OCUL - NASDAQ

Good morning, and welcome to the Ocular Therapeutix Second Quarter 2025 Earnings Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded and will be available for replay on the Investor Relations section of the Ocular Therapeutix website. I would now like to turn the call over to Ocular’s Vice President of Investor Relations, Bill Slattery, Jr. Please go ahead, Mr. Slattery.

Good morning, everyone, and thank you for joining us today. Earlier this morning, we issued a press release and filed our quarterly report on Form 10-Q outlining our financial results and business updates for the second quarter of 2025, along with several updates to our registrational program for AXPAXLI in wet AMD. Ocular's Executive Chairman, President and CEO, Dr. Pravin Dugel, will summarize recent business highlights before we move to our question-and-answer session. Joining Dr. Dugel for the Q&A portion of the call will be Donald Notman, Chief Financial Officer and Chief Operating Officer; Sanjay Nayak, Chief Strategy Officer; and Steve Meyers, Chief Commercial Officer. We refer everyone to this morning's press release and our Form 10-Q for a comprehensive update of second quarter 2025 financial and business results. During today's call, 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 risk 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, I'd like to hand the call over to Dr. Pravin Dugel to review our recent updates. Pravin?

Good morning, everyone, and thank you for joining us today. 2025 is shaping up to be a defining year for Ocular Therapeutix. As we look back on the progress made over the first half of the year, I'm proud to say we are continuing to execute with precision, speed and scientific integrity. Last month, we updated our corporate branding to reflect who we are today, a company advancing with purpose backed by the momentum of our SOL trials and fueled by our unwavering commitment to patients. These changes represent more than a new look. They mark the next chapter in our evolution as a retina-focused company at the forefront of innovation. Our mission remains unchanged to redefine the retina experience in hopes of preserving vision for the long term. For millions of patients around the world, wet AMD remains a relentless progressive disease. Despite recent advances in therapy, the burden of frequent injections remains unmanageable for many with nearly 40% of patients in the U.S. discontinuing treatment within the first year. This is unacceptable to us. And it's exactly why we're advancing AXPAXLI, a treatment designed to offer best-in-class durability, meaningful efficacy and real-world flexibility. Our registrational program for AXPAXLI includes the SOL-1 and SOL-R studies. These are thoughtfully crafted complementary trials with bespoke patient populations designed to derisk outcomes and answer key questions physicians will have on the durability, flexibility and repeatability of AXPAXLI. If approved, we believe AXPAXLI has the potential to be the first product for wet AMD with a superiority claim based on the SOL-1 trial. This trial is designed in alignment with the FDA's guidance for conducting a superiority study, which has enabled us to secure a Special Protocol Assessment or SPA, SPA agreement for SOL-1. Recently approved anti-VEGF products and current competitive Phase III wet AMD trials are all based on non-inferiority to aflibercept 2 milligrams. To our knowledge, SOL-1 is the only Phase III superiority trial being conducted in wet AMD. And if we're successful in gaining FDA approval, we will potentially be the only wet AMD product with a superiority claim in the label for the foreseeable future. Combined with our non-inferiority trial, SOL-R, we believe AXPAXLI has the potential to unlock unprecedented durability with dosing of at least 6 months and potentially as infrequently as every 12 months. We believe this dynamic will allow us a unique and potentially dominant position compared to all other products in the commercial landscape and could enable an opportunity that spans millions of patients worldwide, addressing the critical needs for a more sustainable, less burdensome treatment with improved long-term outcomes. This morning, we're excited to share several updates across our SOL -1 and SOL-R programs, including initial plans to incorporate a single long-term open-label extension study for both SOL trials and updates to our rescue criteria for SOL-R. These updates are designed to further enhance AXPAXLI's commercial profile and underscore the confidence we have in this program. We'll also provide a financial update that highlights the flexibility and optionality we've secured as we approach the SOL-1 top line data readout in the first quarter of 2026, continue to advance our manufacturing and commercial infrastructure and evaluate expansion opportunities for AXPAXLI in nonproliferative diabetic retinopathy and diabetic macular edema. Finally, we are pleased to announce that we will be hosting an Investor Day on September 30 in New York City, which we encourage everyone to join either virtually or in person. Let's first discuss our SOL studies. I am pleased to report that both SOL-1 and SOL-R trials continue to move forward expeditiously. Trial conduct has been exemplary and retention across both studies continues to exceed our expectations, underscoring the strength of our sites, the commitment of our investigators and the quality of our operational planning. Let me start with SOL-1, our superiority trial for AXPAXLI. Following the successful randomization of 344 patients in December 2024, the trial has maintained exceptional retention as we prepare for top line data in the first quarter of 2026. As part of the ordinary course of our trial monitoring, we periodically review rescue data on a masked basis. And what we look at are primarily 3 things: first, the number of rescues. We need patients to be rescued to demonstrate a difference between aflibercept and AXPAXLI; second, the cadence of rescues, whether they occur in a distribution that is consistent with our hypothesis as to how aflibercept patients would behave and how AXPAXLI patients would behave. And third, whether the rescues are on protocol or not as this goes to trial conduct and the reliability of data we are generating. I am pleased to share that the vast majority of rescue events remain fully aligned with the prespecified criteria outlined in the SOL-1 protocol. Simply put, patients are staying in the trial and physicians are waiting until patients meet the predefined threshold of a 15-letter loss in visual acuity from baseline before administering rescue treatment in the vast majority of cases. That's not just a procedural win. It's also a powerful testament to the integrity and reliability of the data we are building. And this reinforces our confidence in the quality of the data set we intend to deliver to the FDA. And when we step back and look at the number and cadence of rescues, again, under masking, we are also thrilled with what we're seeing. This is based on our expectations of the difference in how the 2 agents would perform over time. We look forward to hopefully confirming that hypothesis once we are able to unmask the study in Q1 of next year and report top line data. We are also excited to announce plans to incorporate a long-term open-label extension study for both SOL-1 and SOL-R, which patients will be eligible to enter following the completion of the 2-year safety follow-up period in each trial. This extension study is a strategic initiative, not a regulatory requirement. We believe it will generate valuable real-world insights into the potential long-term benefits of using a non-pulsatile treatment like AXPAXLI in addition to providing long-term safety data. The study is designed to assess key outcomes such as vision preservation, antifibrotic activity and the potential consequences of delaying AXPAXLI treatment in control arm patients. Our hypothesis is straightforward. If non-pulsatile dosing reduces the risk of fibrosis and atrophy, the AXPAXLI arm patients will have the potential for better long-term visual outcomes than the control arm patients who have a 2-year delay before they initiate AXPAXLI treatment. Importantly, we expect this extension study will have significant commercial implications. In today's evolving landscape, retina specialists and payers alike are seeking long-term data that validates durability. We believe this study will enhance confidence in AXPAXLI's sustained performance and support broader adoption upon launch. We're extremely excited to take on this effort as part of our commitment to delivering a long-lasting flexible and non-pulsatile solution that could potentially deliver improved long-term visual outcomes on a treatment regimen that is sustainable for patients, caregivers and physicians. Turning now to SOL-R, our non-inferiority trial comparing AXPAXLI dosed every 24 weeks to aflibercept dosed every 8 weeks. We continue to advance this study with strong momentum and unwavering conviction in both our strategy and execution. This trial was deliberately designed with a 6-month screening and loading ramp to identify and exclude patients who demonstrate unstable anatomy, particularly those with high fluctuations in central subfield thickness. These are precisely the patients who could introduce variability and compromise outcomes in a non-inferiority trial. Excluding them is a strategic choice because a failed trial due to noise is not a risk we are willing to take. With enrollment complete in SOL-R, we expect to have top line data in the first half of 2027, and we believe the structure of this trial gives us key advantages needed to succeed by derisking the patient population. The primary endpoint for SOL-R is to demonstrate non-inferiority in the mean change in best corrected visual acuity at week 56, which is a highly favorable time point. It falls 2 months after both the last AXPAXLI dose and the corresponding aflibercept injection for the control arm. Importantly, this endpoint is at a singular time point. It is not blended over multiple visits. Separately, as part of our ongoing effort to ensure SOL-R reflects real-world clinical decision-making, we've streamlined and simplified the rescue criteria. The rescue criteria in SOL-R is now based on a greater than 5 letter loss in visual acuity plus a greater than or equal to 75-micron increase in central subfield thickness. This change aligns the trial more closely with how physicians determine when to intervene in the real world and simplifies the criteria for investigators to reflect their everyday clinical practice. This also reflects our confidence in AXPAXLI based on what we are seeing under masking in SOL-1. This is critically important, so let me reiterate. The change in SOL-R rescue criteria reflects a thoughtful and proactive effort to further bridge the gap between clinical trial design and clinical practice. This is not an FDA requirement, but rather a strategic decision we have made from a position of confidence in AXPAXLI’s ability to deliver meaningful outcomes in a trial setting that is more clinically relevant for physicians. SOL-R remains robustly powered at 90% to meet the non-inferiority margin of minus 4.5 letters at week 56 based on our written FDA feedback and alignment. Let me step back a moment. In just over 1 year, we have built a world-class team, advanced a groundbreaking program in wet AMD, and we enrolled and advanced 2 complementary registrational trials for AXPAXLI, all the while maintaining excellent quality, speed and operational precision. From inception, these trials were intentionally designed to be complementary, not redundant, each addressing distinct yet synergistic clinical questions that together form the foundation of our registrational strategy for AXPAXLI. SOL-1 is focused on durability with redosing after the 9-month primary endpoint at weeks 52 and 76. SOL-R is focused on repeatability of AXPAXLI every 6 months and real-world applicability. Our clinical design strategy for both trials leverages a rigorous screening and loading phase to select bespoke, derisked patient populations for randomization. This is a critical differentiator and one that we believe could meaningfully reduce patient variability in each trial and strengthen the probability of success in both trials. Together, these trials seek to address the most important questions physicians and patients will have about AXPAXLI’s durability, repeatability and flexibility. If successful, these trials may support an unprecedented and potentially the first and only superiority label in retina that enables dosing every 6 to 12 months in a chronic disease where most patients currently require monthly or bimonthly treatment. Perhaps most importantly, both trials are built on the foundation of FDA alignment with clear guidance around endpoints and trial design. And neither study uses sham comparators, consistent with FDA's stated preference to avoid introducing bias in masked studies. This has been clearly stated in the FDA's guidelines, which they have reiterated in person and in writing numerous times. This thoughtful strategic design gives us confidence not only in our clinical program, but also in our ability to bring forward a product that redefines what's possible in retinal disease. Pending successful outcomes, we plan to submit our NDA shortly after the SOL-R 56-week primary endpoint. This strategy allows us to deliver a comprehensive package to the FDA that intends to address durability, repeatability, flexibility and safety of AXPAXLI. Notably, because axitinib is already FDA approved for non-ophthalmic indications, we plan to leverage the 505(b)(2) NDA review pathway, which has the potential to shorten the review time line for AXPAXLI by 2 months compared to the traditional review pathway for new molecular entities. Moreover, both trials have been designed in close alignment with the latest FDA guidance. So one under a SPA agreement and SOL-R informed by written formal feedback. With a strong clinical and regulatory foundation in place for wet AMD, we're now preparing to expand our reach towards the next horizon, diabetic eye disease. Earlier this year, we received positive FDA feedback on our proposed trial design for patients with diabetic retinopathy. The unmet need here is immense. Despite available therapies, fewer than 1% of NPDR patients are treated. And yet with AXPAXLI, we may be able to offer a long-acting solution that reduces the risk of progression with just 1 or 2 treatments per year. Recall that in our HELIOS study, 0 patients developed a vision-threatening complication with a single injection of AXPAXLI at 48 weeks compared to almost 40% in the control arm. Additionally, all patients in the AXPAXLI arm that had diabetic macular edema saw improvement at week 48. Although these results are from a relatively small Phase I study, we believe this is an area where AXPAXLI's profile could drive real change, not just in patient outcomes, but also in how retina specialists approach disease prevention. We look forward to sharing more details about our NPDR and DME strategy at our upcoming Investor Day, which will be held on September 30 in New York City with virtual access available. This will be an important event. We'll walk through how SOL trials work together to support what we expect will be a differentiated AXPAXLI label in wet AMD. We'll share new insights on the extension study design for both of our SOL trials. We'll introduce our next steps in NPDR and DME, including the clinical trial design informed by recent FDA feedback, and we'll begin to articulate the global commercial opportunity for AXPAXLI, both in wet AMD and beyond. You can register for our Investor Day by visiting the Events page on the Investor Relations section of our website. We believe this event will clearly demonstrate the breadth and depth of our strategy and why we believe AXPAXLI is poised to redefine the standard of care in retinal treatment. Let me now turn to our financial position. We ended the second quarter with over $390 million in cash and cash equivalents. In June, we opportunistically raised gross proceeds of approximately $97 million through our existing at-the-market or ATM facility. Opening the ATM this quarter was a deliberate decision to provide us with maximum financial flexibility as we head into the most significant data readout in Ocular's history. We expect this increased capital will support several key initiatives we'll be speaking more about in our upcoming Investor Day, including investments in commercial infrastructure, preparation for the SOL -1 and SOL-R extension study and planning for FDA-aligned future studies in NPDR and DME. Importantly, we remain disciplined stewards of capital. We remain well financed with expected runway into 2028, which is well beyond anticipated top line data readouts for both SOL-1 and SOL-R. Our cash guidance does not yet factor in the full impact of potential clinical trial activities for AXPAXLI in NPDR or the long-term extension study in wet AMD as we remain at the planning phases for these programs. 2025 is already proving to be a breakout year for Ocular Therapeutix. In just the past few months, we have advanced 2 complementary registrational trials, aligned with FDA on next steps in diabetic eye disease and laid the groundwork for commercial readiness in wet AMD. If approved, we believe AXPAXLI has the potential to be the first product for wet AMD with a superiority label. This would likely be the only product with a superiority label for the foreseeable future with redosing potentially as infrequently as every 12 months. This profile would provide AXPAXLI with a unique and potentially dominant position compared to all other products in the commercial landscape, unlocking an opportunity in wet AMD alone that spans millions of patients worldwide. To summarize the updates on today's call, first, both SOL-1 and SOL-R continue to advance with exceptional retention, trial integrity and physician adherence to protocol, reinforcing our confidence in the quality of data we are generating. Second, in SOL-1, the vast majority of rescue treatments remain aligned with the protocol-defined 15-letter loss threshold. Third, building on this momentum, we plan to incorporate a long-term open-label extension study for both SOL trials. This is a strategic effort to potentially generate long-term safety and visual outcomes data with a non-pulsatile treatment that could meaningfully support physician confidence and market adoption. Fourth, we have high confidence in the success of SOL-R, and we expect top line data in the first half of 2027. With a 6-month screening and loading phase designed to exclude unstable patients and a primary endpoint at week 56 timed 2 months after the most recent AXPAXLI and aflibercept injections, we believe we have taken steps to derisk the patient population and maximize the opportunity for success. Fifth, we've streamlined and simplified the SOL-R rescue criteria to a greater than 5 letter loss plus a greater than or equal to 75-micron increase in central subfield thickness. We believe this change enhances SOL-R's real-world relevance and reflects our continued confidence in AXPAXLI. Sixth, we are preparing to expand into NPDR and DME. Following positive FDA feedback, we believe AXPAXLI could redefine treatment in diabetic eye disease, offering durable protection with just 1 or 2 injections per year. Seventh, we remain well capitalized with over $390 million in cash and expected runway into 2028 well beyond anticipated top line data for both SOL-1 and SOL-R. Our recent sale of $97 million of common stock under the ATM provides financial flexibility to support both near-term execution and long-term strategic investments. And finally, we look forward to hosting our Investor Day on September 30 in New York City, where we will provide deeper insights into the SOL trials and the SOL trials extension study, our diabetic eye disease strategy and our global commercial vision. At Ocular, we're not just developing a drug. We are redefining the retina experience with confidence, clarity and conviction. We hope you all plan to join us at our Investor Day on September 30. Thank you again for your time and continued support. Operator, we are now ready to take questions.

[Operator Instructions] Your first question comes from Biren Amin with Piper Sandler.

Congrats on all the progress. I have a multipart question for SOL-R. So I guess first question, when do you expect to complete randomization of the 555 patients that are required for the trial? Second question, what drove the change in the rescue criteria for the study? And I think you removed the 10-letter loss requirement for the rescue criteria. So if you could just confirm that? And third, I guess, was there anything like on a mass basis that you saw in SOL-R that basically drove that change in the rescue criteria? And I guess, why was that -- why was this changed on at this time? So those are, I guess, the 3 questions that I have on SOL-R.

Thank you for your questions. So let me just answer that in order. First of all, as far as randomization is concerned, look, we will update you when appropriate. What we’ve said very clearly is that our nrolment has been completed and that the trial conduct is going superbly. We’re very, very happy with the way that the conduct of SOL-R and SOL-1 for that matter is going on. As far as what drove the change, I just want to be very, very clear on this. This modification of the SOL-R rescue criteria was based purely for a strategic advantage, purely for strategic advantage. It was not required by the FDA, and it was based on a position of confidence as far as what we’re seeing in the mass data in SOL-1 is concerned. To put it very simply, if you step back and if you look at 3 studies, and I say 3 because I include the SOL extension study, there’s a purpose. Again, this is simplistic, but it’s actually quite effective. There’s a purpose for each study. The purpose for SOL-1 is a superiority label. That’s very important to us. The purpose for SOL-R is clinical use and clinical relevance. The purpose for the SOL extension study is data generation that supports the superiority label as well as the long-term clinical advantage. And what we have done from a position of confidence is to go ahead and modify the rescue criteria for SOL-R to better get it towards its goal, which is data generation for clinical use and clinical relevance. And why now? It’s really quite simple. It’s because of 2 things. One is, again, it’s from a position of confidence. One is because we see the SOL-1 mass data, and we’re very, very excited by it. We’re very confident. Our confidence continues to grow as we see the mass data. And the second reason is the feedback that we get from our investigators. What we want to do is we want to set this drug up to be adopted immediately upon its approval. And by reflecting rescue criteria that are going on in the community currently, we’ll make it much more adaptable immediately and answer all the questions that need to be answered for full acceptance. And that’s really the reason. Again, this is a decision that’s made from a position of confidence and it reflects a strategic advantage that we will enjoy. Thanks for your question, Biren.

Next question, Tazeen Ahmad with Bank of America.

Pravin, I just wanted to clarify how you're thinking about any potential for a shortened review time line given that you're going to file your application after SOL-R reads out. Do you have any preliminary feedback from the agency? Or would this be something that you would need to discuss with them? And would you need the full SOL-R study data in hand in order to get any kind of clarity? Or could you start a process before that in terms of filing? And then secondly, when should we think about the pace with which you'll start for preparing for the potential launch of drug?

So Tazeen, thank you for your question. First of all, look, our expectation of what the FDA wants has not changed. And the FDA has been very clear in stating that they want 2 well-controlled, well-masked studies with positive results. They are well aware of what we’re doing. You remember that we do have a SPA for SOL-1. We have a written Type C confirmation for SOL-R. And we expect to be able to submit for approval immediately following a positive result for SOL-R, which is at 56 weeks. Now what we also said was that we do have a drug here that will qualify for a 505(b)(2). Now remember, the typical pathway that most people are used to is the 505(b)(1), which is a new molecular entity. This is usually reserved for drugs that have never been approved with drug particles that have never been approved or drug API that has never been approved. In our case, because AXPAXLI has been previously approved, we believe that the 505(b)(2) path will shorten our time period by at least 2 months. In regards to launch activities, look, you will be seeing some discussion in our Investor Day, and I hope everybody will be able to attend our Investor Day. We will outline for you our outlook in terms of a national as well as a global commercial strategy at that time. Thank you, Tazeen, for your question.

Next question, Tara Bancroft with TD Cowen.

So I want to go back to the theme of Biren's questions. But -- so for the updated rescue criteria, can you just help us to better understand how the number and timing of the rescues will be viewed by the FDA when evaluating the primary endpoint for SOL-R and how that differs from the previous criteria?

Yes. So Tara, thank you for your question. There is really no change whatsoever in how the FDA would look at this in terms of the primary endpoint or anything else like that. Again, as I stated earlier on, this modification was based purely on getting a strategic advantage and making this drug immediately adoptable because it reflects what is being done clinically. There is absolutely no FDA requirement whatsoever, and we expect no change in terms of the way the FDA regards the study. Thank you.

Next question, Colleen Kusy with Baird.

Congrats on the progress. I understand this change in rescue criteria is not a regulatory decision, but did you speak with the FDA about this change in criteria? Or would you plan to do so? And then can you just confirm, I think the rescue criteria that you're no longer using is just a pure 10-letter loss with no fluid stipulation. And so how do you think removing that criteria would impact the primary endpoint?

Yes. Colleen, thank you again for your question. Just like I said to Tara previously, this has nothing to do with the FDA whatsoever. It's a purely strategic decision. It will have no issue whatsoever with the primary endpoint. This is really not an FDA discussion. This is a pure strategic decision that we've made to better reflect the purpose of SOL-R, which is to completely define this drug to be adoptable immediately for clinical use. There will be -- this is -- again, I'll reiterate, has nothing to do with any kind of an FDA requirement. It's a pure strategic decision. Thank you, Colleen.

Got it. That's helpful. And one follow-up, if I can. Just from an operational standpoint, obviously, SOL-R is already kind of up and running and the change is happening in the trial. So can you speak to what percent of rescues in SOL-R were for the other criteria? And does this change by chance delay the primary endpoint readout?

Yes. So Colleen, again, this doesn’t do anything for the time for the endpoint at all. This does not delay or change the timing of SOL-R one bit. Recall that one of the great benefits that we have in SOL-R is the trial design. The trial design is unique in completely derisking the patient population as much as we can. Recall that what we have here is a very well thought-out ramp where we have 5 loading phase – 5 loading injections, and we have a unique design in having 2 opportunities to observe patients for instability. So it’s quite a long ramp, and it really doesn’t change anything in terms of the patient outcomes whatsoever. Thanks for your question.

Next question, Kelly Shi with Jefferies.

Congrats on the great progress. Maybe for the first one, for the single long-term extension study for both trials, maybe could you explain to us the rationale and the purpose of such design? How much long-term data do you think you need to collect for commercially meaningful impact? And also I have a follow-up.

So Kelly, thank you for your question. It's an important question. So let me kind of step back a little bit and answer this in a more holistic way. Especially at this time and appropriately, it's important to sort of reflect what these trials are doing and why they fit in and how they fit in. And what I'm about to say, I want to be very, very, very clear. I'm going to talk from a position of confidence everything that I've said regarding this drug has been from a position of confidence. And my confidence in this drug has not changed one bit, and I stand by absolutely everything that I've said. What people ask me often is really what defines success for this drug. And people look at numbers as many people do. And there's nothing wrong with that. And obviously, we're very confident about the numbers. We've got to hit the primary endpoint. We're very confident about the way the clinical trial is going as far as both trials are concerned. But in this case, SOL-1. But really, what will define, in my opinion, the real success of this drug is being able to get a superiority label. And let me explain that. What you see now in this field is really a morass of me-too drugs, and that's based on non-inferiority studies. As far as I know, SOL-1 is the only superiority study that's active. And in fact, I don't even know if another superiority study that's planned. So what does that do in terms of the advantage that we would have, right, if we're fortunate enough to get a superiority label. So what I would say is -- let me answer that question in terms of the doctor, and let me answer that question in terms of the company itself. As far as the doctor is concerned, the doctor wants to be in a position to choose the drug, the best drug possible for the patient. And if there is a pressure based on competition, based on pricing and so on and so forth and step therapy, the doctor may have to wait until the patient is actually worse on a lesser drug before being able to switch to a better drug or the drug that's desired. And oftentimes, what happens in this case, as has been shown in previous diseases in retina is that the patient really never recovers. There's damage done that's irreversible. Now why have we extended the SOL studies and why have we put in the questions that we want to answer? Well, one of the questions very clearly is what happens to patients when there's a delayed adoption to AXPAXLI. And we want to be able to see if that causes any damage that's irreversible. If there's an advantage, we believe there will be to start AXPAXLI right away. So from a doctor's point of view, that extension study question is very, very important. From a company's point of view, having a superiority label puts a great deal of value in the drug as well as the company. It puts the drug in an entirely different orbit. Again, I don't know of any other drug that is currently being investigated based on superiority. So getting the superiority label, putting these studies together to answer the proper questions to support that superiority label, particularly the SOL extension study is going to be very important in terms of the value of the drug and value of this company. Thank you for your question.

Super helpful. I also have a follow-up, if I may. So besides meeting the regulatory bar for AXPAXLI’s 2 pivotal trials in wet AMD, curious what is the commercial bar in your mind for AXPAXLI to gain dominant position in the wet AMD market in terms of how many letters of BCVA loss from baseline maybe at 36 weeks or 52 weeks?

Yes. So Kelly, it’s a great question and it’s an appropriate question. Thank you for the question. First of all, look, the most important thing for us to do is to conduct the study in a way that we will allow this drug to show itself. And we’re very, very firmly committed to doing that. And our confidence in this drug has always been great and continues to grow every day in terms of meeting the primary endpoint. That’s what we have to do. From that point on, what we intend – we’ll have a lot of data. And what we intend to show is data that will show a clear profile of this drug. We’ll have data regarding the delta. We’ll have data regarding the visual acuity, regarding anatomy, so on and so forth. And what we also intend to do is to show the data in a way that maximizes the confidence in the translation of a positive SOL-1 study to SOL-R. We realize how important that is, and I hear that. It is very important, although we realize that the patient population is different in a bespoke manner and intentionally so, the drug is the same. And I totally get the fact that when we show the positive SOL-1 data, it has to be shown in a way that allows you and everybody else to be very confident the translation of that success to SOL-R, and we will do that. So based on all of those things and based on us having the potential to get a superiority label, I think we’ll have more than enough data that physicians can look at the culmination of all the results that are there and say, this is a drug that will be translatable to the way I go ahead and treat my patients and the superiority label allow me to make sure that I can use this the way I want to use it for my patients and that drug will be protected. That’s the important part. Thank you, Kelly.

Sean McCutcheon with Raymond James.

And just picking up on that last point, Pravin. Can you speak to the impact of having 12-month follow-up for SOL-1 as a read-through to SOL-R and whether you anticipate having visibility into a meaningful proportion of patients out to, say, 15 or 18 months on SOL-1 at that point to get a read on the impact of redosing?

Thank you. It’s a great question. I appreciate the question. I think, as I say, we will be providing – we’ll have a lot of data right away, and we’ll be providing data in a way that we will absolutely head on address that issue. As of now, I can’t tell you that we’ve advised you to what data cuts we’ll be providing. But look, I hear you. I hear everybody, the company hears everybody in saying, we need to provide you with that link from SOL -1 to SOL-R. We’re absolutely going to be set up to do that. Thank you for the question.

Next question, Lisa Walter with RBC Capital Markets.

Maybe a first one on SOL-1. Just wondering if you can clarify a detail for us on off-protocol rescues? For the on-protocol rescue injection criteria, very clear that patients must lose 15 letters or more. But wondering where patients who have hemorrhage fall into, whether they fall into the off-protocol or on-protocol rescue criteria?

Lisa, thank you for your question. Look, in every single study and having done clinical trials for 30 years before this job and the job before, what I’ll tell you is that in every single clinical trial, there is a section there that says that the patient may be rescued per the doctor’s discretion. And that has to be there to pass the IRB. That is to protect the patient. And the doctor can rescue the patient based on his or her decision if they feel that, that is the safest thing for the patient. As far as the protocol for SOL-1 is concerned, it clearly states that the primary endpoint is based on the rescues. And the rescues consist of 15 letters or more of loss of vision or any kind of hemorrhage that threatens the macula. Now what I will say and what we’ve been saying over and over again is that the vast, vast majority of patients here are being rescued based on the loss of 15 letters of vision and the protocol is being followed. And that’s very important. Thank you, Lisa, for your question.

Next question, Yi Chen with H.C. Wainwright.

Could you please remind us what was the rescue criteria for SOL-R before the change? And how do you expect the change to impact the number of patients being rescued? And also, could you comment on whether there was a change in real-world practice in terms of rescue criteria during the past several years?

Yes. So thank you for the question. So as I say, the reason that we made the change, as I keep saying, is that it was made purely for strategic reasons. There was no FDA issue whatsoever. As far as the practice patterns are concerned, what I can tell you is when we spoke with our PIs and when we saw what we saw based on a masked basis with SOL-1 we felt that we did not want any questions whatsoever as to the relevance of the rescue criteria. We wanted to make it as liberal as possible because we were very confident in the drug. And remember, we have a patient population here that is derisked and selected after a 6-month loading phase with 2 opportunities to observe for instability. So we will be randomizing patients that we feel are about as derisked as we can have them based on the ramp that we have. So having seen what we’ve seen and having heard the Pis, our decision was to say, we have enough confidence in this drug now that we can go ahead and allow the rescue criteria to be as liberal as possible, so there’ll be no question in terms of adoption whatsoever. Again, it was made purely for that strategic reason. And we believe that, that will allow for a significant strategic advantage. Thank you for your question.

Next question, Jon Wolleben with Citizens JMP.

Just kind of piggybacking on the same rescue criteria theme. You mentioned kind of the investor feedback and the read-through from the SOL-1 to SOL-R criteria, but the criteria is different. So wondering what was the specific feedback you received to prompt this change? And then a second one, you mentioned your expectation was in line in SOL-1 for the cadence of rescues. Wondering what is your expectation for the cadence of rescues for EYLEA versus AXPAXLI?

Yes, Jon, thank you for your questions. So again, going back to the rescue criteria, the feedback really we got was very, very simple. It was, look, I want this drug. I want this as soon as it’s out there, and I want to make sure that my rescue criteria now in terms of what I do for patients is aligned with what I see from SOL-R. And people have different rescue criteria in real life, but we wanted to make it so that even folks that will be rescuing based on the most liberal criteria are able to basically have a translation directly from SOL-R. And again, this reflects our level of confidence in this drug that we see in a masked fashion. As far as your question regarding the cadence of rescue in SOL-1 is concerned, let me go back to what we’re looking at. We’re looking at 3 things, as I’ve said. The first one is the number of rescues. We’re looking at the cadence of rescues, which means that we wanted to make sure that we see a pattern of rescues that we expect. And we absolutely do. We have great confidence that we’re seeing the kind of rescues that we would expect, again, in a masked fashion. And the third thing that we look for is we look to make sure that these rescues are being done on protocol. And on all 3 of those parameters, we are very, very, very happy. And we continue to see a consistency in those patterns, as I’ve said from the very beginning, that gives us a great deal of confidence in the results of SOL-1. Thank you for your question.

Greg Harrison with Scotiabank.

This is [ Joe Thomas ] on for Greg Harrison. Just one, based on the updates today, just how should we and investors be thinking about the interplay of the eventual time to market for AXPAXLI with the potential superior label to competitors who might possibly enter the market slightly sooner?

Thank you. Look, I keep on emphasizing that, that’s one thing that I think is really quite underappreciated, which is the position that we will potentially have with a superiority label. Again, I’ll reiterate if you just kind of step back and look at this market, every drug is based on a non-inferiority study. The difference between these drugs are very slight, if any, at all. And when you have a situation like that, when you have a morass of drugs that pretty much look the same, the competition is basically based often on pricing with very little to distinguish the drugs. And as someone who’s practiced for 30 years, I realize that the downstream pressures of something like that. And the downstream pressures of something like that is that the relationship that a doctor has with a patient is taken away or at least impacted because the choices that are made for the drug are being forced to be made based on pricing. And oftentimes, the consequences of that are really very bad for the patients. Again, we have studies in chronic diseases in retina where if the patient is started on the proper drug in a delayed fashion, the vision never recovers. The vision may improve, but really never recovers to the extent that it should have been. And again, as I said earlier on, this is a major point of study for extension – our SOL extension study. We will have unique data there where we’re able to see what happens to patients who are started on AXPAXLI after a 2-year delay. We’ll have an opportunity to see if that catches up or not. And when we see something like that happening where there’s irreversible visual loss from a delay in treatment, that has a tremendous impact on patients chronically. So with the superiority label, our expectation is that we’ll be in a different orbit. We will be immunized from the rest of the drugs and the rest of the pressures that they may feel. This will add a great deal of value to the drug, to the company. And most importantly, we believe that this will allow for better patient care and better long-term outcomes. Thanks for the question.

Next question, Lachlan Hanbury-Brown with William Blair.

I was curious on the reason for starting the open-label extensions now versus having them up and running previously. Pravin, you mentioned that obviously, you've been in the space for a while, seeing the data from all these studies showing long-term benefits. So knowing the value that, that can provide, like why did you not originally start them? And why did that change now?

Thanks for your question. There’s really no reason other than logistic. At a certain point, you start these studies with what you see under masking with, again, with a great deal of confidence and you step back and you say, what questions can we answer with this drug and what questions would be most clinically relevant to be answered. And that’s the questions that we’re asking. Again, we’ll have a lot more detail regarding what the extension study will look like and further questions that we’ll be asking in the extension study in our Investor Day on September 30. Thank you for the question.

[Bill Maughan] with Clear Street.

So you mentioned excluding patients with high fluctuations in OCT from the trial to reduce noise, which makes sense. But just looking down the road, do you expect any impact on the commercial effort either by a restrictive label discussing -- excluding these patients or just understanding among the prescribing community that these patients were excluded from the trial?

Thank you for the question. No, quite the opposite, quite honestly. So let’s just speak from the doctor’s point of view as well as from a label point of view. From a physician’s point of view, what we’re providing is a cure patient population by reducing the noise, we’re actually providing much more valid scientific data. So from a physician’s point of view and a clinician’s point of view, the data that we’re providing – by providing a pure scientific patient population provides for a pure comparison. So quite the opposite as far as a clinician is concerned. From a enrolment point of view, that’s never ever been the case. And the most recent example that I have from a personal viewpoint is my last company. In IVERIC Bio, the same question was asked about label restrictions. If you recall, all the studies were done with patients with extrafoveal geographic atrophy. In fact, not a single patient with foveal involving geographic atrophy was ever studied. And this question was always brought up. And as you can see in the label, there are no restrictions at all. And there are numerous examples of that going all the way back to ANCHOR and MARINA and visual acuity restrictions in terms of patient nrolment to Panorama, for instance, looking at diabetic retinopathy in only a certain group of patients. So history has shown that as long as you conduct a proper scientific study that’s well masked, well conducted, there really will be no label restrictions. Thank you for your question.

Serge Belanger with Needham & Company.

This is [John] on for Serge today. Congrats on all the progress, Pravin. Just to touch on again the translation of SOL1 data to SOL-R, considering the distinct purposes and criteria you noted for each trial. Do you view the readout of SOL-1 as a derisking event for SOL-R or more so complementary considering they're answering different questions?

Thank you for your questions. It’s a great question. So what I will tell you is, look, it’s clearly both. Again, I’ll repeat this. I know there’s a great deal of interest in looking at the SOL-1 results and seeing the translation into SOL-R. That, in my mind, is completely appropriate and understandable. The patient populations are deliberately different. The drug is the same, and we will address that. I hear you. I appreciate it. We will address that in the data cuts that we will release to give you confidence in the translation of a positive SOL-1 study to SOL-R. Now having said that, I will also say that there are several 2 important things that are right in front of you that should give you a great deal of confidence. One is the patient selection and the other is the clinical trial design. As far as patient selection is concerned, look, every single anti-VEGF study that I know looks the same. After 2 or 3 injections, visual acuity stabilizes. Every single one of them, and the curve looks exactly the same no matter what the anti-VEGF agent is. We’re going well beyond that. We’re injecting 5x prior to randomization. Not only are we doing that, but we have 2 unique windows, 2 opportunities to look for instability. So the patients that we’re randomizing are about as derisked as we can make them. So that in itself should give a great deal of confidence in terms of patient selection. The second thing in regards to clinical trial design, remember that our primary endpoint is at week 56. It’s a singular endpoint. It’s not a blended endpoint. It’s a singular endpoint. This, in our opinion, is an optimal endpoint because it’s 2 months after the last AXPAXLI injection and the last aflibercept injection. So given those 2 things, you already should have quite a bit of confidence in the success of SOL-R. But having said that, I completely understand and hear that the SOL-1 positive results will have to allow you to translate that success into SOL-R. We hear you, we understand you, and we intend to address that. Thank you for your question.

This concludes our question-and-answer session. I will now turn the call back over to Dr. Pravin Dugel for closing remarks.

Thank you very much. Once again, I'd like to thank everyone for taking the time to join our call today. We look forward to updating you on our progress. If you have any follow-up questions, please contact Bill Slattery, our Vice President of Investor Relations. Please also register for our Investor Day. Have a great day, everybody. Thank you.