Good morning, and welcome to the AGTC Skyline three-month interim data analysis conference call. Today's call is being recorded. Before we get started, I'd like to remind everyone that during this conference call, AGTC may make forward-looking statements, including statements about the potential of AGTC-501 as a treatment for XLRP, the ability to use the interim Skyline results as a predictor of the success of the final Skyline and VISTA clinical trial results, and whether these results will support future regulatory filings for AGTC-501. Actual results could differ materially from these discussed and these forward-looking statements due to a number of important risk factors, including uncertainty inherent in the clinical development and regulatory process, the extent and duration of the impact of the COVID-19 pandemic, and other risks described in the Risk Factor section of AGTC's most recently filed annual report on Form 10-K and other periodic reports filed with the SEC. AGTC undertakes no obligation to update any forward-looking statements after the date of this call. For introductions and opening remarks, I'd like to turn the call over to Sue Washer, Chief Executive Officer of AGTC. Please go ahead Good morning, and thank you all for joining us. We are very excited to be reporting favorable safety and positive efficacy results for the three-month interim data analysis of the phase II Skyline clinical trial. As a reminder, the Skyline trial is an expansion of the phase I/II trial designed to assess the safety and efficacy of AGTC-501, our gene therapy candidate for the treatment of X-linked retinitis pigmentosa, or XLRP, in a patient population that meets the entry criteria used in the phase II/III VISTA trial. In addition to Susan Schneider, our CMO, and Jonathan Lieber, our CFO, we are pleased to have Dr. Robert Sisk joining us today. He is the Director of Pediatric Vitreoretinal Surgery and Director of Ophthalmic Genetics at the Cincinnati Children's Hospital and the Cincinnati Eye Institute. During today's call, I will provide a brief overview of the rationale and design of the Skyline trial, as well as key takeaways from the interim analysis. Susan will then review the data from the trial's three-month interim analysis in more detail, and after our prepared remarks, we will take your questions. With respect to the design of the Skyline trial, there is a high dose group and low dose group, referred to as Group A and Group B. As this interim analysis was conducted on data that remains masked to patients, sites, and the company, we do not know which group is the high or low dose group. We have chosen this approach because it will maintain the integrity of our analysis out to the 12-month primary endpoint, which we believe will be important in providing the FDA with the most robust data possible. There are some key takeaways from the three-month interim analysis that I would like to highlight. First, we are reporting a robust improvement in visual sensitivity, the primary efficacy endpoint for both the Skyline and VISTA clinical trials. This includes a response rate in visual sensitivity of 62.5% in Group B, which is well above the 50% response rate for which the VISTA trial is powered. In both the Skyline and VISTA trials, a response is defined as an increase of at least 7 dB in at least five loci. We also saw a 25% response rate in Group A. This clear difference in response between the two dose groups is significant in that regulatory authorities requested that this trial and the VISTA trial include masked arms that would show dose differentiation. Three-month results for performance on the Ora Visual Navigation Challenge, or MAZE, are trending toward improvement, which we believe could provide value as a supportive endpoint. We observed improvements in lower light levels passed, increased speed at the same light level, and/or reduced errors at the same light level. This was the first use of the MAZE in our clinical trials or any XLRP trial, and we are pleased with the results of the MAZE we have seen to date. With respect to Best Corrected Visual Acuity, or BCVA, the three-month Skyline data show a trend toward improvement that we believe could provide value as a supportive endpoint. The three-month results in Skyline were less pronounced than what we have previously reported for the phase I/II trial, but this is not unexpected given that patients enrolled in Skyline had higher BCVA at baseline compared with patients in the phase I/II trial, and therefore had less room for improvement in visual acuity. AGTC-501 continues to be well-tolerated, which is consistent with our phase I/II experience, and no clinically significant findings related to the study agent have been reported to date in Skyline. Our favorable safety profile is especially notable given the issues that many of our peers in the XLRP space have seen with respect to intraocular inflammation and safety issues that have been reported for some AAV-based candidates in other indications. We believe that the strong safety data we have seen across our trials is the result of our focus on product design, extensive preclinical testing, and improved surgical consistency. We believe this is the strongest data set and most favorable safety profile compared to any data publicly available to date, and will contribute to what we expect will be a differentiated product profile for our XLRP candidate. If we have consistent data across the phase I/II, Skyline and Vista trials, we would intend to prepare a BLA filing. I would like to take a moment to provide a brief review of XLRP. XLRP results from the degeneration of rod and cone cells in the retina due to an absence of the retinitis pigmentosa GTPase regulator protein, also known as RPGR. XLRP is an inherited retinal disease that affects about 20,000 boys in the United States and EU, which is a substantial patient population for a rare orphan indication. Currently, there are no treatments for XLRP, and patients progress from early night blindness between the ages of six and eight to increasingly constricted visual fields, with most becoming legally blind by the age of 45 and completely blind in their late 50s or early 60s. This slide illustrates the care we take in the design and testing of our product candidates even before we begin human clinical trials. Prior to selecting a final product candidate for clinical development, we complete extensive preclinical testing in both non-human primates and, in the case of XLRP, in naturally occurring dog models. This animal research is critical as we believe it provides the foundation for the favorable results we have seen to date in our clinical trials. For example, we specifically chose our capsid because of its ability to drive gene expression in non-human primates, as primates have different ocular structures than lower mammals. The graph on the bottom left corner of the slide shows that our engineered capsid results in up to twice the levels of expression in non-human primates than other capsids used in ophthalmology gene therapy. We believe that many of our peers use mouse models, which are not nearly as representative of the human eye as non-human primates and, in fact, can give the opposite results. We also conducted extensive work in a naturally occurring dog model of XLRP, allowing us to get detailed insight into how our products affected the actual clinical phenotype. Slide 7 provides an overview of the phase I/II trial, which was a standard dose escalation trial over an 80-fold dose range. Over this entire dose range for the 20 centrally treated patients, we saw a favorable safety profile. We are using group two and group five doses, boxed and highlighted in yellow, from the phase I/II trial in both the Skyline and VISTA trials. These two doses are approximately 10-fold apart. Here's a snapshot of the phase I/II data that we have previously reported. AGTC-501 has demonstrated a 50% response rate at 12 months for patients in the high dose groups that meet the inclusion criteria for Skyline and VISTA trials. All responders were responders by three months and stayed responders through 12 months, the latest data available. BCVA showed supportive evidence of a biological response through month 12, with statistically significant differences between treated and untreated eyes. Finally, we recently presented data showing that improvements in visual sensitivity in these patients correlated with improvements in retinal structure as measured by OCT at both months 12 and 18. We expect to report full two-year data from this trial in the second half of 2022. Our goal in the Skyline trial was to be able to repeat the favorable safety profile and the robust efficacy improvements in visual sensitivity seen to date in the phase I/II trial. We now believe we have accomplished this. Now I will turn the call over to Susan, who will review the three-month interim Skyline data in more detail. Thank you, Sue. Before I dive into the data, let me briefly review the Skyline trial rationale and design. Skyline is a multi-site expansion of the ongoing phase I/II study in which patients are randomized to either a high or low dose of AGTC-501. This trial is our first opportunity to verify the positive outcome seen in the phase I/II trial in a masked fashion, a feature important to the regulatory authorities, and to assess the performance of the mobility maze in a population that uses the same entry criteria as Vista. At month 12, we will report on the primary endpoint. Patients will then be eligible for fellow eye dosing. I will begin by describing the efficacy data and the very positive results for the primary endpoint of visual sensitivity. As shown here, we observed robust improvements with a clear difference in response between the two dose groups, group A and group B. Recall that the trial remains masked such that we, the sites, and the patients do not know which of the groups was in the high or low dose group or which patients were in each group. On the left side of this slide is the proportion of patients achieving a 7 dB or more improvement in at least five loci, which is how we defined a response. The response rate at month three was 25% and 62.5% for groups A and B respectively. A clear dose difference is demonstrated between groups A and B. The threshold for success in terms of improvement in visual sensitivity is a 50% response rate, and the VISTA trial is powered to show a 50% difference in either dose group compared to the untreated control arm. Although these results exceeded the current standard set by the United States Food and Drug Administration, or FDA, that at least five loci increased by at least 7 dB, the improved loci were not pre-specified, as also required by the FDA standard. However, these very positive efficacy results are aligned and consistent with mean sensitivity outcomes shown in the graphs on the right side of this slide for all 13 patients, as measured within the central 36 loci, or for the entire treated area within the bleb. What is evident in presenting these visual sensitivity outcomes is that regardless of how we look at these data, we see compelling improvements in visual sensitivity and a clear differentiation between dose groups. In addition, there is a clear difference noted between treated and untreated eyes. None of the untreated eyes were responders, and none had improvements in mean visual sensitivity. This slide summarizes microperimetry results. Here you can see six of 13 patients have improvements in at least nine loci and range up to 17 loci that are above 7 dB in their treated eye. Of note, all six of these responders also had a mean improvement in visual sensitivity across the entire treated area. In the third column, we also see positive trending in the target number of five pre-specified loci in this three-month analysis, with responder patients achieving up to four pre-specified loci, improving by seven or more decibels. There is also a clear difference in loci response and mean improvement in visual sensitivity between treated and untreated eyes. We believe that this level of improvement in visual function is very clinically meaningful, that the data clearly show a beneficial effect of AGTC-501 for XLRP patients, and that the totality of data collected will add to the strength of a BLA filing if we see consistent results in the VISTA trial. Here you can see an example of a patient that we consider to be a responder, as demonstrated by MAIA microperimetry heat maps and retinal sensitivity change by a cumulative histogram plot of the individual loci. The left side of the slide shows the heat maps for treated and untreated eyes. Compelling visual sensitivity data is evident in the treated eye, increasing in both magnitude of effect as well as overall area. Increases in magnitude are shown by brighter colors, such as orange changing to yellow from baseline to month three, and a numeric increase of 2.6 dB to 7.5 dB. Increases in the area of sensitivity in the treated area are seen with color changes from black to orange. A marked difference is also seen between the treated and untreated eye, which is seeing no increase in magnitude or area. This positive change in both magnitude of effect and in overall area of improvement in visual sensitivity is very important to patients with XLRP. Recall that in XLRP, patients lose their peripheral vision initially. This progresses down to tunnel vision or being only able to see within a small pinpoint area before eventually losing even this small area of central vision. We believe the ability to not only see better in this very small central area of vision, but also to have a wider area in which to see, would be a clinically meaningful change for patients with XLRP. In the histogram on the right side of this slide, we can see at these data numerically for each of the loci within the testing grid, which has a total of 68 loci. Shown here is the retinal sensitivity change from baseline for each of the loci in the treated eye in red and in the untreated eye in gray. We see a shift to the right of the red bars, indicating improvements in the treated eye. This patient had substantial improvements across multiple loci with a 7-dB or more improvement in many more than 5 loci. A total of 13 in this case. Here is a summary of the histogram plots for all 13 patients evaluated with individual patient data for retinal sensitivity change. For all loci within the grid at month three. Six responders meeting the 7-dB 5 loci definition are highlighted in green. Two additional patients with positive changes and clear improvements are highlighted in yellow, and five patients with no notable improvements are in white. Of note, patient 10, shown in the bottom left corner, could not be assessed for retinal sensitivity due to a misalignment in the MAIA microperimetry grid at the month three assessment. We anticipate reporting retinal sensitivity data for this patient at month 12. Looking at the visual sensitivity data for both the phase I/II and Skyline clinical studies side by side, we see similar and robust improvements at month three in both studies, durability of effect out to month 12 in the phase I/II, and much tighter variability in Skyline as compared to the phase I/II study. We believe this tighter variability is due in part to adjusting the inclusion/exclusion criteria for Skyline based on learnings from the phase I/II study, as well as a more refined and consistent surgical technique, providing a consistent volume of study agent to a consistent location. Based on improvements in visual sensitivity observed in the phase I/II trial, showing that responders at month three remain responders at month 12. We anticipate seeing the same for Skyline, further demonstrating durability of effect. We believe that the similar results seen in both clinical trials will provide robust support for AGTC-501 as a product that will benefit patients. The mobility maze data show positive trends with improvement on the light level passed and/or improved speed or reduced errors at the same light level. At month three, there were two patients who passed the maze with at least a two-level improvement in luminance or light levels, three with a one-level improvement, and two with improvement in speed without an increase in errors, for a total of seven patients, or 54%, showing some improvement at this time point. Importantly, four of the six patients with improved visual sensitivity also showed improved mobility maze performance, representing what we believe is supportive evidence of the maze for the primary visual sensitivity endpoint. There are several important points to consider in evaluating the maze results. First, there is a potential ceiling effect in how much patients may improve due to their better baseline BCVA. It's also important to recognize that previous use of this maze was conducted with patients who had both of their eyes treated. One of the key goals for conducting Skyline was to gain experience using the maze in this patient population and to incorporate learnings from the Skyline experience into the phase II/III VISTA trial. We believe this maze will provide supportive evidence that AGTC 501 provides functional vision benefits. Let us turn our attention to the patient characteristics as there were some differences between the phase I/II clinical study and Skyline. With respect to age, patients in Skyline were generally younger, ranging from eight to 36 years, than in the phase I/II trial, who ranged from 19 - 48 years. Mean ages for each dose group are shown at the bottom of the slide, and you can see that the mean ages of 40 and almost 30 years in groups two and five of the phase I/II trial are higher than the mean of 21 and 22 years of age in groups A and B in Skyline, respectively. In looking at additional baseline characteristics, the phase I/II patients generally had worse baseline BCVA, averaging approximately 20/50 to 20/63 Snellen equivalent, compared to approximately 20/40 in Skyline. The phase I/II patients had worse baseline mean sensitivity compared with Skyline patients. Despite these clear baseline differences in age, visual acuity, and visual sensitivity, the improvements seen in both clinical trials in the visual sensitivity analysis were still very similar, demonstrating that a wide range of XLRP patients could potentially benefit from treatment with AGTC-501. We continue to see a favorable safety profile in our XLRP program. We are very pleased that review of safety data demonstrates that the study agent, AGTC-501, is generally safe and well tolerated. To date, no PSUs or endophthalmitis have been reported in the Skyline trial. The majority of ocular adverse events, or AEs, were non-serious, with no apparent difference between dose groups. Two ocular serious adverse events, or SAEs, were recorded. Neither was deemed related to study agent. There was one non-ocular SAE reported that was also deemed not related to study agent. Non-serious ocular AEs related to study agent were all grade two. They were uncommon and balanced across the two dose groups. We therefore believe that the higher dose group, which is a tenfold higher than the lower dose group, is not exhibiting a difference in safety profile. There were no ocular SAEs related to study agent. With respect to the two ocular SAEs that were reported, one was deemed related to the surgical procedure, the other was related to corticosteroid use. Safety is of paramount importance in clinical development. We believe that this favorable safety profile is a key aspect of differentiation for AGTC-501 as a potential therapeutic option for patients with XLRP. To summarize this masked three-month interim analysis for Skyline, we believe we have demonstrated positive and robust efficacy improvements and a very favorable safety profile comprising a positive benefit-risk ratio for these XLRP patients who, as a reminder, unfortunately, have no currently available treatment options. To reiterate the key takeaways that Sue reviewed at the start of the call, we have shown robust improvements in visual sensitivity, the primary endpoint for both Skyline and Vista. There is a clear difference in response between the two dose groups in Skyline, with a 62.5% response rate in visual sensitivity in dose group B. At month three, the first time point to assess the mobility maze in this study, or for any XLRP trial, results demonstrated positive trends overall and a correlation to improvements in visual sensitivity, with four of the six visual sensitivity responders all improving on the maze. Best Corrected Visual Acuity remains a supportive endpoint of improved visual sensitivity. Although the Skyline results are less pronounced than those for the phase I/II clinical study. This could be due to better baseline BCVA in Skyline patients. We look forward to reporting additional data at month 12 across all the endpoints in this trial, including macular structure, which we believe is another important and objective supporting endpoint. The month three safety results meaningfully contribute to the body of data collected as they show a clean safety profile for AGTC-501. We believe, given the VISTA trial replicates what we have seen in the phase I/II and Skyline, that the regulatory agency will consider this totality of data favorably as part of an overall BLA submission package. As Sue noted in the phase I/II clinical study, all responders were responders by month three and remained responders at month 12. Consequently, we expect the findings reported today to be durable, and we look forward to reporting out month 12 Skyline data in the first half of 2023. Let me briefly review the VISTA phase II/III trial design. This trial will have three arms, two treatment arms that will include the same Group two low dose and Group five high dose groups as in Skyline, and a completely untreated control arm. The primary endpoint is visual sensitivity, analyzed as the% of patients with at least a 7-dB improvement from baseline in at least five pre-specified loci at month 12 and compared to the% of patients meeting the responder definition in the untreated control arm. The trial is statistically powered to detect a 50% response rate threshold, even if there are unexpected responders in the control arm. The current plan calls for all eligible untreated control eyes to receive treatment at month 12, and those eyes will be followed for an additional 12 months. Mean improvement in visual sensitivity across the entire treated area, BCVA and the mobility maze will continue to be assessed as supported endpoints, and we will also use a validated questionnaire tool for patient-reported outcomes, or PROs. To gain insights into the patient's experience and impact on activities of daily living following AGTC 501 administration. I'd like to also point out that we plan to conduct an interim analysis during VISTA, at which time we expect to have 12-month data from Skyline and 24-month data from the Phase I/II clinical study. We currently intend to present and discuss the totality of these data with the FDA and to seek any appropriate protocol amendments or potential trial acceleration, including early dosing of the contralateral fellow eye in patients. Operator, you may now open the line for a question-and-answer period. Thank you. We'll now be conducting a question-and-answer session. If you'd like to be placed into question queue, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing star one. One moment please, while we poll for questions. Our first question today is coming from Joseph Pantginiss from H.C. Wainwright. Your line is now live. Hi, everybody. Good morning. Thanks for taking the question and congratulations on the data. Nice to see the additional increments today. So I've two-part question, and I'm assuming that Dr. Sisk is on the call too. I guess want to focus on the importance of what you mentioned earlier about the surgical consistency and the blood coverage. That seems like it's a major contributor to be able to see today's data. The second part of the question is, it maybe it's a good time to remind people, you know, why the FDA, you know, came up with these particular numbers regarding the 7 dB and five loci. Well, thank you, Joe, for those questions, and we definitely agree that surgical consistency is important. Dr. Sisk, maybe you can comment on that and the improvements and consistency we've seen in between the Phase I, II and the Skyline trial. Sure. One of the nice things about this particular indication is that with patients having on average moderate to high myopia and increased posterior curvature, the angle that the cannula that we use for the injection as it enters comes in fairly tangentially, which allows some control of direction. Because of that, it tends to allow us to cover the macula in its entirety pretty readily with good consistency among surgeons. AGTC has a rigorous surgeon training program that includes both animal labs as well as proctoring with experienced surgeons and holds regular surgical rounds on each of the cases that are completed so that each of the surgeons can learn from each other and see what is increasing safety and providing the most consistent results. As a result of that, I think we generally are seeing very consistent surgical technique among the various surgeons who are performing these cases. Thank you, Dr. Sisk. I'll kind of start off with the 75 part of your question, Joe, and ask Susan to jump in. One of the issues that is always true in ophthalmology that people, including the authorities, are concerned about is bias. I think we all know that in visual acuity, there is some significant effect of patient effort in how well they do on visual acuity. All patients know that if they just try to read a lower line, that that's a better result. In visual sensitivity, the light that is flashing, the intensity of it or the location of it, the patient doesn't know. We firmly believe that there's not as much bias in visual sensitivity as there is in visual acuity. Further, that the precedent for visual sensitivity in the 75 was set many years ago in the glaucoma space, which is obviously a much different indication, a larger indication where there are available treatments and with machines that weren't as sensitive and robust as the MAIA that we use concurrently. We certainly understand where the precedent came from, but really believe that with robust data within the specific indication, that we can have that discussion with the FDA about how meaningful these changes are for patients. Susan, do you have any comments to add to that? Even Dr. Sisk, if you had comments to add. Dr. Sisk, I'll defer to you first. Sure. From having treated some of these patients, they express a significant improvement in their ability to function, particularly in dimmer light situations. They report ability to see colors more true. They notice an improvement. I think we're just starting to scratch the surface of that with the mobility course. Although I agree that when we're only treating one eye in this fashion, that we're kind of giving handicapped results at this point. After the bilateral treatment, it'll be very interesting to see how they perform. I do think that the MAIA probably is going to be the best indicator for the reasons that Sue mentioned. Particularly when patients have such relatively good baseline visual acuity. One of the challenges with this is that, in selecting patients, we're trying to maintain safety by treating patients who already have some vision deficit at baseline. It makes it worth the risk to undergo the surgery to inject a subretinal bleb. At the same time, with those patients, there's already been significant reduction in the photoreceptor anatomy at baseline and the associated potential. We're striking a more narrow window with Skyline and VISTA compared to what we did with the phase I and II. Ultimately, I think that will allow us to see more robust gains on the microperimetry in that population. Just to add on to that, with the 7.5, 7 dB at five loci, we're not seeing borderline results here across the board in these responders. As we pointed out, we're seeing patients with 17, 13, 12, way beyond five loci in the results that we're presenting at three months today. Those are also reflected in the heat maps, where we're seeing magnitude and area of effect with improved visual sensitivity, which we feel is quite compelling. Great. Thank you so much for all the added color and congrats again. Thank you. Next question today is coming from Yanan Zhu from Wells Fargo. Your line is now live. Hi, thanks for taking my questions and, also congrats on the great data here. So I wanted to ask a little more about the 75 with pre-specification, which remained the FDA's recommended way to utilize this endpoint. So how do you think about your. You know, how have you been pre-specifying, and how do you foresee any potential change in your strategy for pre-specifying? Also I'm wondering from Dr. Sisk's perspective, you know, this, you know, at least at the moment, remains FDA's preferred endpoint. You know, how do you think this could evolve, whether FDA should or could adjust this kind of requirement? Do you think there is any flexibility there? Thank you. Well, thank you Yanan, and good morning to you. I'll kind of set the stage and again have Susan and Dr. Sisk jump in. We are attempting to pre-specify and predict which loci will improve using a algorithm that was developed by a third-party machine learning company. We will certainly feed in all the data we now have from Skyline into that algorithm and see if we can't perfect it and improve it and improve our predictability, because we did hit on some of the loci that we predicted. However, we will firmly state, as we have stated many times, that the patient does not care which loci improve. They want to see an improvement in their vision. We really feel that the ultra specificity of having to pre-specify is not clinically relevant to the patient. As I said before, we understand where it came from in a desire to eliminate bias. Again, due to how the MAIA functions, we do not feel that there is that level of bias in the visual sensitivity test. We believe, and certainly I would welcome Dr. Sisk to comment on this. We believe that the totality of data, the consistency of the data, the safety of the data, and the experience that the patients have is what is going to win the day with regulatory authorities. This is not uncommon in orphan drug development, where there's no precedent within XLRP. Remember, this precedent was set in a glaucoma indication. Now, you know, I don't know if Dr. Sisk or Susan want to add additional comments. Dr. Sisk, I'll defer to you. Sure. I was gonna, Sue, I think you said that really well. Which is that when you have an orphan disease and you're relying on indications from even another branch of ophthalmology, that it may not perfectly fit. The totality of the data and the multiple endpoints that are being collected, I think are going to be supportive. In the phase I and II data, we also saw correlation with improvement on the ellipsoid zone on OCT in patients who were responders. I think when we have on multiple metrics that have improvements both anatomically and functionally, I think that makes a very clear case for benefit that the FDA can weigh. I expect them to be reasonable in that respect, understanding that for an orphan disease that some new endpoint perhaps will have to be created and the extra step of pre-specification in this situation does seem irrelevant. Got it. That's really, really helpful. Thank you for that answer. Sue, if I have one more question, if I may, that is about the dose level or assignment. Obviously you are, I think, also blinded to the assignment here. You know, it looks like this seems to be a straightforward situation if we assume group B is a higher dose. But how should we think about it in your opinion? When we ultimately see the data, you know, if the data is different from our assumption, you know, how should we then, you know, evaluate the situation? Thank you. Yanan, I think that's a very good question. We are masked. We do not know which is the high dose or the low dose. The data is compiled by a third-party vendor, and we get those individual heat maps without dose assignment. While we can look at the individual data on visual sensitivity, we don't know which of those patients is in which group. The third party vendor compiled that data and gave us the group A and group B compilation without our knowing. As I said, we think this is really important. Masking is very important to the FDA in ophthalmology. We want that 12-month data to be as robust as possible. We're trying to do everything we can to make sure patients and physicians can't kind of figure out which dose they're in. The masking is being held for a very specific reason. I think the question of what if dose B is the low dose is a very valid question. I think that how we would think about it is that we would think about, well, maybe that's great. We have a dose that is very effective, that is consistent over time and in a masked fashion. In the grand scheme of things, I think you always wanna use the lowest dose that has clinical efficacy. I think from a go forward point of view, we would not have a problem with dose group B being the low dose. If you remember from the Phase I/II, we did see activity across a broad range of doses. The n, though, in the phase I/II for each dose was very, very small, as small as three patients per group. It's hard to make a final determination from a dose escalation trial, which is why we're doing the Skyline trial. We would not be concerned if it ended up being dose group two that provided us this very robust and consistent data. Thank you. Next question today is coming from Kristen Kluska from Cantor Fitzgerald. Your line is now live. Hi, good morning, everybody, and let me also add my congratulations on these data. I know you've often spoken about the importance of this three-month timeframe, as you've seen a lot of synergies with the data at the 12-month time point. How are you starting to think about trends beyond that, especially considering you recently had some data for the 18 months and of course, the two-year data is guided for the second half of this year. You know, specifically, are there any other things you think will be notably different to consider with this patient population beyond these time frames and synergies, especially considering, this different state at baseline? That's a very good question, Kristen. Thank you for joining us today. I think that what we know from the phase I/II is that for visual sensitivity, which is the primary endpoint, we know that what we see at three months is maintained. T his has been true across other trials that we work on, whether it be achromatopsia or even the original XLRS program that we have, is that once you get to three months and see that response, it's very consistent. We also saw that to be true in visual acuity in the phase I/II. Of course, those patients were starting out at a lower visual acuity level. I think what we'll be watching for going forward, and I'm gonna ask Susan to comment on the macular structure, since this is the first time we've ever used the MAZE, to see whether that might change over time and improve. We'll specifically be looking at macular structure because we didn't see that change and that improvement until later in the trial. Susan, you might comment on how we saw that mature over time. Sure. Thank you, Sue. One of the adjustments we've made from the phase I/II to Skyline and to VISTA is that patients have to have detectable ellipsoid zone to be eligible for the clinical trial, as well as minimal but present retinal sensitivity by the MAIA. We believe that this will help us with durability of effect over time. The other thing I would add is that this is a progressive disease. In the untreated eye, we would expect that not to improve over time, actually to decrease over time, giving us potentially a bigger delta going past month 12 to month 24. In the changes that we see, as Sue said, after three months. We'll be looking at those more closely at month 12 in particular in the EZ. Those could fortify our results. Okay, thank you for that. Then I understand of course the FDA requirements and the the definition of what they consider to be a responder. Just looking across, some of the individual patient data you provided for us, wondering if you have an idea from each dose, what% of patients you would genuinely say showed at least some level of improvement, whether this is on the maze, whether this is on visual sensitivity. Have you also looked at the different baseline characteristics while blinded, of course, for each dose? Thank you again. Kristen, thanks for the question. I will say first, starting on the second part of your question, it's impossible for us to do any baseline characteristic analysis to outcomes, because then that would be unmasked. It would be impossible for anybody to remain masked if they knew the specific baseline of each patient outcome. We have not done that analysis. We have no further information there. We know that in general, as Susan said, we did tighten the inclusion criteria on macular structure because we saw in phase I/II that patients with very poor nonexistent macular structure didn't have a chance of success. What we see when we look at the different kinds of endpoints is actually consistency across the endpoints in the number of patients or the percentage of patients that improve on visual sensitivity, that improve on the maze, that have positive trends in visual acuity. Again, we aren't specifically matching those up because then that would certainly if any of the PIs or patients started looking at that kind of data, they might be able to figure out which dose groups they're in. We are remaining masked there. There is very good consistency, as we pointed out, in the maze that four of our six visual sensitivity responders, you know, our vendor confirms that those are a part of the responders on the maze. We feel there is good consistency amongst the data. As Susan pointed out, when you're looking at the visual sensitivity data, no matter how you slice it, whether you're looking at mean improvement over the whole area, mean improvement over the whole grid, mean improvement in the central 36, or number of loci that improve above five, those patients are all very consistent, and the results are all very consistent. Thank you. Next question is coming from Zegbeh Jallah from Roth Capital Partners. Your line is now live. Thanks for taking my question. Again, congrats on the progress. Really exciting data. I think the first one for me here is just a clarification question, regarding the algorithm that's pre-selecting, the five loci. I was wondering if the algorithm selects the same area for every patient or is it patient specific? Zegbeh Jallah, thank you for that question. It is good to clarify that. That's an easy clarification. It's different for every patient. Every patient's baseline readings on the MAIA, and they're done three times, are fed into the algorithm, and specific loci are picked for each patient. Thanks. Yeah, that's helpful. The second one is almost a variation of a question that was just asked. I think, you know, just looking forward, was wondering, is there any additional data from, say, the six-month update that you're looking for to gain additional conviction in the data? Or is this three-month data compelling or even more compelling than originally expected? We are not planning a six-month interim analysis. We selected the three months because we were very confident looking across all of the work that we've done in ophthalmology, including the preclinical work in animal models, that three months was the appropriate time point, and we've never seen any change between three months and six months. The one thing we expect to see going forward is at the 12-month analysis, we will see that macular structure data that Susan talked about. That is the time when we would be able to add that. I think that just the fact that we were able to do a second experiment and get the same results is giving us a lot of confidence going forward. Thank you. Lastly, any comments on the enrollment progress of VISTA? I know you can't provide numbers or anything like that, but just, you know, anecdotal evidence or comments from clinicians about, patient interest in the study. I imagine, like I said, that this data is likely to also boost interest. Yeah, we have had very good interest in VISTA. We have utilized our mobile vision centers that we've talked about before. We have two of those now, and they've been crisscrossing the country doing all of the pre-screening for VISTA. There's been very good uptake, and interest in the trial so far. Thank you. Next question is coming from Daniil Gataulin from Chardan. Your line is now live. Yes. Hi, good morning, and thanks for taking the question and congrats on the data. Have a very quick question, with respect to baseline characteristics, and your observations in Skyline, with respect to to better baseline characteristics. Do those affect your strategy at all for enrollment for VISTA? Well, thank you for joining us today, Daniel. I'll put that question to Susan to talk again about what the differences in macular structure baseline characteristics are between the two trials. Thank you, Sue. Basically we really don't have any plans to change the inclusion/exclusion criteria for VISTA moving forward. We're mindful of the potential label. We did see a 50% response rate in the Phase I/II. What we see with these data at month three may impact initial results for Skyline, but we have consistency of results as we've shown in mean sensitivity over time. The point about the baseline characteristics for best-corrected visual acuity is that patients coming in on average with 20/40 visual acuity versus 20/50 or 20/63 have less of a possibility or that ceiling effect to improve over time. Same with the mean sensitivity coming in. Better mean sensitivity in the Skyline trial. Nonetheless, we still see very compelling results at month three, and those are helping us move forward with plans for VISTA. Okay. Got it. Thank you. That was very helpful. Congrats again. Thank you. Next question today is coming from Yun Zhong from BTIG. Your line is now live. Hi, thank you very much for taking the question. Just wanted to confirm one detail about the procedure about pre-specification of the low side. Does that happen before injection? I understand the FDA's requirement is to remove bias and to kind of show predictability, but the feedback that we heard from physicians is that it's a extremely high bar. I wonder, do you have any alternative evidence to show that it's really not due to any. That you can claim that there's no bias and kind of predictable. Thank you, Yun, for the question. I think that's a challenging question to ask. I think what the FDA would like to see, to enable them to consider a broader definition is they do wanna see randomized, blinded, well-controlled data. That is when they could look at it and be able to see in a randomized blinded fashion, that the visual sensitivity changes are meaningful, clinically meaningful to the patients and not biased. I think the problem with the feedback and the interaction with the FDA with the phase I/II trial is that patients all knew which dose group they were in. As we said at the beginning, the FDA really wants patients to be blinded so that they don't know what dose they're in, and their knowledge of what dose they're in not affect their effort to do well on the test. I think that it is the blinded controlled data that we have, and that's why we're being very fastidious about not unmasking ourselves, because we think this is the very data that we need to take to the FDA to have a robust interactive discussion about the specifics of visual sensitivity as an endpoint. Okay. Maybe another very specific question. I saw that on slide number 14, patient number seven seems to have a deterioration in treated eye as compared to the untreated eye. I understand that must be an outlier, but is that related to any safety findings that you made from the study? Yeah, that's a very good observation, Yun. Susan, I know that you can answer that question. Yeah. Thank you for the question and very astute finding there. Yes, we recall we had 2 ocular serious adverse events. Neither was determined to be related to the study agent, but one, a visual impairment, was deemed related to the study injection procedure. In that one, that is that one patient, and that had a surgical complication, unfortunately. Thank you. Next question today is coming from Dae Gon Ha from Stifel. Your line is now live. Hey, good morning, guys. Thanks for squeezing me in. A couple of questions. I'll start with the visual sensitivity precedent question. Can you remind us, have there been approvals since the glaucoma precedent based on this visual sensitivity? O n the second question for the maze test, I guess for Susan, what would be the physiologic reason for patients to improve beyond the three-month measurements that you provided today? And I guess any granularity on what baseline lux levels were for these particular patients. And then thirdly, for John, can you remind us what the cash on hand is based on your recent equity raise? Thanks very much. Good morning, Dae Gon. Thank you for the question. I'll answer the first one, and then Susan, you can talk about the maze test and the importance of bilateral and the differences between when this has been used before. And then John, you can follow up with the cash and runway question. There actually have not been any approvals, even in the glaucoma precedent, using visual sensitivity in this way, for products. People have, you know, in ophthalmology, the major approvals have been on visual acuity or lowering of intraocular pressure in the case of glaucoma. Even with that precedent many years within glaucoma, they were not able to meet that. This is a new way to look at visual sensitivity. As we've said, we think it's the most important endpoint for XLRP patients because that's what they're losing. They're losing visual fields over time. I think that's why Susan pointed out that not only are these patients seeing an increase in magnitude within a certain area, the area of visual sensitivity is improving. It's like going from being able to just see somebody's nose to being able to see somebody's whole face, which we think is obviously very clinically meaningful. Susan, you wanna address the maze test? Sure. Thank you, Sue. In the mobility maze, we did see positive trends and improvement. Recall this is the first time that the mobility maze has been used in XLRP. This is our first look at it, and it is at month three. We'll have more outcomes at month 12 that we look forward to reporting out on. We do believe that to date, with the mobility maze, reported outcomes have been for bilateral treatment, and we do feel that that has an effect on outcomes. In addition, the maze doesn't discern between visual acuity or sensitivity. If a patient comes in with good visual acuity, that could overall affect the outcomes of the mobility maze, and we could be still seeing a little bit of this ceiling effect with respect to the maze, which we'll be taking a closer look at. I do wanna point out that we did have those seven patients that showed some improvement. Two of those patients at month three did show an improvement of two or more luminance levels, and three patients showed an improvement of one luminance level, with the other two also trending in the right direction. We feel this is a good first maze, and we'll be looking more closely at that. We did see also a parallel to visual sensitivity responders. We believe we're trending in the right direction here. Dae Gon, I'll comment to address the last part of the question. We have cash into calendar year 2023. That hasn't really changed. We cashed in our 10-K that we filed yesterday at just shy of $68 million. We do think that enables us to get to a number of the important milestones, and mostly, many of which weren't discussed on this call because it was focused on, obviously, the three-month data. We've got non-human primate data coming from preclinical studies for our preclinical programs. We, of course, did talk about the 24-month phase I/II data in XLRP coming in the second half of this year. We've got obviously the 12-month Skyline data coming in the first quarter of next year as well. We think we are reasonably well-financed for the near term. Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over to Sue Washer for any further closing comments. Thank you. We are very excited about the data across both the Skyline and the phase I/II trials, and believe they provide evidence that supports a differentiated profile for AGTC-501 with respect to both safety and efficacy. Additionally, in keeping with our rationale for conducting Skyline, the data reported today also provide insights that we may incorporate into the VISTA trial, maximizing our likelihood of success, and it provides a third group of patient data to support a potential BLA submission. This three-month interim Skyline data will be presented at two upcoming medical conferences. Dr. Andreas K. Lauer will be presenting during the Macula Society meeting, and Dr. Rajiv Anand will be presenting during the American Society of Retina Specialists annual meeting. We are confident that the improvements in visual function, especially in the primary endpoint of visual sensitivity, will be meaningful to patients with XLRP who today have no treatment options and face a bleak future in which they will inevitably become legally blind. We believe that the FDA will consider the totality of all the data we include in our BLA filing and will also take patient perspective into account, as they have done in a number of other rare progressive diseases for which there are no treatments. We are also confident that we have and will continue to generate more robust and comprehensive efficacy data and that AGTC-501 has the potential to be best-in-class therapy. We look forward to providing additional updates from our XLRP clinical program. 24-month data from the phase I/II in the second half of 2022. Twelve-month data from Skyline in the first half of 2023, and interim data from the VISTA trial in the first half of 2023. We are fully committed to advancing AGTC-501 as rapidly as possible. As always, I'd like to thank the patients and their caregivers whose participation makes our trials possible, as well as the investigators and their staff at our clinical sites and the entire team of dedicated AGTC employees. We also thank our shareholders for their continued support. Thank you all for joining us today. Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.