Good morning and welcome, everyone. Adverum recently issued a press release providing the details of the company's LUNA 52 Week and OPTIC 4-Year Analysis. In addition, the company provided details of the Pivotal Program. The press release is available in the Investor Relations section of the company's website at investors.adverum.com. Today's call will be led by Dr. Laurent Fischer, President and Chief Executive Officer. The webcast will include prepared remarks from Dr. Star Seyedkazemi, Chief Development Officer; Dr. Rabia Gurses Ozden, Chief Medical Officer; and Jason Mitchell, Chief Commercial Officer. In addition, Dr. Seyedkazemi will moderate a key opinion leader panel. It is our pleasure to also welcome esteemed retina specialist Dr. Charles Wykoff, Director of Research of the Retina Consultants of Texas and Professor of Clinical Ophthalmology at the Blanton Eye Institute of Houston Methodist Hospital; Dr. Mark Barakat, Director of Clinical Research at Retina Macula Institute of Arizona; and Dr. Szilard Kiss, an Adverum board member and Distinguished Professor of Ophthalmology, Director of Retina Service at Weill Cornell Medical College. As a reminder, we may be making forward-looking statements, including statements related to the potential of Ixo-vec and plans and milestones regarding Ixo-vec, which are based on certain assumptions made by Adverum based on current conditions and expected future developments. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which are described under the captioned risk factors in Adverum's filings with the Securities and Exchange Commission. For further details, please visit our website. At this time, it is my pleasure to turn the call over to Adverum's President and Chief Executive Officer, Dr. Laurent Fischer. Laurent? Thank you, Mike, and thank you all for joining us today to discuss these exciting results from the Luna 52-week analysis and the long-term Optic 4-year data. On this slide, you'll see the key topics we'll be covering today, including insights from our KOL panel featuring Dr. Charles Wykoff, Dr. Mark Barakat, and Dr. Szilard Kiss. I'm joined today by my exceptional team, who will be available to answer questions later. As Adverum moves forward towards Pivotal Trial and ultimately commercialization, I want to give a special shout-out to our two most recent hires, Dr. Rabia Gurses Ozden, our Chief Medical Officer and former board member, who previously led Ocular Therapeutix's innovative phase III program, and Jason Mitchell, our Chief Commercial Officer, who played a key role in the launch of Syfovre, the first treatment approved for geographic atrophy. I'm excited to leverage Rabia and Jason's expertise as we prepare to bring a transformative, potentially best-in-class gene therapy product for wet AMD patients to market. It is my distinct pleasure to welcome our retina specialists and key opinion leaders, Dr. Charles Wykoff, Dr. Mark Barakat, and Dr. Szilard Kiss. We will hear from each of them later, and I believe it will be incredibly valuable for the audience to gain their firsthand perspectives on Ixo-vec, a one-time interventional gene therapy for patients with wet AMD. We believe that Ixo-vec has the potential to shift the current treatment paradigm by providing significant long-term benefits and potentially lifelong preservation of vision for patients. Without further ado, I'd like to briefly summarize our press release from earlier today and share the key takeaways. Today's clinical updates highlight Ixo-vec's potential as a best-in-class treatment for wet AMD, while also underscoring that we have effectively de-risked both our phase III Pivotal Program and our commercialization strategy. We have consistently demonstrated outstanding clinical activity, exceeding our targets of having more than 50% of patients injection-free and achieving a greater than 80% reduction in treatment burden within this hard-to-treat patient population. Together with Optic and Luna, we now have established a tenfold safety margin with greater than four years of follow-up, reinforcing the robustness of our data. Notably, zero patients at the 2E11 dose in Optic had inflammation at year one and through year four, and no patients in Luna at the 6E10 dose had inflammation on 52 weeks or any subsequent visit. Importantly, patients have unequivocally expressed a clear preference for Ixo-vec over their previous standard of care and would overwhelmingly recommend it to family and friends. And finally, we will provide the details of the phase III Artemis study, which will include a broad patient population supporting a broad label and which we intend to initiate in the first half of next year. Taking a step back, it's important to appreciate the product profile of our gene therapy candidate. Our vector is engineered for the sustained delivery of aflibercept, a treatment that has been administered in more than 70 million eyes. Our Pivotal Program is built on the foundation of 5+ years of clinical experience with Ixo-vec. And with the 6E10 dose we plan to take forward into Pivotal Studies and ultimately to market, we have established a tenfold safety margin relative to the highest dose we've tested. Our pioneering work in ocular gene therapy and long-term learnings from these five-plus years of clinical experience in Optic enabled us to further optimize the benefit-risk profile of Ixo-vec in Luna, where we evaluated both a lower dose and an extended prophylaxis. Today's results confirm Ixo-vec's product profile with potentially transformative lifelong benefits for patients. On this next slide, we summarize the clinical data at different doses across our trials conducted in hard-to-treat patients. Here you can see the rationale for moving forward with a 6E10 dose and really beginning to understand that the combination of an easy-to-use steroid eyedrop prophylaxis with a 6E10 dose results in an optimal product profile where at 52 weeks, in these patients requiring 10 annualized injections the year prior, we saw an over 80% reduction in treatment burden, over 50% of patients free of injection, and no inflammation at 52 weeks with nearly all patients off steroid eyedrops. Two important questions that we receive both from retinal specialists and investors are: one, how reliable is the long-term benefit of Ixo-vec? And two, how predictable is the safety profile of Ixo-vec overall? We have long emphasized that fixating on the presence of anterior chamber or vitreous cells at week 20, 24, 28 does not capture the big picture of Ixo-vec's potential and overall therapeutic impact. Given that Ixo-vec provides sustained delivery of aflibercept for over five years and potentially for the lifespan of patients with wet AMD, it truly is the long-term benefit-risk profile that matters most to both patients and retina specialists. We're happy to confirm today that we've answered both questions head-on. Ixo-vec delivers reliable long-term benefits and provides a predictable, favorable overall safety profile. First, on the benefit side, the four-year Optic data provides us with a long-term perspective, notably that approximately 80% of Optic 2E11 patients who were injection-free through year one remained injection-free through year four, and that approximately 90% of Optic subjects who were injection-free through year two remained injection-free through year four, meaning that if you're injection-free for an extended period of time, the likelihood of ever needing another injection greatly diminishes. Second, on the safety side, in both OPTIC 2E11 and in Luna at both doses, no new patients presented with inflammation after week 30, and if patients had inflammation, it resolved by year one. This paints an important picture. If you never presented with inflammation, you're unlikely to ever have inflammation, and if you did have inflammation, it was asymptomatic, easily treatable with local steroids, and ultimately went away. Ixo-vec has the potential to offer a shift in the treatment paradigm of wet AMD by offering constant therapeutic levels of aflibercept and preserving vision for years after one injection, with a benefit-risk profile that keeps improving over time, lasting not just a few weeks, but for several years and possibly for life. Now, taking a step back to look at the landscape, obviously, wet AMD is a large and growing market as the population ages. Considering today's standard of care with interventional injections given anywhere from every four to every 16 weeks, the current market trends and the future projections indicate that even a moderate adoption of Ixo-vec could position it to become a blockbuster product. On the next slide, real-world evidence continues to underscore the clear unmet need in wet AMD. The primary challenge remains a significant treatment burden, which has a profound impact on both patients and their families. As a result, many patients are chronically undertreated, leading to poor vision outcomes, as shown in this slide. Multiple clinical studies and real-world evidence, including the IRIS Registry, which tracks 160,000 patients in the United States, highlight that while vision improves initially with anti-VEGFs, these gains are often lost over time. This is largely due to a decreasing number of interventional injections administered year after year, resulting in a gradual vision deterioration. Even more concerning is the fact that this data does not capture the up to 40% of patients who discontinue therapy within two years and over 50% who stop after five years. In contrast, Ixo-vec offers the potential to deliver a sustained level of Aflibercept in the eye after a single injection, providing continuous therapeutic benefits over five years and likely for the duration of the patient's life. Here, we can see the key reasons why patients are often undertreated. Barriers to treatment in this age group include comorbidities, life events, hospitalizations, needle anxiety, lack of transportation, and more factors that contribute to missed visits, missed injections, ultimately compromising vision. Remarkably, even 20 years after anti-VEGFs became available, and despite years of incremental improvements, physicians continue to identify longer durability, improved vision, longer anti-VEGF suppression, and stable anatomy as the greatest unmet needs in the treatment of wet AMD. Ixo-vec, as a gene therapy with the potential for lifelong benefit and to date, is the only modality with the potential to address these unmet medical needs and effectively tackle undertreatment. As discussed, even the latest approved treatments do not extend therapy beyond 16 weeks, and only a minority achieve that goal. Other than gene therapy, other classes of agents in development do not promise the transformational years-long efficacy we see. Ixo-vec holds the potential for one-and-done interventional injection that could provide years and possibly lifelong therapeutic benefits. The data we're presenting today underscores this promise, showing the potential to preserve vision and maintain fluid control for over four years, with stable levels of anti-VEGF maintained for up to five years so far. Before I hand it over to Star to review the data, let me quickly recap the key points about Ixo-vec. Ixo-vec utilizes our proprietary 7m8 vector developed through directed evolution across multiple species to efficiently cross the inner limiting membrane and transduce the retina. This unique capability enables interventional dosing, setting it apart from the wild-type vectors. 7m8 is the gold standard for retinal transduction and is currently being used in three clinical programs. Notably, it is the only interventional vector with peer-reviewed preclinical and clinical data published. Furthermore, Ixo-vec relies on a single transgene to express robust and steady aflibercept levels without being encumbered by additional transgene. It also leverages aflibercept, a trusted and proven agent effectively blocking neoangiogenesis that has been used in over 70 million eyes worldwide. Star? Thank you, Laurent, and thanks, everyone, for joining us today. It is my pleasure to walk you through the Optic 4-year and Luna 52-week top-line results of Ixo-vec, which have laid the foundation of our planned phase III trials and the transformative product profile we intend to successfully launch for the treatment of wet AMD. Optic was a first-in-human trial in a wet AMD patient population with severe disease activity who required frequent anti-VEGF treatment. We evaluated Ixo-vec at the two higher doses of 6E11 and 2E11, with short courses of steroid prophylaxis, including a 13-day course of oral prednisone and a six-week regimen of steroid eyedrops. The two-year results from the study were previously published, showing excellent visual and anatomic response and substantial reduction in treatment burden with both doses of Ixo-vec. We also observed lower rates of inflammation with the 2E11 dose. Today, I will focus the OPTIC portion of my presentation on the four-year analysis from the long-term extension study in which patients were followed on a quarterly basis for efficacy and safety. Before we describe the LUNA trial, it's important to note our extensive preclinical data package, which informed its design. The data in NHPs across three logs of Ixo-vec doses show less-than-dose proportional aqueous humor Aflibercept levels and lower inflammation scores with lower Ixo-vec doses, even without the use of corticosteroids. These data led us to the hypothesis that a lower dose of Ixo-vec would provide similar clinical activity with lower rates of inflammation. Taken together, the learnings from OPTIC and NHP data informed the design of the phase II LUNA trial, for which we had two goals: to determine the optimal dose and to determine the prophylactic regimen for the phase III program. Moving to the Luna design, Luna is a double-masked phase II study in patients with wet AMD who required frequent anti-VEGF treatment. The study evaluated the efficacy and safety of the 2E11 and a new 6E10 dose. Luna also evaluated multiple extended steroid prophylaxis regimens. Response to anti-VEGF was confirmed during screening. 60 patients were randomized one-to-one to one of the two doses of Ixo-vec. The prophylaxis regimens included topical steroid eyedrops alone, or topical steroid eyedrops with an Ozurdex implant, or both of those with or without oral steroids. Patients were eligible for supplemental Aflibercept injections if they met any of the criteria outlined on the slide, including an increase in CST of greater than 75 microns from baseline, which required confirmation by our central reading center, loss of at least 10 letters in BCVA from baseline due to new or worsening IRF or SRF, or presence of new vision-threatening hemorrhage due to wet AMD. Today's clinical data will focus on the top-line results from the Luna 52-week analysis, with context from both the 52-week and new 4-year Optic results. Here are the demographics and baseline characteristics of patients enrolled in the Luna and Optic trials. Patients enrolled in both studies had been diagnosed with wet AMD for approximately three-plus years and had received an average of 10 annualized anti-VEGF injections in the year prior to receiving Ixo-vec. Let's now start the efficacy overview. Here, we present individual patient aqueous aflibercept levels in both Optic and Luna for all patients with available samples. We measure levels of aflibercept in the aqueous, but it is important to note that we have published NHP data showing protein levels are up to seven-fold higher in the retina than in the aqueous. Our latest clinical data demonstrate consistent and predictable therapeutic aflibercept levels over time. We now have patients in Optic with five years of follow-up, and we can conclude that aflibercept levels we observe at week 12 are reliably sustained for as long as we have measured them. The aflibercept levels that we have measured in the 31 subjects at the early time point in Luna fall within the levels observed in Optic. Double-clicking on the 6E10 levels in Luna, we see a tight range of values that fall within the therapeutic range we've observed. Importantly, we now have two patients in the 6E10 dose cohort with 52-week Aflibercept levels, further strengthening our position that early Aflibercept levels are associated with sustained long-term Aflibercept expression. How do the sustained Aflibercept levels translate to clinical outcomes? Here, we present four-year treatment burden reduction for Optic 2E11, in which patients who required an average of 10 injections prior to Ixo-vec have achieved sustained disease control with fewer than two injections on an annual basis. This represents an over 80% reduction in injection burden. Remarkably, nearly 50% of patients remain free of injections at four years. Moving to the next slide, here we see the four-year swim lane plot for the 2E11 patients in Optic, where we see long-term freedom from injection that even improves year over year. With the long-term results and the predictable profile we observed in Optic, let's now review injection burden reduction in Luna. At 52 weeks, patients in Luna benefited from over 80% reduction in annualized injection rates, with over 50% remaining free of injections. These results are consistent with our observations in Optic at the same time point, after which we saw treatment burden reduction and injection-free rates reliably maintained through four years of follow-up. The swim lane plot of all patients in Luna with all available visits, including the 52-week results, demonstrates an unparalleled durability profile and the greatest treatment burden reduction for any product under development for wet AMD. First, on the left side of the graph, we can clearly see that these patients required frequent anti-VEGF injections prior to entering Luna. On the right side, in this hard-to-treat patient population, we met the goals we set out to achieve. You see that over 50% of patients remained injection-free at one year. Importantly, patients who were supplemental injection-free at the 52-week visit have remained supplemental injection-free thereafter, further emphasizing the reliability of Ixo-vec's efficacy. Let's now transition to a review of clinical outcomes, including vision and anatomy. In the Optic trial, we continue to see maintenance of vision and excellent fluid control over the entire four years of follow-up. These results reaffirm the robust and durable treatment effect we can anticipate with Ixo-vec on CST, a marker of disease activity leading to years of reliable benefit for patients and providers. From an efficacy perspective, the 52-week Luna results are consistent with Optic in that BCVA and CST are maintained with both doses. This is an important consideration as we work towards addressing the question of dose selection for the pivotal program. Let's now transition to review safety results from the Optic trial, again focusing on the 2E11 dose through four years. Ixo-vec was generally well tolerated. The results were consistent with the published two-year results in that inflammation was dose-dependent, did not impact vision, and when present, was responsive to topical eye drops. Inflammation resolved in all patients. Notably, no OPTIC 2E11 patients had inflammation at year one and through year four, establishing a favorable long-term safety profile for Ixo-vec. In LUNA, Ixo-vec continues to be well tolerated, with no Ixo-vec-related SAEs reported in the study to date. All Ixo-vec-related AEs were either mild or moderate. The most common Ixo-vec-related AEs included dose-dependent anterior inflammation, which was responsive to local corticosteroids and anterior pigmentary changes with no impact on vision. With the 6E10 dose, patients had no inflammation at week 52 or at any subsequent visit. Local prophylaxis was extremely effective in minimizing inflammation, though we did not see additional benefit of Ozurdex plus eye drops over eye drops alone. Inflammation, if it occurred, resolved by week 52 and through the latest follow-up. With the 6E10 dose and topical eyedrops, the dose and prophylaxis selected for the pivotal program, only a single patient in Luna had inflammation at any time point, which resolved prior to week 52. Now let's take a closer look at the heat maps from Luna. Extended local prophylaxis was highly effective in minimizing inflammation across both doses. Inflammation, if it occurred, responded to local corticosteroids and resolved over time. No patients had inflammation at week 52 or at any subsequent visit. Considering these data from a different lens, a key question is what proportion of patients need steroids and for how long. On this slide, we look across both doses and in the cohort of patients who received local regimen. We see that the proportion of patients receiving steroids for either prophylaxis or inflammation treatment goes down over time, with only one patient in each dose group remaining on steroids at week 52, which were both for the treatment of trace cells. No additional patients began receiving steroids for inflammation beyond the 52-week visit. Now let's compare steroid utilization in Luna relative to Optic at 52 weeks. The prophylaxis regimen in Optic was much shorter relative to the extended regimen in Luna. With Luna's regimen, fewer patients needed steroids beyond prophylaxis, total steroid use was reduced, and overall incidence of inflammation was also greatly reduced. Let's now dive into important subgroup analyses. On this slide, you can appreciate the impact of Ixo-vec on CST, the most sensitive biomarker of disease activity. In patients with CST of 300 microns or less at baseline, CST was stable through 52 weeks across both doses. Notably, in patients with mean CST greater than 300 microns at baseline, we saw CST reductions, which were maintained through 52 weeks. The results again underscore Ixo-vec's benefit in a broad patient population. On the next slide, we show the same analysis, except this time including also patients who were injection-free throughout the study to confirm that Ixo-vec is driving these efficacy results. Elucidating this point further, as previously shown on the top graph, Ixo-vec maintained vision with both doses at 52 weeks. And on the lower graph, you can appreciate the effect of Ixo-vec alone in patients who received no supplemental injection and also maintained visual outcomes. Finally, we look at the subset of patients who had been diagnosed more than a year before Luna and received up to six injections in the year prior, representative of a population requiring less anti-VEGF treatment. In these patients, we observed even better outcomes and higher injection-free rates with Ixo-vec. In summary, we are delighted with the emerging profile of Ixo-vec at 6E10, combined with simple topical steroid prophylaxis. The 6E10 dose in Luna demonstrates an optimized benefit-risk profile with an injection-free rate of over 50% at one year and over 88% reduction in treatment burden while achieving visual and anatomic outcomes. Steroid eyedrops have proven to effectively minimize inflammation, with no patients having inflammation at or beyond the one-year time point. We now have established a 10x safety margin with over four years of follow-up in hard-to-treat patients. These data are supported by the long-term durability, efficacy, and safety results from Optic, in which patients in the 2E11 dose group remain free of inflammation at one, two, three, and four years. It is an exciting time for us as we advance this simple in-office and potentially transformative gene therapy to phase III for treatment of wet AMD. I will now hand the presentation over to Rabia to provide you an overview of our Ixo-vec's phase III program. Rabia. Thank you, Star. Good morning, everyone. What an exciting dataset to design a pivotal program for. On these next slides, it will be my pleasure to share the details of our pivotal program, including our first of two phase III clinical trials, the Artemis trial. Before I get into the details of Artemis, I would like to highlight the foundational aspects of our pivotal program. This program is built on more than five years of clinical experience with Ixo-vec, where we have established a tenfold safety margin. Notably, we have conducted numerous advisory boards and individual meetings over the past few quarters and have received significant input from investigators and the broader community of retina specialists, for which we are greatly appreciative. Importantly, our studies are designed to establish Ixo-vec as a transformative product that not only addresses unmet need but also is aligned with patient preferences, which, as Laurent will discuss, we have already studied extensively. Our Artemis phase III design also incorporates feedback from multiple interactions with the FDA, including our end-of-phase I Imeeting, which we believe has de-risked key aspects of this trial. Finally, we believe our product profile is suitable for all patients with wet AMD, and as such, our pivotal program is designed to study Ixo-vec in a broad patient population, including both treatment naive as well as treatment-experienced patients. Our first phase III trial, Artemis, is a randomized double-masked on-label aflibercept control trial in wet AMD. This is a two-arm non-inferiority trial with an objective to demonstrate that a single intravitreal injection of Ixo-vec 6E10 achieves comparable visual outcomes to on-label aflibercept 2 milligrams while significantly reducing the treatment burden. We will enroll approximately 284 patients randomized one-to-one across the trial arms. The primary endpoint is the mean change in BCVA from baseline to the average of weeks 52 and 56. This is a one-year primary endpoint, testing 4.5 letter non-inferiority margin. Every patient at the beginning of this trial will receive three loading doses of aflibercept 2 mg. As mentioned, we are enrolling treatment naive and previously treated patients with active wet AMD. Patients will need to have the BCVA between 35-78 letters to qualify for the trial. After two aflibercept loading doses, we will confirm anti-VEGF response, then inject the third loading dose of aflibercept and start the topical steroid prophylaxis for all patients in both arms. Patients will return at week one to be randomized into one of the trial arms. We are using sham injections for masking purposes in this trial. Patients randomized to the Ixo-vec arm will receive a single injection of Ixo-vec, and the patients randomized to the control aflibercept arm will receive a sham injection at week one. Then the control arm will receive aflibercept injections every two months, and the Ixo-vec arm will receive sham injections every two months. All patients in both arms will be seen monthly to evaluate disease activity and are eligible to receive supplemental aflibercept injections using pre-specified criteria to protect masking and the primary and secondary endpoints. To summarize, this phase III design is within the draft FDA guidance, including a proper masking strategy as agreed by the FDA in our end-of-phase II meeting. As Star pointed out, our Luna data demonstrated robust clinical activity in patients with varying degrees of retinal fluid at baseline and in patients with highly active disease who require frequent anti-VEGF injections. Our clinical data also showed strong benefit in patients with less active disease who require less injections. Therefore, the Artemis trial is designed to demonstrate Ixo-vec's potential best-in-class profile in a broad wet AMD population. We believe this design will lead to a broad label, global reimbursement, and maximize the probability of clinical, regulatory, and commercial success. Additionally, the design of phase III trial is intended to inform future treatment decisions in a broad patient population and will also accelerate trial enrollment. As a last note, we are delighted to share that as of today, over 100 clinical sites have indicated interest in participating in our Artemis trial. I will now pass the presentation to Laurent to go over the patient preference survey results in Luna. Laurent. Thank you, Rabia. Building on these truly incredible results and the Artemis pivotal study design, I would like to address another two key questions from our stakeholders. First, will patients use gene therapy? And second, isn't the steroid prophylaxis too burdensome? Anticipating this question, our team thoughtfully included a prospective patient preference survey in the Luna trial, and now we have patients' answers, which is a resounding yes for Ixo-vec. First, patients not only will use gene therapy, but they actually clearly and without a doubt preferred to the prior standard of care intravitreal injections. Second, they also told us that the topical steroid eyedrop is not difficult to manage and, in fact, found it either easy or very easy to manage. Nearly overwhelmingly, they would recommend Ixo-vec to their friends and family with wet AMD. Taking a step back, patient preference is defined as a patient's perspective, expectation, and goals for health, as well as the process involved in evaluating the potential benefits, harms, and costs of each management option offered to a patient. If we reflect on recent events in retina, patient preference and direct consumer advertising have driven adoption of novel therapies. For example, Genentech launched the very first DTC ad campaign in wet AMD titled "Open Up Your World," which has been significantly contributing to over $4 billion in annualized sales. If you ask retina specialists about their firsthand experience, they will tell you that patients now often walk into their office and ask for the treatment that extends injections to every 16 weeks, an interval that has actually realized only in a minority of patients. Now, let's look at the results of our patient preference survey in closer detail. At 52 weeks, patients were asked, one, would you prefer Ixo-vec therapy over the prior treatment you received to treat your wet AMD? Two, would you want to receive Ixo-vec in your other eye if you had wet AMD in both eyes? And three, would you recommend Ixo-vec to your family or friends if they had wet AMD? Remarkably, more than 90% of all Luna patients responded yes to all three questions. This number is a staggering reflection of the remaining unmet need in wet AMD. On the next slide, we asked patients whether they view the steroid prophylaxis as easy to manage. Not surprisingly, oral steroids were not easy to manage. On the other hand, no patients felt that topical eyedrops alone were difficult to manage. In fact, they deemed it either very easy or easy to manage, underscoring our decision to move forward with topical eyedrops alone in the phase III. Let's double-click on the next slide on patient preference for a pivotal dose and prophylactic regimen, 6E10 with topical steroid eyedrops. We believe that these results speak volumes towards Ixo-vec's commercial potential and underscore its potential best-in-class product profile. All patients, or stated in another way, 100% of patients in Luna at the pivotal dose and prophylactic regimen indicated that they preferred Ixo-vec over the prior intravitreal injections and that they would elect to receive it in the fellow eye. Again, 100% of the patients at the dose and prophylactic we're moving forward with said yes they would also recommend Ixo-vec to their family or friends with wet AMD. The fact that each one of these metrics points to an overwhelming preference for Ixo-vec and that these metrics have improved from the six-month interim analysis to today points to the fact we made earlier that with gene therapy, benefit-risk continue to improve over time. With that, it's time to pass things over to our Chief Commercial Officer, Jason Mitchell. Jason. Thank you, Laurent. Good morning, everyone, and thank you for being a part of this exciting event. I'm thrilled to join the very most seminal moment as we look to advance Ixo-vec into pivotal trials and establish Ixo-vec, our transformative gene therapy as the new standard of care for patients with wet AMD. From a commercial readiness perspective, I'd like to touch on our market opportunity and how Ixo-vec is well-positioned to capitalize on this commercial opportunity. Wet AMD continues to negatively impact over one and a half million patients in the U.S. and over 20 million patients worldwide, many with wet AMD in both eyes. The market's already large and still growing. The U.S. wet AMD market is estimated to be $9 billion next year and to grow to $13 billion in 2035. This growth is driven by an aging patient population and rising prevalence as life expectancy increases. These factors point to the blockbuster potential for a new therapy that can transform how wet AMD is treated. We believe Ixo-vec can be that transformative product. Ixo-vec's emerging product profile addresses both the physician and patient unmet need we outlined earlier. There are four key elements that we expect will drive adoption. The first is a target product profile with powerful and durable efficacy. This will not only provide physicians, patients, and caregivers reduced treatment burden, but also the opportunity to sustain vision over their lives, a vision currently lost due to the need for frequent injections. The second is a predictable safety profile, well-studied with four years of experience in Optic and manageable with steroid prophylaxis. The third will be the ability to seamlessly integrate with the current operational framework employed by retina practices. Busy retina specialists currently treat 50 or more patients a day in their office, so a solution that can let them order, store, administer, and bill a product in an office location will fit well with how they currently run their practice. This will also be a driver for patient access as it allows patients to be treated by the same physician they've already been seeing in the same location they're used to going to. And the fourth is that this target profile is one that we believe patients and physicians will actively choose. Physicians lose up to 40% of patients who drop off injections over two years. So this is their opportunity to keep those patients treated and sustain their long-term vision. And for patients, the ability to keep vision through as little as one injection compared to regular lifelong injections has already proved meaningful. In Luna, the vast majority of patients preferred Ixo-vec to their prior treatments. We believe this preference will play out in the commercial space with an increasingly educated and engaged wet AMD patient willing to be active in their treatment choice. Finally, we believe these four elements of our product profile will resonate powerfully with another important stakeholder, payers. A product that maintains long-term vision potentially with only one treatment provides a unique opportunity to discuss the societal benefits of sustaining vision and potentially reducing the burden to the healthcare system. Now that we've discussed the target product profile, how do we think the market will respond? While we cannot predict the future, we can learn from past successful launches in wet AMD. What we learned from blockbusters like Eylea and Vabysmo is that physicians want to try new treatments in their hard-to-treat patients. Using this chart of IRIS Registry data on real-world utilization of wet AMD patients, this hard-to-treat patient population is noted on the left side with patients needing seven or more injections a year. Only after these new products demonstrate better durability in patients with severe disease, do physicians feel more comfortable utilizing these new therapies in a broader patient population. Because of Ixo-vec's demonstrated efficacy and durability, we believe this pattern of treatment adoption positions Ixo-vec well. We have designed our phase III to demonstrate Ixo-vec works well in hard-to-treat patients as well as a broader patient population. And as such, we are poised for commercial success. While we believe Ixo-vec will be commercially successful in wet AMD, we can't forget that gene therapy is a regenerative medicine with considerations unique to this modality. Wet AMD is likely to be the first large market indication for a gene therapy product, and with it comes unique drivers. In terms of epidemiology, traditional gene therapy treats small patient populations. However, this is a different paradigm than orphan disease gene therapy, with wet AMD having a high prevalence and large annual incidence of new patients and new eyes. This epidemiology also creates a different economic paradigm. We'll be able to approach pricing from a mass market lens and be commercially successful at a much lower price per patient than any traditional gene therapy. While production costs are a significant consideration in most gene therapy, we'll use a dose for the eye that will be 100-10,000 lower than systemic gene therapies and have a lower COGS as a result. Finally, there are market drivers in wet AMD that previously may not have been at play for gene therapy. Poor real-world vision outcomes are well-documented. Creating urgency to use a new therapy can address this issue. And while gene therapy will be new in wet AMD, in our case, the treatment's already validated and familiar to retina specialists. Ixo-vec is a sustained delivery of aflibercept, a mega blockbuster anti-VEGF that's been administered over 70 million times by retina specialists. Lastly, of critical importance for regulatory and ultimately commercial success of any gene therapy is, can you make it consistently, reliably, and at an appropriate scale? In gene therapy manufacturing, experience matters. Virovek has been at this for quite some time, all with the same global CDMO. Ixo-vec is well-positioned with all phase III material already produced. In addition, Ixo-vec is already being manufactured at commercial scale in a cost-efficient Sf9 suspension process that enables low COGS. So with that, I believe it's time to shift gears to our KOL panel with Star moderating. Star. All right. Good morning. Let's get started. Great to see all of you. Szilard, Charlie, Mark, welcome. Thank you very much for taking time out of your busy schedules to join us for the webcast today. So we'll start the questions with Szilard. At the one-year time point, what was your expectation for the bar for success going into the Luna study, and did Luna achieve that bar? Thank you so much, Star. It's a pleasure to be here. And the answer is absolutely. You know, I was looking for safety and efficacy in Luna, and Luna achieved both those bars. You know, there's been a promise of gene therapy in a broad patient population such as wet macular degeneration, and Luna met that. You know, the promise is coming true. You know, what's notable about the results of Luna is when we have 50% injection-free rate and a greater than 80% reduction in injection burden, this is in patients who are very difficult to treat. And so Luna, combined with the four-year Optic data, shows that the promise of gene therapy in a broad patient population such as wet AMD is coming true. Thank you so much, Szilard. We are definitely excited about the results. Charlie, coming to you, you've been an investigator in both Optic and Luna and now have over five years of clinical experience with Ixo-vec. High level, how have these results from today's presentation and, of course, your input into all of it, how have these data informed safety and the overall benefit-risk profile, especially at the 6E10 dose and the prophylaxis regimen we are advancing to phase III? Thanks, Star. Great to be here with you and Laurent and the entire team. You know, historically, we have learned a tremendous amount about ocular gene therapy over the last 10 years. And in many ways, Ixo-vec has led the way at every one of those steps. It's important to remember that this program led by Optic was the first major intravitreal gene therapy program that had meaningful efficacy results. And in Optic, we learned a lot about viral dose, steroid prophylaxis, and this balance between efficacy and inflammation, which I think is ultimately the key consideration here. You know, the initial dose of 6E11 was simply too high. The efficacy was excellent, but that balance of efficacy and inflammation was not optimal. And therefore, the team methodically paused and, after a careful look at the data, performed a critical phase II program that has informed our entire field tremendously. And through this process, and now with one-year Luna data at the 6E10 dose, we've learned that that dose can maintain strong and durable efficacy and that that extended prophylactic regimen that we crafted together with topical steroid is sufficient to manage the immune response. And within that regimen, when inflammation does occur, it's manageable and does not appear to have an impact on vision and ultimately resolves with the Optic long-term data. So overall, I do think the totality of data here with human data out to 5+ years speaks to the predictability of Ixo-vec with an acceptable safety profile with that extended prophylactic regimen that I think will be valuable clinically. I think the next major step is to enter phase III, and I believe the time is right, and I am supportive of that transition. Thank you, Charlie. It's certainly been an honor to work with yourself and all of the investigators in Luna as we've worked hard together to generate these exciting results. Mark, we'll come to you. Would you speak to the efficacy that you've observed in your experience in the clinical trials with Ixo-vec, and how does this compare to currently approved agents that you're using in the clinic, and how would you incorporate Ixo-vec in your practice pending its approval? No, thanks, Star. A pleasure to be here with you. So in terms of efficacy, I think both Optic and Luna are very exciting data sets, and I think we can all agree on that. And so how do we transition that to the real world? I would argue the same way we do most new agents, most new drugs. You start out in your difficult-to-treat population. You can define that many different ways, but you know the frequent flyers. So initially, maybe like the 15% or so of the wet AMD patients that need frequent injections, you see what the response looks like. And then you frankly transition into a much broader population. Given the safety benefit and the safety profile and the efficacy profile, I can see that being half of the patients. There will always be a good number of patients that do well on the standard agents. We're very lucky to have standard agents, but this has the potential to be transformative. Thank you, Mark. Really appreciate your input there. So maybe for all of you, and we'll start with you, Charlie. Today, we presented Luna data demonstrating the effectiveness of the local corticosteroids and how they minimize inflammation. Ixo-vec is becoming quite predictable with no new onset inflammation after week 30 across both trials and 100% of inflammation resolved by year one. Based on these data, do you believe Ixo-vec has an acceptable safety profile? Thanks for asking the question so directly. You know, safety really is a critical issue. We've seen major challenges with multiple recent products in retina, both commercially and in development, and the field is keenly aware of safety issues and challenges, importantly putting patients first. But to adequately address safety, it's important to always think about that relationship between benefit and risk, and high-need anti-VEGF neovascular AMD patients are living with tremendous burden and known risks, and to be able to trade frequent, essentially indefinite intravitreal injections for a potential one-time treatment is an option that many patients would be excited to be able to consider. The key point here, I think, is that Ixo-vec is a well-described benefit-to-risk profile with four years of data now, and this data facilitates an informed discussion. In that context, you know, I personally have many patients that would rather use topical steroid eye drops for a defined period of time and be able to have a meaningful chance of not receiving additional injections, and if they do need additional injections, having that number be likely meaningfully less than what they were receiving before. So overall, yes, I think at this point, Ixo-vec has an acceptable safety profile, and many patients would be interested in considering its use. Thanks, Charlie. Mark, coming to you next. Anything to add here? And I actually am interested. I'm going to ask you the question outright. Is the safety profile for Ixo-vec acceptable for you after seeing the data from Optic and Luna? I mean, and look, look, the short answer is yes. The long answer is it's not all about Luna. It's about Luna plus Optic, right? So we have a very robust data set here that goes out to years. You're talking three years. You're talking four years in the Optic trial. And now we're looking at Luna. And it was done, kind of echoing Charlie, it was done very systematically. You're looking at several different prophylaxis regimens. You look at it systematically to see which is better, which works better, what duration lasts better. It's all about being predictable. If I have a new treatment that has great efficacy, but I don't know when the inflammation will happen or how bad will it be or how do I treat it, I'm going to be a little wary. Basically, you're giving me the tools to deal with the possible issues, and they're well controlled. So the answer is yes. Thank you, Mark. Szilard, I know it's hard to go third, so I'm coming to you. Anything to add here on the safety? Well, you know, absolutely, Star. You know, the third retina specialist on this call says yes, it's acceptable. You know, it's predictable and it's controllable and it's acceptable. But I just want to point out that it's not only acceptable to the three retina specialists on this call, but the patient preference speaks for itself. You know, with direct-to-consumer advertising, we have patients coming in who've seen advertisements for treatments and are asking about it. And so these patients want to know, you know, can we do better in terms of decreasing treatment burden? What do we do, you know, when they have a lifespan of 20 years, 25 years? Are we going to keep injecting every six weeks? And the answer is potentially no. You know, with gene therapy, some drops, long-term safety and efficacy is extremely favorable for Ixo-vec. And the patient preference really showed that in the Luna study. Thank you so much, Szilard. It's so critical always to really highlight that patient perspective. And we're going to get back to that actually in a bit. You all touched on this in terms of the steroid use throughout the trials and in Luna, and have we really worked to try to optimize it? And we absolutely believe we have as we head into phase III. Steroid use was generally considered potentially a barrier to adoption of gene therapy. Mark, Charlie, I'm interested in particular with your, in your perspective as investigators in these trials and particularly with Ixo-vec, what are your thoughts about the steroid regimen that we've selected to advance to phase III, please? Mark, let's start with you. Perfect. So thank goodness I don't have to use oral steroids. I'm going to come back to that. I love that finding from Luna because, frankly, dealing with oral systemic steroids is manageable, but why would I want to manage that? Now, with topical treatment, we're all very comfortable with topical steroid treatment. We know how long it takes. The patient can do it at home, and you minimize any other systemic issues. And I think it's actually very manageable, right? So going from needing monthly, bi-monthly injections to needing some drops for a predefined period and maybe later on, every now and again, I think it's very reasonable. I'm not really surprised by the patient preference. If I were to get injections or drops, I would rather take drops. Thank you, Mark. Charlie, any comments on the use of steroid eye drops for prophylaxis for gene therapy? Yeah, I think Mark's absolutely right. You know, in some ways, this question gets to the heart of the Luna trial. You know, many development programs want to go straight from early phase trials into pivotal trials. I certainly understand that. But there are risks with that approach. And in this context, Luna was intentionally designed as a traditional phase II trial to better structure the phase III program. We've learned a lot from the phase II trial, just as we've talked about. I think the summary is that patients can readily tolerate the topical drop regimen. I've used that now extensively with patients in Optic and Luna, and the vast majority of patients can very readily adopt that regimen. Excellent. Thank you so much, Charlie. And you transitioned to phase III. So let's all of us then transition to that part of the Q&A. And Szilard, we'll start here with you. Based on your knowledge of the Ixo-vec data and, of course, firsthand experience, what do you think about the design of the phase III Artemis trial being a non-inferiority trial in a broad patient population? Star, I think it's well understood, straightforward, high likelihood of success based on what we've seen in patients. You know, I appreciate the fact that there was input from stakeholders, including retina specialists. How would you use gene therapy if it became available? Well, many of us would start with a patient population that has received anti-VEGF. So I appreciate Artemis, including previously treated patients. In addition, there are some patients who come in and want to get sort of the latest and greatest without the need for repeated injections. And so Artemis includes that patient population as well. In addition to really reflecting what may be the real-world use of Ixo-vec, it really increases the enrollment. You know, we've got all these patients in our practices, new patients coming in, patients who've been treated for some time. I think there's a high likelihood of success based on all those things that I've outlined. Thank you, Szilard. Mark, coming to you for your thoughts on the Artemis phase III design, anything you'd like to expand on the patient population. Will this study enable you and generate the data that you need in order for you to make the treatment decisions that you will be making with this therapy? No, no, absolutely. Look, the fact that you have a broad patient population is, of course, going to be of benefit. Later on, when I have this in clinic, I will want to know, well, how do heavily previously treated patients respond to this? Or how will newcomers, as you all heard, latest and greatest, will want this as well? So it is broadly informative. That's number one. Number two, from a clinical trialist perspective, that makes it much easier to enroll as well because you have a much broader patient population to choose from. It's not patients that must have been previously treated. You can pretty much look at all comers and look at the pros and the cons. So I'm actually relatively excited with the trial design looking forward. And then, as I said, in clinical trials, that's kind of where you start. You start with the previously treated patients, see how they respond, and then you move on to the other patients that may want to get a little bit more extra benefit. We agree. And this was clearly definitely a goal for us was to really generate the data in that broad patient population. We know that Ixo-vec is highly effective in that hard-to-treat patient population. You've got to be very effective in that patient population if you're a gene therapy and you want to be a viable gene therapy. And then, of course, we wanted to also include treatment naive patients to broaden the population to further strengthen its probability of success and generate the data that we know you will be looking for. So agree with you 100% there. Charlie, what are your thoughts about the design of Artemis and your comments and its likelihood for success? Yeah, I agree with Szilard and Mark completely. And the two additional sort of comments I might make is, first of all, the control arm is notably strong. You know, it's rare in the space to see that a Q8 aflibercept arm is allowed to get additional rescue injections. I think that makes a lot of sense in our clinical practice. We do have some patients, especially these high-need patients, that can't go every two months. And so I think it makes sense to allow that control arm to get monthly treatment when necessary. And I think that that's impressive and speaks to the belief in the product that the team has to allow that control arm to get treated. And the second one is, you know, it's interesting how the field has evolved with pivotal trials, right? When you look back at the ranibizumab port delivery trial, right, the goal there was to maintain vision and show stability, which they did reliably, but there was no vision gain in that program. I think, you know, now the regulatory clarity is that we need to show vision gain to allow an adequate comparison with the control arm. And I think that makes sense. Therefore, you know, we need to adapt in the field, you know, responsibly to be able to show that gain. That makes sense, therefore, to include treatment-naive patients that are much more likely to have that vision gain that's very well characterized over decades. I think it makes a lot of sense, and I agree, there's a high likelihood of success. Thank you, Charlie. Really appreciate it. You all touched on this patient preference. We generated very exciting, informative data that also really represents the patient's voice, which is often lost, unfortunately, in our clinical trials. We're very, very, in a sense, driven to be able to capture a diverse patient population and to be able to represent their views. Were you surprised by the patient preference data? How do you envision the patient preference could impact adoption for gene therapy? Mark, I'll come to you first. Oh, yeah. I mean, as I mentioned before, not really terribly surprising to take patients. These are previously treated patients. On an annualized basis, they were getting nine, ten injections. And so they know what they were getting before, and now they know that basically exchange injections for drops. That's one, right? Two, how does patient preference drive things? Well, I mean, initially, it really didn't. If you go years back, we had one or two treatments. It is what it is. But now that, you know, we have a broader array of options that are coming available, it is going to make a much bigger difference. People are coming in asking for treatment. Now, they may ask for treatments that they're already on. So maybe not a fully informed market, but that is happening. It will happen where people ask for longer durability, less treatment, same effect. It's just a matter of time until something like this gets adopted. Thanks, Mark. Charlie, what are your thoughts in terms of, you know, your patients coming in and how are they getting their information, and does that impact treatment decisions? Yeah, absolutely. Patients are more educated, knowledgeable, and sophisticated about their care than ever. They're getting data from direct-to-consumer advertising, but also online, from family, from friends, more readily than ever before. And I think that ultimately, that's a good thing. It's certainly a transition and change, right? Can always have resistance, right, at all levels of life. But here, I think that that's a good thing. And as more products come into the space, I think that's healthy, right? Doctor and patient choice, I think, is paramount. And to be able to have, you know, choice, I really, it's important that those choices are informed. And there will be a lot of patients looking for options that can reduce their frequent need of injections going forward. Excellent. Szilard, anything to add on this topic? The patient preference really sort of echoes what the retina specialist preference is. I think in the presentation you put up, that ASRS survey, you know, there's an unmet need here. There's an unmet need on both sides. And Ixo-vec is filling that unmet need. Excellent. Thank you so much. What an honor to share this panel with you. This brings us to the end of our KOL panel. Thank you again, Charlie, Mark, and Szilard for joining us today. I'll pass it over to Laurent before opening the call to Q&A. Thank you, Star, and thank you, Charlie, Mark, and Szilard for joining this excellent panel today. On the following slides, I will present Ixo-vec's impact on treatment burden based on the Luna study at six months and one year, as well as from the Optic study out to four years. I will also compare how Ixo-vec stacks up against other in-office gene therapy agents that are currently in development. Let's start by looking at the reduction in annualized injection. As shown, Ixo-vec demonstrated superior reduction in annualized supplemental injection at both six months and one year in the Luna study. Importantly, the Optic study shows that these improvements remain durable through at least four years of follow-up. Now, let's examine the injection-free rates in this hard-to-treat population studied in both Luna and Optic. Achieving high injection-free rates in these patients who required ten annualized injections prior to Ixo-vec represents a much higher bar. And here again, the results are even more striking. Ixo-vec shows a 45% greater relative efficacy compared to the next best agent. As we discussed earlier, one of the key advantages of gene therapy is the potential to deliver lifelong benefits after one injection. When we looked at the injection-free rates across both studies conducted in hard-to-treat patients, it is clear that Ixo-vec consistently achieves over 50% injection-free rates at both 6E10 and 2E11 doses at one year, results that are unmatched by any other program. And importantly, these results are sustained in the Optic study, where approximately 50% of patients remain injection-free through four years, with steady aflibercept levels measured through five years and counting. This is truly a game changer and demonstrates the potential transformational impact of a gene therapy program like Ixo-vec. On the next two slides, I will revisit key points we covered that give us confidence that we have de-risked the phase III study and future commercialization of Ixo-vec. First, the best-in-class efficacy we've demonstrated is built on over five years of clinical experience with Ixo-vec and was confirmed at 52 weeks in Luna at the 60/10 dose. Second, our Optic four-year landmark data, at a dose ten times higher than the 60/10 dose we're investing into phase III, confirms that Ixo-vec's safety profile has been de-risked with an established tenfold safety margin, including an easy-to-manage steroid eyedrop prophylaxis and with best-in-class activity. Furthermore, our clinical data shows that Ixo-vec provides both a reliable long-term benefit and predictable safety outcomes. Specifically, if patients remain injection-free for an extended period of time, the likelihood of needing an injection in the future greatly diminishes. From a safety perspective, if no inflammation was observed within the first year, patients did not experience inflammation later on. In the few cases where inflammation did occur early, it was manageable with local steroids, did not impact vision, and ultimately resolved. Finally, the patient preference, as reflected in our survey, further highlights the continued unmet need in wet AMD and underscores Ixo-vec's potential to bridge that unmet need and be broadly adopted by patients and retina specialists alike. Looking ahead, we're pleased that Ixo-vec's best-in-class product profile strongly supports advancing our phase III Artemis study, which we expect to initiate in the first half of 2025. With that, I believe it's time to transition to the Q&A portion of the call. Mike? Our first question comes from the line of Joon Lee. Joon, please ask your question. Congrats on the clean safety, and thanks for taking our questions. For the phase III Artemis, how would enrollment of treatment naive patients and the injection of loading doses impact placebo response? And what are your primary assumptions for the phase III Artemis? And also, the four and a half non-inferiority margin implies an FDA endpoint. What are your plans for the second global phase III? Thank you. Great. Thank you, Joon. I really appreciate the question. Before I pass it on to Rabia, clearly, we're excited about having over 100 sites that have expressed interest in starting and being involved in that study that is looking at a broad patient population. And the second study we haven't discussed, obviously, in great detail. We expect that potentially one of the differences is to have a non-inferiority of four letters, which has been required by EMA and other studies. But at a high level, we expect that second study to be fairly similar. On the rest of the questions, I'll pass it on to Rabia, our Chief Medical Officer. Thank you, Joon, for the question. We select this population because we believe Ixo-vec has the potential to treat all patients with wet AMD, and our study design is intended to address the broadest patient population, including those patients with hard-to-treat disease who we think will be treated first in a commercial setting, simply because they have the highest treatment burden and have the potential to see the greatest reduction. The patients coming into trial, and they are going to receive three aflibercept injections before enrollment in the trial. There, you know, having treatment naive patient population there, they're going to likely show highest BCVA achievement. And then ultimately, all patients are going to go into trial after gaining those visual acuity. That's why our expectation is not, you know, there's not going to be a placebo effect. Having treatment naive and previously treated patients combined in this trial and giving them three aflibercept injections during the screening period is going to negate that placebo effect. That's really helpful. And if I could squeeze in one more follow-up, you know, as a newly elected administration is looking to cut costs, do you think the current CMS spending on anti-VEGFs are material enough to be noticed by this DOGE department headed by Vivek and Elon? And if so, any thoughts on the impact to, you know, things like one-and-done gene therapies for wet AMD? Thank you, Jun. That's a very interesting question. Obviously, we know that, you know, gene therapy has been seen to be very costly in the past. Here, actually, in ocular gene therapy, because of the doses we're giving and the benefit we see, knowing that actually Medicare Part B covers a significant amount of the spend, I mean, all the spend actually for, it represents a significant amount for the government, for CMS, we believe that we could potentially be not only cost-effective, but cost-saving, where actually we could reduce the overall cost of treatment, knowing that these patients live for 10 to 15 years. So you're correct that currently, once you're diagnosed with wet AMD, you're signing up for lifelong injections that are costly, and not all patients even benefit from them because they stop or lose vision. Here, with a single injection that delivers aflibercept for many years and potentially for life, we could be truly cost-effective and cost-saving. Our next question comes from the line of Joe Thome from TD Securities. Joe? Hi there. Good morning. Congrats on the update, and thank you for taking my questions. Maybe one for the company and one for the physician panel. On the phase III trial, is there a targeted proportion of patients that you would like to see that are treatment naive versus treatment experienced? Do you have pre-specified subset analyses in that treatment naive, newly diagnosed subset to maybe provide a little bit of a comparison to other gene therapy trials in progress? And maybe for the physician panel, when you think about moving into a broader patient population, does your bar for injection freedom change at all versus what we saw in Luna, especially in the context of potentially every six-month dosing for chronic therapies also in development? Thank you. Thank you. A great question. Obviously, you know, we designed the study to have a broad enrollment factor to represent the patient population we intend to treat and have the broadest label. We balance across treatment norms the proportion of treatment experienced, treatment naive, and having treatment experienced patients allows us to have patients with less variability and therefore a slightly smaller study than if they're all treatment naive. So those are the benefits of those. And of course, you know, in future analysis, we'll be looking at those very different, those different patient populations and how they perform. So this will all be part of the opportunity we'll talk about in the future. You know, and also, I would say that our expectation is that, as you've seen in patients that had six or less injections in Luna, a significantly higher% of patients being free of injection at year one, which is what we expect. And then I'll pass it on to our panel who wants to answer the question, either Charlie or Mark since you are both involved in the study and you've seen a range of patients. Your thoughts on expectations for treatment reduction in naive versus more experienced patients? Yes. Thanks, Laurent. Happy to jump in there. I agree with the points. You know, I think that wet AMD, while we sort of, it depends if you're a lumper or a splitter here, right? I mean, they certainly all have chronic disease, and the large majority need ongoing anti-VEGF injections. But there is probably a variability in the VEGF levels within these patients' eyes and also their clearance rates of different pharmacotherapies that sort of dictate what their interval might be and how many injections they need. And therefore, with a biofactory approach such as Ixo-vec that we know creates a stable level of therapeutic protein through five years of human follow-up, very impressive to have that long-term data in hand, we know that that stable level, you know, is going to be differently therapeutic in different patients. I think the vast majority of patients, these high-need patients, that is sufficient to dramatically reduce the treatment burden. Now, is it going to reduce the treatment burden to zero for all patients? I think the answer there for the heavily pretreated patients, at least, is no, that we're looking at a 50% or greater percentage of patients getting to zero injections at one and done. And that's really what patients kind of resonate around, is that opportunity to be zero injections. But that said, the patients that do need ongoing injections, almost all of them have had a dramatic reduction in the frequency. And that also is quite meaningful for patients. And just as you pointed out, there's new drugs being developed that may be more durable. You know, there are also new monitoring devices. Now, home OCT is available. And how we incorporate that here, I think, is a critical component of this, right? Can these patients be screened at home for slow recurrence of fluid that could help us dictate when they need retreatment? I think that combining this type of therapy with new diagnostic and management approaches, I think, is a key to this long term. So, I mean, I completely agree with Charlie's point. I would just like to add that we're fortunate that we're looking at therapies that last longer, or at least that give us the potential for longer durability. That said, the way I would approach a patient in the clinic is great. You get on this treatment, we see what the durability is. And yes, there will be the expectation of the occasional necessary additional treatment, whether that is with the six-month agent, a three-month agent, or, in this case, possibly a five-plus-year agent in this case. So the expectation, you're right, it's about managing expectations. If you have a high treatment need, a high treatment burden, these patients will need treatment. And for them, it's a success. You know, they don't need to be zero treatments, just much fewer drastic reduction. And our next question comes from the line of François Brisebois from Oppenheimer. Frank, your line's now open. Hi. Thanks for taking the questions and the great presentation. So I was just wondering, maybe for the KOL panel, can you just help us understand what, in general, is more important? I've heard kind of little comments about it, but is it injection freedom or is it burden reduction? And on that note, you know, I guess I'll just start with that, and I'll follow up with another one. Thank you. Thank you. Thank you, François. Before I pass it on to the KOL, I think, you know, the goal of the gene therapy program, and since we started, was, you know, preserving visions for life. We believe that now with our ability to train patients' eyes to make aflibercept for life, potentially, we may be able to achieve that. So vision preservation, I think, is the greatest goal. We know that 40% within two years of diagnosis, 57% after five years stop treatment altogether. We don't really talk about this phase and what happens to them. But I will leave it on, you know, to the experts to talk about, you know, whether it's stabilizing fluid and whether it's actually reducing the treatment burden. I think fluid is a disease marker, a biomarker of disease activity. It's called wet AMD for a reason. And I think, obviously, you know, reducing the fluctuation in CST is also important. But I'd love to get maybe Szilard's opinion on his thoughts about what's most important in treatment and what he's looking for. Thank you, Laurent. Very important question. And just to echo what you said, patients care about vision, right? If you're not preserving vision over the long term, it really doesn't matter what you're doing to the treatment burden. And to answer the question that was posed, you know, I think both are important, right? If you're getting an injection every six weeks, you're getting, you know, eight, 10 injections a year, then reducing that to one injection a year is going to be extremely significant for you. In addition, 50% reduction at one year, or I should say 50% injection free at one year, is clinically meaningful. When a patient is sitting in front of me and they've needed repeated injections for a long time, I can confidently say that they have a one-in-two chance, at least with the Luna data, to not need another injection over the next year. I can also say that even if they do need an injection, that's significantly reduced. You know, we also forget about what happens after a patient gets an injection. Some of my patients are out for a day. They can't go to work if they're still working. You know, they're resting. They've got the irritation from the injection itself. And so we toss these numbers up, but we don't really appreciate what the patient has to go through. I think that's appreciated in the patient preference data. So function number one, both are important: reduction of burden and injection free. And I think Ixo-vec hits both of those, all three, I should say. Great. And maybe if I can just, you know, Laurent brought up the competitive landscape and what's been shown. There's a lot of a couple of other gene therapies in development here. So how is that 50%? It keeps coming up in terms of injection freedom, even in very hard-to-treat patients. Is that something that's critical when you try to cross-compare with other drugs in development, or is that kind of a moving number, the 50%? Thank you. Thank you, François. I think, you know, for these regenerative medicines that clearly are somewhat more complex but have a much higher efficacy than what you see with the current standard of care, we want to have the greatest efficacy. And the difference here is that with gene therapy, unlike other treatments, you have one shot, one opportunity to get the best efficacy for life. You very likely will not be able to be retreated. And so that's, I think, an important metric. And of course, we know that as we go to a broader patient population, that efficacy is even better. I think this is an important point. I think if you only focus on naive patients, there are a lot of treatments that could work quite well. There, I think, you know, whether gene therapy is the first choice or not, that's a different question, maybe over time. But certainly, I think being able to address these hard-to-treat patients for us at Adverum is really critical. But I'd love to have, you know, Charlie, and maybe you can comment on that. Yeah, it's an important question. And, you know, it's always hard to cross-trial compare, especially hard when you don't have actually pivotal data from many of these different programs in development. I think, you know, assuming all of the ones in development became approved, it's a balance. It's a balance between ease of access, right? Is it an in-office procedure? Is it a surgical procedure? It's a balance between efficacy, and it's a balance between safety. I think all three of those are key components that patients and physicians are going to consider. I think overall, you know, the market for exudative retinal diseases is huge, and neovascular AMD is the largest component of that. We've already seen that multiple players can be successful in the space. So I think that there's a huge unmet need for new therapeutics that both bring greater vision and also more durability, which itself can translate to better vision long term. There's a lot of opportunity here. I think that an interventionally delivered gene therapy that has a very meaningful reduction in the treatment burden is going to be successful in the commercial landscape. Our next question comes from the line of Graig Suvannavejh from Mizuho Securities. Graig, your line is now open. Good morning. Thanks for taking my questions. Congrats on the tremendous efficacy and safety data with the 52-week Luna data as well as the four-year optic data. Just a few questions, if I could. One, it was very interesting patient preference study results where it looks like 100% of patients prefer the product. Obviously, those patients were already in, you know, treated with Ixo-vec, have probably good experience. So I'm wondering if you have a sense, if you've done any market research, a broader interest by wet AMD patients who perhaps haven't been on Ixo-vec on their view and interest in the product. So that's my first question. And then my second question is for the KOLs who are joining the call. Thanks for your input and feedback. You know, based on our conversations with retinal specialists, there is a lot of interest in gene therapy, but I think the kind of summary view that at least we've been able to glean is that at least previously, ahead of this data or before this data set, gene therapy, broadly speaking, was viewed more as perhaps a more niched opportunity. So I'm wondering, in light of this data, which at least we found to be very excellent, what is going to be needed to drive kind of overall broader acceptance of gene therapy in light of the other products that are on the market? And do you see this as a gradual uptake of the gene therapy class or perhaps something more dramatic in light of the data today? Thanks. Great. Thank you, Graig. I really appreciate the question. You know, we designed this patient preference survey to really understand how Ixo-vec can impact patients' preference over a treatment that had not been tested in a broad patient population. All these patients, as you know, were treatment experienced, on average, 10 injections annualized in the best centers with the best investigators, including some of our KOLs today, and we were not totally surprised, but very pleased with the percent preference, you know, 100% preference at 6E10 with steroid prophylaxis. 100% said they were treating the other eye. Obviously, we think it's important to people with bilateral disease. We want to be able to offer that in both eyes. I think maybe even more surprisingly, it was saying that 100% would actually recommend it to a family or friend. While we haven't done research yet in the, you know, patient population that has not been exposed to Ixo-vec, we wanted to know from the patients who had experienced it, how did that fare? And an important component of that was also to understand how easy or very easy to manage the steroid prophylaxis eye drop would be for, as part of the treatment, which are required for, you know, roughly six months. So those were important elements that we wanted to understand. I think as there's more DTC and companies that are promoting the patient's voice, we also have the intent to continue to raise the patient profile and their voice and their interest and talk about their experience because we all are potential patients. One out of 500 of us at the age of 60 will have either wet or dry AMD, and one out of five at the age of 90. And, you know, knowing what the genetic makeup of my family, I'm going to get there too. So we all want to think about that and care about it. And as far as, you know, adoption, I'll maybe pass it on to Mark, you know, your thoughts about how gene therapy will be adopted initially and then over time. You know, that's a great question. It's an important question. So, you know, I agree with the sentiment right now that right now, gene therapy is a niche product. Why? Because when the general retinal community thinks of gene therapy, you think this is new, this is untested, we have to manage a lot of inflammation. And so essentially, this data actually informs that, you know, essentially is a counter-narrative to what we have assumed gene therapy is. Is gene therapy difficult to manage? Is the prophylaxis difficult to manage? I don't want to convert my AMD patient into a uveitis patient. I mean, here we have that, again, going back to that, we have data, years-long data from Optic in addition to Luna, multiple prophylaxis. And what we see is on topical drops, patients are, it's predictable, it's well-managed, you don't have flares. So what I personally suspect will happen is this. Initially, there will be the early adopters as per usual. It will be the difficult-to-treat patients, of course. And then as word spreads that this is actually relatively easy to do. You have a formula already. You don't have to discover how to treat these patients. It's already been laid out for you with this phase II trial. Then all of a sudden, people realize, well, the floodgates will open. So it will gradually increase and become more and more prevalent. Our next question comes from the line of Lisa Walter from RBC. Lisa, your line is now open. Oh, got it. Thanks so much for taking our questions and congrats on the progress today. Just a couple for me. As you make preparations for the phase III start in the first half of next year, just wondering if you are considering treating more patients at the 60/10 dose with the selected steroid prophy regimen just to gain more patient experience with this treatment combo before you commit to a large study, given we only know 10 patients have been treated with 60/10 and prophy drops so far. Then just a clarifying question. The one 60/10 patient who required additional prophy at 52 weeks due to trace BC cells, just wondering if you can comment whether they have stopped any further prophylaxis past 52 weeks. Thanks so much. Yeah, thanks, Lisa. Great question. I think we were really proud about this program is that we have both four years of follow-up at tenfold higher doses, and we have now the 60 patients in Luna in addition to the 30 patients in Optic and more patients treated overall to give us the confidence that we have the greatest package of any company with the longest durability going into the phase III study. So we have established and clearly demonstrated that steroid eye drops work really well. In fact, we were the first to pioneer that in our Optic study. And what we've learned there is that it worked really well, just needed to be a little bit longer. And what we've learned with Luna is that the combination of steroid eye drops or steroid drops with Ozurdex worked really, really well. So local steroids work well, 6E10 dose is less inflammation. We have great efficacy, and we have really more data than anybody else going into phase III. It gives us that great confidence. And, you know, of course, we've been following these patients, you know, for more than five years. The first patient was actually dosed six years ago, and that patient is doing great. So no other company has had that duration of follow-up before they got into phase III. So the most comprehensive patient program of anybody else going into phase III in wet AMD. I will pass it on to Star to answer the second question about the one patient at 60/10 that had traces BC cells that was on steroids at 52 weeks. Yes. Thanks, Lisa, for the question, Star. As you mentioned, we had the one patient actually in the entire cohort, 60/10 cohort of this study. So it's more than 10 patients, actually. So it's 30 patients that were enrolled in the 60/10 cohort, and only one patient remains on steroids for inflammation. And the patient is actually in the taper period of that treatment. So they're on a very low dose, and we expect that they'll be tapered off shortly. And our next question comes from the line of Matthew Caufield from H.C. Wainwright. Matt, your line's open. Hi. Good morning, guys. Can you hear me okay? Yep. All right. Great. Great to see the consistent progress. Congratulations. Just a quick kind of high-level question for the KOLs. Do you have any concerns whether patient compliance to the topical steroid could be less consistent at all ultimately in the real-world setting, or will the motivation to avoid injections otherwise keep those patients consistent with the inflammation management? Thanks a lot. Thank you, Matt. It's really a great question. And obviously, you know, we've thought about looking at various alternatives, and it turns out that these patients obviously are quite focused on preserving their vision. They understand that we, you know, the trade-off is between injection and taking the eye drops. And many of them tell us that they brush their teeth several times a day. Putting eye drops is not a concern. And we see that, in fact, reflected very clearly in that patient preference survey where they actually said, you know, 95% steroids are either very easy or easy to manage. But, you know, it's clearly something we want to educate patients around and will be make sure they understand that this is a part of their treatment. And for, you know, six months, they need to take eye drops. But let me pass it on to maybe, you know, Szilard first to get his thoughts on how patients' compliance and how they follow their, you know, direction when they get to these new treatment options. Laurent, thank you so much. An excellent question. You know, I think compliance with any treatment regimen is always a concern. I think you partly answered your own question. You know, to avoid injections, patients will take drops. Moreover, it would be a concern if, you know, this was a five-year drop regimen, but it's not a five-year drop regimen. It's a very reasonable drop regimen with a taper. And so I think that patients, when properly educated for those who haven't received injections, will be compliant. So overall, I'm not concerned. I think that, you know, in this case, compliance will ultimately not be an issue in the real world. Charlie, do you want to add anything to that? Yeah, I agree. It's a defined, well-defined drop regimen. And I think the majority of patients that want to use gene therapy will say, yeah, this is doable rather than getting injections. You know, it's interesting, though, in Optic and Luna, you know, I have had, you know, many patients, again, that prefer that that concept of drops over injections and have had a few patients that have been, you know, that have stopped using their drops for whatever reason, right? They lose a bottle, they can't get the refill in time, or they just forget, or they travel and they didn't put it in their bag. So you're right. There's a lot of hiccups that happen in the real world. That's part of the reason why injection frequency drops off. Things just happen in the real world. It's interesting. In a few of those, there have been some rebound inflammation. That's some of the cases of inflammation that we've seen in the trial programs. And in all of those cases that I'm aware of, certainly all of mine, you know, when you restart the drops, the inflammation responds just as we have learned now with five years' worth of data, and you get the patient back on track. And so it's not like, you know, if you stop using drops, like everything's going to be lost. We've actually had that experience in patients, and we've seen that you can get them right back on track. And our next question comes from Aydin Huseynov from Ladenburg. Aydin, your line's now open. Hi, good morning, everyone. Thank you for the presentation and congratulations with the 52-week data. I have a couple of questions. So given that Artemis is sort of all-comer trial, it will include naive patients. And this question is to the panel. Would it make sense to try for these naive patients the lower dose of gene therapy if you had one? Because for naive patients, we don't know the required frequency. So would it make sense to try these patients with even lower dose gene therapy if you had one? Just this is for panel. So thank you for that. Excellent questions. I think what we've really clearly demonstrated now over the two studies, starting with Optic and now Luna, is that we were able to dose down from the 60E11 to 60/10 tenfold. And at tenfold, in the hardest-to-treat patients, we see 88% treatment reduction, 75% of patients with less than one injection, and 54% injection-free with essentially no patient with more than one AC cell, right? And all patients free of inflammation. Knowing that with gene therapy, you have one shot to get it right, to get the right dose in the right patient, and that dose is well tolerated. Also, that dose gave us very steady, robust therapeutic levels of aflibercept in the eye that we expect to be for life. We think this is the right balance of benefit-risk with 6E10 for the broadest patient population. I'll ask Charlie if you want to comment on that since you were involved in all of these trials from the highest dose to the one we have today and your thoughts about moving forward with 6E10 in a broad patient population. Yeah, I think it's fair to say that the dose response here for Ixo-vec has been thoroughly and adequately explored. You know, when you come into humans with any new drug, right, you do your best, you do your best effort based on the preclinical data to judge what that therapeutic level will be in humans in a safe range. And in this case, you know, with 6E11, it was too high, as we've discussed. You know, it was really good efficacy, but the inflammation risk was more than we wanted. It was not optimal. And therefore, we titrated down. And I think we have found the sweet spot with Luna, with a complete year's worth of data for patients with Luna and many patients beyond a year, showing that predictable rate of inflammation with maintained efficacy. But I think, you know, in an ideal world, it's an interesting question, right? If you had endless time and endless resources, maybe all programs should have multiple phase two trials to really understand things 100% before you move forward. But I think that that's just not realistic for any development program. I think this development program in particular has done more than is absolutely necessary before moving into phase III. And I think it's the right time to move forward at this time with the 6E10 dose. Okay. Thank you. Another question I have for the management. So this is a little bit sort of loaded question. It's about timelines and costs. So would you be able to share the timeline for the first pivotal trial, for the second pivotal trial, and the costs for each of the trials? This is for just the modeling purpose of to understand when this can be launched. Great. Well, thanks for the question. As we mentioned, we plan to start our Artemis phase III study in the first half of next year. We've been working diligently, and we have over 100 sites that are ready to enroll in this study and excited to start and enroll in patients in this study. And because we have a broad patient population, we think it'd be easier and faster to enroll. Hard to know exactly what that looks like, but you can look at more of the most recent trial in phase III with Ocular Therapeutix that I think enrolled in less than a year. You know, I can't promise that this is something we can achieve or exceed, but I know we have the best team in the field that is really focused on that. And then on the cost of the trial, I will pass this on to our Chief Financial Officer, Linda Rubinstein. Hi, Aydin. Thanks for the question. On a per-patient basis, it's not a surprise that gene therapy trials tend to be more expensive than other modalities. Our goal is clearly to fund phase III for both studies, and that'll include making sure that we fund the company to conduct the CMC activities and pre-commercial activities, as well as just to run the company, you know, while we're conducting those trials as we advance on the path to BLA. And our last question comes from the line of Daniil Gataulin from Chardan. Daniil, your line is now open. Daniil? Yes. Can you hear me? Yep. Go ahead. Yes. Yeah. Thank you for taking the question and congrats on the progress. Is the patient survey showing 100% of those who've received treatment in one eye wanting to get it into the fellow eye? Can you share your plans for what a fellow eye study would be and when do you plan on carrying it out? Thank you. Thank you, Daniil. That's a great question. Obviously, we have patients with bilateral disease that were enrolled in our Luna study. They've told us that that worse eye that got the gene therapy is now the better eye, and they'd like to get it in both eyes.P So we will plan to start a bilateral study in parallel with a phase III trial that will allow patients coming out of the studies that we've conducted to enroll in those trials. Those plans are being put in place, and the goal is to have, you know, roughly 15 patients that have received bilateral Ixo-vec before we file our BLA filing. And we know from non-human primate data that we've already published, now also confirmed by a human study recently, that we can dose both eyes effectively and safely, and we will plan to do that in the upcoming months. So thanks for the question. That's a great question. Thank you. Okay. That concludes our question and answer session. I'll pass it back to Laurent for closing remarks. Great. Before we conclude, I really want to thank first the patients who participated both in the Luna and the Optic trial, as well as their families and caregivers. And I want to thank our investigators who supported both Luna and Optic, as well as the clinical site teams, their coordinators, and Dr. Charles Wykoff, Dr. Mark Barakat, Dr. Szilard Kiss for joining us today. I also would like to thank my entire team at Adverum that worked tirelessly to make this event happen, and thank you, everyone, for listening and for taking the time to join us on this call today and ask great questions. We really appreciate the support and look forward to updating you on the progress of our pivotal program. Operator, you can now conclude the webcast.