Good morning, welcome to the Ocular Therapeutix SOL-1 Data Review 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 one 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 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. This past Friday, February 27th, 2026, we presented detailed results from the SOL-1 phase III clinical trial of AXPAXLI, also referred to as OTX-TKI in wet AMD at the 49th Macular Society Annual Meeting. We refer everyone to the Macular Society presentation slides and video recording for a comprehensive update of the clinical data released. The presentation is available on the events and presentations section of our investor relations website. Today's conference call will begin with brief prepared remarks from Dr. Pravin Dugel, Ocular's Executive Chairman, President, and CEO, Dr. Peter Kaiser, Ocular's Chief Development Officer, Dr. Arshad Khanani, Director of Clinical Research at Sierra Eye Associates in Reno, Nevada, and Steering Committee Chair for the SOL Program.
Darius M. Moshfeghi, who is a rescue monitor in the SOL-1 trial and is Chief of the Retina Division, Byers Eye Institute at Stanford University School of Medicine, and Dr. Jeffrey S. Heier, Ocular's Chief Scientific Officer. Following the prepared remarks, Dr. Sanjay Nayak, Ocular's Chief Strategy Officer, will join our presenters for the question and answer session. During today's call, certain statements we will make 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. I'd like to hand the call over to Dr. Pravin U. Dugel. Pravin.
Thank you, Bill, and thank you all for joining us this morning. It has been nearly two weeks since we announced positive SOL-1 top-line results, and as we've continued to analyze the data set, our conviction has only strengthened. The message remains simple: We have a drug. A drug that is active, durable, and well-tolerated, delivering sustained VEGF suppression with evidence of activity up to 12 months in 66% of the AXPAXLI treated subjects. That is simply unprecedented, and it cannot be matched by our nearest competitor. This is not incremental progress. This is not another modest extension in dosing interval. This is transformative durability with continuous, predictable disease control. At the 49th Macula Society Annual Meeting, we answered several questions raised after our top-line announcement.
We demonstrated just how difficult it is to achieve superiority in wet AMD and reinforced that the endpoints most relevant to clinical practice strongly favor AXPAXLI. Remember, no other novel mechanism has ever demonstrated superiority to anti-VEGF in an FDA-aligned phase III study. We believe this represents a lasting point of differentiation since very few, if any, sponsors are likely to take on this difficult challenge. With positive SOL-1 data in hand, we are now preparing for our NDA submission. The transformative durability, continuous VEGF suppression, and safety profile demonstrated in SOL-1, combined with a seamless workflow integration, likely positions AXPAXLI for immediate and rapid adoption pending FDA review and approval. Most importantly, it provides new hope for patients who have lived with the burden of treatment injections and fear of irreversible vision loss for far too long.
With that in mind, it is my pleasure to hand the call over to Peter Kaiser, who will spend a few minutes on AXPAXLI's mechanism of action presented this past Friday at Macula Society. Arshad Khanani will then talk about the detailed SOL-1 efficacy results, followed by Darius M. Moshfeghi, who will provide an update on AXPAXLI's safety profile. Finally, before we move to Q&A, Jeff Heier will speak more about our plans to submit our NDA for AXPAXLI with SOL-1 alone. Peter, please go ahead.
Thanks, Pravin. Ocular Therapeutix is and will always be a company grounded in scientific evidence, first and foremost. With that in mind, let me explain why AXPAXLI is fundamentally different from the anti-VEGF therapies we use today. Current anti-VEGF drugs work outside the cell in the extracellular space. They bind specific VEGF molecules, primarily VEGF-A, outside cells, preventing them from activating receptors that drive abnormal blood vessel growth and leakage. This approach has transformed retina care, but it's also incomplete. Multiple VEGF receptors are involved in neovascular AMD, particularly VEGF receptors 1 and 2. Blocking just one ligand, like the most pathologic VEGF-A, may allow other pathways to compensate. For example, VEGF-C can become upregulated when VEGF-A is suppressed. None of our current anti-VEGF agents address that. Axitinib, the active drug component of AXPAXLI, works very differently.
Instead of blocking VEGF outside the cell, axitinib works inside the cell at the receptor level. It blocks activation of all VEGF receptors by targeting the ATP binding site, effectively shutting down the signaling cascade that drives leakage, inflammation, and neovascularization irrespective of the concentration of VEGF in the extracellular space. In simpler terms, it's a more comprehensive blockade of the VEGF pathway, and it does this with very high potency and selectivity. Independent kinase profiling performed under physiologic ATP and drug conditions shows that axitinib produces greater than 90% inhibition of all VEGF receptors, with almost complete inhibition of the pathologic VEGFR-1 and VEGFR-2. In addition, axitinib produces greater than 85% inhibition of all the PDGF receptors, which are involved in vessel stabilization and fibrosis.
Coupled with this targeted selectivity when tested appropriately at physiologic ATP levels and therapeutic drug concentrations, axitinib does not inhibit off-target kinases like JAK1 or TIE2. In fact, none of the TKIs in development for retinal diseases meaningfully inhibit the JAK pathway at physiologic ATP and therapeutic drug concentrations. The bottom line is that axitinib is very potent and selective for the receptors that lead to retinal vascular diseases. The second part of the Ocular story is drug delivery. AXPAXLI combines axitinib with Ocular's tunable ELUTYX hydrogel platform, a platform leveraged from our FDA-approved product, DEXTENZA, which has been safely used in more than 700,000 eyes. The ELUTYX hydrogel technology is a tunable and fully bioresorbable polyethylene glycol platform. It does not leave any hydrogel remnants for 12-18 months like some other programs.
It is injected through a standard 25 gauge needle and does not require surgery. The hydrogel releases axitinib in a controlled, predictable manner with zero-order kinetics, providing continuous drug levels in the retina and choroid for up to 9-12 months. That sustained, steady axitinib delivery is what allows for consistent VEGF and PDGF pathway suppression over time. Unlike other polymer systems, drug release and hydrogel resorption are synchronized. Physicians know when the drug is gone and when redosing may be appropriate. When you combine a highly potent pan-VEGF intracellular inhibitor with a strong pan-PDGF inhibition delivered through a bioresorbable hydrogel platform that provides predictable long duration release over 9-12 months, you get a therapy designed not just to compete in the market, but to redefine it.
What I've shared is a scientific foundation behind the positive SOL-1 clinical results, which I would now like to ask the steering committee chair, Arshad Khanani, to speak more about. Arshad.
Thanks, Peter. It's a privilege to work through the efficacy results from SOL-1 that were presented on Friday with the benefit of the expanded data set now in hand. What I'd like to do today is to focus on not just on the numbers, but on what they mean clinically. It's important to remember who the 344 subjects enrolled in SOL-1 were. These were not poorly seeing patients with scarring and fibrosis. After two aflibercept loading injections, on average, subjects were randomized with approximately 20/25 vision. Approximately two-thirds of the subjects had gained 10 letters or more from enrollment to randomization. This was one of the best seeing phase III populations we had ever enrolled in terms of BCVA. This was by design because the trial sought out a population that was expected to lose vision over time.
Against that backdrop, AXPAXLI met the primary endpoint in SOL-1 convincingly. At week 36, 74.1% of AXPAXLI subjects maintained vision, defined as losing fewer than 15 ETDRS letters, compared to 55.8% in the aflibercept arm. That reflects a 17.5% risk difference and a p-value of 0.0006. At week 52, 65.9% of AXPAXLI subjects maintained vision after a single injection with statistically significance over aflibercept and a p-value of less than 0.0001. That represents sustained disease control over an entire year in a population selected to fail. If we were to look at the proportion of subjects who lost greater than or equal to 10 ETDRS letters. This key secondary endpoint also emphatically favors AXPAXLI.
Only one-third of AXPAXLI subjects would have met this threshold at week 36 compared to over half of the aflibercept subjects with a nominal P value of 0.0029. By week 52, still less than half of the AXPAXLI subjects would have lost more than 10 letters. Let's talk about anatomy because that's how we actually practice. Treatment decisions are typically driven by fluid on OCT. In SOL-1, AXPAXLI delivered consistently tighter anatomic control. At week 36, 55.9% of subjects maintained central subfield thickness within 30 microns of baseline compared to 37.8% with aflibercept. That separation persisted through week 52. We also saw lower total fluid volumes and reduced fluctuation over time. When you look at specifically at patients who were dry at baseline, over 80% maintained vision at nine months with AXPAXLI.
That level of predictable fluid control is what gives clinicians confidence to extend intervals. Rescue data reinforces the durability story. At week 36, 74.7% of AXPAXLI subjects were rescue-free. At week 52, 68.8% remained rescue-free, in each case based on the on-protocol rescue criteria. The Kaplan-Meier curve is particularly striking, showing meaningfully delayed time to first rescue for AXPAXLI compared to aflibercept. For example, the higher rate of rescues in the aflibercept arm at week 28 was not reached in the AXPAXLI arm until six months later at week 52. If we were to consider subjects who had zero or one rescue treatment in the AXPAXLI arm, 81.2% of AXPAXLI subjects made it to week 36, while an astonishing 72.4% made it to week 52.
When looking at the ITT BCVA curves, I think it's important to step back and ask what those curves are actually capturing. The ITT analysis is confounded by rescue interventions, with many more rescues taking place in the aflibercept arms. Remember, at week 52, roughly 2/3 of AXPAXLI subjects remained rescue-free compared to a minority in the aflibercept arm. We also know that AXPAXLI's hydrogel bioresorption occurs around week 36, so some softening of effect beyond that point is biologically expected. In that context, it's actually quite encouraging that so many AXPAXLI subjects maintain control out to week 52 without rescue. Importantly, in SOL-R, all subjects will be proactively redosed at six months. Seeing this level of durability without mandated redosing gives me even greater confidence in the fixed interval paradigm being prospectively tested in SOL-R. Taken together, what do we see? We see superiority on vision.
We see sustained anatomic stability. We see high rescue-free rates. We see durability extending toward a 9-12 month treatment horizon. For a single injection in an FDA-aligned phase III trial, that combination is unprecedented. With that, it's my pleasure to hand the call over to Darius to talk more about safety. Darius?
Thank you, Arshad. It's great to be speaking with everyone again today. In retina, you can have compelling efficacy and impressive durability, but if retina specialists are not completely comfortable with the safety profile, adoption stalls. What gives me confidence in AXPAXLI is simple. There's nothing in this data set that would make me hesitate to use it in my own patients. Let me be very clear. There were no treatment or procedure-related serious adverse events and no safety events that commonly derail retina programs. No endophthalmitis, no occlusive or non-occlusive retinal vasculitis. There was one singular non-treatment related ocular SAE, a cataract with greater than 30 letter loss at detection, but the patient's vision quickly recovered after routine cataract surgery. Cataracts are common in this age group, and this did not represent a concerning safety signal.
Some have focused on the higher rate of non-serious ocular events, and the main driver was vitreous floaters in 12.4% of AXPAXLI subjects. It's important to understand that the timing of these small floaters correspond to the tunable hydrogel dissolution and drug elution. They did not adversely affect visual acuity. They were not associated with inflammation, and they were not associated with cataracts. When recording adverse events, we rely on classifications from the Medical Dictionary for Regulatory Activities, or MedDRA. At the time of SOL-1, there was no MedDRA code for drug particles, so our expectation is that they were recorded as floaters. That can inflate the category. Clinically this is not a concerning signal.
Beyond floaters, there's been some discussion of cataracts in 7.1% of AXPAXLI subject. Cataract rates were consistent with what we see in wet AMD trials in this older population. Again, nothing novel, nothing alarming. Intraocular inflammation was observed in small number of cases, but these were all mild to moderate and resolved with topical therapy or observation. People seem to forget that the Lucentis package insert includes a 19% rate of vitreous floaters, 11% rate of cataract, and 13% rate of vision blur or vision disturbance. Yet more than 12 million doses of Lucentis have been administered since it was approved in 2006. Moreover, in the real world, missed visits are common. These are elderly patients. They get sick. Their spouses get sick. Transportation falls through. Life happens. With current anti-VEGF therapies, missed treatment visits can result in irreversible vision loss.
A therapy that maintains disease control for up to 12 months, like AXPAXLI showed in SOL-1, provides a significant buffer against that risk. From a clinician's perspective, that is powerful. Just as importantly, AXPAXLI is likely to require no surgery, no concomitant steroids, no implant retrieval, no special monitoring for remnants. It is delivered through a standard intravitreal injection exactly how we already practice. Based on the SOL-1 data, I believe AXPAXLI has the profile to support immediate and broad use in wet AMD because it has a reassuring safety profile, continuous disease control, superiority, and the potential to meaningfully reduce treatment burden. From where I sit as a clinician and as someone who closely monitored this study as a former rescue monitor, there is nothing rate-limiting here. I see a therapy that has the potential to meaningfully advance the standard of care. Jeff, over to you.
Thank you, Darius and Arshad. We are lucky to have you both as collaborators as we continue to communicate the strength, consistency, and real-world relevance of the SOL-1 results. Before we move to Q&A, I want to take a couple minutes to explain why we believe AXPAXLI is exceptionally well-positioned for NDA submission and potential FDA approval based on SOL-1 alone. As many of you have seen by now, the FDA recently announced in the New England Journal of Medicine that one adequate and well-controlled pivotal trial is the new default option for FDA approval when supported by confirmatory evidence. This includes factors such as statistical significance, alignment with the FDA, and totality of evidence. When we look at SOL-1 through that lens, we believe it checks every box.
First, the SOL-1 superiority trial was designed in direct alignment with the FDA's 2023 draft guidance for neovascular AMD clinical trials. The guidance recommends that one comparator arm have the same dosing schedule as the investigational drug, and SOL-1 did exactly that. This gives us clean, unbiased evidence of relative efficacy and durability. There is no inference required. The FDA has also stated that sham injections are not recommended due to inadequate masking and potential bias. SOL-1 did not use sham injections. Second, this was an adequate and well-controlled study, and importantly, it was conducted under a Special Protocol Assessment or SPA agreement. That means the FDA aligned in advance on the trial design, patient population, control arm, masking, endpoints, and the statistical analysis plan, which was included with the SPA submission and agreement. Third, the magnitude and statistical strength of effect are compelling.
The primary endpoint at week 36 achieved a P value of 0.0006. The key secondary endpoint at week 52 achieved a P value of less than 0.0001. Across visual, anatomic, and rescue-based measures, the consistency of results is striking. Fourth, confirmatory evidence. The VEGF pathway is one of the most well-established mechanisms in all of medicine. AXPAXLI targets a validated pathway that has defined the standard of care in wet AMD for over two decades. We also have extensive real-world evidence showing that in the U.S., up to 40% of wet AMD patients discontinue anti-VEGF therapy within the first year alone, largely due to the injection burden. A therapy that meaningfully extends durability, like AXPAXLI did in SOL-1, directly addresses that unmet need.
Finally, we will be filing via the 505(b)(2) pathway, leveraging prior FDA findings on axitinib systemic toxicity. Axitinib is already FDA-approved in non-ocular indications. Its pharmacology and systemic safety are well characterized, and our manufacturing is U.S.-based, a priority for this administration, both of which support regulatory efficiency and reliability. We are actively preparing our NDA and plan to submit following our planned meetings with the agency. Our goal is simple: to bring AXPAXLI to patients as quickly as possible. With that, operator, we are ready to take our first question.
Thank you. As a reminder, if you would like to ask a question, please press star one on your keypad. You can remove yourself from the queue by pressing star two. Our first question comes from the line of Tazeen Ahmad with Bank of America. Please go ahead. Your line is open.
Hi, guys. good morning, and congratulations on presenting really positive updated data. I wanted to ask about commercial preparation. Now that we have a clear picture of what the product looks like, and you believe that you can get approval with this one study, have you pulled forward your efforts for preparation? Can you give us a sense about what kind of size of the sales force you think you would need? just remind us what EYLEA and Lucentis type of drug marketing teams look like, and if you think you'd need the same size or a different size. Then, have you scheduled your meeting to actually talk about the data with FDA? Thanks.
Good morning, Tazeen. This is Pravin. I'm happy to answer that. Thank you for the question. We are building a company that is a standalone company to market this product globally. We've always said that. We've committed to that. The actions that we've taken really validate what I've just said. As you know, recently, we announced the hiring of David Robinson. We're very fortunate to have David. David is the architect of the EYLEA launch, probably the most successful launch in our industry. As far as the sales force question is concerned, we're very well supplied with that. As you recall, we are selling DEXTENZA. We have a very capable sales force that we're very proud of. At the peak of Lucentis sales, I believe that Genentech had about 50 to 60 reps.
We're already there. You know, it's not so much the number of reps. It's really the networking. It's the concentration within ophthalmology, and that's one of the very big reasons that we've kept DEXTENZA under our umbrella. We're really proud of the commercial team that we have and their capabilities. We're very well set up for commercialization here. We're also scaling up, as I've said before, through automation, et cetera, not only for wet macular degeneration but also for diabetic retinopathy, which is three and a half times the size of that. Now, with a single submission, we've also accelerated the entire program. In terms of commercialization as well as the scale-up of manufacturing, all of that has been significantly accelerated because our goal is to get approved with a single trial. Thank you for that question, Tazeen.
Back to the operator.
Thank you. We will move next with Biren Amin with Piper Sandler. Please go ahead. Your line is open.
Hey. Yeah. Hi, guys. Thanks for taking my questions. Now that you've had time to analyze SOL-1 fully, I want to get your thoughts on read-throughs from SOL-1 to confidence that SOL-R could achieve non-inferiority against aflibercept 2 mg every eight weeks. That's the first question. Second question, I think on regulatory, would you expect FDA will want you to identify patient populations that benefit from AXPAXLI, or would you expect a broad label based on the SOL-1 trial data? Thank you.
Biren, good morning. Thank Thank you again for your question. For the first one, which is the translation of the SOL-1 data to SOL-R confidence, Arshad, maybe I can ask you to start that, and then with the FDA question, maybe I can give that to Jeff afterwards. Arshad, if you can go ahead with the first question that Biren asked, which is the translation of SOL-1 data into greater confidence for SOL-R.
Thank you, Pravin. Thank you, Biren. Good morning, everyone. I think that's a very good question, Biren, and I think looking at the SOL-1 data, it provides me high confidence that we'll be able to potentially achieve non-inferiority in SOL-R. The reason for that is, as you recall, we have a long run-in period in SOL-R to actually exclude patients that are high need. You get 3 anti-VEGF, and then you wait for 8 weeks, and if they have accumulation of fluid or disease activity, they're exited from the study, so they're not randomized. As you recall, in SOL-1, we have a whole spectrum of patients, the VEGF responsive patients, most of them gain 10 letters or more, but that doesn't screen out all the high-need patients.
Of course, the number we shared before, 77.1%, would have been rescue-free using the criteria for SOL-R even though we are including the high-need patients from SOL-I. The totality of the efficacy data we have seen.
I'm very confident that we'll be able to potentially meet the non-inferiority in the SOL-R study.
Arshad, thank you. Yep. Thank you, Arshad. Jeff, I think, do you wanna go ahead and add to what Arshad might have said as well?
I think that as we've looked at different studies and we've seen their responses in these types of studies, I think we're confident that the patients we've treated in SOL-1 and we've looked at the analyses will translate very well to SOL-R. The treatment responses we see there look like they'll do very well. I think the fact that we've selected out the patients that are most likely to be the most challenging, that have the highest anti-VEGF need, will give even more confidence to SOL-R. There was original work out of VIEW 1 and VIEW 2 that Peter Kaiser, Namrata, Andrea, and myself were instrumental in performing the analysis, and it shows that there's a small group of patients who have a very high need.
If you take those patients out of these analyses, and that's for all drugs, they're all of the anti-VEGFs, you have a much greater response rate. We're very confident that this will translate well. Biren, to your second question as to what do we expect on the label. I would not expect any sort of restriction on the label at all. I would expect a very broad label. In none of the approvals for the anti-VEGFs to date, despite different inclusion and exclusion criteria, we've never seen a restriction on the label. I think not only when you look at our SOL-1 data, but even when you look at our previous studies, like the treatment-naive patients in the Australia Study, these patients respond well.
I would not expect any type of limitation or restriction, and I would expect a broad label as we've always seen previously.
Jeff, thank you. Biren, thank you for the question. You know, from my perspective, let me just say for both parts of the questions that you asked, the translation from SOL-1- SOL-R, one of the things that we tend to forget is the patient population. Remember in SOL-1, we specifically picked a patient population that was going to lose vision, that was thoroughly anti-VEGF dependent. It's almost the exact opposite for SOL-R. Here we have a patient population that has a large ramp, the biggest ramp that I think we've seen, to ensure stability, to make sure that they're actually not anti-VEGF dependent. It's really quite the opposite.
The way I look at this is that, look, if we can have a rescue-free rate in this patient population that is the opposite of SOL-R, arguably the most difficult to treat in the sense of having patients who are designed to lose vision, who are anti-VEGF dependent and have a rescue-free rate of nearly 80%, when we have meticulous selection for stability as we have with two opportunities to observe, I can't help but believe logically that that rate will be much higher than that. I think the confidence that we can take from the SOL-1 results and translate into SOL-R, is really quite significant. We haven't had much time with this dataset.
I think you will see, I can tell you very confidently, further data cuts coming up which will give you even more confidence in SOL-R. I think this is at really an all-time high as far as our confidence is concerned, again, not just for SOL-R, but also for our diabetic retinopathy studies. As far as the FDA question is concerned, you know, what I would say is the FDA has said very clearly for decades now that the label that they would give, and obviously we're not in labeling discussions with them, but the label that they give is based on the disease and not based on the clinical trial. This has been shown over and over again.
If you go all the way back to ANCHOR and MARINA, there are restrictions as to vision, and clearly you see that with Lucentis there is no restriction in the, in the label whatsoever. If you look at PANORAMA, there are restrictions as to the severity of diabetic retinopathy. EYLEA has no restrictions as far as the, the severity of diabetic retinopathy is concerned. Most recently, my last company, remember we hadn't treated a single patient with fovea involving geographic atrophy, not a single patient, yet the label of IZERVAY is very broad, allowing for treatment for all the geographic atrophy. That's gonna be no different for us, I believe. Remember, we have SPA to back this up, assuring us, at least validating a superiority track forward. Thank you again for your question, Biren. Next question.
Thank you. We will move next with Colleen Kusy with Baird. Please go ahead. Your line is open.
Great. Good morning. Thanks for all the helpful color, and thanks for taking our questions. Maybe first for Dr. Khanani, Dr. Moshfeghi, just based on the overall data that we've seen, how would you plan on incorporating AXPAXLI into your practice? What type of patients would you use it in? Would you not use it in? If you could just comment, obviously, there was a large meeting of retina specialists over the weekend at The Macula Society. If you could just comment on kinda how your colleagues are thinking of adoption as well.
Colleen, thank you again for the question. This is Pravin, and that's a perfect question to ask both Arshad and Darius, as well as Peter and Jeff, because they're all practicing physicians. Let's start with Arshad first. Arshad, the question was, how would you incorporate AXPAXLI when it becomes available in your patient population?
Thank you, Colleen. It's great to hear from you. You know, looking at the totality of the data, you know, I'm thinking about my clinical practice, we have a large number of patients that are on Q eight -week or less frequent dosing. Those patients that are maintained on current treatments carry a very high treatment burden. AXPAXLI is automatically going to help those patients as a monotherapy, reducing their treatment burden to maybe, you know, six, nine, or 12-month injection with just a single treatment. These patients are looking for better treatments coming in the future because they're getting tired of getting six injections or even less or more. That's the maintenance population that's already in my clinic. Looking at the data, there's two other patient subtypes that I will definitely use AXPAXLI on. Number one is treatment-naive patients.
When a treatment-naive patient comes in, you tell them, "You're going to get two or three monthly injections, and then we'll extend them." Then they say, "Well, how long can I go?" My answer is, "It depends on the need. You may go six weeks, you may go eight weeks, you may go 10 weeks." Majority of them are stuck between, you know, 8-10 weeks, even if they're not high need. Those patients, if they're dry after the two anti-VEGF injections, as we saw in the data, 80% more than 80% went nine months in terms of maintenance of vision.
It's really exciting to see that if we have a treatment option in these patients who respond well to anti-VEGF, we can give them hope that now you can go six, nine, and 12 months instead of a few additional weeks like we currently do. The last patient population is a high-need patient population that's getting injections every four to six weeks, even with the Vabysmo and Eylea HD. What we can do for them is to use AXPAXLI to treat and extend them to an extended interval. Instead of coming every four to six weeks, they may be able to go every three to four months with a foundation baseline therapy with sustained delivery and sustained disease control.
Last thing I would say, Colleen, is that retina specialists will figure out the way they want to use AXPAXLI for their patients. You know, they may be fixed dosing every six months or may treat and extend. I think I'm really, you know, excited to have it in our hands. My talk with all the physicians at The Macula Society, which is a very high, you know, membership-only society, I got so many messages after looking at, you know, after sharing the efficacy data that they're excited to use AXPAXLI in their clinical practice. Back to you, Pravin.
Thank you, Arshad. Maybe I can go to Darius. It's a really important question, and thank you for asking it, Colleen. Maybe I can ask Darius to answer that. Then after that, I know Peter and Jeff also practice, so maybe they want to answer that as well. First Darius, then maybe Peter, then Jeff. Darius, go ahead.
Thank you, Pravin. Colleen, I think it's a great question. You know, in my own practice, for the last 20 years, I've been a strong believer in continuous dosing. You know, most of my patients are being treated on a Q4- Q8 regimen. Some of them have been stretched out recently to Q12 weeks, but I'm a believer in trying to maintain visual acuity as opposed to keeping fluid away. We've seen throughout, you know, many, many different studies with anti-VEGF agents that continuous anti-VEGF inhibition, irrespective of the presence of fluid, is the number 1 predictor of great visual acuity. When I look at the patient population of patients with wet AMD, I think my entire population is eligible, and I'm going to incorporate it right away, whether that's previously treated or incoming patients.
The second aspect of that is that a lot of stuff happens in our patients. It's an elderly patient population. They travel. They have spouses who may or may not be also compromised with respect to their overall health. They may be far away. When I have something that can lock in visual gains and maintain, you know, absence of fluid over a long period of time, I view this as a safety extender as well as a primary treatment intervention. If I can get my patients on a six-month to nine-month to a 12-month dosing, that's good for them, and it's also good for, you know, my overall practice. Regarding my practice, like many of the people here, we're just busting at the seams.
This is something that I can incorporate immediately into my practice without having to do any special evaluations, interventions, leave and go to the operating room. No, I can do this all within the context of my clinic. Similarly to Arshad, Jeff, and Peter, I was down at The Macula Society. It seems like there's a lot of interest in this medication moving ahead, and everybody's excited to see how it moves through the regulatory process. I'll return it back to Pravin.
Darius, thank you. Maybe Peter, and then Peter why don't you pass it on to Jeff to answer this question. Why don't you go first?
Sure. Thanks, Colleen, for the question. As you know, Jeff and I still see patients in our clinics. I'm at the Cole Eye Institute seeing patients. You know, when you talk to patients, unlike what many physicians will tell you, the thing they hate most are injections. So when you think about it, anything we could do to reduce that is something they're going to absolutely embrace. The other big thing here, which is lost on most physicians, most physicians in the back of their brain think, "Well, there's no question that the results of my patients are as good as clinical studies." The reality has been shown in numerous publications. It's not one. Every publication on real-world data shows that nice improvement that we all see.
A tail off over time. If you look at our data from the SOL-1 study that tail off occurs early, right? We see a slight tail off, you see a stability over time. That stability is what I think is really gonna be important for our patients. It allows us not to have to worry if we're gonna be missing a visit or they miss a visit because life happens, they're gonna miss visits all the time. Currently, when I see that happen, even with some of our second and third generation longer durability drugs, their vision drops and sometimes drops very precipitously. We have them covered with AXPAXLI. It allows us to go much, much further.
To me, I personally would be using this in the majority of my patients, because to me this is exactly what they want. You know, whether to use them in treatment-naive patients because I think the label, as Jeffrey Heier mentioned earlier, is gonna be unrestricted. You know, we do have data in totally treatment-naive patients with the treatment with OTX-TKI from baseline from our Australia study, but I don't really think that's how we're going to use it. I think in the future we'll probably be trying the patients and then getting this on board to maintain patients over the long term. I'll pass it on now to Jeffrey Heier.
Yeah. Thank you, Peter, and thank you Colleen for the question. You know, what you've heard from the three before me is there's clearly a significant need, and we see the potential to use this in virtually all of our patients. The one thing that keeps going over and over in my mind is when I'm in clinic, the recurrent theme of burden not only to the patient but to families and caregivers, the constant negotiation with patients that they wanna keep stretching it out. When you speak to clinicians individually, they say, "Well, I'm really good about maintaining the follow-up on my patients." We constantly underestimate the misses, the adherence to schedule that goes on with patients.
Not only the confidence to be able to extend patients long, but the confidence to know that when those unforeseen misses happen, when there's an illness, when there's an injury, when patients can't get in and then don't reschedule for another three months, having drug on board to control the disease will be absolutely invaluable.
Thanks, Jeff. Colleen, let me just give you two more of my thoughts over here. One is that remember we have a second goal with this drug as well, which is to have better long-term outcomes. One thing that hasn't been mentioned is that we believe that we're gonna have less fibrosis, less atrophy, and that's gonna result in better long-term outcomes as well. I don't want that to get lost there. I'm sure we'll be doing other data cuts that will look into that. The last thing that I would say, in the 30 years that I've been doing this, there's not been one single drug that has been tested that has not done worse in the community than in the clinical trials. There's a good logical reason behind that.
You wanna have the best patient population, the most de-risked patient population who are gonna respond as well as possible in the clinical trials. In the community, the drug will really never do as well. It'll always do a little bit worse. I think this will be the first drug, at least in my career time, that will actually do better in the community than in the clinical trials because of the way the trials are designed. The patients that are selected, as I've said before, are patients who are designed to lose vision. When this drug is out there in the community amongst patients that are stable, as you've just, as you've heard from others, patients that are not necessarily as anti-VEGF dependent, the results actually will be the better in the community than even in the clinical trials.
Thank you for your question. operator, next question.
Thank you. We will move next to Sean McCutcheon with Raymond James. Please go ahead. Your line is open.
Hey, guys. Congrats on the day. Thanks for the question. For me, can you give a bit more detail on the floaters, you know, the origin, how they were found and classified, whether they were seen in the visual field, and the window during which the drug particles were observed and subsequently cleared? Thanks.
Great. Sean, thank you for your question regarding floaters. Maybe I can pass that on first to Darius to explain a little more detail about the safety data. After Darius, after that, maybe you can pass it on to Peter, because I think Peter can talk a little bit more about the mechanism of the dissolution of the drug itself. First, to you, Darius.
Hey, Sean and Pravin. Thank you very much for that question. First off, you know, vitreous floaters are very common, in these in anti-VEGF approaches and intravitreal injections in general. You'll recall that the rate was 19% on ranibizumab. The timing of this was in the window that you were referring to is around the time of between 24 or 36 weeks is when we would expect the dissolution of the device inside the eye over time. The classification of floaters corresponds to that. The MedDRA classification does not have currently, for drug particles, and so we believe that this was the time that the device was dissolving, and the timeline corresponds to that. The patients had no adverse events associated with this. Back to you, Peter.
Thanks. Very good question, Sean. It's something that's been asked by many people. First and foremost, you know, if you look at vitreous floaters as an adverse event, you have to understand how they're, like, monitored in a clinical study. Usually in a clinical study, and I've done way too many, patient comes in, you ask them how they're doing, anything that's bothering them. If they say, "Yeah, I'm seeing floaters," then you put it down as a MedDRA term that they saw floaters. In contrast, in this clinical study, we specifically had a webcast with our investigators. In that webcast, we went over how this drug works, how it dissolves over time or bio resorbs over time, when we expect to see drug elution, and what that drug elution looks like.
You know, we had pictures from phase I that we showed the investigators. We actually even had a case report form where the unmasked investigator had to at every visit say, "Do I see the implant? Do I see any drug elution?" That has to be filled out at every visit. Unlike many clinical studies where vitreous floaters are described by the patient, in this study, they're put onto the adverse event table by both the patient as well as the physicians. That's one big difference. Despite that, the numbers are consistent in SOL-1 versus all the other clinical studies out there. That's number one.
Number two is sort of what you alluded to with your question, which is, you know, what is this? Is this just a, like, vitreous, and because you put something into the vitreous, the vitreous has been changed in some way, or is this something else? You know, when we really looked at the data and we presented this at SOL-1, as a, as a scatter plot, the majority of these patients, the floaters occurred right about when we expected drug elution to occur, about 27-29 weeks. You know, people say, "Well, you know, is this the big snowstorm effect? You know, what's happening to these patients?" No. They're not noticing this. The change in visual acuity is essentially nil, less than one letter.
The second part of question is does this disappear? We expect it will, and it's something we will be looking at. In the two weeks we had to prepare for this talk, we certainly didn't have time to pull all of those patients' case report forms. Remember, this was happening relatively late, really up against the 52-week cutoff for the study. We really are gonna look very closely as to the resolution of this. Vitreous floaters in other clinical studies don't disappear. In our study, we'd expect they would. It's something we will obviously be looking at and let you know in the future.
Peter, thank you. Sean, again, thank you for the question. The rate is very much in line with other studies if you just look at that as a whole. These are all physician-reported. We asked physicians to look for them. Had no impact on vision whatsoever. Not patient-reported, no impact on vision. The floaters were there because of the MedDRA coding. There is no code for drug. Although because of all of this, we will have a code for drug in the MedDRA classification, I think, starting next summer. Again, I think it's an issue that has been very, very clearly addressed head-on. Let's go to the next question. Operator.
We will move next to Lisa Walter with RBC. Please go ahead. Your line is open.
Oh, great. Thanks so much for taking the question. Congrats on the progress. Maybe just a question for the retina doctors on the line, Arshad and Darius, Peter and Jeff. Wondering what would be your strategy in the real world to start AXPAXLI in a treatment-naive patient? Would you start off with two anti-VEGF injections like in SOL-1, then add on AXPAXLI? Would you use more anti-VEGFs to get going or maybe fewer? Just curious how you would apply this into your practice?
Lisa, good morning. Thank you for your question. I'm chuckling and laughing because what you said is exactly what everybody else says to me, believe it or not. I'm also still a retina doctor. Nobody remembers that. That's okay. Let's go to Arshad first with that, with that answer. Arshad, why don't you go ahead, and after that, maybe Darius and then Peter and Jeff if they wanna comment. Go ahead, Arshad.
Thank you for the question. You know, I think clinical practice, we try to optimize the durability for every patient, and there's a heterogeneous, you know, patient set that we see. There are many patients that come in and you give them one anti-VEGF, and they're completely dry and doing well. Those are the patients I'll use AXPAXLI right away after the 1st injection. There are patients who need two or three loading doses to control their disease. I think it's gonna vary on the patient type that we are seeing in terms of, you know, how we're gonna manage those patients. There are patients who want fixed dosing, and there are patients who want treat and extend.
I think, as I said earlier, I think retina docs will figure out what works best for them and for their patients in terms of optimizing the disease control using this sustained delivery platform, and hopefully we can optimize their outcomes. Yeah, variable one injection and then AXPAXLI maybe two or three, then AXPAXLI. It's just gonna depend on the patient, how they respond.
Thanks, Arshad. Darius, maybe to you and then Peter after that.
Yeah. Thank you, Pravin and Lisa. you know, everyone's gonna treat how the patient rolls into their practice and what their practice pattern is. As I said before, my bias is towards continuous dosing historically. When I look at this, I view this as a long-term maintainer of both vision and keeping fluid at bay. I would like to get on board and treat immediately with an anti-VEGF agent and then nearly simultaneously add in the AXPAXLI. The reason for that is I would want to lock in my gains as early as possible. I don't know if this takes a while to work or if it works immediately from the beginning, and we'll find out more about that as we evaluate the data over time.
My bias would be that if I could do an anti-VEGF and an AXPAXLI early on and then as I don't have to worry about what happens down the road, I could go and say at, you know, 24 weeks or at 36 weeks, I'm maintaining this patient on potentially 2 doses per year. That's a fantastic win for my patient population. They're coming in at that point where I don't have to worry about any sort of variation in either visual acuity or in fluid accumulation. I'll turn it back to Pravin.
Peter, do you want to comment on that too?
Yeah. I agree with everything that's been said so far. Lisa, it's a good question. You know, how are we going to use this, and are we going to use this in treatment-naive? The idea of putting this on early, as Darius just mentioned, is very appealing and is certainly something we're probably going to do. This is especially true outside the United States. Outside the United States, they a lot of the insurance plans outside the US really limit the number of injections a patient can get in many countries, Italy in particular. The ability to put this on board early and to get that coverage is really important. The other thing is many of my patients in Cleveland have Medicare plans that require step therapy.
Like, even if I wanted to put them, for instance, on aflibercept or EYLEA HD early on, I can't, right? I have to start with Avastin, I got to switch to a Lucentis biosimilar, maybe an aflibercept biosimilar. Finally, nine, 12, 18 months in after I've shown three injections of each one of those don't work, I can finally put them on a drug I really wanted to put them on from baseline. The reason for that is very clear. None of those drugs are actually any better than any of the others. They all were proven in their phase III clinical studies with non-inferiority studies. In contrast, SOL-1 was a superiority study. We'd expect that the label would reflect that.
When we've talked to payers, they expect that too. What that would mean is there wouldn't be step therapy. Exactly what you're saying. Could you use it in a treatment-naive patient? Well, in traditional Medicare, you could use whatever you want. Most of my patients don't have traditional Medicare, because of that, there would be step therapy. We would expect we wouldn't be required to follow step therapy, you could use OTX-TKI in those treatment-naive patients without stepping through other drugs. In my opinion, I agree with Darius. I would be putting this on very early to keep those patients maintaining that vision gain that we saw early. This is not how we used it in the study, so it's something we'll need to look more closely at.
Thank you, Peter. Thank you for your question, Lisa. Back to the operator for the next question.
Thank you. We will move next to Clara Dong with Jefferies. Please go ahead. Your line is open.
Hi. Good morning. Thanks for taking my question. Just kind of follow up on the read-through to SOL-R. In SOL-1, patients were dry at baseline, showed a very strong separation for AXPAXLI in maintaining the vision. Would you view this dry baseline subgroup in SOL-1 as the closer analog to SOL-R patients, given the patient screening in that trial excludes subjects with early persistent fluid? Just from the commercial perspective, what data from SOL-R would most meaningfully further expand the adoption beyond what SOL-R already supports today? Thank you.
Clara, good morning, thank you for the question. I can probably answer that. As far as the SOL-R patients are concerned, you know what I would say is, look, we expect a great deal of stability from the SOL-R patients. We have a ramp that's a six-month ramp with two opportunities to observe. There'll be more details that I'm sure we'll share down the road regarding that patient population. Yes, I do expect these patients to be absolutely stable. You saw from Arshad's talk, how well this drug does, particularly when the patients are stable and when there's a fairly dry OCT. As far as the clinical information from SOL-R is concerned, let me be very clear on this. Our expectation is that we will be filing with SOL-1 alone.
Our expectation is that this drug will be approved with SOL-1 alone. As Jeffrey Heier said from the podium in The Macula Society, that process has already begun. We haven't detailed that process to you, as that wouldn't be appropriate to detail our interactions with the FDA. I do want to assure you that that process has begun. We believe that there's more than enough information with SOL-1 alone to use this drug very effectively in the community. You've heard that from all of the doctors here. Nonetheless, we are continuing SOL-R. SOL-R is going extremely well. It's being recruited and randomized and executed very, very efficiently. SOL-R will add a great deal of information, but I don't want you to think that we feel that that's a requirement whatsoever. It is still continuing.
It adds a great deal of flexibility when the FDA looks at our application. It will also give us a lot of additional information, but not necessarily essential information, but additional information. Jeff, do you want to comment on that as well?
Yeah, I do. Again, thank you for the question. When we looked at SOL-1, and this has been shown, we expect a very high or very low rescue rate based on what we've seen in SOL-1. Keep in mind, SOL-R is going to likely be even less because not only do we have those same guidelines as we're seeing in SOL-1, but the idea that patients won't have fluid above a certain level, they'll be followed for not just four weeks, but eight weeks. Over that time, they can't have fluid above a certain level or fluctuations above a certain level. That gives us even more confidence that the control of disease in SOL-R is going to be stronger than it was in SOL-1.
Thank you, Jeff. Clara, thank you for your question. Next question please, operator.
Thank you. We will move next to John Wolleben with Citizens. Please go ahead.
Hey, thanks for taking the question and a thorough update. Wondering about regulatory strategy here, 'cause you're in an interesting situation where SOL-1 was designed for a 9-month primary endpoint, redosed at 52 weeks, and you'll have some repeat dosing later on. What is your initial proposed label duration with FDA, and how does that evolve over time?
John, good morning, and thank you for the question. Look, obviously, we're not in any labeling discussions with the FDA, but our expectation is that we will have the best label that has ever been issued in our field. This will be a superiority label that we will have. For obvious reasons. We will have flexibility of dosing of every six months to 12 months. If the question also, and I think this may be where your question may be going, saying if we had, do we have enough experience with cases that are repeated? The answer is we feel that we do and a great deal of flexibility as well. Remember that every patient at week 52 in SOL-1 was redosed. In-house, within SOL-1 alone, we have a lot of redosing experience.
That's under masking, of course, but every patient at week 52 has been redosed. Clearly with SOL-R, we have a lot of redosing experience as well, with that study continuing. The flexibility comes in as to what the FDA can and wants to do, regarding, you know, further discussions that we'll be engaged in. They can certainly look at the repeat-dosed patients in SOL-1 alone. They can certainly look at SOL-R under masking, or SOL-R unmasked as well. That would be really their call. We have a great deal of flexibility. But our expectation for the label is the only superiority label with a flexibility of dosing, encompassing 6 months to 12 months. Thanks for your question, John. Next question, please, operator.
Thank you. We will move next to Yi Chen with H.C. Wainwright. Please go ahead. Your line is open.
Thank you for taking my questions. My first question is regarding the vitreous floaters, will they eventually be absorbed, or could they accumulate with the redosing? What is
Yi, good morning.
I'm sorry. Good morning. Pardon me. What is physician's experience with vitreous float, floaters caused by Lucentis?
Great. Yi, thank you for your question, and good morning again. I think Peter started to answer that question regarding the durability of the floaters, but let me pass it on to him first and anybody else that wants to add on after that. Peter, why don't you go ahead. The question was about the expected durability of the floaters and, regarding, physicians' experience with floaters in general.
Thanks, Yi Chen. I think it's a very interesting question. As I mentioned before, floaters are something that we've seen in almost every one of our clinical studies, and you specifically mentioned a very high floater rate in the Lucentis studies. Those floaters in general don't disappear. They're different than our floaters and that there's something that's changed in the vitreous. Remember, in the ranibizumab studies, unlike aflibercept and faricimab numbers, or faricimab in particular, those numbers have way less injections in the MARINA and ANCHOR studies. Jeff and I were very involved in those studies. Recall that we gave Lucentis every month, right? We were injecting a volume into the eye monthly.
That would explain a very high rate of floaters because you have a very high rate of change of the vitreous. In terms of the floaters that we're seeing here, we believe most of these are related to drug elution, so they're going to resolve. The time point for resolution is probably the time point for bio-resorption or actually in this case, dissolution of the drug itself. The drug will reabsorb into the eye over time. That should take roughly one to three months is where we would expect to be. The last part of your question, you said, you know, do we expect these to increase over time? Unlike other molecules that are being tested in this space, we don't have any drug remnant at all, right?
once the drug is bio-resorbed and the drug is diluted or eluted, we would expect there to be essentially no floaters, and no buildup of drug remnants in the eye or actually I would call them more polymer remnants than drug remnants, if that makes sense.
Thank you, Peter. Arshad, did you want to add on to that as well?
Yeah, Pravin. I think, you know, I can share my experience as the top site in phase one. As mentioned earlier, in clinical trials, we report everything and anything. The hydrogel sits inferiorly far away in the periphery, and once the hydrogel dissolves, there's drugs still left. If I see that, I call it floaters. I did not see any patients where actually the drug came in the center or caused any vision issues or symptoms by patients. I was just reporting it because I saw something that we were still learning, and now we know that this is just a part of bioresorption of the hydrogel followed by the drug.
I think, you know, it can get confusing for people when they say floaters and they say, "Oh my god, what's gonna happen when you look at the data?" The one thing I look at is the vision. It has no impact on the vision. That means that it's actually not in the center of the vitreous impacting vision. You know, I was also part of the gray book trials, and those floaters were intense in actually in the center of vitreous impacting vision. I think I just wanna share my experience as an investigator that this is a transient event that in clinical trials we report and none of my patients actually have symptoms. As Peter mentioned, this is very different than if you have something that stays in the eye for a long time.
This is just transient effect, and this is explained by the biology of how this drug works.
Thanks, Arshad. Yi, it's a really important question. What I would say is the first thing to ask is to say, what is it? Because not all floaters are the same, right? It could be blood, it could be, it could be vitreous vacancies, it could be anything. Silicone oil. It could be any of those things, could all be classified as being floaters. The first question to ask is what is it? Here it's very clear. This is drug. This will go away as we expect it to go away with the drug and it's transient. The second thing to ask is where is it? Arshad alluded to this. Just remember how these floaters were actually seen.
They were not simply seen with what we call a 90 diopter examination, which is right at the slit lamp, but they were seen with indirect ophthalmoscopy when looking very far out in the periphery in an area where you may see retinal tears and things like that. This is something the patient would never see because it's so far out in the periphery that you have to use an indirect ophthalmoscope to be able to see it. Where this occurs is really important. The last thing, as Arshad said, is, does it have any impact on the vision? We gave you the numbers, and it's absolutely no impact on the vision whatsoever. I think those are the really important things to realize. Not all floaters are the same. This is drug. We expect this to go away.
It's way out in the periphery. Patients don't see it. This is entirely physician-reported. Thank you for the question, Yi. Operator, next question.
I have a follow-up, actually. The for the floaters and cataract for the aflibercept 2 mg in the SOL-1 trial, they appear to be much lower than the aflibercept prescribing information. Which one is more representative of the patient's experience in real world practice?
I'm sorry. Could you ask that again? I didn't completely understand.
Yeah, I got it. I got it, Pravin. I got it.
Yeah.
Basically, you're asking, you know, why is the EYLEA rate in SOL-1 different than the EYLEA rate in other clinical studies, like for instance, VIEW 1, VIEW 2. Is that correct?
Yeah. Yeah. Yes. Yeah.
Yeah. There's an easy answer, right? Many people miss this, is that, remember, the aflibercept patients, at least half of them, only got one injection of aflibercept versus after loading, versus in the VIEW 1, VIEW 2, they were getting treated either every month or every other month in VIEW 1, and then in the other studies every eight weeks. Every time you inject into the eye a volume of fluid, you're disrupting the vitreous. These are older patients, and when you do that, you're apt to develop floaters. This is a very common occurrence in an older population of patients. The rate in the VIEW studies or in the PULSAR and PHOTON for EYLEA HD would be closer to reality than the aflibercept rates in SOL-1.
Peter, thank you. That would not only just be the floater rates, but I think that would be in everything else as well. If you're gonna do a real-life comparison, in the adverse events table, everything would have to be multiplied by four on the EYLEA side as well for a fair comparison. Thank you for that. Thank you for that answer, Peter. Thanks for the question, Yi. Operator, the next question, please.
Thank you. We will move next with Lachlan Hanbury-Brown with William Blair. Please go ahead. Your line is open.
Hey, guys. Thanks for the questions, and congrats on all the data. I guess maybe a question for Dr. Khanani. You've talked about how, you know, anatomy is what you're really treating most of the time in the clinic. Here we see good stability, but it does stabilize at maybe 20 or so microns above the sort of lowest point that you get with loading. Just wondering just sort of how you view that. Does that kind of increase matter to you? Are there any sort of clinical implications? Maybe also, somewhat related, but, like, how would you think about monitoring patients in clinic? You've talked about how you would use it, but obviously there are a small number of patients that need a rescue. Would you still have to bring every patient in every few months maybe to monitor them?
Lachlan, thank you for the question. Good morning. Great question. Arshad, why don't you go ahead?
Yeah, absolutely. That's a really good question. You know, clinically, when you look at, you know, the amount of fluid that bothers us is usually the fluid in 40 to 50 micron range. Here you know that, you know, 55.9% of subjects maintain CSFT within 30 microns from baseline at 9 months. I think you bring a good question that the 20 micron increase is likely driven by those high-need patients that were likely not dry after the two injections. The way we do that in clinical practice is we are going to go after the patients that are completely dry after one or two injections. Those are patients that can be, you know, extended quickly. Now, it's going to depend on physicians', you know, comfort level.
Initially, they may want to bring those patients, you know, maybe two or three months later just to check for fluid. They may wanna monitor them with home OCT imaging. I think there are a lot of different scenarios that we can use. One thing, you know, we know that what impacts long-term vision is actually fluctuations in anatomy, and those range around 40- 50 microns or higher. There was a sub-analysis we worked on, in terms of quartiles of patients, in terms of CSFT fluctuations in the HAWK and HARRIER studies. We learned a lot from that data set in terms of fluctuations and impact on vision.
The bottom line is that we will figure out the high-need patients and then watch them more closely versus majority of the patients who are dry after the first one or two injections. They can be predictively extended. As Darius said earlier, I think this comfort level of sustained delivery in the eye gives us the confidence that if patient misses a visit or don't come for their follow-up, we will still be able to control their disease and not have impact on their long-term vision.
Arshad, thank you. Jeff, did you want to comment on this too?
Yeah, I'd like to. I think this is a very important question. When we're concerned about fluctuations with conventional anti-VEGF treatments, that's because we know those drugs are no longer present. When you see fluctuations in those patients or when you see any fluid, you know that there's nothing on board. This is different with OTX-TKI in that our expectation is we've got drug on board for an extended period. We know that these mild amounts of subretinal fluid are very well tolerated, especially when you have treatment on board. You're not going to see the fluctuations that you do with the peaks and troughs of intravitreal injections. These patients are going to tolerate this much better because there's something on board.
I think when we follow patients over time and we try to learn more about this, we're going to understand what the ranges are for our patients and how we're going to treat. There will be a number of physicians like Darius who will just adopt the every six months approach and say, "I'm very confident that I can maintain disease with six-month dosing." There will be others that will look for more of an extended approach, and they'll follow patients on their own. They'll come up with their own regimen for following these. That will certainly be less frequent visits and figure out what will work for each patient and each physician. Having this drug on board for extended periods of time is what's going to give them the confidence to manage these patients in a whole different manner than what we've been used to.
Thanks, Jeff, and thanks, Arshad. Lachlan, thank you for the great question. operator, next question, please.
We will move next to Serge Belanger with Needham. Please go ahead. Your line is open.
Hi, good morning. Thanks for taking my questions. First one, can you just comment a little bit on the number of mild to moderate intraocular inflammation events that you reported, just how common these are in these patients when you're using anti-VEGFs? Secondly, regarding the patient population in SOL-1, I think one thing that stood out in the presentation was how unique this patient population was. Just curious is, you know, how common are these patients in your practice or is it just a function of they're not typically evaluated in a clinical study that makes them unique? Thanks.
Serge, thank you. Good morning. Thank you for the great questions. The first one, regarding the IOI, Darius, maybe I can go to you with that, and anyone else that wants to comment after that. Darius, why don't you go ahead.
Thank you, Pravin. Also Serge. It's a great question. We're always worried about safety. It's important to recall that we really saw no safety signal whatsoever in this trial. It was an extremely safe trial overall, particularly for the AXPAXLI agent. Specifically, the things that we're worried about are things that can cause irreversible visual acuity loss, so either endophthalmitis or retinal vasculitis, specifically the non-occlusive retinal vasculitis or occlusive vasculitis that have been seen with other medications. We haven't seen any of those. We did have nine cases of mild to moderate inflammation, which either spontaneously resolved, and that was a vitreous cell one which may have been drug remnants or responded to topical medications.
This is in line with what we see in both our clinical practice, where we're giving frequent injections in our patient population and also within other studies. Really the take-home here is that there were no vision-threatening events from inflammation in this trial. I'll return it back to Pravin.
Darius, thank you. I think just as we mentioned floaters in terms of how all floaters aren't the same, I think it's important also to say that not all inflammation is the same. There's inflammation that's mild to moderate as this was perhaps related to some drug remnants that was classified that way. We'll know more about that later on. I think what's really important here is what we mentioned in the slide. There was no cases of endophthalmitis, and very importantly, no cases of vasculitis, either occlusive or non-occlusive. You know, the person here, Jeff Heier, who's been in a lot of boards regarding safety and so on and so forth, also should be commenting.
Jeff, maybe you can make some comments regarding IOIs and how we should think of them in terms of the severity of the IOI. Also, whether the location of whether it's anterior, posterior vasculitis versus anterior segment inflammation, et cetera. Maybe you can make some comments here, Jeff.
Yeah. I think as you highlighted, Darius and Pravin, it's you first of all have to differentiate how serious this is. Mild to moderate inflammation that resolves readily with topical treatment is of much less concern to us than the more severe types of inflammation that are often associated with vasculitis occlusive disease. We confirmed with all of the uveitis cases that there was none of this present, and that was reconfirmed on fluorescein angiography and also determined by the reading center not to be present. That's very reassuring. You also have to keep in mind that in clinical studies, we actually encourage the investigators to look carefully for this. Even mild amounts of inflammation that would often go unnoticed and often go untreated, were detected readily here and treated just as we would want in any clinical trial.
We're not seeing anything that worries us in terms of vision loss associated with these or concerns that this is more of a signal than we would normally see with conventional treatment. This, the mild to moderate severity, the consistent response, the absence of any significant visual changes gives us confidence that our safety looks good.
Yeah. I'd also add that there's one patient who probably was the most severe, who in retrospect probably shouldn't have been in the study anyway, and that was a patient with uveitis. It was bilateral, clearly not due to the drug and recurrence. A history of uveitis that in retrospect probably shouldn't have been in the study to begin with. Going to your second part of the question, Serge, which is how representative is the SOL-1 patient population in a community practice? Arshad, maybe I can ask you to answer that question.
Thanks, Pravin. I think when I look at the patient population, this is a population that require, you know, very active anti-VEGF treatment, and they respond well to it. I think the bar here is very high in terms of maintaining vision for these patients over a 9- 12-month period. I think this patient population usually doesn't get studied in many trials because they get excluded because the visual acuity is 20/25 here on average, or they gain 10 letters or more. What we have is we have a unique patient population that was designed to lose vision. It's a lot of our patients who actually behave like this in our clinical practice, that they will come in and they'll get one or two injections, and they will have vision gains.
It does not exclude the high-need patients. As I said earlier, it does include patients who are frequent need. I think the bottom line is that if you're studying a patient population that's designed to lose vision and you're able to maintain vision in majority of these patients, up to 12 months, I think the bottom line for me is it gives me confidence that I can use AXPAXLI very confidently in my practice, to have predictable disease control for 6-12 months in majority of the patients.
Thanks, Arshad. I think this is exactly why I said that I expect this drug to be the first one that I've ever seen that actually performs better in the community as opposed to in clinical trials. People ask me all the time, "What is it about the data that's most impressive? Which slide?" I don't think it's a single slide. I think it's the consistency of all the slides. Most importantly, it really is what matters to doctors the most, which is the OCT, which is the ultimate representative of disease control. Every single thing that you look at in terms of disease control favors this drug. The OCT is the obvious one. The other one that may not be quite as obvious is retinal hemorrhages.
As you all know, retinal hemorrhages is what we use to sort of as a barometer for aggressive disease. If you look at the baseline characteristics, there are more cases of retinal hemorrhage in the other arm, in the AXPAXLI arm to begin with, indicating that there were more severe patients who had more aggressive disease in the AXPAXLI arm. When you look at the end, at the end of the study, it actually reversed. They stayed in the EYLEA arm. However, there are very few in the AXPAXLI arm at all. That's another indicator of better disease control. I think the consistency of the data that we see over and over again is the most impressive thing as opposed to any particular slide.
I think this is also why this drug will do so much better in the community than even in the clinical trials. Let's go to one question more. Operator, one question there.
Thank you. We'll take our last question from Bill Maughan with Clear Street. Please go ahead. Your line is open.
Hey, good morning, and thank you. My question is on your upcoming meetings with the FDA before submission. What key points do you still need to gain alignment on or confirmation of? What is your regulatory strategy in Europe? Thank you.
Yes. I can dive into that first, and if Jeff wants to comment afterwards, certainly going back to the New England Journal article, et cetera, please feel free to go ahead afterwards, Jeff. The first one, as far as the FDA is concerned, Bill, what we've said very clearly is that the process has already begun. Look, we said this way back in December. We did a lot of work during our quiet time, and, you know, it clearly has come full circle with that New England Journal of Medicine article. Jeff has very nicely outlined how we fit really all the requirements that the FDA had. We typically don't discuss the details of our conversation, so that's not something that I'm prepared to do.
When appropriate, we certainly will guide you and update you. As far as OUS is concerned, look, one of the things in OUS is not just the, the drug and the trial design, et cetera, it's also the impact that the drug may have on society. That's, that's actually looked at quite, you know, quite carefully. Peter previously already alluded to that, saying that the impact that this drug is gonna potentially have on society there in terms of patient care is enormous. Not just there, but also here. There, with the EMA, et cetera, that is considered even more than in the U.S. FDA. We're in very good stead with them. Our, our discussions continue with them, and we're very confident that this drug will be approved on a global basis.
Jeff, any comments that you wanna add in terms of the regulatory pathway, particularly U.S. FDA with a single trial?
Yeah. I think that's an excellent question. We were already looking carefully and planning on submitting under the 505(b)(2) pathway, which, as you know, allows reliance on established safety and efficacy from already approved drugs. Axitinib was approved in 2012 for renal cell carcinoma. Couple that with the recent New England Journal of Medicine article, which talks about the new default being a single study and lists certain factors that are important for the strength of that submission, the statistical significance, the science, blinding, alignment with the FDA, supporting secondary data. All of that really puts us in a remarkably unique situation where we have multiple alignments here, not just with the FDA and these factors, but also the 505(b)(2) pathway. That puts us in a very unique position for this submission.
Thank you, Jeff, and thanks for the question, Bill.
Thank you.
Operator?
Thank you. This conclude our question and answer session. I will now turn the call back to Dr. Pravin Dugel for closing remarks.
Thank you. Once again, on behalf of Ocular Therapeutix team, I'd like to express our deepest gratitude to the investigators, to study coordinators, and the clinical teams whose commitment made SOL-1 possible. Most importantly, I would like to thank the patients and their families who chose to participate in this trial. Your trust, your courage, and dedication are what allow innovation to move forward and make advances like this possible. We are incredibly proud of what this team has accomplished, and we remain focused on bringing AXPAXLI to patients as quickly and as responsibly as possible. Thank you all for all your continued support. Thank you all for being here today, and have a great day, everybody.
Thank you. This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect.