Hello, everyone, and welcome to the 44th Annual JPM Healthcare Conference. My name is Max Marks, and I'm an associate on the JPM Healthcare Investment Banking team. And today it is my pleasure to introduce Neurogene and CEO Rachel McMinn. Thank you so much. Good morning. I'm Rachel McMinn, founder and CEO of Neurogene. It's my pleasure to provide an update on the strong progress we have made and our outlook for the year ahead as we continue to advance the potentially transformative genetic medicine for the treatment of Rett syndrome. During this presentation, I will be making forward-looking statements that are subject to risks and uncertainties. Please refer to our annual and quarterly reports filed with the SEC for full disclosure on the risk factors that may impact our company. In 2018, I founded Neurogene with a clear mission: to develop life-changing gene therapies for people and families affected by devastating neurological diseases. Today, we are closer than ever to delivering on this mission with our lead program, NGN-401 for Rett syndrome. Our approach is based on four core pillars. First, we start with a deep understanding of the disease biology to address the root cause. Second, we select a delivery method that allows our therapy to reach the right cells in the right regions of the brain and nervous system. Our proprietary EXACT technology platform is designed to precisely regulate how much therapeutic protein is expressed in each cell to maximize therapeutic impact and avoid the harmful risks of overexpression. Everything we do is driven by the needs of patients and families in our minds. Our approach is rigorous, deliberate, and focused on delivering meaningful, lasting change for those living with devastating neurological diseases. NGN-401 is an example of this comprehensive approach to deliver a potentially best-in-class treatment for patients and families in need. We have made substantial progress in 2025, and 2026 is shaping up to be even more transformative. Our lead program, NGN-401 for Rett syndrome, is currently dosing patients in our Embolden registrational trial, which is designed to serve as the primary basis for FDA approval and support a broad label. Earlier this week, we announced that immediately following alignment with the FDA on the Embolden trial design, we dosed multiple participants in the fourth quarter of 2025. This rapid pace illustrates the enthusiasm from our investigators and the patient community. The strong demand is driven by the compelling interim clinical data from Phase I/II trial. These data demonstrate a potential best-in-class product profile with remarkable functional improvements across the cardinal features of disease, with developmental milestones that have accumulated over time and remain durable through up to 24 months of follow-up in our pediatric participants. These data give us confidence in a successful outcome for the Embolden registrational trial. With a clear path to registration, we are rapidly advancing towards commercialization into a multi-billion-dollar market opportunity. We are well-positioned to transform a community that is burdened with lifelong, high-intensity medical care, and we believe that NGN-401 has the potential to offer a promising treatment option for this community. As we look ahead, Neurogene is poised to significant value inflection with multiple catalysts this year. Anticipated near-term milestones include: one, completion of Embolden enrollment and dosing in the second quarter; and two, presentation of additional clinical data from Phase I/II trial mid-year this year, which will include a minimum of 12 months of data on all participants. To set the stage, Rett syndrome is a devastating disorder that robs young girls of their abilities and independence, turning everyday moments into lifelong challenges for families. It is a disease characterized by developmental delay that occurs in the first six to 18 months of life, followed by a period of regression in which children lose many of the previously attained developmental milestones. Parents watch helplessly as their children, who could once hold on to their favorite toys, feed themselves, or speak a few words, lose these basic abilities. Many of these children never learn to walk, and those that do struggle with the basic tasks of getting around the house, navigating obstacles, things like going up the stairs. Thereafter, there is a period of relative stability. We're starting around the age of three years of age. It is rare for children to gain any new developmental milestones. Cardinal features of the disease include severe impairments in hand function, communication, and gross motor function, as well as autonomic dysfunction. The root cause of this disease is driven by a lack of functional MeCP2 protein in the brain and nervous system, which ultimately leads to disruption of neural networks and proper neuronal functioning. With NGN-401, we believe we have the potential to unlock a multi-billion-dollar market opportunity. Rett syndrome is one of the more prevalent rare diseases, with an estimated 15,000-20,000 patients in the major markets and an incidence rate of one in 10,000 females worldwide. There is no disease-modifying treatment available, with current treatment options limited to symptom management and lifelong intensive supportive care. Payers are familiar with Rett syndrome and value meaningful functional changes that show improvements in activities of daily living. The market is already well-established to support premium-priced gene therapy product that can deliver durable, clinically meaningful outcomes. Gene therapy is a treatment that can only be given once, so it's critically important to purposefully design and deliver a construct with a biology-first approach. NGN-401 is the only gene therapy designed to safely deliver a full-length protein to key areas of the brain and nervous system to maximize efficacy. Full-length gene enables functional MeCP2 protein on a cell-by-cell basis. Our proprietary EXACT transgene regulation technology maintains MeCP2 protein production within the target therapeutic window and avoids overexpression toxicity. Multiple nonclinical studies show that ICV administration delivers the broadest targeting of the brain and nervous system, which is critical for restoring functional MeCP2 protein to the cells that drive Rett syndrome. This purposeful design has translated to the compelling Phase I/II clinical results that I will now walk through. Phase I/II trial is an open-label, multi-center trial designed to assess the safety, tolerability, and efficacy of NGN-401. We completed dosing in both the pediatric and adolescent adult cohorts in the second quarter of 2025, and we shared an interim update from the study in November of 2025. This chart summarizes the baseline characteristics of all eight pediatric participants. You'll see we have patients enrolled from ages four through eight years and who represent the full spectrum of genetic and disease severity in classic Rett syndrome. As of the data cutoff, participants had a range of follow-up from six to up to 24 months. To summarize the results, NGN-401 led to clinically meaningful, deepening, and durable improvements across key Rett syndrome domains. 100% showed functional improvements in one or more domains of hand function, gross motor function, and communication. 35 total developmental milestones were gained, which were also durable, with no plateau observed, including up to 24 months following treatment. Importantly, these multi-domain gains enable increasingly complex activities, enhancing independence and health-related quality of life. An 88% achieved an improved Clinician Global Impression of Improvement, or CGI-I score. The 1E15 vector genome dose of NGN-401 continues to be generally well tolerated. To put these data into context, we know from our caregiver research that what matters most to families is a treatment that can meaningfully improve daily living and enhance independence. In our market research, caregivers consistently highlighted that improvements in the core domains, hand function, communication, and gross motor function, were the highest priority. For example, we have heard repeatedly that meals are a big drain on caregivers, where they are required to feed their child every bite of food. If their child could use her hands to help feed herself, that would be very meaningful. For communication, it is a constant struggle for caregivers, as many girls are unable to express the most basic of their needs or follow simple instructions. Improvements in this domain would be tremendous for families to make the day-to-day better and strengthen connections. And for gross motor function, enhancement here to increase mobility would substantially reduce the physical burden on caregivers in the day-to-day living, whether it's going to school, getting in and out of the car, or just moving around the house. Together, these domains represent the areas that families value most for a treatment to translate into meaningful improvements in quality of life. With this feedback in mind, I'd like to take you through a new presentation of the data that we'd previously shared, but just illustrated in a way that is condensed so that you can observe and understand some of the enthusiasm that we have, and so you can understand why we're so excited about this interim data and why we believe NGN-401 is positioned to be best in class. If you look at the x-axis, you'll see we have the different time points post-treatment with the numbers of patients followed out to that level of treatment. On the y-axis, you'll see we have different colors representing the different domains, whether it's hand function, communication, or gross motor function. Starting at three months, you can see that participants have begun to achieve developmental milestones across all of the core domains, hand function, communication, and gross motor function. By six months, in the same total number of patients, you can see a doubling in the developmental milestone gains, which is quite striking in and of itself. However, moving beyond that, as we look out to nine months, to 12 months, and to patients who've been followed for more than 12 months, you can see that despite the number of patients declining, because we don't have all of that follow-up, the number of milestones is actually continuing to increase. In order for that to be true, and what is true is that there's a number of things to point out here. One is that the domains, the developmental milestones that we're seeing here are durable. Second, we're seeing that the number of milestones per patient is increasing over time. And third, we're seeing that the multiple domain gains are across all of these core functions. We just want to highlight these data because it really gives you a sense of what you would expect to see as you start to restore some of the neural networks within the brain and nervous system. And so this is really consistent with the design and underlying biology of what it's going to take to not only restore MECP2 function, but to enable those neural networks to develop and grow over time. Examples of the milestones achieved include girls being able to feed themselves, drinking from a juice box that they're holding on their own, or being able to follow instructions for the first time. On gross motor function, we're seeing girls either sit independently or even as complex of an activity of being able to climb the stairs. Let me now take you through the Embolden trial design. The data from Phase I/II trial support the design of Embolden, which is depicted here. Embolden is a single-arm, baseline-controlled, open-label trial evaluating NGN-401 in 20 females with classic Rett syndrome who are three years and older and have completed the regression phase of the disease. Age three was chosen because it is rare for a girl with Rett syndrome to gain or regain a developmental milestone at this age or above. The primary endpoint is a composite of CGI-I, or that clinician global impression of improvement, from baseline and any one of the developmental milestones from, again, over baseline from a pre-specified list of 28, and the primary endpoint is being measured at 12 months. Key secondary endpoints include a CGI-I score of less than or equal to two and a gain of at least two developmental milestones. 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 provide the safety and efficacy data to support a broad label. As mentioned earlier, we have already dosed multiple participants and expect to complete dosing in the second quarter of this year. Here you'll see a list of the pre-specified list of 28 developmental milestones being evaluated in Embolden. We developed this list through a rigorous review of the natural history data, feedback from thought leaders and caregivers, and it was reviewed and accepted by the FDA. To put all of this into context, we believe we are well-positioned for success in the Embolden trial. On the left, you can see that there was an 80% response rate in Phase I/II trial based on the Embolden trial definition as of the data cutoff. This responder rate far exceeds the 35% minimum response rate, which is the success threshold required for the registrational trial. On the right, we outline many of the key design elements in Embolden that were carried over from Phase I/II trial. These include the same one-time 1E15 vector genome dose, the same immunosuppression regimen, and the trial sites are being conducted at Rett Centers of Excellence. We also maintained standard CGI-I training across all sites and continued our rigorous approach of independent central review of video-based milestone assessments. Together, we believe these data and these key design elements de-risk Embolden outcomes. We are laser-focused on clinical execution and, in parallel, starting to lay the foundation for commercial success. Our team is working closely with Rett Centers of Excellence where the Embolden trial is being conducted so that we can be in a position to quickly convert these sites into commercial sites. In addition, we have a fully integrated end-to-end CMC capability in place to produce commercial product out of our internal manufacturing facility. Finally, over the past year, we've completed robust payer research that confirms strong reimbursement potential for both NGN-401 and the procedure. In addition, there's optionality for an outpatient pathway to further simplify reimbursement. This sets the stage for educating payers about NGN-401 and for further market readiness and reimbursement work on the horizon. Looking ahead, Neurogene is in a strong position as we enter 2026. We expect to complete dosing in Embolden in the second quarter of this year. We also expect to present new safety and efficacy data from Phase I/II trial mid this year and initiate additional clinical readiness activities. We continue to have a strong balance sheet that provides runway through the first quarter of 2028. This capital is expected to fund operations through key milestones, including the Embolden data readout, BLA submission, and important key pre-launch activities. With compelling data, a clear regulatory path, and a strong financial position, we believe Neurogene is poised to transform treatment for Rett syndrome. Thank you so much for joining us, and we appreciate your support. Thank you, Rachel. And now we'll move on to the Q&A portion of the session. So one question that we're getting is, what is it about Phase I/II data that's been reported to date that gives you confidence in the Embolden trial? Yeah, thanks very much. As I outlined in the presentation, we are seeing a robust response rate from the patients who've been followed for a full 12 months. That would be the first point that I would make. In addition, we did convert Phase I/II trial into a registrational trial design. When you think about this, many of the elements Phase I/II have been carried directly over into the Embolden trial. Importantly, though, as we continue to monitor and follow these patients, we are seeing benefits across the spectrum of Rett syndrome disease, both in terms of genetic as well as disease presentation, and then finally, from a safety perspective, we have dosed multiple patients, so 10 patients in Phase I/II trial at the 1E15 vector genome dose. We've disclosed this week that we have dosed an additional set of multiple patients in the fourth quarter of 2025. So we are continuing to build that safety database as well. So taken together, when you think about the efficacy data continuing to show durability, improvements over time, reproducibility in patients that have been more newly dosed, as well as a robust safety database that we're continuing to build, we feel very confident in the outcome of the Embolden trial. Thank you. And when we look at gene therapy trials for Rett syndrome, what are some important factors to look for beyond just meeting the primary endpoint? Yeah, it's a good question because I think there's been a lot of discussion and focus on the responder rate and the primary endpoint, which of course is very important. But we know that we have a high response rate, and generally speaking, it's great to be able to have a regulatory pathway that allows us to move forward with this responder definition. But I think part of what you're getting at here is that this is a chronic, debilitating, devastating disorder. And families are looking more than just for a definition of a single milestone gain. They are looking for improvements across the spectrum of disease, across multiple areas of their disease, whether it's communication, their ability to use their hands, gross motor function, and even beyond that in autonomic domains. So it's going to be really important as we continue to follow these patients over time. This is a complex, chronic disease. So being able to show durability, being able to show responses and gains in skills and milestones as patients are followed chronically is going to be very important to be able to have a sense of what does disease modification look like with a gene therapy product? Thank you. Yeah, it all makes sense. And sort of with the broader Rett syndrome landscape, how do you see the treatment landscape evolving? Yeah, so this is a really exciting time for Rett syndrome. We believe that this is a multi-billion dollar opportunity. But when you think about the families out there, there's somewhere between 15 and 20,000 families with Rett syndrome in the major markets, as I've talked about, an incidence rate of one in 10,000 females. When you think about that, that's almost 200 babies being born every year just in the U.S. with Rett syndrome. And as we look on the horizon right now, there's only symptomatic treatment. There's nothing that's available to really treat the root cause of disease. And soon, families are going to have options. There's potentially two gene therapy products for families to provide hope and promise of being able to not only begin to transform the natural history of disease, but to have these girls move from having no ability to gain any level of function after they go through this regression period, but to really be able to start to begin to build on skills over time and fundamentally shift where they would otherwise be without a gene therapy treatment. From a payer perspective, there is a product. While it's symptomatic, it is approved for the treatment of symptoms, and many families have tried that, and payers are very familiar with Rett syndrome, so this is exciting for us because we're not starting from ground zero in terms of educating payers, and the market supports that this is an incredibly burdensome disease on families. Being able to show durable, clinically meaningful functional changes is a message that is well received by payers. And we believe really does establish the ability to get reimbursement in the future for a product like NGN-401 that would be in the price range of what you typically expect for a gene therapy product. Thank you. And you touched on this a bit, but with the potential to have two disease-modifying treatments approved in the coming years for Rett syndrome, how do you think about the market? Is it a winner-take-all market? Yeah. Look, we know from thought leaders and from caregivers that what matters most is really, again, being able to shift this disease from stasis to growing the abilities and the skill set of these children that are devastated by this disorder. So this is a high-impact rare disease where efficacy really, really matters, especially in the face of a one-time treatment. What we've learned is that the delivery mode itself is not really the driver of that treatment decision. And from a reimbursement perspective, there's not going to be a problem being able to be reimbursed for whether it's an IT lumbar or an ICV administration. So that's really the good news. So we do think that there's room in this market for multiple players. It's a really big market. You don't need a lot of penetration into the market to really unlock multiple billions of dollars from an opportunity set. So I think we're very excited. At the end of the day, it's really going to be the data that's going to drive adoption. And more of that to come as both we and others continue to follow patients over time to really establish the product profile of these new agents. Thank you. And shifting gears a little bit, where do you stand with enrollment in the Embolden trial? Yeah, look, Embolden is enrolling rapidly. There's a lot of momentum, a lot of enthusiasm from the community, from the clinicians. We're so thankful to everybody who has participated and plans to participate. We're pleased to say that we have all 13 of our clinical trial sites that are now active and ready to enroll patients. There is no staggering, so it's really just a matter of fighting the current, barring the flu season, which has obviously been a difficult environment. We've been able to dose multiple participants safely and efficiently in our current infrastructure. We plan to continue to do so over the coming months. As I mentioned in my prepared remarks, our guidance is to complete the Embolden dosing, not just enrollment, but dosing of all patients in the second quarter of this year. Thank you. Can you speak to the interest from physicians and caregivers for NGN-401 and more broadly, gene therapy for both Rett syndrome in general and in the trial? Yeah. So look, again, there's just tremendous enthusiasm. This is really the first time that this community has had any prospect for a treatment, let alone two treatments that could potentially address the root cause of the disease. I think people understand that these are sort of the first agents, and we're still learning about them. But there's a lot of enthusiasm. Caregivers, when you listen to these stories, when they're given a diagnosis, it's a really devastating diagnosis because you know that your child is going to require lifelong intensive care. So I think there's just tremendous enthusiasm, akin to what you see in other high-impact rare disease markets. So we're going to continue to support the caregivers and KOLs as much as we can by providing data and continuing to follow these patients and really help people understand the overall profile. But we couldn't be more thankful for the support of the thought leaders who were involved in the trial, as well as the participants and their families who were supporting and generating the data required to really flesh out the product profiles of NGN-401 and other treatments in development. And with the trial, can you talk about expectations for the new data to come in mid-2026? What should investors look for, or what would success look like, and what are some potential forms for releasing the data? Yeah. So to date, we have presented data from eight pediatric patients that were enrolled into Phase I/II trial. With the planned data update mid-2026, this will be the first time that we'll have a minimum of 12 months of data on all 10 patients. So not just the eight pediatric participants, but the two additional participants where there wasn't sufficient follow-up. So we'll have all of that data, 12 months of data for everyone to see. Beyond that, again, what's so important here is not just looking at the snapshot of patients that have been enrolled with that data, but as we think about what defines success, it's going beyond that just initial responder rate and really looking at over time, are we seeing this continued reproducibility that we've seen in the first number of patients, right? Whereas you follow patients over time, you get this restoration in the neural networks that leads to greater motor function, greater independence, a deepening of response over time, and a durable accumulation of developmental milestones. Thank you. And you mentioned in your prepared remarks that early commercial readiness activities are underway, and also there's more on the way this year. Can you elaborate on what else is planned for this year, and what is the footprint you'll need for a commercial build-out? Yeah. Look, we're rapidly advancing towards commercialization with a highly de-risked program, and as you see, we're building a strong foundation for a successful product launch. Examples include positioning the Embolden clinical trial sites for rapid conversion into commercial sites, so we're already having those conversations and really understanding how those individual sites work and what's needed to give them everything they need to make this product available very quickly after launch. We're also on the CMC side preparing to manufacture a commercial-grade product at scale internally at our Houston facility, and then finally, on the payer market research, we've really been able to confirm strong reimbursement potential for NGN-401. As we think about 2026, we plan to continue these activities and all of the early additional commercial readiness activities you would expect us to be preparing. Examples include additional market research. So as more data become available on both the number of patients as well as the duration of follow-up on both products, it will be really important as that data matures to better understand which are the families and segments of the market that will be the biggest drivers of adoption. On the commercial front, excuse me, on the CMC front, this is a big year for initiating performance qualification runs or PPQs. And then, of course, on the payer side, we're going to continue the work that we've done already and sort of go deeper on that front. From a commercial infrastructure perspective, while there's still work that we'll be doing to flesh this out further, again, this is a relatively small number of prescribers. So we'll have a lean commercial infrastructure. And we're already working with many of the Rett Centers of Excellence to make NGN-401 available. And we'll continue to expand that reach and make sure that we are making access as smooth as possible for both the institutions as well as the caregiver and patient experience. Thank you. And when you think about Neurogene, what does the company look like in two years' time? Two years, it's a really exciting time. As you think about Embolden being a 12-month endpoint and put that together with our guidance of completing enrollment in the second quarter, we're very focused on moving the ball here and advancing NGN-401 as safely and efficiently as possible from the clinic into commercialization. So we're very enthusiastic about this best-in-class potential therapy and really beginning to transform this market for Rett syndrome as we've talked about. As we think about activities of daily living and having durable multi-domain improvements and really taking some of the burden off of these caregivers who really take the brunt of this disease. The other thing I would just put a plug in for is that we do have multiple very exciting discovery research programs, and while we're not going to go into those details today, we are excited and we're continuing to move that work forward as well, and we really look to expand our pipeline and look forward to discussing more about our pipeline at the appropriate juncture. Thank you, Rachel, and with that, I'd like to open it up to the audience if any questions. Do you have any closing remarks you'd like the audience to know? I think just in closing, I would say Neurogene has, again, had an incredibly productive year of execution in 2025. When you think about kind of where the company started, how quickly we were able to quickly and safely be able to enroll patients in the second quarter of 2025 to complete the dosing of Phase I/II trial and to go from that in the second quarter to really less than two quarters later, we were able to not only dose our first patient, but dose multiple patients in our registrational trial really gives you a sense of the execution abilities at Neurogene and going to continue putting our heads down and executing in 2026 so that we can very efficiently continue to move NGN-401 closer to commercialization. So just want to thank, again, all of the stakeholders involved, whether it's our FDA reviewers, our patient communities, our investors, our thought leaders that have been with us in lockstep for another transformative year in 2026. Thank you all for your attention. Thank you, everyone. With that, have a great rest of the day.