Neurogene Inc. (NGNE) Earnings Call Transcript & Summary

And 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, and thank you for joining us today to review the Phase I/II data of NGN401 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, and we undertake no obligation to update any forward-looking statements. Our speakers from NeuroGene today are Dr. Rachel McMinn, Founder and Chief Executive Officer; and Dr. Julie Jordan, Chief Medical Officer. We are pleased to be joined by Dr. Bernhard Suter, Medical Director of the Bluebird Circle Ret Center at the Texas Children's Hospital and Associate Professor of Pediatrics and Neurology at the Baylor College of Medicine and an NGN-401 principal investigator. We also have Christine McCail, President and Chief Financial Officer, available for the Q&A session. With that, I will now turn the call over to Rachel.

Thank you, Lena. Good morning, everyone, and thank you all for joining us. As many of you know, Rett syndrome is a devastating neurological disease with no approved disease-modifying therapies. NGN401 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 and 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, and 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 2 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. And 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 developmental reordered progress, not isolated for an adult, and all patients have a profound unmet need. A single idea frames everything today. In Rett syndrome, developed a positive update on dates that we need to support that the atonement for this devastating disease. In the 10 participants treated at 115 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 1 or more developmental milestones and improved on the CGII. At 12 months, has 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 game continues to build. Total milestones gained in the 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 benefit. -- 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 1815 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 Bolton. Earlier this month, we announced completion of dosing in embolden surpassing our enrollment target by 25% and dosing 25 participants within our original time line 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 onetime 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 a median time to improvement was 2 months. The treatment effect was durable and increased over time. Milestone gains increased by 95% from 6 to 12 months and by 147% from 6 to 12 months or beyond. There were no milestones lost in any participant as far as 30 months at post treatment. The treatment effect was multi-domain and was observed across participant age, disease severity and genotype. 7 of 10 participants gained 2 or more developmental milestones, and these milestones were in 2 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, reduce caregiver burden and enhance 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 6-month, 12-month and beyond time points support a clear path to a strong BLA submission, exceeding the embolden minimum success threshold by 2.4x at 12 months. The average milestone gains increased from 1.9 at 6 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 multicenter trial evaluating the safety, tolerability and efficacy of NGN-401. Key eligibility criteria, the key clinical assessments of CGII, CGIS and developmental milestones, as well as the Rett syndrome growth motor scale and Rett syndrome hand function scale are consistent across those 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 E15 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 1 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 incident rates of gaining or remaining at or after age 3 when regression is complete, and they were all deemed clinically meaningful by payer givers. We apply the embolden milestone criteria directly to the Phase I/II data. First, we established which milestones were absent a baseline using medical history, caregiver reports and videos. We evaluated post-treatment milestone gains utilizing independent central review of video documentation using the same prespecified 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 4 to 18 years old. Baseline CGI-S scores were 4 to 6 or moderately ill to severely ill, and the participants represent the full spectrum of genetic severity and classic red syndrome. As of the data cutoff of June 16, 2026, participants had a range of follow-up from 12 to 30 months. I am pleased to turn the call over to Dr. Suter, 1 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 red syndrome and can share what this disease looks like in the clinic? Red syndrome is a rare and devastating neuro development of this order, most often caused by spontaneous autogenic 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 it becomes rare for children to gain or regain developmental milestones, resulting in lifelong pervasive disability that requires intensive medical support in Boston 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 Red syndrome include loss of expressive and receptive communication, loss of purposeful hand function with repetitive movements called steriotopy, gate abnormalities and mobility challenges and autonomic function, including breathing irregularities to phase 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 Red syndrome. [Presentation]

Thank you to the 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 red 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 where progress haults and the independents never fully emerging. In 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 Red syndrome, we often reference the Denver 2 framework, which is 1 of the most widely used developmental assessment tools in pediatrics and neuro development. The Denver 2 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 Red syndrome, that process is interrupted, children develop in an apparently normal manner, then between 1 and 3 years of age, they regress. And the critical point is that once that regression happens, it is exceedingly rare to regain those milestones or gain new ones. The child development freezes, the curve flatten 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 curves climbing again and across multiple domains. And if that happens, the impact will be what families care about the most. Greater independence in reduced caregiver burden, that is the hypothesis we set out to test. I'll now walk through the data from the first 4 patients with 2 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 7 years old, and her regression has been complete for several years before treatment. At baseline, she had very limited functional hand use, limited health feeding, walked on tip tose froze often needed help on every stair and could an indicator wishes or follow a simple command. The dotted line is the day she received NGN 41 and everything to the right occurred after treatment. What we started was not random. In fine motor, she progresses from a rating draft and dropping object to drinking from a cup at PinSagra using utensils to feed herself and transferring objects between hands. A particularly difficult scale in red syndrome as it requires 2-handed coordination. To provide additional context, transferring objects is among the more advanced skills under validated red syndrome and function scale. In gross motor, she progresses from needing help on every stair to climbing stairs up and down independently and held to toe walking, a key milestone under Denver tool and in communication, she progresses from not following command or indicating wishes to following a command, waiving 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. But the more important point is the pattern. These milestones emerge sequentially across domains consistent with restarting development rather than an isolated change. And here is what that looks like in daily life, getting in and out of the bath tub 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 2 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 2 shows the same overall pattern. At age 4, several years post progression prior to treatment at baseline, she had no functional hand use, limited mobility with frequent fall, could not bend over and had minimal communication, unable to follow commands or make choices. Following NGN401, what we observed is not just improvement, but another example of developmentally ordered stepwise reemergence of milestones across domain. 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 waste to touch the floor, a milestone included on the Denver 2 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 improvements in strength coordination and motor planning. And 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 data, 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 games translate into greater independence. She is now participating more independently in family meals, beginning to feed herself and hold her own drink. She moves through her environment with more confidence, spending, navigating and picking up objects with less physical assistance and less constant supervision. And importantly, she's more connected with her family, responding when called, following instructions and communicating with simple but meaningful words. Participant 3, 6 years old at the time of dosing in several years post progression, 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 maximum support to stand or walk. Communication was also very limited with no ability to follow commands or make choices. Following NGN401, we again observed milestone gains across domains in the 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 is also the second participant in the trial who can now follow instructions post treatment in 2 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 fit to stand and the support of 2 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 as 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 NalTime, 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 activity. Participant 4, 7 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 nonambulatory and had severely impaired communication. After NGN401, 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 meal times, feeding herself using lutensils 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 line 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 needs and wants to her caregiver, which is high on the caregiver priority list. Taken together, these 4 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. And importantly, these gains translate into meaningful functional change, including self-feeding, following instructions, setting 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, and 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 KPIs in the trial. Most importantly, thank you to the participants and the family who have enrolled in the study. I will now turn the call over to Julie to continue the review of the Phase I/II data.

[Audio Gap] 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 NGM-401 to patients and families. Thank you for your attention, and with opportunity to Wingate in any you...

[Operator Instructions] Your first question comes from Berit.

And congratulations on this data. you take the data, was there any tenant for societal may be rapid onset to be special thinking about or in in Chairman and what for...

Thanks, Richard, for the question. This is Rachel. So no, I think what you're pointing out is that Rett syndrome is inherently a heterogeneous disease, right? There's different ages, there's different baseline severities there's different genotypes. And what you're seeing here is that 100% of participants are responding. -- we can confirm that 100% of participants have gained at least on developmental milestone in the last 12 months. And we are seeing a broad response regardless of age, both in the younger as well as in the older cohort as well. So I think we're -- we're very pleased with the overall product profile, demonstrating a robust effect across the population.

Your next question comes from Patrick Dolezal with LifeSci Capital.

Congrats on that. Just given the robust depth of response with 3.7 milestones gained per patient in the 12 months and another milestone game 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. And then the second question, assuming patients in embolden have a similar experience with milestone gains continuing to stock over time. How can you ultimately market those claims post commercially?

Thanks, Patrick. So 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 the gene therapy. 12 months, as you know, is important for regulators to make a determination of efficacy. But it's really the data beyond that. It's going to be important to demonstrate a number of things, including durability and continued improvement to support the overall meaningfulness of a onetime 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. 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. But as Dr. Studer also described, what we're seeing is this multi-domain coordinated response that suggests the restart of development. And so 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 Debjit Pataday with Guggenheim Securities.

How would you characterize the time course and the importance of the CGI score versus the developmental milestones -- and given the data that was presented today, if you were to prioritize our therapy between the 2 gene therapies, which 1 would you choose and why?

Yes. So I'll take the first question, and then I'll ask Dr. Suter to give his overall perspective as a clinician and also any perspective 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 2 months. So 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. But 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. So it really is very consistent, if anything, is a predictor of future developmental milestone gain. And then Dr. Suter, could you talk a little bit about your perspective on how to prioritize gene therapy? And your own experience and your conversations with families.

Sure. So what I'm learning from my discussions with families is that ultimately, families care mostly about efficacy overall. And I think we're still in a phase where we will learn about ultimately about the efficacy, but NGN401 definitely has demonstrated in individuals, very, very promising course of developmental gains. So I have no fear that this would speak to families strongly in terms of choosing this gene therapy.

And if I may have 1 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?

Sure. That's another 2-part question. So 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. So very -- everything is on track from a CMC perspective.

Your next question comes from Mani Foroohar with Leerink Partners.

Congrats again on continued durable data showing benefits for these growth families. As we get closer and closer to an eventual regulatory filings, commercial availability, but presuming positive and bolden data help us understand how the evolution of this data will confirm the restart to developmental progression and how that informs your commercial and competitive strategy and messaging on an MSL basis, perhaps more than a sales basis.

Sure. So 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. So just to weigh in there, these developmental milestones are really not gain in a random fashion. But really, as you would expect them to occur biologically, right? So these individuals gain these milestones, reaching and tapping then subsequently whole handcraft than financing or based manipulation of object along with gains on other domains that are also acquired in a developmentally order sequence, which really clues us in that this is a restart of biological development and not random acquisition of individual skills.

And then I'll take the commercial strategy question. So 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 1 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, but 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 development that we've seen with what was our data. That leads into the second important strategic imperative that we're employing, which is to establish clear differentiation of NGN-401 with long-term clinical evidence. And there's where the MSLs come into that perspective. So 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. And 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. And 1 more quick follow-up, if I may. We talked a little bit about commercial positioning, et cetera. Can you give us a heads up on where you are in terms of managing manufacturing process capacity? Obviously, this is a large pool of patients that are diagnosed treated, many of whom already rolled off debut. How can we think about volume and capacity to be upon a vent for commercial launch and potential investments around infrastructure and for manufacturing.

So 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 and that can help to begin to support inventory build. We also have plenty of capacity available next year and beyond and owning our own manufacturing facility, it gives us the strategic flexibility to be able to support the adoption rates projected for commercial supply. So 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.

Your next question comes from Paul Matteis with Stifel

Congrats on the data. So as it relates to the efficacy, I wanted to just clarify 1 thing. Did you say that every single of the 47 milestones gained has been individually durable and all have been gained and sustained. And then for Dr. Suter, just from your clinician experience, have you ever seen patients in the age range in this Neurogen trial gain a milestone or 2 at this point in time in development spontaneously?

So to confirm, yes, all of the milestones are durable and sustained. Dr. Suter, do you want to talk about your experience.

Yes. No, I mean we followed our center, a couple of hundred red individuals. And I can say with confidence that, yes, you might see an individual skill gain, but you will not see a multi-domain scale acquisition as we've seen on the study.

Your next question comes from Mitchell Kapoor with HC Wainwright.

This is Aman on for Mitchell. Congrats on the fantastic data. I was just wondering from our perspective, we have brought up the ICV administration. And in your view, does it bold in enrollment and dosing support the ICD adoption, hypothesis or do you still see families decline or hesitate because of the route of administration?

So 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 for families in a onetime gene therapy. But from our perspective, we've had -- 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 and 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. So it's a onetime treatment that is lifelong and this is a lifelong disease. But Dr. Suter, please elaborate.

Sure. Yes. 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 -- and we know that ICV injection really gets the product to the brain areas where it matters the most. It's a fairly routine procedure for skilled neurosurgeon. It's performed on a daily basis across the U.S. and families do not are not deterred from this procedure at all. When they -- when we speak about the gene therapy. And suffice it to say that we have continuing in interest on the sites of families for this gene therapy.

So even after enrollment, you're seeing some demand come in.

Your next question comes from Whitney Ijem with Canaccord Genuity.

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 update on thinking about a potential 6 months in terms.

Thanks, Angela, for the question. And you can see, obviously, from our data that we have very robust data at 6 months with an average of 1.9 million milestones for patients, and that continues to deepen very significantly over time. We have asked the agency in the past several times, and 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. So the agency has been very clear that they're looking for a 12-month primary analysis for gene therapy in Rett syndrome. And so that is -- our trial design remains a 12-month primary endpoint.

Our last question comes from Simas Jorn with Rodman Renshaw.

My question is for Dr. Studer. So Casa is planning to meet with the FDA and then communicate a 6-month interim data to the -- in the first half of 2027 assuming that it does get approved based on 6-month interim data. How much do you think that roughly 6-month difference in data timing to Intesa and neuro gene therapy will realistically impact adoption of NGN104. RTs going to wait for the 12-month data from Intesa as well before deciding or patients are just going to go for which therapy is approved first.

Thanks, Sima, for the question. So I'll start and then 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. So it's important to note, in addition to that, that we will be continuing to follow our Phase I/II cohort -- and 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. But of course, next year, you can tack on another year a follow-up to that and then the year after, you'll have even more data. So you'll have some patients with more than 3 years of data coming out from the Phase I/II and 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. So there'll be embolden data. There'll be Phase I/II data. And so in that context, then Dr. Suter is a timing of a few months difference of 1 therapy being available for another therapy is that the main driver -- or are there other factors that families will consider?

Yes, I don't think that will be the driver. Really, ultimately, I'll circle back to what I said all along, it will depend on the efficacy data itself.

That concludes our Q&A session. I will now turn the conference back over to Rachel McMinn for closing remarks.

Thank you, operator, and 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.