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  Title	Ocular Therapeutix, Inc. (NASDAQ:OCUL) Q4 2024 Earnings Call Transcript
  ID	7471122
  External ID	7598836519
  Author	Monkey Transcripts
  Published Date	March 4, 2025, 7:20 a.m.
  Summary	Ocular Therapeutix, Inc. (NASDAQ: OCUL ) Q4 2024 Earnings Call Transcript March 3, 2025 Ocular Therapeutix, Inc. misses on earnings expectations. Reported EPS is $-0.29 EPS, expectations were $-0.24.
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  URL	https://www.insidermonkey.com/blog/ocular-therapeutix-inc-nasdaqocul-q4-2024-earnings-call-transcript-1471218
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  Content	Ocular Therapeutix, Inc. (NASDAQ: OCUL ) Q4 2024 Earnings Call Transcript March 3, 2025 Ocular Therapeutix, Inc. misses on earnings expectations. Reported EPS is $-0.29 EPS, expectations were $-0.24. Operator: Good morning, and welcome to the Ocular Therapeutix Fourth Quarter 2024 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. [Operator Instructions] As a reminder, this conference call is being recorded and will be available for replay on the Investor Relations section of the Ocular Therapeutix website. I would now like to turn the call over to Ocular Therapeutix's Vice President of Investor Relations, Bill Slattery Jr. Please go ahead, Mr. Slattery. Bill Slattery: Good morning, everyone, and thank you for joining us today. Earlier this morning, we issued a press release and filed our annual report on Form 10-K outlining our financial results and business updates for the fourth quarter and full year of 2024 along with several updates to our registrational program for AXPAXLI in wet AMD. Ocular Therapeutix's Executive Chairman, President, and CEO, Dr. Pravin Dugel, will summarize recent business highlights before we move to our question-and-answer session. Joining Dr. Dugel for the Q&A portion of the call will be Donald Notman, Chief Financial Officer and Chief Operating Officer; Sanjay Nayak, Chief Strategy Officer; and Steve Meyers, Chief Commercial Officer. We refer everyone to this morning's press release and our Form 10-K for a comprehensive update of fourth quarter and full year 2024 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 variety of factors, including risks and uncertainties identified in the Risk Factors section of our annual report on Form 10-K and our other SEC filings. With that, I'd like to hand the call over to Dr. Pravin Dugel to review our recent updates. Pravin? Pravin Dugel: Thank you, Bill, and thank you to everyone for joining us today. 2024 was a transformational year for Ocular Therapeutix. We sharpened our focus and embraced a single, bold mission: to redefine the retina experience. Today, disrupting the treatment paradigm in wet AMD is our top priority and we are executing with speed, precision and confidence to bring AXPAXLI to patients who need a more sustainable and effective treatment option. Despite established and effective treatments for wet AMD, the burden of frequent dosing leads up to a 40% of patients discontinuing treatment in the first year alone effectively allowing themselves to go blind. Patients deserve better and AXPAXLI has the potential to become the standard of care by offering a long-lasting flexible treatment option. And wet AMD is just the beginning. With compelling early clinical results in non-proliferative diabetic retinopathy and diabetic macular edema, we see a significant opportunity to expand into these and other highly prevalent retinal indications where millions of patients remain untreated. This morning, we announced several exciting updates that enhance and accelerate our registrational program for AXPAXLI, positioning us incredibly well as we move toward clinical data and a potential NDA submission. Let's get right to it. First, we recently received FDA approval for an amendment to our special protocol agreement for SOL-1 that incorporates redosing in all patients at week 52 and week 76. We believe this amendment unlocks the potential for AXPAXLI to secure an unprecedented six to 12 month dosing label in wet AMD, showcasing what we believe to be best-in-class durability. The impact of this cannot be overstated. The most recent approvals in this indication extend durability by about two weeks in most patients, yet they have rapidly gained market share and generated significant revenues in a very short period of time. With AXPAXLI, we're talking about a different orbit altogether with the potential to extend durability by months. As part of this amendment, the 36-week primary endpoint for SOL-1 remains unchanged, but we're required to maintain masking until week 52 to provide additional information on durability up to and to allow potential label permitting redosing at 12 months. As a result, we now expect to report topline data in the first quarter of 2026. While this slightly shifts the timeline for SOL-1 topline data, we believe the long-term benefits of this strategy are tremendous and will be abundantly clear at the end of this call. Most importantly, this strategy should allow us to accelerate our timeline for a comprehensive regulatory submission for AXPAXLI in wet AMD, as I will describe. Moreover, we expect the additional data for repeat dosing will provide valuable insights into AXPAXLI extended durability, potentially supporting even greater flexibility on the product label. SOL-1, a trial that many thought would never be enrolled, completed randomization in December 2024, well ahead of expectations, with 344 subjects randomized across more than 100 clinical sites in the US and Argentina. Trial conduct is now our top priority. We are thrilled to report that subject retention has been exceptional to date, and the vast majority of rescue treatments, as we have reviewed on a masked basis, remain in-line with the prespecified criteria established in the SOL-1 protocol. We have also optimized SOL-R, our non-inferiority study, to align with the changes in SOL-1. Because redosing is now incorporated in SOL-1 and retention in the trial is exceptional to date, we are reducing the size of SOL-R from 825 subjects to approximately 555 subjects randomized while maintaining robust statistical power of 90% to evaluate a primary endpoint base on our expectations of how AXPAXLI will perform. SOL-R was initially designed to include 825 subjects to meet the minimum FDA requirements to receive an unrestricted label for redosing. Now that subjects in SOL-1 are also being re-dosed, we're afforded the flexibility to reduce the number of subjects in SOL-R. This reduction should accelerate the SOL-R timeline for reporting data, enhance capital efficiency and maintain the scientific rigor needed for regulatory approval. Remember that SOL-R is a non-inferiority trial comparing AXPAXLI administered every 24 weeks against 2 milligram of aflibercept administered every eight weeks. The primary endpoint is the mean change in best corrected visual acuity, or BCVA, at week 56. And patients will be followed until week 104 for safety. Importantly, as per the protocol agreed to by the FDA, the non-inferiority margin for the AXPAXLI arm at the lower bound is minus 4.5 letters of mean BCVA when compared to 2 milligram of aflibercept dosed every eight weeks. This is also in line with the FDA's draft guidance, which we are adhering to by incorporating an 8 milligram aflibercept masking compared to our arm with the exact same dosing frequency as the AXPAXLI arm. Additionally, our prespecified supplemental injection criteria are strategically designed to ensure trial integrity and preserve clinical relevance. These criteria are consistent with previous non-inferiority studies and include a combination of vision loss and OCT changes. By aligning these standard non-inferiority trial rescue protocols, we believe the SOL-R study remains well positioned to demonstrate AXPAXLI's durability and effectiveness in a repeat dosing setting. SOL-R enrollment continues to be strong. We previously announced 311 subjects enrolled across various stages of loading and randomization as of January 10, 2025. This momentum puts us in a great position to advance our registrational program efficiently and effectively. Here at Ocular, our clinical trial design strategy using the loading phase to select patients for randomization and thereby potentially derisking our patient populations has been a key differentiator. We designed SOL-1 and SOL-R to work together with each trial seeking to answer critical questions about AXPAXLI durability, repeatability and flexibility. These studies were developed to be complementary and not redundant, ensuring that together they provide a robust clinical data set that could support both regulatory approval and commercial adoption. SOL-1 is focused on durability, evaluating whether a single dose of AXPAXLI can maintain vision for 36 weeks compared to a single 2 milligram aflibercept injection. This study was designed to establish superiority and to set a new benchmark for long-term efficacy in wet AMD treatment. With the recent SPA amendment incorporating 52 week and 76 week redosing, SOL-1 now also provides important insights into extended treatment intervals and long-term redosing potential. SOL-R, on the other hand, is designed to address more frequent repeat dosing and potential real world applicability. By comparing AXPAXLI every 24 weeks to 2 milligram aflibercept every eight weeks, SOL-R evaluates how AXPAXLI performs relative to a common, but burdensome, treatment regimen. The study is structured to provide critical evidence supporting the feasibility of an every six months treatment paradigm, one that we believe is aligned to preferences of retinal specialists and that could dramatically reduce the burden of care for patients and caregivers alike. Both studies were thoughtfully aligned with regulatory guidance. So, one supported by SPA and SOL-R validated by Type C written response received from the FDA in August 2024 along with a subsequent written response received from the FDA in December 2024. Importantly, neither study utilizes sham for masking, adhering to the FDA's clear stance that sham can introduce bias expressed through the agency's written feedback and public comments. The FDA previously agreed that together SOL-1 and SOL-R could constitute two adequate and well-controlled trials to support a potential NDA and label for AXPAXLI in wet AMD. Pending a successful outcome, we intend to submit our NDA after the SOL-R 56-week primary endpoint is reached. By integrating these complementary approaches, seeking to demonstrate both best-in-class durability in SOL-1 and sustained repeat dosing in SOL-R, we believe we are enhancing the potential for successful trials that support a differentiated commercially attractive label. The dual nature of these trials allow us to generate a comprehensive clinical data set that has the potential to support a strong regulatory submission and a compelling value proposition for patients, retina specialists and payers. Beyond wet AMD, we see a tremendous opportunity for AXPAXLI in non-proliferative diabetic retinopathy, or NPDR, and diabetic macular edema, or DME. Diabetic retinopathy is the leading cause of blindness in the working age population in the US. Despite the availability of anti-VEGF therapies, fewer than 1% of the 6.3 million NPDR patients in the US receive treatment today, largely due to the burden of frequent injections. AXPAXLI has the potential to transform this landscape. Our proof-of-concept HELIOS trial demonstrated compelling results for AXPAXLI in both NPDR and DME. In this trial, we showed that a single AXPAXLI injection may prevent vision threatening complications for up to 12 months. Additionally, all patients in the AXPAXLI arm that had DME saw improvement at week 48. So, what does this mean? That means that I, as a retina physician, can say to a patient, your risk with diabetic retinopathy of developing vision-threatening complication year upon year is 30% to 40%. However, if you come to see me just once or twice a year, much like you go to a dentist for teeth cleaning, I may be able to reduce that risk to almost zero. That is a powerful message. I'm happy to inform you today that we expect to receive FDA feedback on our clinical trial design for NPDR and DME in the first half of this year, paving the way for our next steps in these important indications. Following receipt of the FDA feedback, we look forward to sharing with you our clinical trial design for these underserved vision-threatening indications. We continue to operate from a position of financial strength with a cash balance of $392 million as of December 31, 2024. We remain laser-focused on execution of SOL-1 and SOL-R. Our disciplined and prudent approach means that we are well-financed and believe we have sufficient cash to fund our planned operating expenses, debt service obligations and capital expenditures into 2028, fully funding our registrational trials in wet AMD and leaving us well positioned to execute on our broader strategic objectives. Our current cash projections do not factor in the impact of clinical trial activities in NPDR and DME as the scope of that program is dependent on FDA feedback. That said, and to be very clear, we do not currently intend to raise additional capital this year. 2024 was a year of transformation for Ocular Therapeutix. And 2025 is shaping up to be even more impactful. What differentiates us is not just the speed and intensity, but also the precision and exceptionally high quality of our execution. In less than one year, we have built a world-class team, advanced a groundbreaking asset and executed a registrational program that puts us in a position of strength as we move toward topline data and a potential regulatory submission and approval. Today, we shared several updates designed to enhance and accelerate the AXPAXLI registrational program, further derisking our path to approval. To summarize: First, the FDA approved an amendment to the SOL-1 SPA to incorporate redosing at weeks 52 and 76, increasing potential label flexibility to every six to 12 months. Second, due to the requirement to maintain masking until redosing at 52 weeks, we now expect topline data for SOL-1, including the 36-week primary endpoint, will be released in the first quarter of 2026. Third, SOL-1 retention has been outstanding to date. And the vast majority of rescue treatments reviewed on a masked basis have been in accordance with the prespecified criteria of the protocol. Fourth, as a result of our updated SOL-1 strategy for redosing, SOL-R has been streamlined with a target randomization reduced from 825 to 555 subjects. This should accelerate the time to both SOL-R data and regulatory filings for AXPAXLI in wet AMD, all the while maintaining strong statistical powering of 90% based on our expectations of how AXPAXLI will perform. Fifth, the non-inferiority margin for SOL-R is set at 4.5 letters, and standard rescue criteria have been prespecified to align with regulatory guidance. Sixth, enrollment has been excellent across both trials. SOL-1 completed randomization ahead of schedule in December. And we previously announced SOL-R enrollment of 311 subjects across various stages of loading and randomization as of January 10, 2025. Seventh, AXPAXLI's opportunity extends beyond wet AMD, and we expect FDA feedback on the clinical trial design for NPDR and DME in the first half of this year. And eight, Ocular Therapeutix is well financed and has cash runway into 2028. We do not intend to finance this year. We're maintaining strong capital efficiency as we advance toward key clinical readouts and a potential NDA submission in wet AMD. We are redefining the retina experience, setting a new standard in treatment durability, flexibility and long-term outcomes. With strong execution, regulatory alignment and clinical momentum, we're well-positioned to become a leading retina company. Thank you for your time and continued support. Operator, we are now ready to take questions. Q&A Session Operator: Thank you. [Operator Instructions] Our first question comes from the line of Tazeen Ahmad with Bank of America. Please proceed with your question. Tazeen Ahmad: Hi, guys. Good morning. Thanks for the updates. A couple of questions for me. Pravin, just given the stats that you provided about the continued strength of what you're seeing blinded in SOL-1 in terms of patient staying in the study as well as the redosing rates coming in as you would have expected from your prespecified criteria, can you give us a little bit more color about why you think it makes sense to make these changes, especially right now? And then, secondly, in terms of making SOL-R a smaller study, just given the high demand that there has been clearly for patients to want to be in the study, can you talk about the reasons of why it wouldn't make sense anymore to have a study of this size just to add a little bit more cushion to the data set that we're expecting? And then, I have one follow-up. Thanks. Pravin Dugel: Thank you, Tazeen. Good morning to you, and again, thank you for your question. What you've raised is a really important point and let me try and give a comprehensive answer. And I think this really speaks to the way we've designed our SOL programs and I include both. These are complementary trials, and I dare say that this is revolutionary and I think really quite historic. I think everyone in the world expected us to have SOL-1 and SOL-2, which really has been the tradition. In every — in just about every trial that I know, it's been the same trial done twice. The second trial certainly is good to get the product approved and confirm the first trial. But when you think about it, it's terribly inefficient, because it really doesn't add any extra information whatsoever. Instead what we've designed is two trials that are always to be taken together and are absolutely complementary in the information they provide. And this I think is a unique and, I dare say, a revolutionary historic concept that will allow for efficiency both in terms of the logistics of the trials, the commercial applicability of the product, as well as the regulatory pathway. The bottom line in what we announced today, the bottom line is that we will potentially get AXPAXLI to patients faster and with a better label. So, let me go through the sequence of events. Two things happened. The first is that the FDA approved our redosing SPA amendment for SOL-1 at week 52 and 56. The second thing that happened is that we noted that the retention in SOL-1 was absolutely superb, under masking, of course. So, based on these two events, we're able to increase the efficiency of both studies. In SOL-1, what we're able to do is to get information on the first year on the durability and flexibility of the drug, because now we have information at month nine, which is the primary endpoint that remains unchanged, and at month 12. And in the second year with redosing, what we're able to do in SOL-1 is to maximize the exposure of the drug to patients and satisfy many of the FDA's safety requirements. So, immediately, SOL-1 became a much more efficient clinical trial. And with that in mind, we're able to pass down that efficiency to SOL-R the way these trials were designed. So, no longer did we need 825 patients in SOL-R, we could maximize efficiency in terms of our resources as well as in terms of getting the filing to the FDA by reducing the size from 825 patients to 555 patients, while maintaining the integrity of the statistics. The impact of this is that we will potentially have a much better label, a label that is a superiority label with flexibility of six months to 12 months. And the second impact, equally important of course, is that we will get to market potentially faster and more efficiently than we were able to before. So, both of those things terribly important in terms of the impact of what's happened today. What I want to note, very importantly also, that the primary endpoint remains unchanged. Remember, the primary endpoint of SOL-1 is at nine months. That remains unchanged. The statistics remain unchanged completely. What we added today, what we announced today were completely added efficiency bonuses. These are complementary trials designed to work together and I believe they work together absolutely beautifully. Tazeen Ahmad: Okay. That's super helpful. And my one follow-up is that, given that, as you said, the primary endpoint stays the same, can you give us a sense of what the FDA might be looking for from redosing now in SOL-1? Pravin Dugel: Well, again, the redosing allows for us in the first year to look to get information regarding flexibility and durability of the drug. Now, we'll have information at month nine. Again, that's the primary endpoint, which remains absolutely unchanged. But additionally, we'll also have information at month 12 regarding durability of the drug. So, potentially, there's flexibility in the label for month nine as well as month 12. And as I mentioned, with the redosing in the second year, there's more exposure of the drug to the patients. Therefore, we'll have even more data in regards to safety. The beauty of this is that when you think about the efficiency of SOL-1 with a single injection in the first year, we'll have information for month nine and month 12, and with repeat dosing for the second year, we'll have increased safety information with more exposure of the drug to patients. Tazeen Ahmad: Okay. Thank you for all the color. Pravin Dugel: Thank you, Tazeen. Operator: Our next question is from the line of Biren Amin with Piper Sandler. Please proceed with your questions. Biren Amin: Yeah. Hi, guys. Thanks for taking my question, and congrats on all the updates. So, maybe Pravin, let me just start with SOL-1. What was the rationale for dosing at week 76? I understand the week 52 dosing, but I was trying to understand, I guess, the rationale for week 76. And then, second question is, for SOL-1, will all patients receive redosing at week 52 and week 76 regardless of the arm, including the control arm? And also, will those patients with prior rescues receive redosing at week 52 and week 76? Pravin Dugel: Biren, good morning, and thank you for your question. The answer for the first one is very simple, we wanted to maximize again the exposure of the drug to patients to satisfy the FDA safety requirements, thus redosing at week 56 — at week 52, I'm sorry, week 52 and week 76 with the study ending at week 104. The answer to your second question, yes, every patient will be redosed at week 52 and at week 76. The redosing will occur with the same drug that the patient was randomized to regardless of rescue. And that's very important. The answer to your question is, yes, everybody will be redosed at week 52 and week 76 with the original drug that they were randomized to. I hope that answers your question. Thank you, Biren. Biren Amin: That does. And I just got a follow-up. So, on SOL-R, as a result of these changes, you clearly reduced the size to 555 patients, which I think — was that primarily due to the safety data that you're generating from SOL-1? Because I think now you would have another 172 patients that are redosed with AXPAXLI from SOL-1, whereas I think you reduced the need for the patients to be redosed with SOL-R by about 108 patients within AXPAXLI arm. Pravin Dugel: And Biren, again, thank you. You're exactly right. Your explanation is exactly correct. What we did was we designed SOL-R originally to have 825 patients to satisfy the FDA safety requirements. And with the redosing amendment that we were able to get from the FDA, we were able to satisfy the safety requirements with both studies combined with the ability to reduce the number of patients from 825 patients to 555 patients, while still maintaining the statistical significance. So, your — answer to your question is exactly correct. Thank you. Biren Amin: Got it. And then maybe one last question. I guess from a timeline standpoint, were these changes to SOL-1 and SOL-R underway or made when the Board constructed your performance base package on Ocular share price hitting — I think there are four different targets between $15 and $30. So, I guess I want to understand if these changes provide increased confidence on hitting those performance targets? Pravin Dugel: Yeah. So, Biren, again, thank you very much for the question. The answer obviously, we have discussions with the FDA that are ongoing and we want to keep those discussions confidential. We don't discuss them publicly as with my discussions with the Board. But suffice it to say that our confidence as a company in the success of these trials are higher than ever. And certainly my confidence particularly is higher than ever and you'll see that everything in this company is aligned to make sure that we ensure the success of both trials. Thank you. Biren Amin: Great. Thanks for taking my questions. Pravin Dugel: Absolutely. Operator: The next questions are from the line of Colleen Kusy with Baird. Please proceed with your questions. Colleen Kusy: Great. Thanks. Good morning, and thanks for taking our questions. So, for the — just to maybe clarify, for the redosing of patients in SOL-1, is that just for the FDA safety requirement for redosing, or do you need to show anything for efficacy in that protocol in the second year? And then, I have a follow-up. Pravin Dugel: Colleen, good morning, and thank you for your question. The answer is that it really is for the safety requirement for the FDA. However, what it does allow us to do, again, is get information given this — because remember, it's not just the matter of taking the second year separately, but also taking the second year in regard to how it affects the first year. So, what it allows us to do is to get that extra information that we will now have not only at month nine, but also at month 12. So, it does allow for the flexibility that we hope to get in the label because we have additional information now at month 12 as well as month nine. But again, we will satisfy the safety requirements, but we will also gain additional information in the second year regarding redosing. So, this is not a requirement for hitting the primary endpoint. I want to make that very, very clear. It's important to emphasize that nothing about the original primary endpoint changes. The primary endpoint remains at month nine and the statistics remain the same. This is added efficiency today. Colleen Kusy: Got it. That's helpful. Thank you. And then, I know when you first shared the SOL-R trial design last summer, I think it was a 48-week endpoint and then — but that was prior to talking to the FDA. Now, you're talking about a 56-week endpoint. So, can you just talk about what drove that change and what that means for your dosing schedule, which I believe AXPAXLI is [still being dosed] (ph) every 24 weeks? So, just kind of talk about that 56-week endpoint, please. Pravin Dugel: Yeah. Thank you, Colleen. So, you're exactly right. I think the first time you might have heard about the 48-week endpoint for SOL-R was in our June Investor Day. And I want to emphasize, if you go back and check your notes then, we made it absolutely clear that we were proposing the SOL-R clinical trial design at risk. And I think those two words, at risk, were mentioned quite a few times in that meeting. And the reason we did that is we made it very clear, very transparently that we had not yet gone to the FDA for formal approval regarding this trial design. That's why it was at risk. Now, we did subsequently go to the FDA and the FDA came back and told us that they preferred a primary endpoint at week 52 or later. And as you know, we have a history of doing everything per the FDA. We wanted to make sure that we did it with a minimal amount of risk possible. In fact, we wouldn't want to take any risk as far as our regulatory pathway is concerned. So, then, we decided, given their preference to pick week 56, and the FDA has now accepted in writing our proposal to pick the primary endpoint for SOL-R at week 56. I hope that answers your question, Colleen. Colleen Kusy: Great. Thanks. And last one, just any timelines for SOL-R recruitment now in light of the decrease in the study size? Pravin Dugel: Yeah. So, Colleen, we did give an update at JPM, as was said in my prepared statements. Since then, what I can tell you is that we've been thrilled with the recruitment of SOL-R, and we will give you an update when appropriate, but it may be a little bit too early at this point. But thank you for your question. Colleen Kusy: Understood. Thanks for taking our questions. Pravin Dugel: Thank you. Operator: The next question is from the line of Kelly Shi with Jefferies. Please proceed with your question. Unidentified Analyst: Hi, this is [Clara] (ph) on for Kelly. Thanks for taking our question, and congrats on the update. So, you mentioned that you intend to submit NDA after 56-week primary endpoints of SOL-R is reached. So, I understand that the primary endpoints do not change, but also just trying to understand whether you would expect to have some long-term redosing durability data in SOL-1 as well by that time? And also just want to clarify whether the FDA requires that portion of data to support the redosing flexibility portion on the label? Thank you. Pravin Dugel: Clara, good morning, and thank you for your question. Very important questions, and I want to make it very clear as to what the FDA requirements are for NDA submission versus the information that we'll gather. To be very, very clear, what the FDA requires for the NDA submission is hitting the primary endpoint in both studies. So, again, the primary endpoint for SOL-1 at month nine remains the same. The primary endpoint for SOL-R is at week 56. And our intention is that with presumably a positive study at week 56 with SOL-R, we will submit the NDA application to the FDA. That is unchanged. We just expect given the announcements today that SOL-R will be recruited with more efficiency given the fact that the sample size is smaller. Now, in regards to your other questions regarding other requirements, yes, the FDA does have safety requirements as you're aware. They will be fulfilled with the combination of patients in the second year in both SOL-1 and SOL-R. In addition to that, we will also have a significant amount of information that we believe we can leverage for commercial success. And some of which you've already talked about and we've already talked about, which is the redosing of this drug that is now available both in SOL-1 and in SOL-R. And remember, we also have a numeric analysis that we're able to do with the third arm in SOL-R, which compares this drug to high dose EYLEA. Now that is not for statistical analysis, that's for numeric analysis, but you can imagine we will have between these two studies a significant amount of data that is not necessarily required by the FDA, certainly it's not required for approval or NDA submission, but we can leverage for our commercial advantage, and we do intend to do that. Thank you for your question, Clara. Unidentified Analyst: Thank you. Operator: Our next question is from the line of Sean McCutcheon with Raymond James. Please proceed with your questions. Sean McCutcheon: Hi, guys. Thanks for taking the question. So, for SOL-R, could you give some detail on what you think the FDA expectations are, what your expectations are for what would be an acceptable number of rescues and timing of rescues regardless of if you hit the non-inferior — land within the non-inferiority margin? Thanks. Pravin Dugel: Sean, good morning, and thank you for your question. Your question is a very important question, of course. So, let me discuss rescues. We mentioned today, I just want to make clear that the non-inferiority margin was 4.5 letters. And I just want to emphasize that, that is because we're exactly in guidelines with the FDA. We've always done that and we expect to do that with everything that we do in regards to study design. In regards to the rescues, we have not detailed the rescue criteria as yet for competitive reasons, but we will do so. But here's what I can tell you. We will detail those when appropriate. You can expect the rescue criteria to be of no surprise. They will be absolutely in line with the traditional rescue criteria that you've seen in the past. The FDA has given very clear guidelines of what they think about rescues, not just for us, but for all studies. The FDA has clearly stated, and this was stated most recently by Dr. Boyd in the American Academy of Ophthalmology meeting, that the first rescue in a non-inferiority study will be allowed as long as it doesn't affect the primary endpoint. And that is a period of approximately three months or so as a rule of thumb before the primary endpoint. All other rescues will be subject to review. And again, that's been stated for a number of years now. That is no different than any other clinical trial, and that is a general statement that still stands. However, what I can tell you is that I believe we will have a huge advantage due to the design of our clinical trials. Remember, these are complementary clinical trials. And remember that SOL-R will never be reviewed by any regulatory agency without a positive SOL-1 study. And when these rescues for SOL-R are being evaluated, it will be evaluated in the context of a positive SOL-1 study. So, the regulatory agencies will have a very clear idea that this drug will last for nine to 12 months based on a positive SOL-1 result. So, again, the rescues will be reviewed in context of a positive SOL-1 study, which will define the durability of this drug, which I will think will be very much to our advantage. Again, this also emphasizes the advantage that we have of having these two complementary studies. Thanks for your question, Sean. Sean McCutcheon: Thank you. Operator: Our next questions are from the line of Jon Wolleben with Citizens JMP. Please proceed with your question. Jon Wolleben: Hey, thanks for taking the questions, Pravin. Two from us. Can you discuss the change in powering for SOL-R now for the primary? And then, stepping back, it seems like these changes have two big implications. One is the accelerate potential timing to a filing, but then also the new label information. But how do you think about the importance of those two? Because my expectation would be if you get a year on the label, the docs could treat and [extend] (ph), as they do anyway. So, how much value is that 52 weeks in the label versus just getting to market quicker? Pravin Dugel: Jon, good morning, and thank you for your questions. Again, very important question. Look, as far as the SOL-R powering is concerned, we haven't guided you to that publicly. But what I can tell you is nothing changes. We had the 825 patient number to satisfy the FDA safety requirements. The powering and the statistics really do not change at all. We're able to reduce the size because of the redosing amendment that was approved by the FDA for SOL-1. The statistics remain very robust and unchanged for us. In regards to your second question regarding labeling, look, as a physician, I can tell you as someone who has practiced for the last 30 years, the label becomes very important for several reasons. One is scientific. It gives you the scientific data of what this drug does, which would be very important to see. The opportunity is there in this study to find out the durability of this drug in a scientific manner. And that is very valuable information for physicians and for patients and for payers alike. The second reason for the labeling is really for the payers, and it will give us a huge commercial advantage. So, our goal strategically is to have the best label that the market has seen, a label that is the superiority label, which will be the first and only of its kind potentially and one with a great deal of flexibility of dosing from six months to 12 months. Thanks for your question, Jon. Jon Wolleben: Thanks, Pravin. Operator: Our next questions are from the line of Yi Chen with H.C. Wainwright. Please proceed with your questions. Yi Chen: Thank you for taking my question. With respect to the NPDR and DME, once you get the FDA feedback on clinical trial design, how quickly do you anticipate to advance those two indications into clinical trials? And do you intend to advance both indications concurrently? Thank you. Pravin Dugel: Yi, good morning. Again, thank you for your question. I'm glad you asked about NPDR and DME, and I'm glad that you put those together because I think it's very important to emphasize that with the HELIO study, we have shown absolutely everything to you, which is every single eye of every single patient. And what you'll see there is not only a remarkable result in non-proliferative diabetic retinopathy, or NPDR, but also in diabetic macular edema, or DME. In fact, every single patient who had diabetic macular edema on entry of that study improved. And what you saw in the Angiogenesis meeting is a remarkable presentation by Dr. Ehlers, where he showed that very clearly that these patients with fluid improved significantly after a single injection after 48 weeks. And so, our goal is to pursue not just NPDR, but also DME. How the trial will be designed? Yi, we don't know yet, because we will still meet with the FDA formally. We committed to doing that in the first half of this calendar year. That has not changed. How quickly we will implement? That depends on that meeting, so I can't say now. But what I can say and what we did say is that we are financed very, very efficiently. We are very disciplined, in our financial expenditures. And our intent is to keep the projections the way they are, which is that we are financed into 2028. And at this point, we do not have any intention of requiring any additional funding this year and that remains. Thank you for your question, Yi. Operator: Our next question is from the line of Greg Harrison with Scotiabank. Please proceed with your question. Greg Harrison: Hey, good morning, and thanks for taking the question. Curious what your expectations are for the percentage of patients that could show durability to 52 weeks without rescue in SOL-1 and to what extent do you think it could be used that way in practice. Pravin Dugel: Greg, good morning, and thank you for your question. The data, first of all, it's very, very valuable information and we don't shy away from this at all because not only because it's very valuable, but we believe that we're going to win quite honestly. We believe that there are a number of patients that will go to 52 weeks. And this is based on the US study. In the US study, we had 60% of patients that went that long with a single injection, and that was in a non-enhanced patient population. As you know, in previous discussions, we've gone through how painstakingly and thoughtfully we have selected our patients in a bespoke manner for each study to derisk the patient selection and derisk the outcomes. And the 60% that I quote to you, it really is in a unselected non-enriched patient population. So, we're very confident of what we will show at week 12. Remember that there are drugs that are in the market now that are approved on label for a two week or so extension, some going to four months, with not very many patients that have actually crossed that threshold in their study. So, from our point of view, we're going to provide very valuable information here to physicians, payers and patients alike, and we have the opportunity to have the best-in-class label as well. Thank you, Greg, for your question. Operator: Thank you. This concludes our question-and-answer session. I'll now turn the call back to Dr. Pravin Dugel for closing remarks. Pravin Dugel: Once again, I'd like to thank everyone for taking the time to join us on our call today. We look forward to updating you on our progress. And if you have any follow-up questions, please reach out to Bill Slattery, our Vice President of Investor Relations. Have a great day everybody. Thank you. Operator: This concludes today's conference. You may disconnect your lines at this time, and thank you for your participation.
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