Welcome to Neurogene's webcast and conference call. Please be advised that this event is being recorded. I will now turn the call over to Lina Li, Executive Director of Investor Relations at Neurogene. Please proceed. Thank you. Good morning, everyone, thank you for joining us today to review the phase I/II data of NGN-401 for the treatment of Rett syndrome. Before we get started, I'd like to remind everyone that we will be making forward-looking statements today. These statements involve known and unknown risks and uncertainties, which may cause our actual results to differ materially from those presented today. I encourage you to review our latest SEC filings, including our Form 10-K and most recent Form 10-Q, for a complete discussion of these risk factors. All of the information we will be presenting is as of today's date, unless noted otherwise, we undertake no obligation to update any forward-looking statements. Our speakers from Neurogene today are Dr. Rachel McMinn, Founder and Chief Executive Officer, Dr. Julie Jordan, Chief Medical Officer. We are pleased to be joined by Dr. Bernhard Suter, Medical Director of the Blue Bird Circle Rett Center at the Texas Children's Hospital and Associate Professor of Pediatrics and Neurology at the Baylor College of Medicine, an NGN-401 principal investigator. We also have Christine Mikail, President and Chief Financial Officer, available for the Q&A session. With that, I will now turn the call over to Rachel. Thank you, Lina. Good morning, everyone, thank you all for joining us. As many of you know, Rett syndrome is a devastating neurological disease with no approved disease-modifying therapies. NGN-401 is a gene therapy designed to deliver functional MECP2. The unmet need is substantial, with an estimated prevalence of 15,000 to 20,000 patients in the U.S. and major European markets, a sizable incidence rate of approximately 175 to 180 new cases each year in the U.S. The market is approximately 50% pediatric and 50% adult, all patients have a profound unmet need. A single idea frames everything today. In Rett syndrome, development stops after regression and effectively freezes. The updated data we're sharing suggests that development restarts after treatment with NGN-401. Over the longer term, with follow-up of two years or more, participants are gaining milestones in a stepwise sequence across domains, similar to what occurs in typical development. The order matters as much as the gains. Milestones are returning in developmental sequence, the signature of development resuming rather than isolated skills appearing. These gains are durable, with no milestones lost in any participant and continue to deepen over time. Everything that follows is evidence of what a gene therapy treatment for Rett syndrome should deliver: the restoration of developmentally ordered prog ress, not isolated skill gains. I'd like to start by thanking the Rett syndrome community for their support of this program and all of those who have participated in our phase I/II and registrational trials. You are the true trailblazers, and without you, this would not be possible. Now, I'm pleased to share the positive updated phase I/II data that continue to support the potential for NGN-401 to be best-in-class treatment for this devastating disease. In the 10 participants treated at the 1E15 vector genome dose, we have observed clinically meaningful, durable improvements with real-world impact for the participants and their families. First, every participant, 100%, has gained one or more developmental milestones and improved on the CGI-I. At 12 months, 80% have met this composite responder definition that is the primary endpoint for the EMBOLDEN registrational trial, which far exceeds the 33% minimum success threshold for the EMBOLDEN trial. Second, the magnitude of gain continues to build. Total milestones gained in this trial were 47, averaging 4.7 per participant. Importantly, these are not random milestone gains. They are occurring in a developmentally ordered, stepwise sequence consistent with a restart of development and the continued ability to learn. Third, these gains translate into real-world benefits, improvements in daily living, greater level of independence, and reduced caregiver burden. Fourth, the improvements are durable and deepening. We now see improvement has continued out to 30 months with no plateau and no milestones have been lost in any participant. Importantly, the 1E15 vector genome dose continues to be generally well tolerated in the phase I/II and EMBOLDEN trials. There have been no treatment-related SAEs or DLTs in EMBOLDEN. Earlier this month, we announced completion of dosing in EMBOLDEN, surpassing our enrollment target by 25% and dosing 25 participants within our original timeline in a broad age range of pediatric and adolescent adult participants. Clinicians and families chose to participate in the phase I/II trial due in part to ICV administration to maximize the potential of NGN-401 as a one-time gene therapy treatment. We remain on track for top-line data in the second half of 2027. Diving deeper into the 100% response rate, here are some of the more detailed data that we will be reviewing today. The clinical response was rapid, and the median time to improvement was two months. The treatment effect was durable and increased over time. Milestone gains increased by 95% from six to 12 months and by 147% from six to 12 months or beyond. There were no milestones lost in any participant as far as 30 months post-treatment. The treatment effect was multi-domain and was observed across participant age, disease severity, and genotype. Seven of 10 participants gained two or more developmental milestones, and these milestones were in two or more key Rett syndrome domains, including hand function, communication, and gross motor function. These data underscore the breadth of response and lead to independence in activities of daily living, reduced caregiver burden, and enhanced social engagement. There have been no new treatment-related SAEs and no DLTs in any participant, and all have reached at least 12 months of follow-up. In totality, these data from the six-month, 12-month, and beyond time points support a clear path to a strong BLA submission, exceeding the EMBOLDEN minimum success threshold by 2.4 times at 12 months. The average milestone gains increased from 1.9 at six months to 3.7 at 12 months and deepened to 4.7 at or beyond 12 months. The over-enrollment provides a larger registrational cohort, strengthening statistical power and potential for a broad label. Before I hand things over to Dr. Suter, I want to briefly review our phase I/II trial design. As a reminder, the phase I/II trial, which subsequently converted to the EMBOLDEN registrational study, is an open-label, multi-center trial evaluating the safety, tolerability, and efficacy of NGN-401. Key eligibility criteria, the key clinical assessments of CGI-I, CGI-S, and developmental milestones. As well as the Rett Syndrome Gross Motor Scale and Rett Syndrome Hand Function Scale are consistent across both studies. Dosing is complete in both trials, with 10 participants in phase I/II and 25 in EMBOLDEN, bringing our total safety database to 35 participants at the 1E15 vector genome dose. The primary endpoint for EMBOLDEN is a composite in which a responder is defined as a participant who shows an improvement on the CGI-I and gains at least one developmental milestone at 12 months. As it relates to developmental milestones in the EMBOLDEN trial, this list was derived from an analysis of the Rett Syndrome Natural History Study and a caregiver survey of meaningfulness. The 28 milestones included here have low cumulative incidence rates of gaining or regaining at or after age three, when regression is complete. They were all deemed clinically meaningful by caregivers. We applied the EMBOLDEN milestone criteria directly to the phase I/II data. First, we established which milestones were absent at baseline using medical history, caregiver reports, and videos. We evaluated post-treatment milestone gains utilizing independent central review of video documentation using the same pre-specified criteria that is being used in the EMBOLDEN trial. By following the same standardized assessment criteria, the phase I/II data are comparable to EMBOLDEN. This chart summarizes the baseline characteristics of the 10 phase I/II participants, reflecting a broad age range with a wide spectrum of disease severity. Participants enrolled range from four to 18 years old. Baseline CGI-S scores were four to six or moderately ill to severely ill, and the participants represent the full spectrum of genetic severity in classic Rett syndrome. As of the data cutoff of June 16th, 2026, participants had a range of follow-up from 12 to 30 months. I am pleased to turn the call over to Dr. Suter, one of our principal investigators, to review the long-term data from the trial and provide context for how the data are maturing in those participants. Dr. Suter? Thank you, Rachel. I've spent my career evaluating and treating patients with Rett syndrome and can share what this disease looks like in the clinic. Rett syndrome is a rare and devastating neurodevelopmental disorder, most often caused by a spontaneous pathogenic variant in the MECP2 gene. This gene is responsible for making MECP2 protein, which is required for normal brain and nervous system function. What defines the disease is a period of regression. Children lose previously acquired developmental milestones, followed by a plateau. By around age three, it becomes rare for children to gain or regain developmental milestones, resulting in lifelong pervasive disability that requires intensive medical support and often 24-hour care. That natural history is critical context because it means that gains in the development after this point are highly unexpected and clinically meaningful if they occur. The hallmark features of Rett syndrome include loss of expressive and receptive communication, loss of purposeful hand function with repetitive movement called stereotypy, gait abnormalities and mobility challenges, and autonomic dysfunction, including breathing irregularities, dysphagia, and severe constipation, as well as seizures. With that clinical background, I'd like to now play a brief video that brings to life the true burden of disease represented by a family living with and caring for someone with Rett syndrome. Taking care of Kendall starts in the morning. Kendall's an early riser. Getting ready for the day, obviously some heavy lifting is involved with that, getting her out of the bed, getting her changed. Her body's very stiff, getting her changed from pajamas into her outfit. Adolescence is starting, so there's lifting her arms to put deodorant on. Mealtimes for Kendall are longer than most. It's always an issue if we're in a hurry. If we have to get to the baseball field, there's really no such thing as a hurried meal for Kendall. Kendall doesn't communicate like you or I would. She uses an eye gaze device. That works well when her body wants to work, which is not always the case. Her brain's telling her body what it wants to do, and her body just simply doesn't listen. Communication can be tough. The biggest unmet need for Rett syndrome, if I think of that question, my mind goes to the movement. Because of this movement, Kendall has never been able to walk on her own. Because of this movement, she is unable to hold a utensil to feed herself. I don't think anyone can even fathom what Rett syndrome is going to do to the life of your family. I'm still learning and realizing what it's done to us and what it's going to do to us every single day. The best way to describe it, I guess, is think about when you were a new parent and you were caring for that infant, and you just had to do everything. The sleepless nights and the exhaustion you feel, that has been the past 11 and a half years of my life. Yes, life is harder for our family, absolutely. Who couldn't be okay with that looking at this smile? Thank you to this family for sharing their story. What you just saw reflects more than a collection of symptoms. It reflects the day-to-day reality of living with Rett syndrome and the profound impact it has on both the child and the family. This is not simply the loss of an isolated skill or milestone, it is the development that is fundamentally disrupted, wh ere progress halts and independence never fully emerges. That context is critical, because to understand whether we can change that trajectory, we first have to understand how development normally unfolds. To frame how development typically occurs outside of Rett syndrome, we often reference the Denver II framework, which is one of the most widely used developmental assessment tools in pediatrics and neurodevelopment. The Denver II maps how developmental skills emerge across multiple domains in a concerted fashion. In typical development, milestones are acquired in an organized, cumulative, and sequential manner, with each new skill building on the last across domains. That is the curve on the left. In Rett syndrome, that process is interrupted. Children develop in an apparently normal manner. Between one and three years of age, they regress. The critical point is this: once that regression happens, it is exceedingly rare to regain those milestones or gain new ones. A child's development freezes, the curve flattens, and that plateau is what drives lifelong dependence on caregivers. The goal with NGN-401 is the panel on the right. This is not about slowing decline. It is about restoring and improving function. Said simply, the goal of any gene therapy is to restart the developmental progression, to get the curve climbing again and across multiple domains. If that happens, the impact will be what families care about the most, greater independence and reduced caregiver burden. That is the hypothesis we set out to test. I'll now walk through the data from the first four patients with two or more years of follow-up, where you can begin to see what that looks like over time and what it translates to in the real world. Let's start with participant one. She is seven years old, and her regression had been complete for several years before treatment. At baseline, she had very limited functional hand use, limited self-feeding, walked on tiptoes, froze often, needed help on every stair, and couldn't indicate her wishes or follow a simple command. The dotted line is the day she received NGN-401, and everything to the right occurred after treatment. What we started was not random. In fine motor, she progresses from a raking grasp and dropping objects to drinking from a cup, the pincer grasp, using utensils to feed herself, and transferring objects between hands, a particularly difficult skill in Rett syndrome, as it requires two-handed coordination. To provide additional context, transferring objects is among the more advanced skills on the validated Rett Syndrome Hand Function Scale. In gross motor, she progresses from needing help on every stair to climbing stairs up and down independently and heel-to-toe walking, a key milestone on the Denver II. In communication, she progresses from not following commands or indicating wishes to following a command, waving to her family in context, and pointing to things that she wants. Overall, this participant gained 11 developmental milestones, completely unexpected in Rett syndrome natural history. The more important point is the pattern. These milestones emerge sequentially across domains, consistent with restarting development rather than an isolated change. Here is what that looks like in daily life. Getting in and out of a bathtub, on and off furniture without help, shopping with a parent, carrying the basket with both hands, getting out of a car on her own, and closing the door after her mom asks her to do so, following instructions in two languages, to carry a backpack up the stairs and shut the door behind her, choosing the right color on command, demonstrating receptive communication, waving to her grandpa on a video call, demonstrating expressive communication. These are not isolated skills. They reflect fine motor, gross motor, and communication working together in a coordinated way, which is what development is supposed to look like. For this family, the result is greater independence, less caregiver burden, and more meaningful participation in daily life. Participant two shows the same overall pattern. At age four, several years post-regression prior to treatment at baseline, she had no functional hand use, limited mobility with frequent falls, could not bend over, and had minimal communication, unable to follow commands or make choices. Following NGN-401, what we observe is not just improvement, but another example of developmentally ordered stepwise re-emerging of milestones across domains. In fine motor function, the participant progresses from reaching for a toy to grasping and manipulating objects, to drinking more independently and beginning self-feeding, skills that directly translate into increased independence in daily activities over time. In gross motor function, she progresses from assisted transition to standing up from a seated position independently, recovering balance after bending at the waist to touch the floor, a milestone included on the Denver II, and navigating real-world challenges like curbs and stairs. She also achieves more controlled positional transitions, such as sitting up from lying down. These gains reflect meaningful improvement in strength coordination and motor planning. Importantly, communication improves alongside these motor gains. She progresses from being unable to follow commands to following verbal instructions, begins using words with meaning, including mama and dada, and she demonstrates increasing receptive communication by responding to her name being called. Taken together, these changes suggest a restart of development over time rather than isolated functional improvement. In daily life, these gains translate into greater independence. She's now participating more independently in family meals, beginning to feed herself, and hold her ow n drink. She moves through her environment with more confidence, bending, navigating, and picking up objects with less physical assistance and less constant supervision. Importantly, she's more connected with her family, responding when called, following instructions, and communicating with simple but meaningful words. Participant three, six years old at the time of dosing several years post-regression, began from a more severely affected baseline and provides another compelling example of restarting development. Before treatment, she had minimal functional hand use and was fully dependent on caregivers for feeding because of severe swallowing difficulty. She could not sit independently and required maximal support to stand or walk. Communication was also very limited, with no ability to follow commands or make choices. Following NGN-401, we again observe milestone gains across domains in a developmental progression. In daily life, these changes are meaningful. In the first example, she is actively engaging with her grandmother, following her instructions to select the correct puzzle pieces by color and participate in play. She's also the second participant in the trial who can now follow instructions post-treatment in two languages, which reflects a meaningful improvement in receptive communication. In terms of mobility, even though she has achieved one formal gross motor developmental milestone, her functional abilities have improved significantly from baseline. She previously required maximal assistance to transition from sit to stand and the support of two caregivers to remain standing. After NGN-401, she now requires only moderate assistance from her caregiver to transition from sit to stand and to remain standing. Reflecting a meaningful improvement in functional mobility and independence while reducing the level of caregiver support needed to safely perform this transitional movement. She now initiates steps from her baseline of an inability to sit without assistance. These are very meaningful gains for families. As she grows, needing less physical assistance will be absolutely critical. The physical demands of supporting a growing individual can place a significant burden on caregivers and may become more difficult or impossible to manage. At mealtime, she shifts from full dependence to active participation, selecting food with her hands and self-feeding rather than requiring spoon-feeding from a caregiver for every bite. For this participant, we are seeing a meaningful shift from near complete dependence towards the early stages of increasing independence for everyday activities. Participant four, seven years old at baseline and years after completing regression, further reinforces the pattern we are seeing across the group of longest duration follow-up. At baseline, she had limited hand use, was non-ambulatory, and had severely impaired communication. After NGN-401, we again saw gains across multiple domains. In daily life, these gains translate into greater autonomy. She is now able to participate more independently at mealtimes, feeding herself using utensils independently and eating alongside her family. At the same time, her gross motor improvements are enabling greater independence. She can now sit up from a lying position on her own, allowing her to reposition herself in bed and prepare to be transferred without full caregiver support. These gains extend beyond mobility into control of her environment. She can turn a light switch on and off, reflecting purposeful hand use and giving her direct control over her surroundings, something that was not previously possible. In addition, she can now actively participate in family celebration, strengthening both communication and social engagement. Notably, she has also greatly improved her ability to communicate with her AAC device, providing more consistent indications of need and want to her caregiver, which is high on the caregiver priority list. Taken together, these four participants with the longest duration of follow-up show a consistent pattern. After treatment, we see coordinated restart of development across domains. These changes are not isolated to a single skill or domain. Importantly, these gains translate into meaningful functional change, including self-feeding, following instructions, sitting up, greater mobility, and more independent participation in family life. While each participant begins from a different baseline and follows an individual course, the overall pattern is remarkably consistent. Progressive acquisition of skills that increase independence and reduce caregiver reliance over time. For me, the biggest thing is that there is potential for more over time. In Rett syndrome, we are faced with a complex neurodevelopmental picture, these data show progress on every developmental domain in an orderly fashion, which is what would be expected biologically with a gene therapy. Thank you for the opportunity to present these data on behalf of my co-PIs in the trial. Most importantly, thank you to the participants and the family who have enrolled in this study. I will now turn the call over to Julie to continue the review of the phase I/II data. Thank you, Dr. Suter. We are very pleased with these results. That trajectory reinforces our confidence in what we expect to see as we follow participants over time. Now let's turn to individual participant level data. This slide shows the rapid response post-dose that deepened over time. The green bars represent participants who meet the EMBOLDEN composite responder definition, improvement on CGI-I and at least one developmental milestone gain. 100% met the composite endpoint at the latest follow-up. At 12 months, 80% met the composite endpoint, far exceeding the 33% response rate needed for success in the EMBOLDEN trial. Importantly, CGI-I improvement is observed at or before milestone attainment, reinforcing that the composite endpoint is both clinically meaningful and achievable. 47 total developmental milestones have been gained, which represents an average of 4.7 milestones per participant. First clinical response occurred rapidly with a median time to response of two months post-treatment. If we now step back from the individual participant level and look across the dataset, we see that these gains are not isolated to a one domain. Developmental milestones are accumulating over time across multiple domains in fine motor, communication, and gross motor function, domains that matter most to patients and caregivers. At each time point, you can see the total number of developmental milestones gained. By six months, the total milestones gained doubles from the three-month mark and continues to increase over time, with milestones increasing 95% from 6-12 months and by 147% at or beyond 12 months to a total of 47 milestones gained at the latest follow-up. Seven of 10 participants gained at least two developmental milestones, and these gains were across two or more clinical domains. These data underscore the differentiated multi-domain response NGN-401 is delivering. In terms of the specific EMBOLDEN milestones achieved in the phase I/II trial, you can see we had a robust 21 of the 28 total possible milestones achieved across the 10 participants. Remarkably, participants achieved all seven hand function milestones, more than half of the gross motor milestones, and seven of eight communication milestones. These multi-domain milestone achievements allow these participants to be more connected to the people around them and participate in their self-care. These improvements also increase their independence in moving and interacting with their environment, ultimately easing everyday care for their families. We are also very encouraged by the meaningful gains we're seeing in the Rett Syndrome Gross Motor Scale, or RSGMS. The RSGMS provides an independent, centrally rated, quantitative assessment of gross motor function that complements the developmental milestone data. As will be highlighted in a poster presentation at the IRSF Scientific Meeting by Dr. Jenny Downs, who developed the scale, the mean RSGMS total score increased by 5.2 points when normalized to a one-year rate. This represents a statistically significant improvement on a scale that typically declines over time in Rett syndrome, where natural history shows a 0.8-point decrease over one year. Notable are the gains in transition skills, which are commonly impaired in Rett syndrome. Specifically, five of seven participants who were unable to move from sitting to standing independently and five of six who could not stand up from the floor independently improved post-treatment. Improvements in these abilities not only reflects better motor planning, coordination, and strength but also reduce the amount of physical assistance required from caregivers. We see similarly encouraging and meaningful gains in the Rett Syndrome Hand Function Scale, or RSHFS, which is a centrally rated quantitative assessment of hand function that complements the developmental milestone data. As will also be highlighted in a separate poster presentation at IRSF by Dr. Downs, 100%, or all 10 participants, demonstrated a gain in hand function over one to two and a half years. A statistically significant difference from natural history data in which only 15% of patients improved over the course of three to six years. Impressively, seven participants showed improvements in both hands. Functionally, these improvements enabled greater participation in everyday activities, including self-feeding, engaging in play, and increased independence in daily routines. In totality, the developmental milestone gains, CGI-I scores, and the RSGMS and RSHFS data provide a compelling body of evidence that NGN-401 is providing meaningful efficacy across the core domains of Rett syndrome. With that, I'll now turn to the safety profile. The 1E15 vector genome dose of NGN-401 continues to be generally well tolerated. All treatment-related AEs have been mild to moderate and are consistent with known AAV-related adverse effects. The majority have resolved or are resolving. There have been no new treatment-related SAEs in the phase I/II trial since our last update. While one participant previously had two reported SAEs associated with sensory neuropathy, a known AAV class effect, those SAEs have resolved, and there are no clinical symptoms. This participant has since become a responder. A separate participant experienced sensory neuropathy, and this participant has also become a responder. Overall, these events appear to be transient, and both participants have improved in CGI-I and gain to developmental milestone. We are pleased that the safety profile demonstrates that NGN-401 continues to be generally well tolerated at the 1E15 vector genome dose, with follow-up now extended beyond 30 months. The efficacy data and tolerability profile highlight why we believe we are well-positioned for success in the EMBOLDEN registrational trial, which I will now describe. As Rachel noted, we completed dosing in EMBOLDEN with a total of 25 participants across a broad age range, representative of the Rett syndrome population and supported by our natural history analysis. The primary endpoint is a responder-based composite endpoint defined as CGI-I of less than or equal to three and gain from baseline of any one developmental milestone. The primary analysis to support the planned BLA submission is expected to occur after the first 24 participants, the primary efficacy population, have completed 12 months of follow-up. The list of developmental milestones is pre-specified and will be captured through standardized video recording and rated by independent blinded central raters. This registrational trial enables us to have a single study designed to have efficacy and safety data to support a broad label. To put our results into context, it's important to understand the natural history of Rett syndrome. Natural history data from the NIH-sponsored Rett Syndrome Natural History Study, accessed through IRSF, show a clear and important pattern. The figures shown here are Kaplan-Meier cumulative incidence curves for example milestones from the pre-specified EMBOLDEN list of 28. Based on longitudinal data from the Rett Natural History Study, the likelihood of gaining a developmental milestone is rare at or after age three. As you can see across these examples by key Rett domain, milestone acquisition rises in early childhood but plateaus by approximately age three, with minimal incremental gain through age six and beyond. Importantly, the lack of meaningful increase between ages three and six demonstrates that these milestones are not simply delayed or spontaneously acquired over time. Rather, the natural history is characterized by a persistent absence of developmental progress. Beyond age three, the likelihood of gaining any individual milestone remains low, typically in the low single digits across domains, and becomes even more limited in older children and adolescents. This is why age three was selected for the EMBOLDEN registrational trial. By that age, the regression phase has passed, and spontaneous developmental gains are not expected, providing a well-defined baseline against which treatment effects can be evaluated within each patient. Dr. Jeff Neul, who led the Rett Syndrome Natural History Study, will present our analysis in a poster at the IRSF scientific meeting. Dr. Neul featured data from three representative treated participants: one participant aged four years at baseline, one aged seven years at baseline, and one participant aged 14 years at baseline. The age-matched cumulative incidence rates for each of the milestone gains range from 0.3%-7.9% in the four-year-olds, 0%-2% in the seven-year-olds, and 0% in the 14-year-olds. These natural history data highlight the rarity of developmental milestone acquisition at or above age three years in Rett syndrome and underscore the significance of the robust clinical responses observed with NGN-401. On the left, you can see that there was an 80% response rate in the phase I/II trial based on the EMBOLDEN primary endpoint definition at 12 months post-treatment. This responder rate is 2.4 times higher than the 33% success threshold required for EMBOLDEN. NGN-401 has been generally well-tolerated in EMBOLDEN. There have been no treatment-related SAEs or DLTs in the EMBOLDEN trial as of the data cutoff date of June 16, 2026. Together, we believe these data de-risk EMBOLDEN outcomes. I will now turn the call back over to Rachel. Thank you, Julie. In summary, we have a robust, clinically meaningful set of data that we believe will support a potential market-leading therapy for Rett syndrome. We are seeing consistent, clinically meaningful, and multi-domain improvements that go beyond isolated milestone gains. Instead, the progressive acquisition of milestones point toward a restart of developmental progression. While the response to treatment was rapid and all participants have gained one or more developmental milestones, we believe the more important focus is the depth of response. At the latest follow-up, we observed an average of 4.7 milestones per participant, with seven of 10 participants gaining two or more milestones across at least two core domains of Rett syndrome, which we believe is unprecedented. As you can see, the number of milestones at six, 12, and beyond 12 months deepens over time. No developmental milestones are lost in any participant, which is critical to support the durability of effect for a one-time gene therapy treatment. 80% of participants met the rigorous EMBOLDEN responder definition at 12 months, reflecting 2.4 times higher than the minimum threshold needed for success. Additional quantitative assessments of the hand and gross motor function showed statistically significant improvements relative to natural history data. In summary, we believe these data will support strong differentiation in a multi-billion dollar opportunity in a disease with a clear and urgent unmet need. We're at an exciting juncture as a company. We've generated compelling long-term clinical data. We've completed dosing in our registrational trial, and we have strengthened our leadership team as we advance our commercial readiness. Looking ahead, we remain focused on several key anticipated milestones. Initiating our PPQ campaign imminently, reporting top-line data from EMBOLDEN in the second half of 2027, and advancing towards a planned BLA submission. Notably, we have used the same process and scale throughout clinical development that we intend to use for commercial manufacturing, limiting comparability challenges. In parallel, we will continue to build the infrastructure needed to support a successful commercial launch. Importantly, we are rapidly advancing towards commercialization with a strong financial position, which we believe will support operations through key value inflection points. Finally, all of this progress is only possible through the extraordinary trust, partnership, and ongoing support from the Rett syndrome community. We would again like to extend our deepest gratitude to the participants, caregivers, investigators, clinical trial site coordinators, and the broader Rett syndrome community. We are excited about the path forward and the opportunity to bring NGN-401 to patients and families. Thank you for your attention. With that, we are ready to begin our question and answer session. Operator, would you please open the line for opportunity to bring NGN-401 to patients and fa milies. Thank you. Thank you. We will now begin the question and answer session. If you would like to ask a question, please press star, then the number one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star, then the number one again. Question and answer. Your first question comes from Ritu Baral with TD Cowen. Your line is open. Good morning, guys. Congratulations on this data. In the current data, was there any signal for [crosstalk] r apid onset, especially thinking about change or any sign of impairment and what this means for the data from EMBOLDEN data. Thanks, Ritu, for the question. This is Rachel. No, I think what you're pointing out is that Rett syn drome is inherently a heterogeneous disease, right? There's different ages, there's different baseline severities, there's different genotypes. What you're seeing here is that 100% of participants are responding. We can confirm that 100% of participants have gained at least one developmental milestone in the last 12 months. We are seeing a broad response regardless of age, both in the younger as well as in the older cohort as well. I think we're very pleased with the overall product profile demonstrating a robust effect across the population. Thank you. Your next question comes from Patrick Dolezal with LifeSci Capital. Your line is open. Hi. Congrats on the data, thanks for taking the questions. Just given the robust depth of response with 3.7 milestones gained per patient at 12 months and another milestone gained per patient when looking out further, up to 4.7 milestones per patient at last follow-up. How should we think about the importance of the 12-month endpoint versus the complete patient experience with extended follow-up? The second question, assuming patients in EMBOLDEN have a similar experience with milestone gains continuing to stack over time, how can you ultimately market those claims post commercially? Thanks. Thanks, Patrick. In terms of the long-term data beyond 12 months, this is very, very important for clinicians and caregivers to really determine the choice of a gene therapy. 12 months, as you know, is important for regulators to make a determination of efficacy. It's really the data beyond that that's going to be important to demonstrate a number of things, including durability and continued improvements, to support the overall meaningfulness of a one-time gene therapy product for all stakeholders, including the FDA, clinicians, and caregivers. As it relates to your second question on how to market those claims, Christine, would you address that? Thank you, Rachel. Happy to do so. Patrick, what we're seeing here is an extremely robust response that is actually supported by the clinical trial design that we have in the trial, both from a primary efficacy analysis as well as from a key secondary perspective. As Dr. Suter also described, what we're seeing is this multi-domain coordinated response that suggests the restart of development. We think that not only will the label be very supportive of collecting milestones, showing the multi-domain response, but also being able to publish on this on the long term, to be able to truly show and establish clear differentiation of NGN-401 with long-term clinical evidence. Your next question comes from Debji Chattopadhyay with Guggenheim Securities. Your line is open. How would you characterize the time course and the importance of the CGI-I versus the developmental milestones? Given the data that was presented today, if you were to prioritize a therapy between the two gene therapies, which one would you choose and why? I'll take the first question, then I'll ask Dr. Suter to give his overall perspective as a clinician and also any perspectives he has from a family perspective. As it relates to the time course, if you look at the chart where we lay out the individual patient data, you'll see that the median time to a CGI-I response was two months. Very rapid. This is the first time that we're disclosing that information, but people can see that the response overall is rapid in the majority of patients. In all cases, what we see is CGI-I either comes before or at the same time as the occurrence and recording of a developmental milestone. It really is very consistent. If anything, it's a predictor of future developmental milestone gain. Dr. Suter, could you talk a little bit about your perspective on how to prioritize gene therapy in your own experience and your conversations with families? Sure. What I'm learning from my discussions with families is that ultimately, families care mostly about efficacy overall. I think we're still in a phase where we will learn ultimately about the efficacy. NGN-401 definitely has demonstrated in individuals a very, very promising course of developmental gains. I have no fear that this would speak to families strongly in terms of choosing this gene therapy. If I may, one more follow-up here. As you prep for commercialization, how are you thinking about the ex-U.S. opportunity, and where are you with respect to CMC currently? Thanks so much. Sure. That's another two-part question. I'll just speak briefly in terms of ex-U.S. From a regulatory perspective, we are engaged with EU regulators. We have prioritized the U.S., but certainly see the ex-U.S. market opportunity as substantial and a priority. From a CMC perspective, we are very much on track. As I mentioned, we are imminently initiating our PPQ campaign, and we'll be completing that this year. Everything is on track from a CMC perspective. Thank you. Your next question comes from Mani Foroohar with Leerink Partners. Your line is open. Thanks for taking the question, and congrats again on continued durable data showing benefit for these drugs and their families. As we get closer and closer to an eventual regulatory filing, commercial availability, presuming positive EMBOLDEN data, help us understand how the evolution of this data will confirm the restart developmental progression and how that informs your commercial and competitive strategy and messaging on an MSL basis, perhaps more than a sales basis. Sure. I think, look, we're very pleased with the overall profile of EMBOLDEN, and I think Excuse me. Of the phase I, II data and this being a helpful view into the future of what we can expect from EMBOLDEN. In terms of the restart of development, I think maybe I'll ask Dr. Suter to make a comment on that, and then as it relates to the commercial strategy, Christine can answer that question. Sure. Thanks, Rachel. Just to weigh in there, these developmental milestones are really not gained in a random fashion, but really as you would expect them to occur biologically, right? These individuals gain these milestones, reaching and tapping, then subsequently whole hand grasp, then fine finger-based manipulation of objects, along with gain on other domains that are also acquired in a developmentally ordered sequence, which really clues us in that this is a restart of biological development and not random acquisition of individual skills. Then I'll take the commercial strategy question. Mani, essentially what we're trying to do here is we've been pretty busy on pre-commercial activities in a couple of ways that are going to impact the answer to your question. The first one is expanding awareness for NGN-401. We've already built a pretty strong network within the centers of excellence, activating sites in that U.S. infrastructure. As Rachel mentioned, we're also actually engaging with ex-U.S. KOLs to start to actually educate them on NGN-401 and educate them on the actual developments that we've seen with our data. That leads into the second important strategic imperative that we've employing, which is to establish clear differentiation of NGN-401 with long-term clinical evidence. There's where the MSLs come into that perspective. Ultimately, it's the short-term data is, we believe, going to help get the drug approved, but it's that long-term data that's going to impact adoption. In regards to what Dr. Suter is talking about, between having MSLs to truly educate on what we're seeing, both with what's going to go on the label, but also publish on the information that Dr. Suter is talking about while we expand the network. We believe that's going to work very well in concert to educate on this in the long term. Great. That makes sense to me. That's really helpful. One more quick follow-up, if I may. You talked a little bit about commercial positioning, et cetera. Can you give us a heads up on where you are in terms of managing the manufacturing process capacity? Obviously, this is a large pool of patients that are diagnosed, treated, many of whom already rolled off DAYBUE. How can we think about volume and capacity to treat patients upon an eventual commercial launch and potential investments around infrastructure and scale-up for manufacturing? I'll take the manufacturing of where we are, and Christine can talk about the investment aspect. As it relates to capacity, as I mentioned, we are initiating those PPQ runs imminently, that can help to begin to support inventory build. We also have plenty of capacity available next year and beyond. Owning our own manufacturing facility gives us the strategic flexibility to be able to support the adoption rates projected for commercial supply. There's no change in scale or process required to meet what we expect is going to be a robust launch. Christine, do you want to take the other part? Sure. On the investments required, in fact, our cash runway guidance already provides for the investments that are required in order to commercialize this product from a CMC perspective with no additional investment. Great. Thanks. That's really helpful, guys. Your next question comes from Paul Matteis with Stifel. Your line is open. Hey, great. Thanks. Congrats on the data. Thanks for fitting me in. As it relates to the efficacy, I wanted to just clarify one thing. Did you say that every single of the 47 milestones gained has been individually durable and all have been gained and sustained? Then for Dr. Suter, just from your clinician experience, have you ever seen patients in the age range in this Neurogene trial gain a milestone or two at this point in time in development spontaneously? Thanks so much. To confirm, yes, all of the milestones are durable and sustained. Dr. Suter, do you want to talk about your experience? Sure. We followed our center, a couple of hundred Rett individuals, I can say with confidence that yes, you might see an individual skill gain, you will not see a multi-domain skill acquisition as we've seen on the study. Your next question comes from Mitchell Kapoor with H.C. Wainwright. Your line is open. Hi, this is Ahmed on for Mitchell. Thank you for taking my questions. Congrats on the fantastic data. I was just wondering, from our perspective, we had brought up the ICV administration. In your view, does EMBOLDEN enrollment and dosing support the ICV adoption hypothesis, or do you still see families decline or hesitate because of the route of administration? I'll just make a comment and then ask Dr. Suter to opine on the conversations he's had with families as it relates to route of administration and what's important for families in a one-time gene therapy. From our perspective, we've seen very robust adoption. Route of administration has absolutely not been a barrier. As you know, we've over-enrolled our trial of EMBOLDEN by 25% in a very short period of time. Families anecdotally have come in actually asking for the route of administration that is really directly delivering gene therapy to the brain because what we've heard is that they feel like they want that gene therapy that can really maximize the distribution. It's a one-time treatment that is lifelong, this is a lifelong disease. Dr. Suter, please elaborate. Sure. Yeah. No, I concur with you, Rachel. Really, what I encounter from families is that their top priority is efficacy. They're interested in the efficacy. We know that ICV injections really get the product to the brain areas where it matters the most. It's a fairly routine procedure for skilled neurosurgeons, performed on a daily basis across the U.S. Families are not deterred from this procedure at all when we speak about the gene therapy. Suffice it to say that we have a continuing influx in interest on the sides of families for this gene therapy. Even after enrollment, you're seeing further demand come in? Yes. Thank you. Your next question comes from Whitney Ijem with Canaccord Genuity. Your line is open. Hi, guys. Congrats on the data. This is Angela on for Whitney. Given the strength of your data and what appears to be a more reasonable FDA over the last couple of weeks, is there any updated thinking about a potential six-month interim? Thanks, Angela, for the question. You can see obviously from our data that we have very robust data at six months with an average of 1.9 milestones per patient, and that continues to deepen very significantly over time. We have asked the agency in the past several times, we know that the agency, given that Rett syndrome, while chronic, is not the urgency to follow patients and show durability is much more important than a short time of follow-up. The agency has been very clear that they're looking for a 12-month primary analysis for gene therapy in Rett syndrome. Our trial design remains a 12-month primary endpoint. Got it. Thank you. Our last question comes from Seema Sheoran with Rodman & Renshaw. Your line is open. Hi. Congrats on the update, and thank you for taking my question. My question is for Dr. Suter. Taysha Gene Therapies is planning to meet with the FDA and communicate the six-month interim data in the first half of 2027. Assuming that it does get approved based on six months interim data, how much do you think that roughly six months difference in data finding between Taysha Gene Therapies and Neurogene's therapy will realistically impact adoption of NGN-401? Are patients going to wait for the 12-month data from Taysha Gene Therapies as well before deciding, or patients are just going to go for which therapy is approved first? Thanks, Seema, for the question. I'll start and hand it over to Dr. Suter for his perspective. Importantly, the EMBOLDEN trial results, as you know, are anticipated to be available in the second half of 2027, well before any gene therapy product would be approved on the market. It's important to note, in addition to that we will be continuing to follow our phase I-II cohort. What you're seeing right now is a snapshot of a minimum of 12 months duration of follow-up in all participants, with up to 30 months of follow-up. Of course, next year you can tack on another year of follow-up to that, the year after, you'll have even more data. You'll have some patients with more than three years of data coming out from the phase I-II, that will be available for the marketplace and likely published in a way that clinicians and families will be able to interrogate the overall profile. There'll be EMBOLDEN data, there'll be phase I-II data. In that context, Dr. Suter, is a timing of a few months difference of one therapy being available for another therapy, is that the main driver, or are there other factors that families will consider? Yeah, I don't think that'll be the driver. Really, ultimately, I'll circle back to what I said all along. It'll depend on the efficacy data itself. Great. Thanks. That concludes our Q&A session. I will now turn the conference back over to Rachel McMinn for closing remarks. Thank you, operator. Thanks everyone for tuning in. We look forward to keeping you informed of our progress in this program. This concludes today's call. Thank you for attending. You may now disconnect and have a wonderful rest of your day.