Hello, ladies and gentlemen. Thank you for standing by, and welcome to 4D Molecular Therapeutics webcast presentation of interim safety and efficacy data from the phase 1/2 PRISM clinical trial of intravitreal 4D-150 in patients with wet AMD. At this time, all participants are in listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. As a reminder, today's call is being recorded. With that, I will hand the call over to August Moretti, Chief Financial Officer, who will make introductory comments. Thank you, operator, and welcome everyone to 4D Molecular Therapeutics 4D-150 interim data webcast. A press release describing the results and development plans related to 4D-150 is accessible in the investors section of the 4D Molecular Therapeutics website, and a recording of this webcast will be accessible on our website after completion of this call. With me today are Dr. David Kirn, our co-founder and chief executive officer, Dr. Bob Kim, our chief medical officer, and Dr. Arshad Khanani, managing partner and director of clinical research at Sierra Eye Associates and clinical associate professor at University of Nevada, Reno. Dr. Khanani is a principal investigator on the 4D-150 PRISM clinical trial. He will present the interim PRISM data today at the 2023 ARVO annual meeting. As a reminder, on this call we will be making forward-looking statements regarding our clinical data from our PRISM clinical trial, product development plans, research activities, and business plans. These statements are forward-looking statements and are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to materially differ from those forecasted. A description of these risks can be found in the Risk Factor sections of our most recent Form 10-K and Form 10-Q, which are on file with the SEC. With that, I'd like to turn the call over to our CEO, David Kirn. David. Thank you, Augie, thank you everyone for joining us today. We're pleased to share with you updates on 4DMT's 4D-150 program, including positive interim clinical data from our PRISM clinical trial. As many of you know, our platform is based on directed evolution technology to design customized vectors with superior therapeutic profiles compared to wild type vectors. To date, we've demonstrated human clinical proof of concept for our platform with three vectors in three therapeutic areas. We're currently developing five clinical stage products for seven patient populations, and our strategy is to become a fully integrated large market genetic medicines company. Our efficient product design and development engine has powered our broad and deep pipeline. Each therapeutic area leverages a proprietary and optimized 4DMT vector plus our product development engine. Today, we'll focus on 4D-150 for wet age-related macular degeneration or wet AMD. This product is also being developed for diabetic macular edema or DME. 4D-175 is our preclinical product for geographic atrophy. As a reminder, 4D-150 was designed as a single routine low-dose intravitreal injection to deliver a payload for expression within the retina that constitutively expresses two therapeutic products targeting 4 VEGF family members. Now let's share our key takeaways for today. We're presenting interim data for all 15 patients enrolled in 3 dose exploration cohorts, 5 patients each at 3E10, 1E10, and 6E9 vg/eye. Over 12 months prior to enrollment, these patients were confirmed to be heavily dependent on anti-VEGF injections. Follow-up at the time of data cutoff on April 3 was from 24 to 64 weeks. The key clinical data findings are as follows. Regarding safety and tolerability, 4D-150 was well tolerated at all three dose levels at all time points and in all 15 patients through 24-64 weeks. 14 of 15 patients had zero evidence of inflammation by all four different eye examination endpoints. A single patient had only trace mixed cells at a single time point that resolved without intervention. No dose-limiting toxicities, 4D-150 related SAEs, or hypotony were reported. For clinical efficacy data. Clinical efficacy data was available on all 15 patients through a maximum of 24 weeks. Clinical activity was demonstrated at all three dose levels. A dose response was observed in favor of the high 3E10 dose level based on supplemental anti-VEGF injections and central subfield thickness or CST on OCT scans. 80% or four of five patients in the 3E10 cohort were completely injection-free, compared to 40% or two of five patients at each of the two lower dose levels. The reduction in annualized anti-VEGF injections for the high-dose 3E10 cohort was 84%, with all injections being given to a single patient. The 3E10 cohort had the longest follow-up of all cohorts, with efficacy data available on all five patients through 36 weeks at the time of data cutoff. Durable clinical activity was observed. All four anti-VEGF injection-free patients at 24 weeks were still injection-free at 36 weeks. In addition, the mean Central Subfield Thickness, or CST, continued to improve with a meaningful decrease of 92 microns. The mean DCVA remained stable. The single injected patient had such severe disease that they would not qualify for phase two enrollment. Extended follow-up beyond 36 weeks, and specifically beyond 1 year, was available for 3 patients in this cohort for up to a maximum of 64 weeks, and durable clinical activity and tolerability were observed. The phase 2 dose exploration stage of the PRISM trial is enrolling briskly, and we're now over 50% complete with enrollment. We expect to complete enrollment of all 50 patients in Q3 this year instead of Q4. We expect to share initial data in the first half of 2024. Now, I'd like to turn the presentation over to Dr. Bob Kim, our Chief Medical Officer. Bob? Thanks, David. Before we dive into the data, I'd like to share a quick overview of the wet AMD market and unmet needs. Prevalence of wet AMD is estimated at 3 million patients in the U.S. and EU. The market is rapidly growing with an annual incidence of 200,000 in the U.S. The global market for anti-VEGF therapies is over $12 billion annually. Approximately 1.5 million patients are currently on treatment. Key unmet needs remain despite existing anti-VEGF therapies. Efficacy duration is generally one to four months, and frequent injections are needed to maintain efficacy. This limitation results in reduced adherence to treatment and suboptimal patient outcomes. We believe 4D-150 has potential to address these unmet needs. Our vector, R100, has advantages compared to wild-type vectors. As shown on the left, conventional wild-type AAV-based vector gene therapy has not been feasible with intravitreal injection due to blockage by the ILM barrier. As shown on the right, our vector R100 was invented in primates for penetration through the ILM barrier to efficiently transduce and express transgenes within the retina, including the macula itself. On the left, we can see that R100 demonstrates significantly superior transduction of human retina RPE cells compared to the commonly used wild-type AAV2 in vitro. On the top right is an in life image from a primate retina 26 weeks following intravitreal injection of R100, demonstrating widespread expression of the reporter gene GFP, including in the macula. 4D-150 is designed for a single dose intravitreal injection to inhibit four key angiogenic factors driving wet AMD and DME. 4D-150 is comprised of the R100 capsid and the dual transgene payload cassette. This payload expresses both aflibercept and a VEGF-C RNAi. On this slide, we see that 4D-150 has a biodistribution and pharmacokinetics that are highly differentiated from aflibercept. With intravitreal administration of a biologic like aflibercept, the highest concentrations are observed in the vitreous, with lower concentrations in the aqueous humor and the retina and choroid, as illustrated in the top row of the figure. Repeated intravitreal injections are necessary to maintain a concentration of aflibercept in the retina that is consistently above the therapeutic trough threshold. On the bottom, we illustrate conceptually the predicted biodistribution and pharmacokinetics of aflibercept protein expression patterns for 4D-150. 4D-150 injection results in sustained aflibercept concentrations that are highest in the retina and choroid, followed by the vitreous and lowest in the aqueous humor. 4D-150 is highly efficient at driving aflibercept expression within the retina and choroid, precisely in the tissues that are critical for clinical efficacy. 4D-150 also has potential advantages versus other AAV competitors. The top dose of the human phase 2 dose range for 4D-150 is substantially lower than the top doses used by other AAV development candidates using suprachoroidal or intravitreal injections. The phase 1/2 highest dose of 3E10 for 4D-150 is only 3% of the highest dose being utilized for RGX-314 by suprachoroidal injection, and only 15% of the dose used with Ixo-vec by intravitreal injection. In summary, we believe 4D-150 is highly differentiated from approved anti-VEGF therapies and other development stage AAV-based therapies. We believe that 4D-150's intravitreal injection route, inhibition of four VEGF family members, anti-VEGF expression directly within the macula, and promising safety profile give it the potential to become a best-in-class product. Let's move on to the interim clinical data. I'd like to turn the presentation over to Dr. Khanani. Arshad? Thanks, Bob. Here's the design of the phase 1/2 PRISM clinical trial with 4D-150. The objectives of the trial are to evaluate the safety, tolerability, and efficacy of 4D-150 in patients with wet AMD requiring frequent anti-VEGF injections. The clinical trial has 2 stages. The first is the open label dose exploration stage, which included a total of 5 patients per dose cohort. 3E10, 1E10, and 6E9. The second stage is the phase 2 dose expansion stage, in which 50 patients are randomized to one of the 2 doses of 4D-150 or aflibercept in a 2- to- 2- to- 1 ratio. Patients received a single intravitreal injection of 4D-150 following an initial aflibercept injection. Topical corticosteroid prophylaxis was initiated 3 days prior to dosing, then tapered over 20 weeks. These patients received no oral, intravitreal, or sub-Q non-corticosteroids. After the first month, patients were followed every four weeks, and the need for supplemental aflibercept was assessed at each visit using pre-specified BCVA and OCT criteria. Key eligibility criteria are listed on the right. As a reminder, these are previously treated patients requiring at least six prior anti-VEGF injections within the prior 12 months in the study eye and documented response to an anti-VEGF therapy. Phase 2 stage enrollment criteria require a higher range of BCVA than was the case in the dose exploration stage. The primary endpoint is safety and tolerability of 4D-150. Key secondary endpoints include change in BCVA and CST and the need for supplemental aflibercept injections using the criteria listed in the lower right. Here we show the baseline characteristics of the 15 patients. Of note, patients in the 3E10 dose cohort had the most severe disease compared to the 1E10 and 6E9 cohorts, as evidenced by the much lower visual acuity, much higher CST, and higher need for anti-VEGF injections prior to 4D-150. The mean annualized injection frequency for the 3E10 cohort was approximately 11. Moving on to the dose exploration data on all 15 patients at 24 weeks, this is the longest available time point for all 15 patients. Looking at overall safety, 4D-150 has been well-tolerated to date without any DLTs or 4D-150-related SAEs. 14 of 15 patients had no inflammation noted by any of the 4 measures on eye exam. A single patient had trace mixed cells in the vitreous at a single time point, which resolved without intervention. 14 of 15 patients completed the protocol-mandated 20-week topical corticosteroid taper and did not receive further steroids. A single patient was continued on topical corticosteroid beyond 20 weeks by the treating physician for non-inflammatory, asymptomatic pigmented cells. We have not observed any cases of hypotony, endophthalmitis, retinal vasculitis, choroidal effusion, or retinal artery occlusion in this trial. This slide shows the primary ocular exam data for scheduled visits in all 15 patients following 4D-150 to date. The data here depicts SUN and NEI scores for inflammation, which create observations of white blood cells, flare, and haze within the anterior chamber and vitreous. Overall, 99.8% of the 480 scheduled assessments were negative for inflammation. Aqueous humor samples were obtained at week 12 and tested for aflibercept levels to assess transgene expression. As Robert Kim previously mentioned, 4D-150 was designed and developed for transgene expression in the retina and the choroid and not in the anterior segment. Background in primate, aflibercept concentrations were significantly higher in the retina choroid than in the aqueous humor. Based on this modeling, we predicted the aqueous humor concentration above the limit of detection are expected to correspond with therapeutic concentrations in the macula. Shown here, 11 patient samples were evaluable at this time. 3 patients had an aflibercept injection prior to 12 weeks, which would confound this assay and therefore were excluded from the analysis. 1 patient's result is pending. aflibercept was detectable in 10 of 11 evaluable samples. A single sample from a patient in the 1E10 mid-dose group had undetectable levels. Of note, this patient still responded to 4D-150 and was supplemental injection-free at the 24-week time point. Mean aflibercept levels shown here clearly demonstrate a dose response. This slide shows longitudinal data on mean BCVA change for all three cohorts. Overall, the BCVA remained generally stable over time for patients in all three dose cohorts. This slide shows longitudinal data on mean CST for all three dose cohorts. Overall, the CST remained generally stable over time for patients in the 1E10 and 6E9 dose cohort. In contrast, the mean CST for the 3E10 dose cohort showed progressive improvement with a decrease of 78 microns from baseline through 24 weeks. Here we present data on supplemental anti-VEGF injections across all three dose cohorts through 24 weeks. On the left side of the figure, the data for anti-VEGF injections in the preceding 12 months is shown for all patients. Different colors represent different approved anti-VEGF therapies. On the right, anti-VEGF injections are shown over time for all patients following 4D-150. A white circle shows a visit at which a supplemental injection was not performed, whereas a red circle shows an injection based on protocol-defined criteria. The 3E10 dose level showed the highest reduction in anti-VEGF injections. 80% or 4 of 5 patients were injection-free at 24 weeks, versus 40% or 2 of 5 for each of the 2 lower dose groups. Here we summarize data for each dose cohort on disease severity at baseline, plus supplemental anti-VEGF injections and mean CST changes through 24 weeks. Despite having the most severe disease, 80% of patients in the 3E10 dose cohort remained injection-free, with 84% reduction in mean annualized anti-VEGF injection rate and with a mean improvement in CST by 78 microns. These data demonstrate promising interim clinical activity across all 3 doses studied, with a dose response observed in favor of 3E10. Let's review data for the highest dose cohort, 3E10, with longer follow-up. This slide shows a safety summary for the 3E10 dose cohort covering week 24-64. All patients had follow-up through 36 weeks and 3 patients had follow-up beyond 36 weeks out to 56-64 weeks. 4D-150 continues to be well-tolerated. We have not seen any 4D-150-related SAEs or any cases of inflammation. This slide shows the same ocular exam data shown earlier, now through 36 weeks for all 5 patients in the 3E10 cohort. The blue boxes highlight the time period from 24-36 weeks. In this period, 5 of 5 patients had uniformly normal exams for all 4 inflammation assessments in both aqueous and vitreous. Shown here in white symbols, for Patient 1, asymptomatic non-inflammatory pigmented cells were intermittently noted. Patient 3 had trace asymptomatic non-inflammatory pigmented cells at a single time point. As previously described, 4 of 5 patients completed their protocol-mandated 20-week topical corticosteroid taper and did not receive further steroids. As mentioned in the prior slide, 3 patients had follow-up beyond the time point shown on this slide, and no inflammation or 4D-150-related SAEs were reported. In terms of mean change in BCVA, you can see here that despite advanced disease, BCVA remained stable in patients in the 3E10 dose cohort through 36 weeks. Mean BCVA was virtually unchanged. Moving on to CST, the slide shows longitudinal data on mean CST for the 3E10 dose cohort through 36 weeks. The mean CST for the 3E10 dose cohort showed progressive improvement through 36 weeks, with a decrease of 92 microns from baseline. This slide shows individual patient data for BCVA for all four injection-free patients. You can see that the four injection-free patients were all generally stable. Patient 1 had a BCVA reduction of 7 letters, which was associated with a worsening cataract. This slide shows individual patient data for CST for all four injection-free patients. You can see that two patients had clinically meaningful reduction in CST. The other 2 patients were stable. In terms of supplemental anti-VEGF injections through 36 weeks, 4D-150 was able to completely eliminate the need for supplemental injection in 4 out of 5 high-need patients. Patient 5 had especially severe disease and was a suboptimal responder. This patient would have not qualified for the Phase 2 enrollment criteria based on a very low BCVA of 28. In terms of long-term durability, in the 3 patients with long-term follow-up to 56-64 weeks, 2 of 3 remain injection-free and 3 of 3 have improved CST. Here we show a case study from a patient in the 3E10 dose cohort. This was a high-need patient requiring 13 anti-VEGF injections in the prior 12 months. You can see the OCT images showing poor disease control with frequent anti-VEGF injections. After a single intravitreal injection of 4D-150, we saw clinically significant improvement in CST as well as a 5-letter improvement in BCVA. Showing the potential of 4D-150 in controlling disease activity in wet AMD. I will now hand the presentation back to David, who will provide closing remarks. David? Thanks, Arshad. Today, we presented promising clinical data on 4D-150. We believe 4D-150 has the potential to be a best-in-class genetic medicine for wet AMD. 4D-150 was well tolerated at all 3 dose levels. 14 of 15 patients had zero evidence of inflammation by all 4 different eye examination endpoints. Clinical activity was demonstrated at all 3 dose levels, with a dose response observed in favor of the 3E10 dose level. At 24 weeks in the high dose cohort, 80% or 4 of 5 patients in the 3E10 cohort were injection-free, with a reduction in annualized anti-VEGF injections of 84%. At 36 weeks in the high dose cohort, the 4 anti-VEGF injection-free patients remained injection-free and with a mean overall CST improvement of 92 microns. Mean BCVA remained stable. The phase 2 stage is over 50% enrolled already, and we've now updated our guidance to complete enrollment in Q3 and expect initial phase 2 data in the first half of next year. We believe this rapid progress signals the excitement of the clinical investigators about the potential of 4D-150 in patients with wet AMD. We just discussed our updated phase 2 guidance. We expect to have phase 3 planning discussions with FDA in Q4 this year. In regards to DME, we remain on track to initiate enrollment for the phase 2 SPECTRA trial, with first patient enrolled targeted for Q3 and initial data in 2024. We're excited to expand it into this indication given our positive interim safety and efficacy data in wet AMD. We'll end with our growing ophthalmology portfolio. This slide reiterates our commitment to developing innovative genetic medicines for large market ophthalmology indications, including wet AMD and DME. We also recently announced the completion of an asset purchase agreement for short form complement factor H, which we believe when combined with our retinotropic R100 vector, will be a differentiated product candidate for geographic atrophy, another large market opportunity. Before we move into Q&A, I'd first like to acknowledge and thank our investigators, clinical trial staff, patients, and their families. Operator? Thank you. We will now begin the question-and-answer session. If you have a question, please press star one on your telephone keypad. One moment please for your first question. Your first question comes from the line of Salveen Richter of Goldman Sachs. Please go ahead. Good morning. Thanks for taking my question. Congrats on the data here. 2 questions here. One, how comfortable are you that you've reached long enough follow-up that you can understand the safety profile at the high dose? How do you think about the risk of late onset inflammation occurring? Secondly, how do you think about the improvements in CST with a slight decline in BCVA at the high dose? You know, I recognize BCVA is more meaningful, but just if you could put that in context in addition to the loss of BCVA letters at the higher dose, in the context of how patients might perform on aflibercept as you move into larger trials here. Well, thanks, Salveen, and good morning. First of all, I think that, you know, the safety signal here is very strong. We have safety data out to 36 weeks on all 5 patients at a high dose level and out beyond a year in 3 patients, and we've reported really, you know, no inflammation, no serious adverse events related to 4D-150 and no hypotony. I think this is the cleanest safety profile that's been presented with a genetic medicine in the eye. I think, you know, if you look at the history of retinal gene therapy, if you're going to see inflammation, you are always going to see it at an earlier time point. I don't think there's any examples of inflammation popping up randomly, you know, well beyond six to nine months. I think we have clearly checked the box that this is extremely well tolerated after a single intravitreal injection, which is a game changer for this field. That safety data is particularly important in large market indications such as wet AMD and DME. In terms of the CST, you know, our, you know, hope was at a minimum it would stay stable. The fact that in patients who've received no injections over approximately 9 months, that their CST continues to improve on 4D-150, I think is just a remarkable biological sign of clinical activity and really, I think bodes well for the future of the product. In terms of the BCVA, it's absolutely stable and within the noise of the assay, we did show that in patients who have not been injected, you know, the mean is close to zero and absolutely overlaps with zero. We're very pleased with the overall BCVA stability as well. Thank you. Thank you, Salveen. Your next question comes from the line of Nalin Tejavibulya. Please go ahead. Hi. Thank you very much for taking my questions. For the first one, for DME, the disease etiology is different from at wet AMD. You know, DME patients tend to be younger and have systemic disease, and that can make them more susceptible to inflammation compared to wet AMD, where patients are old and, you know, have more, much more confined disease to the eye. For phase 2 SPECTRA, could you please provide more details on what patient age groups you would be looking to enroll? Do you think that the 20 weeks of topical treatments would be sufficient, or, you know, would you potentially need the kind of similar oral plus topical regimen that was used in the XLRP program? For the second question, could you please provide clarity on whether the patients who did not have significant reduction in treatment burden, if you would consider redosing those patients? Thank you. Well, thank you, Nalin, for the question and good morning. In terms of the SPECTRA study for DME patients, we're really excited about this opportunity. To our knowledge, we'll be the only genetic medicine company treating patients in this important and very large and growing market with high unmet medical needs. One of the exciting things here is that historically, agents that have worked in wet AMD and been effective have also been highly effective in DME. If anything, DME patients tend to be a little bit more responsive at even lower doses of these agents, these anti-VEGF agents, than in wet AMD. you know, we're thrilled with that potential. We're also thrilled with the safety profile that we've seen to date, with 14 out of 15 patients, showing 0 inflammation and 1 patient having trace mixed cells at a single time point. I think, you know, we have a very, very strong safety and tolerability profile and efficacy and clinical activity profile going into the SPECTRA study. You correctly point out that these patients are younger and will have a broad enrollment criteria initially. We are really pleased with the performance of our steroid regimen. You know, we're using a simple all-topical regimen, which is important in diabetics, not to, if you can avoid it, not to use systemic steroids, oral steroids or the like. You know, we're thrilled with an all-topical regimen. We don't use oral steroids or sub-Tenon injections or other maneuvers, and we think this is going to hold up in DME. Importantly, in DME, we'll be starting down at the 5E9 dose level, which we think has a strong chance of having clear clinical activity and tolerability. We'll be less than 1% of the dose that showed hypotony and other significant inflammation problems with the Ixo-vec product candidate. We think we're in a really very good dose range to be in for safety, and we believe there's a strong likelihood of clinical activity. In terms of the wet AMD and redosing, again, as a first in human study, we always start with the most advanced patients. These patients are extremely advanced, particularly that patient 5 in cohort 1, with a baseline BCVA of 28 was a clear outlier and would not qualify for phase 2 on that basis, and had had 13 injections in the preceding year. Really, I think that patient was very useful for safety data, which was confirmed, but it's not relevant for phase 2. With regards to redosing of patients who need an additional boost, that's certainly something we could consider in the future, and we may explore that. At this point, we don't think that's necessary, and we're excited about the signal we're seeing. Thank you very much. Your next question comes from the line of Josh Schimmer of Evercore ISI. Please go ahead. Great. Thanks for taking the question, thanks as well for the detailed presentation. A lot of useful information in here. First I just want to reconcile the answer you gave to Salveen about the uninjected patients in the high-dose thermal being stable in terms of visual acuity. What I thought you said was a patient who had a deteriorating cataract. I guess that, does that imply there was one patient who had deteriorating vision and that might have been from the cataract as opposed to the underlying disease that was a little bit harder to manage? Thanks, Josh, and good morning. So we presented individual patient data for the 3E10 cohort out to 36 weeks for patients who are completely injection-free to see how, you know, 4D-150 managed those patients. You know, as we showed, we have a patient who had 0 letter changes, 1 with a 1 letter change and 1 with 5. The 1 patient, and these are, sorry, +5 and +1, so in fact, 3 patients were stable or slightly improved within the noise of the BCVA assay. We did comment on the 1 patient. Patient 1 had progressive cataract and dropped from approximately, you know, stable with approximately -2 or 3 letters down to -7. With the surgery of that cataract, we expect that to pop right back up. Overall, the BCVA data in patients who've not been injected for approximately nine months is either stable or slightly improved. What happened to the BCVA of the patient who actually did require subsequent, anti-VEGF antibody injections and then high-dose A? You're saying the patient who did require injections? Correct. Yeah. Yeah. That, that patient was bounced around a lot. Their baseline BCVA was 28, which is low. That patient bounced around anywhere from decreased to, you know, to the criteria of getting another injection, which was 10 letters, up to, you know, within the range between zero to 10. Very severely advanced disease would be excluded. No, certainly no evidence of toxicity in that patient. No evidence of retinal damage, but a highly variable BCVA readings in that patient. In the high-dose arm you had that patient who didn't seem to derive significant benefit. On the other hand, you had one patient who had a fairly dramatic reduction in CST. Do you have the aflibercept intravitreal levels that might help correlate why one patient did so well and one patient didn't? Yeah, it's a great question. Overall, you know, the mean aflibercept in this cohort was approximately 250 and with a range of about roughly 60-600. Patients were well above the threshold that we had targeted for activity. I think above that threshold. We did see a dose response in terms of dose and aflibercept levels at the mean cohort level. We did see a correlation with efficacy. We think being in that range of dose is important. Beyond that, on a patient-by-patient basis, we don't see that predicts as long as patients are, again, in this therapeutic range. You know, the patient who got injections, patient 5, again, the significant outlier would not be enrolled in phase 2. You know, they got 13 injections in the preceding 12 months. That suggests they don't have any evidence of any sort of durable aflibercept benefit. I think patients like that who are not going to respond to the protein and have BCVAs well below the phase 2 cutoff are, you know, highly unlikely to respond. Those will be patients that we exclude going forward. Okay. Thank you very much. Josh, if I wasn't clear, you know, that patient did have expression. Okay. Thank you. Your next question comes from the line of Kostas Biliouris of BMO Capital Markets. Please go ahead. Good morning, everyone. Thanks for taking the question. Congrats on the data. A couple of questions from us. The first one is on the traced mixed cells that you saw in one patient. Can you confirm whether this is the same case as the one you described in the previous readout in November, or this is a new case? Thank you. Then I have a follow-up. It's the same case. There was a single episode at a single time point of traced mixed cells. Again, you know, in these very advanced wet AMD patients, it's possible these traced cells would be picked up periodically, just even in patients on standard anti-VEGF therapy. That's something, we're looking at. No, this is the same case. You know, otherwise, 14 of 15 are 100% inflammation-free and well over 400 evaluations. Great. Thanks. Can you talk a little bit about how the aflibercept levels in the highest dose compare with the aflibercept levels of patients who are under Eylea? Right. I think what's important is, as Bob Kim our CMO showed in the presentation, our biodistribution and mechanism is actually very different from standard protein Eylea. In contrast to Eylea, where you get these spikes and then troughs, spikes and troughs, with poor adherence out in the real world and breakthrough disease and progressive damage to the retina, what we have is a stable, what we believe is a stable expression of aflibercept in the anti-VEGF C directly in the macula where it's needed. In primates, when we look at levels in the retina, they're very significantly higher than they are in the vitreous. What we see in the aqueous is really the tip of the iceberg. What we're targeting is to be in a dose range that is equivalent or above the trough levels at 8 weeks with the aflibercept protein in the retina. When we do those calculations, we get approximately 25 nanograms per mil in the aqueous would predict for, you know, therapeutic levels in the retina. Obviously, the error bars in such assays are pretty wide, so it's possible, you know, they definitely cross zeros. It's possible to still have efficacy in a patient who's undetectable, as we showed at that one patient. At the mid-dose 1E10 was still injection-free at 24 weeks, despite being undetectable at 12 weeks. You know, I think that's how we think about this. The amount in the aqueous is really irrelevant. What matters is what's being expressed in the retina. I think what we're seeing here is, that we're above the threshold for efficacy in the vast majority of these patients. Perfect. Thank you so much. Congrats on the data again. Thank you, Kostas. Once again, ladies and gentlemen, if you have a question, it is star one on your telephone keypad. Your next question comes from the line of Mani Foroohar with SVB Securities. Please go ahead. Hey, guys. Thanks for taking the question. Apropos the non-responder in the 3E10 cohort, this was on a baseline of 28 letters. Can you walk us through, given what we know about the injection criteria, what triggered those rescue injections? 'Cause apropos having a relatively low baseline letters, putting on a 10-letter loss should be relatively difficult. Was it a question of fluid? What drove the injection volume in that patient? Then I have a follow-up. Yeah. Thanks, Mani. Good morning. So as I said, that patient's an outlier who would not qualify for phase 2. These are the sorts of patients that we put on phase 1 humans studies. That patient had injection criteria that were determined either by CST or BCVA, primarily CST. You know, what had crossed that threshold on both criteria at different time points. Again, I think if you look at the responsiveness to the aflibercept protein itself, there's no evidence this patient is deriving any sort of durable benefit from that either. You know, with 13 injections that proceeded 12 months going into this and, you know, even further injections on study. This patient appears to be relatively refractory to any sort of durable benefit from the aflibercept protein. Okay, that's helpful. As one digs into the data, how does that inform your sense of what the universe of patients that are appropriate for this therapy would be? If one starts excluding those most severe patients slash non-responders, how are we going to find them from the potential commercial opportunity? What proportion of currently treated wet AMD patients would fall into that sort of too far gone, too low BCVA? How are we going to define that population? Yeah, that's a great question. I think given our safety profile and the simple intravitreal injection, we have an opportunity to have a very broad label. you know, I think, clearly the vast majority of patients are having clinical activity with 4 out of 5, and this study still being injection-free at approximately 9 months. And don't let's not forget, even these patients were very advanced and very severe, disease with high need, wet AMD. I think we'll be able to treat the majority of high-need patients as well as now that we have this sort of, this, clinical activity and tolerability signal, we can move into earlier stage patients as well and eventually, you know, even treat patients soon after diagnosis. I think the population, as we show more and more data, will allow us to go earlier and earlier stage. We think at the end of the day, we should be able to treat the vast majority of patients with wet AMD. Great. That's helpful. Forgive me, we don't have the, we don't have the slides. I know it'll be released later on today. Do you guys could slide back to the slide with the patient-level BCVA, for the patients in the highest dose cohort, the first cohort? I've had a couple of inbound investor questions around what rescue injection rate would look like if one applied something like on the, like a -5 letter, perhaps, you know, more restrictive metric, which could be appropriate for patients which have, that have a lot more vision to save. It's, it's hard for me to do that math without the raw data on hand. Like, what would that do to the injection-free rate and... Not the injection-free. I'm sorry. What would that do to the injection reduction rate if one applied a negative five-letter bar? Yeah. Well, you know, as I said, there's clear, strong clinical activity here, robust aflibercept detection in the aqueous, which bodes very well for a high level expression in the retina. The injection criteria that we're using are very standard. They're identical to some other studies in the field, and they were set by key opinion leaders that we relied on to set those criteria. These are rigorous criteria. You know, 75 microns or more progression and 10 letters or more on BCVA. Some studies will use two consecutive, 5-letter changes, 5-letter worsening, as a cutoff, but that is again two consecutive. We think these are robust. We don't think that using something, you know, other criteria in the field would change these results significantly. you know, we think these are robust, strong criteria for detecting clinical activity. I think also in addition, you know, the decrease in the CST actually, you know, we certainly hoped as part of our target product profile to see a stabilization of CST. We actually saw a significant improvement in 2 patients and strong, stable disease in the other 2 with a mean decrease of 92 microns. Those are patients who had zero rescue injections over the course of 9 months. I think that clearly signals strong clinical activity, even these patients with very advanced disease. Great. Just one last question I just got in from, an investor who's listening in. Can you confirm that there were no changes in intraocular pressure, for all patients off steroids? Yes, we can confirm that. Great. Thanks, guys. On to phase 2. All right. Thank you, sir. This concludes the question and answer session. I will now turn the call over to Dr. Kirn. All right. Well, thank you for your attention and your excellent questions today. We're excited about these interim data. We're also excited by the enthusiasm that physicians are showing in terms of enrollment on the phase 2, with that now being more than 50% enrolled and completion targeted for Q3, which is again an update of our guidance from Q4, now moving forward to Q3 for completion of enrollment. We look forward to sharing phase 2 data from this study in the first half of 2024. Thanks, and have a great day. This concludes today's conference call. You may now disconnect your lines.