Ocular Therapeutix, Inc (OCUL) Q3 2026 Earnings Call Transcript

Good morning, and welcome to the Ocular Therapeutics 3rd Quarter 2026 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the prepared remarks, we will conduct a question and answer session. If you would like to ask a question, please press star 1 on your telephone. As a reminder, this conference call is being recorded and will be available for replay on the Investor Relations section of the Ocular Therapeutics 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 third quarter of 2026. We will begin today's call with prepared remarks, summarizing recent business highlights from Dr. Praveen Dougal, Ocular's Executive Chairman, President, and CEO, Dr. Nadia Wahid, Ocular's Chief Medical Officer, And David Robinson, Oculer's Global Chief Commercial Officer. Donald Notman, Oculer's Chief Operating Officer, will join for the question and answer session. We refer everyone to this morning's press release and our Form 10-Q for a comprehensive update of third quarter of 2026 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 factors, including risks and uncertainties identified in the risk factors section of our annual report on Form 10-K and our other SEC filings. On today's call, we will discuss our investigational product candidate, X-Paxley, also known as OTX-TKI, which is in development for wet age-related macular degeneration and non-proliferative diabetic retinopathy. As a reminder, the safety and efficacy of X-Paxley have not been established by the FDA or any other regulatory authority, and X-Paxley has not been approved for marketing. With that, I'd like to hand the call over to Dr. Praveen Dougal to review our recent updates.

Thanks, Bill, and good morning, everyone. 2026 has been an extraordinary and truly transformational year for ocular therapeutics. We've achieved landmark Phase III superiority results in SOL1, established a clear regulatory path forward toward our first potential approval for X-PAC-SLEE and wet AMD. And continue to generate compelling clinical evidence showing X-Paxley's durability and disease control. As we approach the end of the year, I believe we are in the strongest position in our company's 20-year history, with an extraordinary opportunity to fundamentally transform the treatment paradigm for retinal diseases. Today, while several bolus treatment agents are either approved or in development, X-Paxly stands alone as the only intravitual sustained release maintenance agent with positive phase three data in wet AMD. With a competitive landscape evolving significantly in recent months, we believe our opportunity has never been greater. I want to begin by addressing recent competitive developments because they reinforce the importance of the fundamental principles that have guided our X-Paxley development strategy from the onset. These include the importance of TKI potency, drug delivery vehicle, and thoughtful clinical trial design, including rigorous patient selection. In drug development, molecular potency matters. The drugs delivery vehicle matters. Rigorous clinical trial design matters. And patient selection matters. First on potency. We have seen potency make a huge difference in wet AMD studies before. For example, Lucentis was considerably more potent than macugin. Similarly, Exitinib, the TKI used in X-Paxley, has demonstrated the greatest potency of the TKIs currently in development for retinal diseases. Exitinib has approximately 100-fold greater potency against VEGF receptor 2 when compared to virulinumab. as well as greater potency in the other VEGF receptors. We believe this distinction is critical to achieving sustained VEGF suppression over extended treatment intervals. Next, delivery matters. As we know from preclinical studies, our bioresorbable hydrogel is capable of delivering consistent And daily release of X-Men. The 9- to 12-month durability observed in SOL1 provides compelling evidence that the hydrogel performs similarly in humans to what we saw preclinically. Equally important as TKI potency and the bioresorbable hydrogel selected to deliver VEGF suppression is the clinical trial design and patient selection of each trial being evaluated. SOL-1 and SOL-R randomized different groups of treatment-naive patients, since the trials were deliberately designed to answer very distinct clinical questions. In SOL-1, our objective was to demonstrate superiority in vision maintenance over a single administration of a Fulbercept 2 milligrams. Accordingly, we prioritized a challenging population specifically selected to lose vision. Nonetheless, approximately 75% of patients receiving expaxly-maintained vision at week 36 primary endpoint, and approximately two-thirds through week 52 following a single injection. In SOLAR, our objective is non-inferiority in BCVA to a flibroset 2 milligrams administered every eight weeks. Accordingly, we incorporated a differentiating six-month screening and loading period to exclude from randomization patients with early persistent fluid or significant fluid variability. These patients are known to have negatively impacted historical non-inferiority trials. Contrast this with recent developments from a peer That utilize a TKI that is less potent against VEGF receptor 2 in trials that combine previously treated and treatment-naive patients and randomized patients before the loading phase. We believe our peers' results do not reflect a limitation of the TKI class, but rather they underscore the importance of getting all three elements right. The TKI? And the delivery vehicle, the trial design, and the patient population. These principles were critical to our success in SOL1, and we believe they provide a compelling foundation for success in SOLAR. Turning to our regulatory process, our highest near-term priority remains the planned submission of our NDA for XPACSLE and wet AMD in the fourth quarter of this year. Following our positive pre-NDA meeting in September, we remain aligned with the FDA on our planned submission package. Our NDA will be supported by Sol 1 Week 52 efficacy data, Sol 1 and InframSolar Week 52 safety data, and a comprehensive body of confirmatory evidence. Importantly, We also plan to submit repeat dosing safety data from patients who have received multiple X-Paxly injections in both Phase III trials as part of the NDA review process. Together, our safety database at the time of submission will include more than 300 patients with at least one year follow-up after X-Paxly treatment, consistent with FDA requirements. We remain on track to conduct the interim solar safety analysis this quarter, with these results to be incorporated into our planned NDA submission. Throughout this process, we have maintained consistent engagement with the FDA, including our special protocol assessment agreement for SOL1, our Type C meeting earlier this year, And most recently, our positive pre-MDA meeting in September. We also remain aligned with the agency on pursuing approval through the 505B2 regulatory pathway, which has the potential to shorten the review timeline by up to 60 days compared with the traditional 505B1 pathway for a new molecular entity. This will be an incredibly important milestone for our organization, and one that reflects years of disciplined clinical development, rigorous execution, and extensive collaboration with the FDA. The incredible progress that we've achieved only occurs when you have a tremendous team in place. Today, you will hear from some of those team members, starting with Dr. Nadia El-Wahid. Oculer's Chief Medical Officer, who will speak to recent updates regarding our clinical programs. David Robinson, Oculer's Global Chief Commercial Officer, who will then review the transformative commercial opportunity ahead.

Nadia, please go ahead.

Thanks, Bravin. Let's start with SOLAR, our second Phase 3 trial in wet AMD. I want to emphasize that our confidence in this important trial remains very strong and continues to grow. While SOLAR efficacy data are not required for our planned NDA submission, we believe positive results could provide additional commercial advantages in the U.S. and support regulatory approvals internationally. At the recent American Academy of Ophthalmology meeting, we presented a post hoc analysis using an AI-based assessment of retinal fluid. This analysis demonstrated that approximately 71% of XFAC-3 treated subjects were quantitatively dry at week 8, meaning they had less than or equal to 10 nanoliters of total fluid volume in the 6x6 mm scan. Under this stringent definition of dryness, remarkably, approximately 70% of these subjects remained quantitatively dry through week 36 following a single X-Faxley injection. We believe these findings provide more than just another illustration of X-Faxley's potential durability. They offer clinicians a potential roadmap for treatment. Achieve initial disease control with a couple of bolus anti-VEGF injections, then transition to X-faxi for long-term maintenance treatment. Importantly, recent SOL1 post hoc analyses have also provided compelling insights into the relationship between early retinal fluid control, durability, and long-term outcomes, reinforcing our confidence in the SOLAR study design. At last week's Empire Forum in New York City, we presented a separate post hoc analysis reporting that approximately 28% of XFACC-treated subjects in SOL1 experienced early persistent retinal fluid or fluid variability, defined as a greater than 30 micron increase in central subfield thickness at week 8. These patients had worse visual outcomes, a 32-week earlier time to supplemental injection, and an increased frequency of needing supplemental injections compared to subjects without early persistent fluid in the same period. And this was consistent across both X-faxi and Aflibirceps treated patients, reinforcing the importance of early disease stability independent of treatment Thank you. And this is precisely where the design of SOLAR becomes so important. SOLAR incorporates a six-month pre-randomization period specifically designed to screen out patients with early persistent retinal fluid or significant fluid variability. Our preliminary analysis indicates approximately 20% of patients otherwise eligible for SOLAR were excluded from randomization because of these characteristics. This is also consistent with historical expectations and closely aligns with the findings from SOL1. In short, SOLR is designed to randomize the very population in which we observed the strongest durability profile for XFAC3 in SOL1. As it relates to SOLAR, I'd also like to address an important refinement to the primary endpoint, which reflects our priority to protect the integrity of our primary analysis. As part of our NDA planning, we will conduct an interim safety analysis on a subset of SOLAR patients to meet the FDA's requirement of at least 300 subjects with one year of XFACC follow-up. We selected Week 52 for the Interim SOLAR Safety Analysis because it's consistent with the FDA guidance, aligns with the 52-week follow-up period in SOL1, and it enables our planned fourth-quarter NDA submission. With the original primary efficacy endpoint scheduled for Week 56, our Interim Safety Analysis would have required unmasking the safety data before all patients completed their primary efficacy assessments. Rather than risk compromising the primary endpoint's statistical integrity, we proactively initiated a process in May after our type C meeting with the FDA to move the primary endpoint from week 56 to week 40. This change ensures all patients will have completed their primary efficacy assessments before the planned interim safety analysis. Importantly, the new Week 40 primary endpoint exceeds the FDA's minimum 36-week requirement, outlined in its draft guidance for neovascular AMD, and is within the treatment effect observed in SOL1. Due to the interim safety unmasking, we will incur only a minimal statistical alpha penalty of 0.0001 towards our primary endpoint. Equally important, we have preserved our key secondary and other secondary endpoints at week 56 and 96, including longer-term evaluations of superiority to FLIPROSEPT 8 mg and the potential prevention of fibrosis and atrophy relative to FLIPROSEPT 2 mg. It was important for us to complete the rigorous process of changing the primary endpoint timepoint. Including protocol implementations, IRB approvals, and FDA interactions before conducting the interim safety analysis in SOLAR. As for our prior guidance, SOLAR will remain masked through Week 96 under our FDA-aligned masking plan, with top-line results on track for the first quarter of 2028. I want to emphasize that the foundation of these changes is to preserve the integrity of SOLAR, and they are aligned with the FDA. We believe this approach accomplishes two critically important objectives simultaneously, advancing our near-term NDA submission while preserving the long-term clinical, regulatory, and commercial value of SOLAR. Beyond SOL1 and SOLAR, we are encouraged by the continued momentum in SOLX, our long-term open-label extension study, with the vast majority of investigators and eligible patients choosing to participate. Importantly, based on our recent analysis of the up to 12-month durability demonstrated in SOL1, we are modifying SOLX's dosing cadence from 24-week treatment intervals to 48-week treatment intervals. Simply put, we believe Sol1 demonstrated that many patients do not require Axfaxi treatment every six months, and this change to Solax reflects our confidence in Axfaxi's durability. This modification is expected to provide commercially valuable evidence supporting XFAC3's potential for an annual dosing, while also evaluating whether sustained VEGF suppression and earlier initiation of XFAC3 treatment may reduce fibrosis and atrophy and improve long-term visual outcomes. Stepping back, our three WET-AMD trials are strategically designed to provide clinicians with a comprehensive roadmap for XFACC's use in clinical practice. ZOL1 established superiority over a single injection of a Fliberceps 2 mg, demonstrated durability extending up to 12 months, and characterized performance in a particularly challenging patient population. SOLAR is designed to demonstrate non-inferiority to on-label Aflibercept 2 milligram administered every eight weeks and to establish the safety of repeat X-Faxley treatment every six months in all patients. And SOLX is designed to evaluate 12-month maintenance dosing and potential long-term visual and anatomic benefits of initiating X-Faxley earlier in the disease course. Together, these studies are designed to establish a comprehensive clinical profile supporting X-Faxi's efficacy, durability, and flexibility, further strengthening its potential to become the preferred sustained release maintenance therapy in wet AMD. As we advance X-Faxi towards potential approval, we are increasingly focused on translating its differentiated clinical profile into meaningful benefits for physicians and patients. David will discuss how we're preparing to deliver on that opportunity. David?

Thank you, Nadia. Besides the opportunity to work with this tremendous team, I was drawn to Ocular for a simple reason, to redefine the retina disease treatment paradigm and improve patients' lives with X-Paxly. Our differentiated clinical profile shown in SOL1. Combined with the significant unmet need in the wet AMD market, positions us to redefine the standard of care and deliver meaningful benefits to patients, physicians, and the broader healthcare system. Central to realizing this opportunity is our belief that X-Paxly addresses a fundamentally different treatment need than the anti-VEGF therapies available today. We believe that it's critical to distinguish between bolus anti-VEGF therapies used to achieve initial disease control and ex-Paxley's intended role as a long-term maintenance therapy. Retina specialists have numerous bolus therapies available today with additional products in development. Physicians can choose the bolus therapy appropriate for their patients to dry the retina over a brief initiation period before transitioning to X-Paxly for long-term maintenance if approved. We view the anti-VEGF therapies as complementary to X-Paxly rather than direct competitors for our intended maintenance opportunity. And importantly, maintenance represents more than 90% of the wet AMD treatment market. We believe a long-duration treatment like X-Paxly will be broadly welcomed as today's frequent bolus dosing leads to over 40% of patients being lost to therapy in the first year alone. Furthermore, following the recent discontinuation of a peer TKI program in wet AMD, we believe X-Paxly has no direct late-stage intravitreal sustained release competitor. Our successful SOL1 superiority outcome also provides a compelling basis for commercial differentiation. If xPaxly were to receive a superiority label, it could also support premium pricing and potentially help avoid traditional step edit requirements. Our market research demonstrates strong physician interest based on SOL1 data alone, including our recent post hoc analysis demonstrating almost 70% of patients remain dry on a strict AI-based algorithm at 36 weeks. We continue to invest in commercial infrastructure, market access, and launch execution capabilities. Our payer team has conducted and continues to advance meaningful preapproval information exchange discussions with 100% of our top priority tier national and regional payer accounts covering roughly 84% of commercial lives. These conversations have been well-received, with clear interest in X-Paxley's potential to deliver fewer injections and stronger disease control through superior durability. Our intention is to be fully prepared for day one, following potential approval, with the capabilities and infrastructure necessary to support rapid physician adoption and broad patient access. I look forward to speaking more about our launch preparation activities in the coming months. With that, I'd like to turn the call back over to Praveen.

Thanks, David. As you've heard today, we are in an exceptional position as we prepare for our planned NDA submission and potential approval in wet AMD. In preparing for launch today, we also announced a change in our board composition as we shift to prioritize commercial expertise. Dr. Riyad Sharif has joined our board of directors, and Dr. Sung Se-Hong will retire from the board at the end of the year. We are incredibly thankful to Dr. Hong for his contributions to Ocular during his board tenure. We are thrilled to welcome Dr. Sharif to Ocular's board at such an important inflection point in our company's evolution. He's a highly accomplished leader with a rare combination of deep ophthalmology experience, global commercial experience, and a proven ability to build and lead successful organizations. Having served in senior leadership roles at Alcon, Novartis, and Sanofi, and now as the CEO of Oculus, Dr. Sharif brings decades of invaluable experience navigating complex global markets, developing commercial strategies, and driving organizational growth. As we advance ex-paxly toward a potential regulatory approval and prepare to establish Ocular as a global leader in Retina, his strategic insights and commercial perspective will be tremendous assets to our board. We're delighted that he shares our conviction in the transformative potential of XPAXL and has chosen to contribute his experience to Ocular's next chapter. In our conversations, Dr. Sharif has shared with me that his conviction only starts with our opportunity in wet AMD. Extending to the opportunity for X-Paxly in nonproliferative diabetic retinopathy as well. In the United States alone, approximately 6.3 million people suffer from this vision-threatening disease, and less than 1% are actually treated. X-Paxly has the opportunity to drastically change this unfortunate reality. Enrollment continues to progress in Helios III, our Phase III trial evaluating once yearly expaxly across diabetic retinal disease, including patients with non-center-involving diabetic macular edema. We remain enthusiastic about this substantial opportunity, and you can expect to hear much more about our diabetic retinal disease strategy in 2027. Financially, we are well positioned to capitalize on the opportunities ahead. We ended the third quarter with $530.6 million in cash and cash equivalents, providing an expected runway into 2028 based on our current assumptions, but excluding the full anticipated expenses of commercializing X-Paxley. We remain disciplined in our capital allocation while investing strategically in our regulatory, clinical, and commercial priorities. Before we move to Q&A, I want to leave you with several important takeaways from today's call. First, we remain on track to submit our NDA this quarter, supported by a comprehensive NDA package and FDA alignment. Second. Recent competitive developments reinforce that TKI potency, delivery vehicle, thoughtful clinical trial design, and patient selection are essential for success. These principles have been foundational to our XPAXLE development strategy and are reflected in our landmark SOL1 superiority results. Third, New SOL1 post-hoc analyses provide a potential clinical roadmap for X-Paxly maintenance treatment and reinforce our confidence in SOLAR, with preliminary SOLAR screening data supporting our patient selection strategy. Fourth, our proactive modification of SOLAR's primary endpoint preserves trial integrity and enables our near-term NDA strategy. While protecting important, longer-term efficacy assessments and remaining in alignment with FDA guidance. Fifth, our three wet AMD trials are designed to establish a compelling and comprehensive clinical profile. Sol 1 demonstrated superiority and durability. SOLAR is designed to demonstrate non-inferiority to on-label of Flibroset 2 milligrams and safety of every six-month repeat dosing. And SOLEX will evaluate potential long-term benefits of annual X-Paxly maintenance treatment. Sixth, we believe X-Paxly has an extraordinary opportunity to establish a new standard of maintenance treatment in wet AMD. And we're building our organization to capitalize on that opportunity. And finally, we continue to advance our broader development program, including our registrational Helios 3 study in diabetic retinal disease, positioning Ocular for significant long-term growth. We have never been more confident in our differentiated approach, our execution, and the opportunity Thank you. We remain laser-focused on bringing Xpaxly, if approved, to patients as quickly as possible and delivering on what we believe is a truly transformational opportunity. Thank you, and with that, we would be happy to take your questions.

Thank you. As a reminder, if you would like to ask a question, please press star 1. Our first question comes from Biran Amin with Piper Sandler. Please go ahead. Your line is open.

Yeah. Hi, guys. Thanks for taking my questions. Maybe on SOLX and the change in the treatment interval to 48 weeks versus 24 weeks. What new data led to this change? And given, you know, wet AMD is a heterogeneous disease, will you offer 48-week frequency to all patients in Solex, or will treatment be guided by functional and anatomic endpoints in Solex? Thank you.

Good morning, Barron. Thank you very much for your question. Let me take a crack at that, and I'm fortunate enough to have Nadia here with me, and I'll let her give you the complete and full answer. So, what I would like to share with you is sort of the package that we have in terms of the information we've provided to clinicians, and SOLEX, this change in SOLEX, is very much a part of that. And I want to also add that that is a reflection of our confidence. In the data that we continue to analyze in SOL1, and the data that we continue to analyze in a patient population that's specifically designed to lose vision. And people forget that. Remember, this is a very select patient population that's specifically selected to lose vision. The fact that two-thirds of these patients were rescue-free with a single injection at 12 months, Gives us an enormous amount of confidence. And now you've heard our presentation in Academy and more recently in New York that shows the level of disease control that this drug is able to obtain. So the decision that was made to prolong the interval is made out of that level of confidence based on the data that we've analyzed. But think of the data set that we'll be presenting to clinicians. So there are three of them. First of all, what is SOL1 answer? Well, SOL1 tells us, first of all, the safety of this drug. We have provided unprecedented patient-level safety data from the onset. I think very few, if anybody, has done that from the onset. SOL1 also gives you an insight into disease control in this very difficult patient population. What was shown is that with a single injection of X-Paxly, at month 9, the OCT is within a stability of 30 microns. The other thing that SOL1 shows, as I mentioned, is the durability of this drug, which is with a single injection within this difficult patient population, two-thirds of patients are rescue-free at month 12. And now adds SOLAR. And with SOLAR, what we'll be able to show is the repeatability of every six-month dosing versus a flibroset on label. With Solex, what we didn't want to do was to simply duplicate that same information with every six-month dosing. Given the amount of confidence that we now have in this drug, we wanted to provide evidence that this drug can last for a year, especially in a patient population that is already stable. So, for that reason, we'll provide the every one-year maintenance data, and that's really the logic behind extending Solex. We've really given the clinicians, I believe, a roadmap of how to use this drug. We've shown that you can use two bolus agents twice, or two bolus injections. And if the eye is dry, you can go ahead and use Xpaxli once, and there's an over 70% chance that that eye will remain dry for another nine months. And remember, our definition of dryness is really the most stringent definition. That's within 10 nanoliters of volume that's ever been used. So putting that all together, I think we've really given the clinicians a roadmap of how to use this drug. Let me pass this over now to Nadia, who will also give you her view of these three different studies.

Thank you, Praveen, and thank you, Beren. So, Praveen, I think you've laid that out really nicely, and I completely agree with what you're saying over here. Let me emphasize, you know, the more we've looked at SOL1 data and the more we've looked at the various different patient subgroups within the SOL1 data, The more our confidence in the durability of X-Faxly has grown, especially in a cohort of patients that, you know, are now in the Solex study two years out from when they started having active disease. And so, you know, part of this change is driven by that confidence in the durability and stability that this medication gives us. And I think also our goal all along has been, you know, while each one of the studies selects, you know, in the SOL1 study, we had a broad cohort of patients that were designed to fail. In the SOLAR study, where we have a cohort of patients that are designed to be stable, together, these represent the majority of patients of wet macular degeneration that clinicians will see in clinic. And so our goal is to provide a roadmap for clinicians to treat these patients, you know, and SOL-X, I think, gives us the opportunity to do that. We, of course, we would like not to just recapitulate the data that we're producing in SOLAR that shows stability with every six-month dosing. Over here now, we're going to show you, backed with the data that we have from the SOL-1 study, how you can go to once-a-year dosing. And I think that this is also reinforced. By what, you know, the decisions that we've taken in our diabetic studies of putting these patients on once-a-year dosing. So, really, as we go along, our confidence in the durability and its ability to maintain stability grows for X-Faxi, and that's what we're hoping to demonstrate with Sol-X.

Thank you, Nadia. Beren, thank you for the question.

Thank you. Our next question comes from Tassin Ahmad with Bank of America. Please go ahead.

Hi, good morning, and thank you for taking my questions. Just a couple to clarify. Pradeen, on the SOL-X extension study, have you already discussed with FDA that you want to make this change to the endpoint? And then just to confirm, is there any read-through to any potential label that you would have with the upcoming filing that you're going to do in the first quarter? And then also, can you just remind us how many patients have received multiple doses from Sol 1 and Sol R and at what intervals those have happened? Thanks.

Tazeen, good morning, and thank you for your question. Everything that we do is aligned with regulatory agencies. We really don't do anything at all, as you know, without informing, discussing, and being aligned with regulatory agencies. So, any changes that are made, including the extension for Solex, which, again, is made out of utter confidence in this drug, has certainly been discussed with and aligned with regulatory agencies. That's very important to say. As far as the label is concerned, Tazine, obviously, it's way too early to have labeling discussions, but we expect our label to be what I've been saying from the very beginning. Again, this is our expectation. We aren't in discussions, obviously, with the FDA as yet. We expect to have really the best label that exists in this field. We expect the first and only superiority label. We expect the flexibility of dosing of every 6 to 12 months with repeatability. As far as repeat dosing is concerned, remember that every patient in SOL 1 at week 52 underwent repeat dosing, and everybody in SOL 1 obviously is undergoing repeat dosing. And when the FDA does look at our complete filing, they'll have plenty of data on repeat dosing based on the SOL 1 patients as well as the SOL 1 safety patients that we're going to provide. Nadia, anything else to add?

Ataseen, thank you for the question. And, Praveen, I 100% agree. I mean, I think all of the 300 or more than 300 patients that we submit as part of our regulatory safety package, either at baseline or at the safety update, will have received repeat dosing. And indeed, at this point, all of the patients that continue to remain enrolled in our trial, whether that be SOL1 or SOLAR or the ones that roll over into SOLX, all of those patients have received repeat dosing. So we have a wealth of data on repeat dosing at this point.

Thank you, Nadia. And Tuzina, I think the emphasis here is that the FDA will have more than enough repeat dosing data to analyze, and we're very happy to provide that to them. Tuzina, again, thank you very much for your question.

Thank you. We will move next with Tara Bancroft with TD Cowan. Please go ahead.

Hi, this is Sam on for Tara. Thanks for the update and taking our questions. So, on the SOL-R primary endpoint change, did the FDA request that you make this change from week 52 to week 40? And it would be helpful if you could walk us through the timeline of your regulatory interactions with the agency on this matter, starting from after the type C meeting until it's finalized. Thank you.

Good morning, Sam, and thank you for your question. So, what I would like to say is, look, we said this from the very beginning. We obviously don't talk about the details of our interactions with regulatory agencies other than to say that there's nothing we do without being aligned with them. Remember what we said from the very beginning regarding SOLAR. We continue to believe that SOLAR, the SOLAR efficacy data, will not be required for approval in the U.S. We continue to believe more confidently than ever, and I emphasize more confidently than ever, that X-Paxly will get approved by the U.S. FDA based on a single trial, which is SOL1. As we've always said with our complete package. However, we've also stated that we believe that solar will be important for some regulatory agencies outside the U.S. We've also stated from the onset that we will do everything possible to protect the integrity of SOLAR. And this is a consistent theme that you have heard. And the third thing is we've always said that everything that we do, we do with discussion with and alignment from regulatory agencies. And what I'll tell you, Sam, is that the discussion regarding the primary endpoint began immediately after our Type C meeting, which was in May, as you know. And the discussion ranged around how to make sure, above all, that the integrity of solar is protected and that there's no questions whatsoever regarding any operational bias. As you also know, the U.S. FDA regards week 36 as an acceptable one-year primary endpoint if you're using treatment-naive patients, and you know this because that's what we have in SOL 1. It made complete sense, and it was completely logical then to say that we would then have an endpoint which would be completely... Would not necessitate any questions about operational bias if we picked an endpoint where patients had already crossed. And at week 40, which is well beyond the week 36 requirement, patients would have already crossed, and there would be absolutely no question about operational bias whatsoever. And again, this is in line with what we have done to protect the integrity of SOLAR and makes complete sense and is completely aligned with regulatory agencies. Having said that, let me ask Nadia to give us some of her thoughts. Nadia?

Thank you, Praveen. And thank you, Sam, for that question. So, first and foremost, everything that we do, we are in lockstep and aligned with the regulatory agencies, and everything that we do is focused on, first, ensuring that we have a successful regulatory pathway, and second, ensuring that we have a de-risked regulatory pathway, So that we can get Axfaxi out to patients as soon as we possibly can. Change is also focused on that very thing. So, the reason for the 40-week change, the change to 40 weeks for the primary endpoint, as Praveen mentioned, was to ensure that at the time of unmasking of a subset of patients For the FDA, for the submission, NDA submission to the FDA, we wanted to ensure that each and every one of the patients in SOLAR had already crossed their primary endpoint time, and that the database for that was frozen, for the primary endpoint was frozen and locked, so that there was no question whatsoever of operational bias impacting our primary endpoint. And that is what drove this decision to change the primary endpoint to 40 weeks. And of course, the week 56 remains one of our key secondary endpoints that we will also look at. And I think part of this change is to ensure – well, all of this change is to ensure the integrity of the trial, but part of this is also driven by the fact that when we look at the data in SOL1, we're increasingly confident about both the efficacy as well as the durability of AXPACC, No matter what time point along that 56-week or one-year pathway we look at, at every single time point along those lines in SOL1, we were seeing exceptionally good results. And you saw that presented this weekend when we presented our data, for example, at the Empire Forum, where we saw that patients who, you know, were dry at the eight-week time point, that, you know, they continued to be dry. Up to the nine-month time point, you know, and so that increasing confidence drove our ability to make these changes and to ensure integrity of our clinical trials and to have a minimal alpha impact on our primary endpoint as a result. Somebody to stop over there, Praveen?

Well, thank you, Nadia, and Sam, I want to emphasize what Nadia said. You know, we spent a lot of time before talking about how the 56-week primary endpoint was optimal based on peaks and troughs and so on and so forth. You know, we're beyond that at this point, and we're beyond that because we are so confident in the X-Paxilid data based on our SOLE 1 analyses that it really doesn't matter, as Nadia said, what time point we use. This drug lasts easily for 12 months in the most difficult patient population that you can possibly select, and these are patients who are designed to lose vision. There is no doubt whatsoever in our mind that in a patient population that's super de-risked and super selected to be stable, as we have with a six-month ramp in SOLAR, that at every time point, this drug will succeed. So at this point, rather than trying to optimize the primary endpoint, the more important thing for us really is to protect the integrity of the trial, to have no discussion whatsoever regarding operational bias, and to be completely aligned with regulatory agencies, and that's the reason behind the decision.

I'd just like to add one additional thing over here. I think we've shown very nice data on fluid that demonstrates the zero-order kinetics and the extended release and sustainability of our medication. And what we've shown is that, you know, once you have that drying in this population of stable patients, that you have rock-solid control all the way out to, you know, nine months, one year. And so, you know, we're much less prone to fluctuations than bolus therapies like a Flibercept, where there is some up and down with the eight-week bolus dosing. And that confidence is really what's driving our ability to make this change.

And to add on to that, you know, look, when Nadia talks about rock-solid stability, Sam, I think it's important to emphasize that the criteria that we're using, which is 10 nanoliters, is the most stringent that I know, and it's about as dry as you can get, and it's important when people talk about dryness. In other studies to ask them, what exactly do you mean by dryness? And I don't know of any other analysis, any other study that has used. a criterion of 10 nanoliters because it's extraordinarily stringent. So when we talk about dryness and rock-solid stability, we really mean this. And remember, this is in the most difficult patient population. This is patients that are specifically selected to lose vision. So if we can have that kind of disease control in patients who are specifically chosen to lose vision, we are more confident than ever that we'll have superb control, even better control in patients that are specifically de-risked to be as stable as possible. Sam, thank you for your question.

Thank you. We will move next with Lisa Walter with RBC Capital Markets. Please go ahead.

Oh, good morning, and thanks for taking our questions. Maybe just another one on the solar primary endpoint change. Just curious if you considered changing the safety interim analysis to week 56 instead to be in line with the timing of the prior primary endpoint. And given the change to 40 weeks, for commercial viability, do you think you will need to hit the secondary endpoint at one year for commercial uptake? Any call here will be helpful. Thanks so much.

Lisa, good morning, and thank you for those questions. You know, first of all, look, the 52-week safety data analysis absolutely coincides with our timing for the full NDA package submission. So, you know, again, our discussions with regulatory agencies are something that we don't make public, but it completely also aligns with our discussions with the regulatory agencies. As far as data is concerned for, you know, week 40 versus week 56, look, in Solex, we'll have data for week 48. We'll have more than sufficient data to show that this drug will last for a year in most patients. If we can, again, it's easy to sometimes overlook the patient population in SOLE1. I want to also, again, emphasize, and I know I've said this before, this is the most difficult patient population. These are patients that were specifically anti-VEGF dependent. We selected for them, and then we took away the anti-VEGF, and we allowed them to lose vision. That's exactly what we did. And in this patient population, if we can have a durability in two-thirds of patients, For a year, I think that provides more than enough data based on the longevity of this drug, and we believe that that will be even greater when you look at the patient population that's specifically chosen in SOLAR, who are the most stable patients that you can possibly have. I want to emphasize what I said earlier on, which is that it's important to look at the totality of our program. Essentially, three different studies here in wet AMD, right? We've got SOL1, we've got SOLAR, and we have SOLX. And there was absolutely no reason to repeat the data that we would have in SOLAR by treating every six months. So we extended that to every 48 weeks. And given together in that triad of programs, I think the clinician will have more than enough information as to the safety, the disease control, as well as the durability of this drug. Nadia, your thoughts?

I completely agree, and thank you, Lisa, for that question. I mean, I think the week 52 time point, by the way, for the safety submission for the FDA makes a lot of sense because it's also consistent with the sole one data, safety data that we have at week 52. So it just makes it so that all of our patients have that safety cutoff at the same time. So I think there's that operational component to it that enables us, that, you know, partly drove the decision. And having said that, you know, we will have, obviously, safety data, not only at the one-year time point, but also at the two-year time point with the SOLAR study, which, as you know, remains masked all the way out to two years. I think SOLAR will provide us a wealth of information that is going to be very useful for clinicians, including superiority against ILIA HD, and including data on long-term outcomes such as fibrosis at the two-year time point. So I think that SOLAR is a critically important study from that perspective. Having said that, and I'm sure you're familiar with the data that we just went ahead and presented in SOL1, I think that we are using post-hoc SOL1 analysis to really provide a roadmap for clinicians to adopt XFACSI and to provide guidelines around adoption of XFACSI in clinic, and that this is data that, you know, this is data that, you know, it's a gift that keeps on giving. You know, as you saw In the analysis that we presented, if we treat patients initially to dryness, which is generally one or two or three injections, we then… Maintain this dryness with a single injection of X-Faxley all the way out to the nine-month time point, and this is data that we presented at both AO as well as did some additional analyses at the Empire Forum that we presented. And I think that this is a really nice roadmap around durability and maintenance therapy that we're now providing to clinicians, which I think is going to be really important, especially in this landscape where we may well be the only in-clinic administered durable maintenance therapy available to clinicians. So, I'm going to end with that and bring it back to you.

Thank you, Nadia. Lisa, thank you so much for your question.

Thank you. We will move next with Jack Allen with Baird. Please go ahead. Your line is open.

Hey, everyone. It's Nick on for Jack. Thanks for taking the question. One I had was just on what communication would you all get surrounding the 52-week safety analysis on SOLAR, and would a failure on the primary endpoint halt the study? So, in other words, if you get past the primary endpoint and we don't hear any news, can we assume that the study is positive? And then also on the 52-week SOLAR, on the NDA submission, are there other gating factors on the submission besides hitting that 52-week SOLAR endpoint? Thank you.

So, Nick, again, thank you. Good morning, and thank you for your question. Just to be very clear, as part of the complete NDA package, we are only providing safety data from SOLAR at week 52. That is all that's been requested, and what that does is to fulfill the FDA's requirement of having at least 300 patients who are exposed to the drug. They don't necessarily require the same target. Usually, they would ask you for the same population of patients age-wise. They don't even require the same dose. It can't be a lower dose, but it can be a higher dose. And that's why we're providing that safety exposure only, no efficacy, just the safety exposure only from SOLAR as part of our complete NDA submission. What we don't want to do is, during the review process, we don't want to be adding new data that would trigger a major amendment, because, as you know, with a major amendment, the clock starts all over again, and we'll lose the advantage that we have currently being in an accelerated track with the 505B2. As you know, the card turn for SOLAR will be at week 96, and that has not changed. So, up to that point, the study will be completely masked, and all we'll be providing is simply the safety data up to week 52, and that's it. Nothing else. No efficacy data, just the safety data. With what we've done today, what we've ensured is that the integrity of SOLAR will be completely protected because when we provide that week 52 safety data, all the patients will have already crossed what is now the 40-week primary endpoint. So there's going to be no risk whatsoever of any operational bias, and there's going to be complete protection of the integrity of SOLAR. Let me see if Nadia has some thoughts on this as well.

So, thank you, Nick, for that question, and exactly aligned with what you're saying, Praveen. The SOLAR study, I just want to emphasize, remains masked. It remains masked all the way out to 96 weeks. While we freeze the database for the primary endpoint at the 40-week time point before we do the safety unmasking, keep in mind that even within the company, even the safety data is actually masked for the company, and that safety data is getting submitted to the FDA, but overall for the study itself, we remain completely masked out to week 96. And there are several good reasons for that, including we need to maintain the masking to be able to produce the superiority data against IVA-8 milligrams, as well as to be able to produce the fibrosis data that we hope to produce, which are all key secondary endpoints for us in the SOLAR study. Of course, what this enables us to do is leverage the patients in the SOLAR study to provide us with those things, which we believe will be very significant advantages, both adoption-wise as well as commercially, as well as significant advantages of durable maintenance therapy. You know, and just based on the, going back to what you were saying, just based on the data that we're looking at, for patients that, you know, don't have early persistent fluid, which, as you know, was the patient cohort that was removed from the SOLAR study. We only have patients who had no evidence of early persistent fluid. You know, we've presented data at this point that shows us that, you know, there's almost No credible paradigm under which SOLAR would not be successful whether we look at week 40, whether we look at week 56, or whether we look all the way out to week 96. So our confidence in the success of SOLAR continues to grow the more we look at our data coming out of SOL1 and the more we look at the data that we've been able to produce out of SOL1 at this point. Praveen, anything?

No, thank you. And, Nick, thank you so much for your question.

Thank you. This concludes our question and answer session. I will now try to call back to Dr. Praveen Dougal for closing remarks.

Thank you. Once again, thank you all for joining us today and for your continued support. We have an incredible opportunity ahead. And we're doing everything in our power to execute on this exciting vision that we have outlined. If you have any questions, please reach out to Bill Slattery, our Vice President of Investor Relations. Have a great day, everyone. Thank you.

Thank you. This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect.