily from how you use the product. I mean all of these KOLs and everybody in my field goes to tons of meetings, nobody uses any drug that I know of in my field per label or per the Phase III trial. I mean nobody does, right, at all. At the end of the day, this company's goal because we are -- we always say this we're for retina by retina. This company's goal is to have this product in the community period, and they'll figure out how to use it. and they will. We're not -- there's lots of questions to answer. They'll answer all of them. We believe that this will be the most impactful drug in the history of retina, but how it will exactly be used is going to be determined by them. Lejla, why don't you start off and then we'll go from there.

No, happy to. So exactly what you said. We're going to use it most likely off label because not -- I completely agree all of the drugs that are out there approved are -- we really use at liberty to help our patients. And what is the help we currently need? What is the community asking for longer duration therapy that's maintaining visual acuity for our patients. So yes, I will feel comfortable based on the trial design and efficacy that I see that I will feel comfortable using in my brand-new patients that are diagnosed with MD, and I want to maintain their visual acuity long term. But I also feel very comfortable to using in all my patients that are currently being maintained on therapy. And that's the majority of my patients in a 50-day -- 50-patient day in a clinic, probably 1 or 2 of those patients are newly diagnosed by AMD. But the rest of them are really kind of continued therapy and maintenance dose for our patients. And I assure you all we very well feel comfortable using those patients, especially based on the efficacy and the safety I'm seeing that. but all of them, literally all of them, new or recurrent patient will very much ask for longer duration therapy for me.

I agree with you. And then I think for me, this label is a little bit more important than others because of superiority because we have about -- when I started 16 years ago, in Reno, we had about 80% to 90% Medicare straight patients. Now we have about 50% Medicare and then others are mainly Medicare Advantage. So we have to go through the step therapy of Avastin to biosimilar Lucentis, biosimilar EYLEA, VABYSMO and then EYLEA HD. And then we are seeing that with the port delivery system that I offer that to my patients, and many of those programs are not accepting as an option because they want you to go through the steps. So I think the unique thing here is that if we can get the superiority label in there, that's going to make a huge difference for the patients, right? Because now and practitioners, we can get this drug on-demand anytime we want. And now we can use it as a monotherapy switch as a layered therapy for our patients. So I think here, that's the part I'm more interested. And the other one is flexible dosing, right? We saw with HD EYLEA. I always said even before the data came out, we want monthly in every 6 weeks, and they did not have it, and that impacted the adoption, and they had to do the ELARA study to get the week label because we had to go 7 weeks and when an anti-VEGF bolus comes out, we usually go with the high-need patients. So I think superiority will be huge to avoid step therapy; and number two, would be every 6 months dosing. Those are the 2 things I'm looking for.

Darius?

Yes. Both of them brought up the excellent points. The key is the flexibility on the downside. The 6-month dosing, not because I am worried about patients that are going to fail at 6 months. because I want to bring them in, standardize, normalize my operation. I want to see him twice a year, giving the injection, take them off the board for ever and then have always 6 months of vision safety in my pocket, okay? They want to go on Safari, they want to go up to Mars, whatever it is that they want to do. I don't have to worry about them. They're off the board, okay? And as a safety kind of guy, that's how I view it. And if I don't have that and I have 9 months or 12 months, which seems amazing, but it's actually impacting how I manage my patient.

I ask because your patients live in Marin County, right? That's why they are like that. So I hope that would lose [indiscernible] County. But the other thing that I would say is, look, we have -- we have -- I keep saying this to people. In my 30 years that I did this, we have never had a single drug with good reason that goes from a Phase III to the community with better results. logically, it shouldn't happen because what you're doing in the Phase II, you're selecting the best patient population. And we also have a need when we launch to make sure that the first experience is really good. This is exactly what's going to happen with this drug. This is going to be the first drug that ever is going to do better in the community than it did in the Phase III study, meaning SOLO-1. And clearly, the first experience the doctor has with this drug is going to be fantastic. And let me just explain that. In the SOL-1 study, what we did was we picked patients who were designed to lose vision on purpose, right? That's not your regular patient population that you see. If this drug did this well in that patient population, it certainly will do a lot better in a stable population. So in a regular doctor's office, the doctor may see 50 patients let's just say of those, I don't know, 1 or 2 may be new, right? The other 49 -- 48, 49 are going to be patients that the doctor has been seeing on a regular basis and are stable and they're frustrated, but they're stable. So the first interaction will go something like this. Ms. Jones, I've got a drug that I just got the results look great, and I know you're really frustrated that you have to be taking EYLEA every 2 months for 5 years. Let me see if this drug can help you, but I still want you to come back in 2 months. And that patient will come back, and the doctor will say, "Wow, you're looking great. Well, let's just extend that a little bit more. And let's just extend that a little bit more. And if you can take a patient who's been on EYLEA for 5 years, every 2 months to every 6 months, they're doing backflips. They're thrilled. So the bar for success for this drug with the first experience with the first encounter is very, very low. And that's exactly what we want. We want everybody to have their first encounter to be absolutely fantastic for the patient and the doctor, and that's exactly what we're set up for.

Pravin, can I just jump in there. So Pravin has alluded to it that it's a patient population that's designed to lose visual acuity. This patient population at best is quartile for, okay? It's 20% to 25% of the overall patient population. They lose vision because their vision is so good to begin with. The remaining 75% to 80% of those patients, they all gained vision. They have not been exposed to this drug yet. Those patients are going to lock in high and they're going to carry it forever. It's going to be transformative when this gets out into the wild.

And I just have to add 1 more comment is our interest is real-world studies, [indiscernible] Summit. So I'm already designing the study. Maybe we'll call it the Dougal study or something. And we'll do it because we want to know, understand how the drug delivers in the real-world patient population. And as you said, majority, almost 90%, 95% start would be previously treated patients. So I think there will learn, right? And that's what we learned about VABYSMO. VABYSMO had [indiscernible] at different lanes in naive patients 12 and 16, we had no experience on previously treated patients, and we found out through truck that we were adding 2 weeks on top of EYLEA 2-milligram with VABYSMO that really help the community understand the anatomic control, and now it's a blockbuster. So we will do that study. And we'll also want to establish real-world safety. So I think those studies are going to come, we just need the approval.

We'll just make sure that you start the Dougle study early because now clearly, it's going to be pulled up a little bit now. Yes, Bill? Sean.

A couple of questions for me, maybe require a little bit less pontificating. Now the study is masked through 96 weeks. But will the DSMB notify you if SOL-R hits or misses the primary endpoint at 56 weeks. If so, will you communicate that to investors? And if it misses does the study start or will continue to stop or does it continue to week 96. And then can you speak to your handling of rescues in the SOL-R stats plan?

Yes. So what I can -- the first part, I can handle and then I'll maybe have Nadia step in here for the second part. What I would say is, look, it's a mass study, right? So the unmasking is going to happen at week 56. The DSMC hasn't made any comments at all. 96, I'm sorry, 86%. And that's just a pure safety committee. So the answer to your question is that it will remain mass because we want to preserve the integrity of the study until it's unmasked at week 96. Nadia, do you want to handle the second one?

I mean I think it's a very traditional nonimperiority study, and that's what our stats and seek to have had discussions with the FDA. And Art can probably talk about this a little bit more, but we have a standard noninferiority margin of 4.5 letters. Outside of that, everything is detailed in our confidential protocol and discussions with the FDA. So I'm going to stop over here.

Yes. Sean, I think it's a very standard way that we're going to look at things. And what I would say is you've heard today from Jeff and Jeff, you may want to comment what the FDA has said. I think it's very, very clear. They haven't changed, right? And what they've said, if you don't have a combination agent and that's a big -- if you don't have a combination agent, the first rescue is going to be allowed as long as it doesn't impact the primary endpoint, and they traditionally consider that within 3 months of the primary endpoint. Every other rescue thereafter is going to be under review. Now I don't know that it could be any more clearer than that. And what I would say is that in any noninferiority study, what you would want is that you would have -- you want the whole gamut of information, as Jeff very nicely put out the check box, which is to say, look, we want to know the number of rescues. We want to know when the rescues occurred, and it's good to know how many patients required multiple rescues. And I think those are standard questions that will be answered by us and should be answered by any other non-inferiority study. Jeff?

Yes. I think it's pretty clear. We've heard it from the FDA and communications, but you've also seen it at meetings such as the CTS this weekend that the injections that are different than the investigational product matter. And when you -- if everybody gets one, that's a rescue. If you get them throughout the course, those are additional injections. And when you get them close to the primary endpoint. Those are viewed differently as well. So they all matter.

Unfortunately, we only have time for one more question, but we will have a cocktail reception to follow up for any follow-up.

[indiscernible] the only thing that stands between their happy hour and the question, but go ahead.

Maybe another on the confirmatory evidence. I think historically, the level of confirmatory evidence is sort of inversely related to the strength of the main trial. You obviously outlined several lines of confirmatory evidence that you have. Did the FDA tell you that you need all of those lines of evidence or that you need a particularly strong degree of confirmatory evidence? Is there any language to that effect or talking about the level of confirmatory evidence that you need to...

Well, what I can tell you is, look, I'll give this to Peter. knowing Peter, if there's one line of evidence, he'll give you 50 just to make sure that you got it. So I think that's exactly what we did to the FDA, Peter.

Yes, I agree. It wasn't like they said, this is what you -- what we want or this is what we need. It was more like we presented everything that we presented. And they were like, yes, that's great. to me, as you said, if you have a weak primary study, then you need stronger confirmatory evidence, we have the -- we have both. We have strong confirmatory evidence and we have a strong study. So it just adds to the package. And yes, like I would do anyway. We're going to give them absolutely everything and more.

Peter is learning how to be a regulatory officer, and Art is teaching him, by the way. So again, we have a cocktail party over there. Please go ahead and proceed over there. Hopefully, the lines will be good. And thank you again for coming here. This is a fantastic day for us. It's a milestone and to share it with you is really an honor and a pleasure, and thank you for being here. We'll make ourselves available as we always do after this. So if you have any questions, we're around, please let Bill Slattery know. We are -- we'll be happy to be on calls with you to answer any questions. As always, look, you'll find us to be about as available as any company, and we're happy to answer any questions and invite any questions from you. Thank you again.